Home About us Contact
|
Home About us Contact | ||
|
|
||
HLA-DR
Terms modified by HLA-DR Selected AbstractsIncreased immature hematopoietic progenitor cells CD34+/CD38dim in myelodysplasiaCYTOMETRY, Issue 2 2006Mariela B. Monreal Abstract Background Myelodysplastic syndromes (MDS) are clonal disorders affecting hematopoietic progenitor cells (HPC). Despite the relevance of clonal CD34+ cells in developing MDS, only few studies analyze the phenotype of this cell population. The aim of this study was to evaluate phenotypic changes on HPC in MDS that could reflect abnormalities in the differentiation process of stem cells. Methods We analyzed the expression of CD38 and HLA-DR on CD34+ cells by flow cytometry in 36 patients with MDS, as well as in healthy donors (n = 12) and patients with other hematological disorders: non-Hodgkin lymphomas and multiple myeloma, both in complete remission (CR) (n = 32); acute lymphoblastic leukemia in CR (n = 17); de novo acute myeloblastic leukemia (AML) at diagnosis (n = 22) and in CR (n = 37); and AML secondary to MDS at diagnosis (n = 19). Cases with available karyotype were grouped according to the International Prognostic Scoring System (IPSS). Results Compared to normal BM, the fraction of immature HPC, characterized as CD34+bright, intermediate FSC/SSC, and CD38dim, was significantly increased in high risk MDS and secondary AML, but not in low risk MDS, (P , 0.001, P = 0.03, and P = 0.7). De novo AML showed decreased immature HPC. High numbers of immature HPC correlated with higher IPSS risk groups (P = 0.05) and showed significant impact on disease progression (P = 0.03). Conclusion Our study confirms that evaluation of CD38 expression pattern on HPC is an easy and reproducible test that allows evaluating the immature subset of progenitor cells. Increased immature HPC in high risk MDS and secondary AML may reflect blocked differentiation of CD34+ cells in these diseases. © 2006 International Society for Analytical Cytology [source] Monitoring of monocyte functional state after extracorporeal circulation: A flow cytometry studyCYTOMETRY, Issue 1 2004Silverio Sbrana Abstract Background Cardiovascular surgery with cardiopulmonary bypass (CPB) induces systemic inflammation and postoperative complications depending on pro- and anti-inflammatory mechanisms. Activated polymorphonuclear cells and monocytes may be responsible for morbidity associated with CPB. Knowledge of the monocyte functional state in particular may help to develop protective interventions. Methods Samples were drawn from venous peripheral blood (basal condition, at 4 and 24 h after CPB) and coronary blood (before and after cardioplegic arrest) of 14 patients undergoing cardiac surgery. The following phenotypic and functional parameters of the monocyte population were studied by flow cytometry: surface molecules expression (CD18, CD11a, CD11b, CD14, CD15, CD45, HLA-DR, and Toll-like receptor [TLR]-4), myeloperoxidase (MPO) content, and intracellular cytokine production (tumor necrosis factor [TNF]-,, interleukin [IL]-1,, IL-6, and IL-8). Results Cardiac surgery with CPB induced down-modulation of surface molecules expression on peripheral monocytes, especially at 24 h after CPB, for CD18, CD11a, and CD11b (P < 0.003) and for the CD15 adhesive cluster (P = 0.0028) and HLA-DR (P < 0.001). At 4 h after CPB, downregulation was observed for CD14 (P = 0.004), CD45 (P = 0.014), and CD15 (P = 0.0056). A loss of MPO was detected in venous peripheral (at 24 h after CPB, P = 0.01) or coronary (at reperfusion, P < 0.02) blood. The CD15 cluster complex exhibited a down-modulation in coronary blood (at reperfusion, P = 0.0003). Spontaneous intracellular production of IL-1,, IL-6, and IL-8 decreased at 24 h after CPB (P < 0.05). Conclusions The down-modulation of integrins and adhesive receptor expression and the loss of MPO suggest a strong activation and shedding reaction of circulating monocyte after CPB, further exacerbated by contact with coronary ischemic vessels. The changes of differentiation antigens may reflect the appearance of a partially immature population immediately after CPB. The reduced proinflammatory cytokine production, observed at 24 h after CPB, suggests a functional polarization of circulating monocytes. © 2003 Wiley-Liss, Inc. [source] n-3 polyunsaturated fatty acid supplementation, monocyte adhesion molecule expression and pro-inflammatory mediators in Type 2 diabetes mellitusDIABETIC MEDICINE, Issue 1 2001M. J. Sampson SUMMARY Aims To examine the effect of n-3 polyunsaturated fatty acid supplements on the monocyte surface expression of adhesion molecules involved in pro-atherogenic monocyte,endothelial interactions, and on pro-inflammatory mediators in Type 2 diabetes mellitus. Methods Twenty-nine subjects with Type 2 diabetes and 21 controls without diabetes were studied. Monocyte expression of leucocyte function-associated antigens 1 and 3, intercellular adhesion molecule-1, and the major histocompatibility complex class II molecule HLA-DR were measured using a laser flow cytometric method. Supplementation with 2.08 g n-3 fatty acids for 21 days was undertaken and measurements repeated. Plasma soluble adhesion molecule concentrations, plasminogen activator inhibitor-1 activity and antigen and pro-inflammatory mediators (cysteinyl leukotriene and monocyte leukotriene B4) were also measured. Results Groups did not differ in monocyte expression of adhesion molecules or HLA-DR, or in leukotriene production although plasma soluble adhesion molecule concentrations were higher in the diabetes groups (P < 0.05). n-3 fatty acid supplementation influenced neither the expression of these molecules nor plasma soluble adhesion molecule concentrations or leukotriene production. Conclusions This study does not support increased monocyte adhesion molecule expression or abnormal monocyte production of pro-inflammatory mediators as mechanisms for increased atherogenic risk in Type 2 diabetes. Cardioprotective actions of n-3 fatty acids may not be mediated through these mechanisms. [source] Cytologic features and frequency of plasmacytoid dendritic cells in the lymph nodes of patients with histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease)DIAGNOSTIC CYTOPATHOLOGY, Issue 7 2010I.A.C., Koji Kishimoto C.T., Ph.D. Abstract Histiocytic necrotizing lymphadenitis (HNL), also known as Kikuchi-Fujimoto disease, is a benign and self-limiting disease. It is histologically characterized by nodal lesions that show the infiltration of histiocytes, lymphoid cells, myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs), along with either apoptotic or karyorrhexic nuclear debris. pDCs have been proposed to be lymphoid early-committed immature DCs which are positive for CD123, CD303, CD68, and HLA-DR but negative for fascin, a mature DC marker, as well as CD13 and CD33,which are mDC markers. In the present study, we analyzed the cytomorphologic features and frequency of pDCs in the lymph nodes of HNL patients. Because the cytologic apprearance of pDCs with Papanicolau staining was quite similar to that of large lymphocytes, immunocytochemistry against CD123 was necessary for the distinction of pDCs. Counting the number of CD123-positive pDCs in the HNL lymph nodes revealed that pDCs more frequently infiltrated the lymph nodes in the setting of HNL than in either reactive lymphadenitis or T and B cell lymphoma. In addition, interestingly, the numberof pDCs did not depend on the age of the HNL lesion, thus suggesting that pDCs are excellent indicators for the cytologic diagnosis of HNL. Diagn. Cytopathol. 2010. © 2009 Wiley-Liss, Inc. [source] Extensive flow cytometric characterization of plasmacytoid dendritic cell leukemia cellsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2005Laszlo Gopcsa Abstract:,Objectives:,Accumulating evidence suggests that non-T, non-B cell CD4+CD56+ neoplasms with lymphoblastic morphology include clinically and immunophenotypically diverse entities. Although their cells of origin or classification are still controversial several entities clearly represent a distinct type of neoplasms that are clinically aggressive. Methods:,In this work we present the immunophenotypic and genotypic features of bone marrow (BM), peripheral blood (PB), lymph node and skin lymphocytes from a patient diagnosed as plasmacytoid dendritic cell leukemia involving the skin, BM, PB, lymph nodes, liver and spleen. For determination of immunophenotypic characteristics of malignant plasmacytoid dendritic cells 73 monoclonal antibodies detecting lineage markers, chemokine receptors, cytokine receptors, activation, and co-stimulatory molecules were used. Results and conclusion:,The malignant cells proved to express CD4+, CD56+ lineage negative leukemia phenotype characteristically positive for CD36, CD38, CD40, CD45, CD45RA, CD68, CD123, CD184, HLA-DR, BDCA2, and granzyme-B corresponding to the preplasmacytoid dendritic cell developmental stage. The presence of CD11a/CD18, CD84, CD91, CD95, ,v,5, CDw197, and the absence of CD52 and CD133 in this case can be regarded as additional features of malignant cells. Completing the immunophenotypes with multidrug resistance function can provide additional information for characterizing pDC leukemia. [source] Influenza A virus abrogates IFN-, response in respiratory epithelial cells by disruption of the Jak/Stat pathwayEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2008Kohsaku Uetani Abstract The innate immunity to viral infections induces a potent antiviral response mediated by interferons (IFN). Although IFN-, is detected during the acute stages of illness in the upper respiratory tract secretions and in the serum of influenza A virus-infected individuals, control of influenza A virus is not dependent upon IFN-, as evidenced by studies using anti-IFN-, Ab and IFN-,,/, mice. Thus, we hypothesized that IFN-, is not critical in host survival because influenza A virus has mechanisms to evade the antiviral activity of IFN-,. To test this, A549 cells, an epithelial cell line derived from lung adenocarcinoma, were infected with influenza virus strain A/Aichi/2/68 (H3N2) (Aichi) and/or stimulated with IFN-, to detect IFN-,-stimulated MHC class II expression. Influenza A virus infection inhibited IFN-,-induced up-regulation of HLA-DR, mRNA and the IFN-, induction of class II transactivator (CIITA), an obligate mediator of MHC class II expression. Nuclear translocation of Stat1, upon IFN-, stimulation was significantly inhibited in influenza A virus-infected cells and this was associated with a decrease in Tyr701 and Ser727 phosphorylation of Stat1,. Thus, influenza A virus subverts antiviral host defense mediated by IFN-, through effects on the intracellular signaling pathways. [source] TLR9 stimulation drives naïve B cells to proliferate and to attain enhanced antigen presenting functionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2007Wei Jiang Abstract Mechanisms that regulate naïve B cell proliferation and function are incompletely defined. In this study, we test the hypothesis that naïve B cell expansion, survival and ability to present antigen to T,lymphocytes can be directly modulated by Toll-like receptor (TLR) agonists. In the absence of B cell receptor stimulation, CpG oligonucleotide, a TLR9 agonist, was particularly efficient in inducing naïve B cell proliferation and survival. Although the expanded naïve B cells did not mature into CD27+ or IgG+ memory B cells, these cells did differentiate into IgM-secreting cells with increased surface expression of HLA-DR, CD40 and CD80. This was associated with an increased potential for these B cells to activate allogeneic T cells. We propose that the activation and expansion of naïve B cells induced by TLR9 agonists could enhance the potential of these cells to interact with cognate antigens and facilitate cell-mediated immune responses. [source] Intestinal double-positive CD4+CD8+ T,cells are highly activated memory cells with an increased capacity to produce cytokinesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2006Bapi Pahar Dr. Abstract Peripheral blood and intestinal CD4+CD8+ double-positive (DP) T,cells have been described in several species including humans, but their function and immunophenotypic characteristics are still not clearly understood. Here we demonstrate that DP T,cells are abundant in the intestinal lamina propria of normal rhesus macaques (Macaca mulatta). Moreover, DP T,cells have a memory phenotype and are capable of producing different and/or higher levels of cytokines and chemokines in response to mitogen stimulation compared to CD4+ single-positive T,cells. Intestinal DP T,cells are also highly activated and have higher expression of CCR5, which makes them preferred targets for simian immunodeficiency virus/HIV infection. Increased levels of CD69, CD25 and HLA-DR, and lower CD62L expression were found on intestinal DP T,cells populations compared to CD4+ single-positive T,cells. Collectively, these findings demonstrate that intestinal and peripheral blood DP T,cells are effector cells and may be important in regulating immune responses, which distinguishes them from the immature DP cells found in the thymus. Finally, these intestinal DP T,cells may be important target cells for HIV infection and replication due to their activation, memory phenotype and high expression of CCR5. [source] Copolymer effects on microglia and T,cells in the central nervous system of humanized miceEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2005Zsolt Illes The random amino acid copolymers FYAK and VWAK ameliorate EAE in a humanized mouse model expressing both a human transgenic myelin basic protein (MBP)85,99-specific T,cell receptor and HLA-DR2. Here we show that microglia isolated from the central nervous system (CNS) of humanized mice with EAE induced by MBP85,99 and treated with these copolymers had reduced expression of HLA-DR, and thus reduced capacity to present MBP85,99 and activate transgenic T,cells. In vitro microglia up-regulated empty HLA-DR2 upon activation with GM-CSF with or without LPS or IFN-,, but not with IL-4 or IL-10. Correspondingly, gene chip arrays showed that the CNS of untreated and YFAK-treated mice differentially expressed pro- and anti-inflammatory molecules during MBP85,99-induced EAE. Interestingly, microglia expressed the full-length ,,,and ,,,subunits of the tetrameric adaptor protein complexes AP-1 and AP-2 respectively, but after treatment with GM-CSF these complexes were cleaved, as had been found in immature dendritic cells derived from bone marrow. Strikingly, in vivo the perivascular lymphocyte infiltration seen in untreated mice immunized with MBP85,99 was composed of equal numbers of hV,2+ MPB85,99-specific transgenic and hV,2, endogenous T,cells, while the much smaller infiltration seen after treatment with YFAK was composed predominantly of hV,2, endogenous T,cells. [source] About the cutaneous targets of bexarotene in CTCL patientsEXPERIMENTAL DERMATOLOGY, Issue 8 2010Anne Chantal Knol Please cite this paper as: About the cutaneous targets of bexarotene in CTCL patients. Experimental Dermatology 2010; 19: e299,e301. Abstract:, There are several approved therapies for cutaneous T-cell lymphoma (CTCL). The retinoids are one of the major biologic response modifiers used in CTCL, producing good response rates but few complete responses. Bexarotene has been demonstrated to act on malignant T-cells by inducing their apoptosis, but nothing is known about its role on keratinocytes and Langerhans cells. Immunohistochemical analysis using CD1a, HLA-DR, ICAM-1 (activation markers), CD95 and CD40 (apoptosis markers) was conducted on frozen sections of bexarotene-exposed cutaneous explants and skin biopsy specimens from patients treated with bexarotene. None of the studied markers was significantly modulated both on cutaneous explants and on skin biopsy specimens after treatment with bexarotene, compared to controls. Langerhans cells and keratinocytes do not appear to play a central role in the therapeutic control of CTCL by bexarotene therapy. The main bexarotene's target thus remains T-cells by inducing their apoptosis, a mechanism that is different from the other retinoids used in CTCL. [source] Neuropilin-1 expression identifies a subset of regulatory T cells in human lymph nodes that is modulated by preoperative chemoradiation therapy in cervical cancerIMMUNOLOGY, Issue 1 2008Alessandra Battaglia Summary We examined the phenotype and function of CD4+ T cells expressing the semaphorin III receptor neuropilin-1 (Nrp1) in human lymph nodes and peripheral blood. In lymph nodes, Nrp1 identified a small regulatory CD4+ CD25high T-cell subpopulation (Nrp1+ Treg) that expressed higher levels of Forkhead box P3 (Foxp3) message and protein than Nrp1, Treg, and various molecular markers of activated Treg, i.e. CD45RO, human leucocyte antigen (HLA)-DR and glucocorticoid-induced tumour necrosis factor receptor (GITR). Similarly to conventional Treg, Nrp1+ Treg proliferated poorly in vitro, and exerted contact-dependent in vitro suppression of T-cell proliferation and cytokine secretion. However, Nrp1+ Treg were more efficient than Nrp1, Treg at inducing suppression. Nrp1 was also expressed on a small subpopulation of CD25int and CD25, CD4+ T cells that expressed more Foxp3, CD45RO, HLA-DR and GITR than their Nrp1, counterparts. In contrast, in peripheral blood Nrp1 identified a minor CD4+ T-cell subset that did not display the phenotypic features of Treg lacking Foxp3 expression and marginally expressing CD25. Hence, the function of Nrp1+ CD4+ T cells seemingly depends on their anatomical location. In a previous report, we proposed that Treg may curb the anti-tumour T-cell response in cervical cancer. We show here that Treg and Nrp1+ Treg levels dropped in the tumour-draining lymph nodes of patients with cervical cancer following preoperative chemoradiotherapy in a direct relationship with the reduction of tumour mass, suggesting that suppressor cell elimination facilitated the generation of T cells mediating the destruction of the neoplastic cells left behind after cytotoxic therapy. [source] CD1d-restricted natural killer T cells are potent targets for human immunodeficiency virus infectionIMMUNOLOGY, Issue 1 2003Richardson Fleuridor Summary Invariant human natural killer T cells (NKT) express a restricted T-cell receptor (TCR) V,24V,11 repertoire. These cells share both phenotypic and functional similarities between NK and T cells. Given the emerging role of NKT cells as critical cells in bridging the gap between innate and adaptive immunity, we examined their susceptibility to productive human immunodeficiency virus (HIV) infection by T-tropic, M-tropic, and primary isolates of HIV. We generated three human NKT cell clones (CA5, CA29, and CA31). Phenotypic characterization of these V,24+ V,11+ clones indicated that they were predominately positive for CD4, CD161, HLA-DR, CD38, CD45RO, and CD95 expression. The NKT cell clones expressed significantly more surface CCR5 molecules/cell and lower CXCR4 molecules/cell than phytohaemagglutinin-stimulated peripheral blood mononuclear cells (PBMC). Consistent with the surface expression of CCR5 and CXCR4, the NKT clones were also selectively susceptible to HIV M-tropic, T-tropic, and primary isolate infection, as evaluated by both HIV p24 enzyme-linked immunosorbent assay and intracellular staining of HIV proteins. The amount of p24 production was dependent on the NKT clone studied and the HIV strain used. Clones CA29 and CA31 were also susceptible to HIV IIIB infection. The virions produced by these clones were able to productively infect PHA-stimulated PBMCs with the same kinetics as for primary infection of CD4+ blast. Collectively, this data demonstrates that NKT cells can be a target for productive HIV infection but with a lag in the time to peak p24 production. [source] Granulocyte/macrophage-colony stimulating factor and interleukin-4 expand and activate type-1 dendritic cells (DC1) when administered in vivo to cancer patientsINTERNATIONAL JOURNAL OF CANCER, Issue 2 2003Sylvia M. Kiertscher Abstract Two rare populations of cells with the features of dendritic cell precursors (preDC) can be identified in human peripheral blood. PreDC1 are HLA-DR+/CD11c+ cells which mature into DC1 capable of stimulating Th1 responses. In contrast, preDC2 are HLA-DR+/CD11c,/CD123+ cells that promote Th2 responses when matured into DC2. We hypothesized that administration of GM-CSF and IL-4, growth factors for DC1, would specifically augment the number and function of circulating DC1 in vivo. Patients with advanced metastatic cancer were treated with GM-CSF (2.5 ,g/kg/day) and IL-4 (4 or 6 ,g/kg/day) for 7 days. Cytokine administration at the highest IL-4 dose produced an average 2.3-fold increase in preDC2 number, but a 6.5-fold increase in preDC1, resulting in an increased ratio of circulating preDC1:preDC2 from 1.4:1 pre-treatment to 4.3:1 after cytokine therapy. DC1 precursors identified after in vivo therapy were larger, more complex and expressed higher levels of HLA-DR, CD11c and CD80 than pre-treatment cells. DC1 isolated from the peripheral blood of patients receiving GM-CSF/IL-4 therapy demonstrated MLR activity comparable to that of monocyte-derived DC generated in vitro from the patients' pre-treatment blood using GM-CSF and IL-4. We conclude that systemic administration of GM-CSF and IL-4 preferentially expands and matures the preDC1 population in vivo. These effects correlate with antigen-presenting activity, providing a mechanism by which systemic GM-CSF and IL-4 might stimulate anti-tumor immunity in vivo. © 2003 Wiley-Liss, Inc. [source] Two Japanese cases of lichen planus pigmentosus-inversusINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 7 2007Aki Kashima MD Case 1 was a 51-year-old Japanese woman. She presented with an asymptomatic brown macule located on the right axilla of 2 months' duration. The smooth macule was 2 cm in diameter with a sharp demarcation (Fig. 1A). Figure 1. Photographs of skin lesions in two patients. (A) Case 1. Well-circumscribed brown macule without an active red border in the central portion of the right axilla. (B) Case 2. Symmetric distribution of brown macules without an active red border in the popliteal fossae Case 2 was a 62-year-old Japanese man. He presented with asymptomatic, symmetric, gray,brown macules located on the groin, axillae, and popliteal region of 6 months' duration. The smooth macules were several millimeters to centimeters in diameter and sharply demarcated (Fig. 1B). Oral or nail lesions, previous inflammatory processes in affected areas, and internal malignancies were absent. A causal relationship with drugs, recent sun exposure, or trauma could not be identified. Findings for work-up, including blood cell count, fasting blood sugar levels, liver function, serum electrolyte levels, serum electrophoresis, urinalysis, antinuclear antibodies, and serological examinations for human hepatitis viruses and syphilis, were within normal limits or negative. The lesions gradually disappeared without medication within 6 months. Biopsy specimens showed a lymphocytic infiltrate with basal vacuolar changes and prominent melanin incontinence in the upper dermis (Fig. 2A). The band-like lymphocytic infiltrate was moderate in Case 1 and mild in Case 2. Immunohistochemistry showed infiltrative CD8+ T lymphocytes with keratinocytic damage, indicating cytotoxic injury of the keratinocytes (Fig. 2B). Both the epidermis and the upper dermis contained CD1a+ cells (Fig. 2C). The keratinocytes focally and weakly expressed HLA-DR (Fig. 2D). These findings were identical in samples from both patients. Figure 2. Light and immunohistochemical microphotographs. (A) Mild, band-like, lymphocytic infiltrate with basal vacuolar change and prominent melanin incontinence in the upper dermis with apoptosis or necrosis of keratinocytes. (B) Epidermal infiltrate of CD8+ T lymphocytes with keratinocytic damage. (C) CD1a+ cells in the upper dermis. (D) Keratinocytes focally and weakly express HLA-DR (original magnifications: A, ×200; B,D, ×400) [source] Implementation of monoclonal antibody fluorescence on the Abbott CELL-DYN Sapphire haematology analyser: evaluation of lymphoid, myeloid and platelet markersINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 2 2006B. JOHANNESSEN Summary Apart from qualitative flags, that are typically inefficient and uninformative, haematology instruments provide little meaningful information about lymphocyte populations or the lineage of atypical or immature elements, The CELL-DYN Sapphire haematology analyser uses integrated optical and fluorescence (488 nm) measurements, with FL1 (FITC) and FL2 (PE) detectors being configured for fluorescent analysis. As monoclonal antibodies (Mab) are widely used as cellular probes, and are likely to constitute the future basis for immunodifferentials, we explored the feasibility of implementing immunofluorescence on this routine haematology analyser. An extensive series of Mab (CD2, CD3, CD4, CD8, CD11b, CD13, CD14, CD16, CD19, CD22, CD33, CD34, CD41, CD42b, CD45, CD56, CD61, CD64, CD235a and HLA-DR) were tested singly or in FITC/PE combinations. Analyser processing and data acquisition was achieved using CD-Sapphire automated CD61 immunoplatelet or CD3/4/8 assay procedures and, apart from mixing EDTA-blood and antibody, no further sample manipulation was required. Downloaded raw files were processed with cytometry software, and all evaluated reagents showed population discrimination analogous to flow cytometry. Practical procedures were straightforward and required minimal operator training. Extended information that can be obtained from monoclonal antibodies with a routine haematology analyser has the potential to extend haematology laboratory practices and positively impact laboratory and clinical efficiency. [source] A case study of familial anti,phospholipid syndromeINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 5 2002S. Bhattacharya Summary Anti-phospholipid syndrome (APS) may have a familial association. In particular, association has been demonstrated between APS and HLA-DR 4, HLA-DR 7 and HLA-DRB1 14 alleles. Here we have described a family sharing the common haplotype of HLA-DR 7 where definite or probable anti,phospholipid syndrome has been identified in six of the seven family members. Apart from the index case, the other family members have demonstrated partial association in spite of sharing the incriminated haplotype. This could be ascribed either to variable penetrance of the involved genes or to the role of an unaccounted for environmental factor. Alternatively, it is possible that the coexistence of the HLA haplotype and the anti-phospholipid antibodies is coincidental. [source] Strategies for developing multi-epitope, subunit-based, chemically synthesized anti-malarial vaccinesJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 5b 2008M. E. Patarroyo ,,Introduction ,,P. falciparum invasion of RBCs ,,Merozoite proteins involved in invading erythrocytes ,,Erythrocyte proteins involved in merozoite invasion ,,The state of current worldwide anti-malarial vaccine approaches ,,A rational approach towards developing subunit-based synthetic vaccines ,,The immune response elicited by conserved HABPs ,,Structural analysis of native and modified HABPs ,,Secondary structure analysis ,,Native and modified HABP 3D structure explains some immunological phenomena ,,Supporting the haplotype , and allele-conscious TCR concept ,,Modified HABPs' 3D structure revealed a fit into HLA molecules ,,Conclusion Abstract An anti-malarial vaccine against the extremely lethal Plasmodium falciparum is desperately needed. Peptides from this parasite's proteins involved in invasion and having high red blood cell-binding ability were identified; these conserved peptides were not immun genic or protection-inducing when used for immunizing Aotus monkeys. Modifying some critical binding residues in these high-activi binding peptides' (HABPs') attachment to red blood cells (RBC) allowed them to induce immunogenicity and protection against expermental challenge and acquire the ability to bind to specific HLA-DRp1* alleles. These modified HABPs adopted certain characterist structural configurations as determined by circular dichroism (CD) and 1H nuclear magnetic resonance (NMR) associated with certain HLA-DR,1* haplotype binding activities and characteristics, such as a 2-Å-distance difference between amino acids fitting into HLA-DRp1 Pockets 1 to 9, residues participating in binding to HLA-DR pockets and residues making contact with the TCR, suggesting haplotyp and allele-conscious TCR. This has been demonstrated in HLA-DR-like genotyped monkeys and provides the basis for designing high effective, subunit-based, multi-antigen, multi-stage, synthetic vaccines, for immediate human use, malaria being one of them. [source] HLA phenotypes and outcomes of hepatitis B virus infection in Taiwan,JOURNAL OF MEDICAL VIROLOGY, Issue 1 2004Ya-Fang Wu Abstract The relationship of HLA phenotype and outcome of hepatitis B virus (HBV) infection was studied in two ethnic groups of Taiwan: Han Chinese and Taiwanese Aborigines. In Han Chinese, the study groups consisted of 98 persons who tested both hepatitis B surface antigen (HBsAg) and anti-HBs negative (Uninfected Group), 324 persons who tested HBsAg negative and both anti-HBs and anti-HBc positive (Recovered Group), and 98 patients who tested HBsAg positive for at least 6 months (Chronically Infected Group). In Taiwanese Aborigines, the study groups consisted of 34 persons in Uninfected Group, 229 persons in the Recovered Group, and 138 patients in the Chronically Infected Group. All subjects were tested for HLA (A, B, DRB1) phenotypes by sequence-specific oligonucleotide probe hybridization (SSOPH). HLA-DR*0406 was significantly more frequent in the Recovered Group, compared with the Chronically Infected Group (P,<,0.001) in Han Chinese. There was a significant excess of HLA-B*4001 (P,=,0.045) in the Recovered Group, compared with the Chronically Infected Group in Taiwanese Aborigines. The observation that different HLA phenotypes associated with recovery from HBV infection in different racial groups implies that various HLA molecules could present different HBV epitopes to induce effective immune responses. J. Med. Virol. 72:17,25, 2004. © 2004 Wiley-Liss, Inc. [source] MYELIN PROTEIN P-0-SPECIFIC IGM PRODUCING MONOCLONAL B CELL LINES WERE ESTABLISHED FROM POLYNEUROPATHY PATIENTS WITH MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE (MGUS)JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 4 2002M Kvarnstrom Monoclonal expansion of B cells and plasma cells, producing antibodies against ,self' molecules, can be found not only in different autoimmune diseases, such as peripheral neuropathy (PN), but also in malignancies, such as Waldenstroms'macroglobulinaemia and B-type of chronic lymphocytic leukaemia (B-CLL), as well as in precancerous conditions including monoclonal gammopathy of undetermined significance (MGUS). About 50% of patients with PN-MGUS have serum antibodies against peripheral nerve myelin, but the specific role of these antibodies remains uncertain. The aims of the study were to establish, and characterize, myelin-specific B cell clones from peripheral blood of patients with PN-MGUS, by selection of cells bearing specific membrane Ig-receptors for myelin protein P-0, using beads coated with P-0. P-0-coated magnetic beads were used for selection of cells, which subsequently were transformed by Epstein-Barr virus. The specificity of secreted antibodies was tested by ELISA. Two of the clones producing anti-P-0 antibodies were selected and expanded. The magnetic selection procedure was repeated and new clones established. The cells were CD5(+) positive, although the expression declined in vitro over time. The anti-P-0 antibodies were of IgM-lambda type. The antibodies belonged to the V(H)3 gene family with presence of somatic mutations. The IgM reacted with P-0 and myelin-associated glycoprotein (MAG), and showed no evidence for polyreactivity, in contrast to other IgM CD5(+) clones included in the study as controls. The expanded clones expressed CD80 and HLA-DR, which is compatible with properties of antigen-presenting cells. The immunomagnetic selection technique was successfully used for isolation of antimyelin protein P-0-specific clones. The cell lines may provide useful tools in studies of monoclonal gammopathies, leukaemia, and autoimmune diseases, including aspects of antigen-presentation by these cells followed by T cell activation. [source] Sequence variation in the hypervariable region 1 of hepatitis C virus and posttransplantation recurrent hepatitisLIVER TRANSPLANTATION, Issue 10 2003Enrico Silini Hepatitis C virus (HCV) shows remarkable genetic variation in both populations and individuals, in whom it circulates as quasispecies (QS). Sequence variation within an infected host has adaptive significance and reflects the modes and intensity of selection mechanisms operating on the virus. We investigated the sequence diversity of hypervariable region 1 of HCV in liver transplant recipients and correlated it with the recurrence of hepatitis. Twenty-six patients were considered during a 2-year period; all had graft reinfection, and 14 patients developed hepatitis recurrence. Cloned sequences were obtained from sera collected before or within 1 month after orthotopic liver transplantation (OLT) and at 3 and 24 months thereafter. Sequence diversity within single sera and over consecutive samples was analyzed quantitatively by matrix comparison and phylogenetic analysis. Propagation of viral QS in the graft was markedly dependent on individual factors. Viral QS in post-OLT sera were less complex and evolved slower compared with immunocompetent subjects with chronic hepatitis. Sequence variation was greater during the first 3 months post-OLT than during the remaining period. Genetic diversity within single samples was not related to hepatitis recurrence or other clinical features. Conversely, sequence diversity over consecutive samples was reduced in patients who experienced hepatitis recurrence, in particular, in those infected with genotype 1b and with an HLA-DR mismatched graft. Selection of viral sequences was markedly impaired in liver transplant recipients and tended to be greater early after OLT. Reduced sequence turnover correlated negatively with the outcome of graft reinfection. [source] B-cell activation in patients with irritable bowel syndrome (IBS)NEUROGASTROENTEROLOGY & MOTILITY, Issue 6 2009L. öhman Abstract, Patients with irritable bowel syndrome (IBS) may have a low grade immune activation. However, little is known about the properties of B cells of IBS patients. We therefore investigated activation level and antigen presenting phenotype of blood B cells of IBS patients. We also examined B-cell responses to lipopolysaccharide (LPS) and probiotic bacteria. Blood samples were obtained from 74 IBS patients and 30 healthy subjects. Peripheral blood mononuclear cells were isolated and stimulated with LPS or an UV-light inactivated bacterial cocktail consisting of the probiotic Gram-positive strains; Lactobacillus paracasei ssp. paracasei 19, Lactobacillus acidophilus La5, Bifidobacterium lactis B612. The phenotype of CD19+ B cells was investigated by flow cytometry before and after 72 h cell culture. Furthermore, IBS symptom severity was assessed. B cells isolated from blood of IBS patients displayed an amplified activation level as demonstrated by increased cell surface expression of IgG, and also the costimulatory molecules CD80 and CD86. Expression of antigen presenting HLA-DR and costimulatory molecule CD40 on B cells was, however comparable in IBS patients and controls. B cells of IBS patients displayed an impaired ability to increase expression of CD80, but not CD86, in response to both LPS as well as probiotic bacteria stimulations. To conclude, blood B cells of IBS patients have an increased activation level. Bacterial component induced expression of the costimulatory molecule CD80, regarded as important for tolerance induction, is impaired. These data suggest that B-cell antigen presentation in IBS patients is associated with altered capacity of providing costimulation to T cells. [source] Glial cytoplasmic inclusions and tissue injury in multiple system atrophy: A quantitative study in white matter (olivopontocerebellar system) and gray matter (nigrostriatal system)NEUROPATHOLOGY, Issue 3 2008Keisuke Ishizawa Glial cytoplasmic inclusions (GCIs) and microglia were quantified in 12 cases of multiple system atrophy (MSA) with special reference to their association with histologically defined lesion severity. The targets of the analysis were white matter (cerebellum, pontine base) and gray matter (putamen, substantia nigra). First, the lesion severity was defined: for white matter, the degree of demyelination and tissue rarefaction were semi-quantified on Klüver-Barrera (KB) sections as grade I (mildly injured), II (moderately injured), and III (severely injured); for gray matter, neurons and astrocytes were counted on KB and glial fibrillary acidic protein-immunostained sections, respectively. Next, the GCI burden was quantified on sections immunostained for ,-synuclein, phosphorylated ,-synuclein, and ubiquitin and the microglial burden was quantified on sections immunostained for HLA-DR. In white matter, the GCI and microglial burdens were the greatest when the tissue injury was mild and/or moderate (grade I and/or grade II), and they became less prominent when the tissue injury became more severe (grade III). In gray matter, in contrast, the GCI and microglial burdens failed to show significant correlations with the lesion severity. Our result suggests that the amount of GCIs as well as that of microglia is reduced when the tissue injury becomes severe in vulnerable white matter areas, but not in vulnerable gray matter areas, of MSA. It also suggests that there seems to be a difference between gray matter and white matter in the way GCIs and microglia participate in the degenerative process of MSA. [source] Remyelination can be extensive in multiple sclerosis despite a long disease courseNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 3 2007R. Patani Experimental studies using models of multiple sclerosis (MS) indicate that rapid and extensive remyelination of inflammatory demyelinated lesions is not only possible, but is the normal situation. The presence of completely remyelinated MS lesions has been noted in numerous studies and routine limited sampling of post mortem MS material suggests that remyelination may be extensive in the early stages but eventually fails. However, visual macroscopic guided sampling tends to be biased towards chronic demyelinated lesions. Here we have extensively sampled cerebral tissue from two MS cases to investigate the true extent of remyelination. Sections were cut from 185 cerebral tissue blocks and stained with haematoxylin and eosin (H&E), luxol fast blue and cresyl fast violet (LFB/CFV) and anti-myelin oligodendrocyte glycoprotein, human leucocyte antigen-DR (HLA-DR) and 200 kDa neurofilament protein antibodies. Demyelinated areas were identified in 141 blocks, comprising both white matter (WMLs) and/or grey matter lesions. In total, 168 WMLs were identified, 22% of which were shadow plaques, 73% were partially remyelinated and only 5% were completely demyelinated. The average extent of lesion remyelination for all WMLs investigated was 47%. Increased density of HLA-DR+ macrophages and microglia at the lesion border correlated significantly with more extensive remyelination. Results from this study of two patients with long standing disease suggest that remyelination in MS may be more extensive than previously thought. [source] Immunohistochemical study of oral lichen planus associated with hepatitis C virus infection, oral lichenoid contact sensitivity reaction and idiopathic oral lichen planusORAL DISEASES, Issue 5 2001H Mega OBJECTIVES:,Oral lichen planus (OLP) is a common mucocutaneous disorder and might be associated to a possible pathogenic relationship with hepatitis C virus (HCV) infection or hypersensitivity to dental alloy. We examined the clinical and immunohistochemical features of OLP associated with HCV infection (OLP-HCV), oral lichenoid contact sensitivity reaction (OLCSR), and idiopathic oral lichen planus (iOLP). The immunohistochemical expressions of CD4, CD8, B cells, Class II major histocompatibility complex antigen (HLA-DR), S-100, HSP60, Proliferating cell nuclear antigen (PCNA) and Ki-67 were compared to study the pathogenic differences of the three OLP groups. MATERIALS AND METHODS:,Three groups of OLP patients, (1) OLP-HCV patients (n=17), (2) OLCSR patients (n=10) and (3) iOLP patients (n=14) were retrieved from clinical records and tissues examined immunohistochemically by the avidin,biotin-complex technique. RESULTS:,The patients with OLP-HCV showed widespread lesions. The proportion of CD8+ cells was found to be significantly higher in the lamina propria of the OLP-HCV patients and a significantly lower proportion of CD8+ cells of the OLCSR patients was noticed in the epithelium or the connective tissue papillae than in the iOLP patients. There were no significant differences in either the number of CD4+ cells or B cells between the three OLP groups. No significant differences in the number of HLA-DR+ cells were found between the three OLP groups and some OLP-HCV patients showed a significant increase of S-100+ cells in the epithelium compared with iOLP patients. There were no significant differences in either the number of PCNA+ or Ki-67+ cells between the groups. The patients showed similar weak expressions of HSP60 in the three OLP groups. CONCLUSION:,The different distributions of the CD8+ cells that could have functionally different roles might be related to the distinct pathogenic mechanisms in the three OLP groups. [source] PTHrP-independent hypercalcemia with increased proinflammatory cytokines and bone resorption in two children with CD19-negative precursor B acute lymphoblastic leukemiaPEDIATRIC BLOOD & CANCER, Issue 7 2007Hidetaka Niizuma MD Abstract Hypercalcemia in childhood acute lymphoblastic leukemia (ALL) is rare and occasionally associated with parathyroid hormone-related protein (PTHrP). However, the pathogenesis of PTHrP-independent hypercalcemia remains unclear. We report two children with precursor B ALL who had marked hypercalcemia (15.8 and 16.6 mg/dl, respectively) and disseminated osteolysis. Serum tumor necrosis factor-, (TNF-,) and IL-6 were markedly elevated, whereas 1,25(OH)2 vitamin D3, intact PTH and PTHrP were decreased or undetected. Analysis of urinary deoxypyridinoline (DPY) or bone biopsy of the osteolytic lesion showed an increased bone resorption, and administration of bisphosphonate improved the hypercalcemia. Patients had ALL with immunophenotype positive for CD10, CD34, and HLA-DR but negative for CD19 and obtained remission with chemotherapy. These findings suggest that increased osteoclastic bone resorption via stimulation with TNF-, and IL-6 may be mechanism causing PTHrP-independent hypercalcemia in some patients with precursor B ALL lacking CD19 expression. Pediatr Blood Cancer 2007;49:990,993. © 2006 Wiley-Liss, Inc. [source] CD19 negative precursor B acute lymphoblastic leukemia presenting with hypercalcemiaPEDIATRIC BLOOD & CANCER, Issue 1 2004Iyad Sultan MD Abstract A 9-month-old infant presented with hypercalcemia and lytic bone lesions. Suspicion for malignancy led to a bone marrow examination, which showed replacement of the marrow by a small round blue cell infiltrate. Flow cytometric analysis of these cells showed an unusual immunophenotype in that these cells were dim CD45, HLA-DR, and CD10 positive, but CD19, CD20, CD79a, and CD34 negative. Southern blotting showed clonal rearrangement of immunoglobulin heavy chain (IgH) which confirmed a diagnosis of precursor B acute lymphoblastic leukemia (ALL). He received supportive treatment with hydration and pamidronate, but had recurrent episodes of hypercalcemia. Once the correct diagnosis of ALL was established, the patient was treated with an infantile ALL chemotherapeutic regimen and the hypercalcemia resolved. This case highlights the usefulness of immunoglobulin gene rearrangement studies in atypical cases of ALL. © 2004 Wiley-Liss, Inc. [source] Erythema Toxicum Neonatorum: An Immunohistochemical AnalysisPEDIATRIC DERMATOLOGY, Issue 3 2001Giovanna Marchini M.D., Ph.D. The recruitment of leukocytes to tissues implicates the involvement of adhesion molecules, cytokines, and chemokines. We therefore performed immunohistochemistry on punch biopsy specimens from cutaneous lesions of ten 1-day-old infants with erythema toxicum using specific monoclonal antibodies directed against a variety of adhesion molecules, cytokines, chemokines, and cell type-specific membrane markers. Biopsy specimens of noninflamed skin from four matched newborns and four adults served as controls. The immunohistologic features of erythema toxicum in all 10 infants included a strong staining of the adhesion molecule E-selectin in the vessel wall and the presence of numerous inflammatory cells that were identified as dendritic cells (CD1a, CD83, HLA-DR, CD40, and ICAM-1 positive), eosinophils (EG2 positive), neutrophils (CD15 positive), macrophages (CD14, CD68, and Mac387 positive), and E-selectin-expressing cells. Furthermore, the lesions showed a high incidence of the proinflammatory cytokines interleukin (IL)-1, and IL-1, and of the chemokines IL-8 and eotaxin. This immunologic activity was reduced or absent in noninflamed skin from newborn controls and adults. We conclude that there is an accumulation and activation of immune cells in the lesions of erythema toxicum, also present in noninflamed skin of 1-day-old infants, but to a lower level. The physiologic significance of the rash remains to be elucidated. [source] Acute lymphoblastic leukemia with the phenotype of a putative B-cell/T-cell bipotential precursorAMERICAN JOURNAL OF HEMATOLOGY, Issue 2 2004Lee Gong Lau Abstract Biphenotypic acute leukemias (BALs) are uncommon. Most are of myeloid-B-cell or myeloid-T-cell lineage. We report herein a 70-year-old man with an unusual acute leukemia where the blasts expressed both B- and T-lymphoid markers. He presented to us with an enlarging cutaneous tumor. The presenting peripheral blood and bone marrow aspirate showed 40% and 90% blasts, respectively, which were negative for the usual cytochemical stains. The flow cytometric analysis revealed that the blasts were positive for CD19, CD20, CD22, cytoplasmic (Cyt) CD79a, CD10, Cyt CD3, CD5, CD7, CD4, HLA-DR, TdT, and were negative for myeloid markers. According to the scoring system from the European Group for the Immunological Characterization of Acute Leukaemias (EGIL), this case was an unequivocal B-cell/T-cell BAL. Conventional cytogenetic analysis revealed 46XY [t(4;11)(q31;q13), add(8)(q24), der(9)del(9)(p21)del(9)(q32q34), ,13, +mar] in all 25 metaphases analyzed. Fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) for 11q23 rearrangements as well as t(9;22) were negative. PCR for both TCR- , and IgH gene analyses revealed polyclonal rearrangements. We postulate that this case of BAL might have arisen from the putative common lymphoid progenitor cell. Am. J. Hematol. 77:156,160, 2004. © 2004 Wiley-Liss, Inc. [source] ORIGINAL ARTICLE: Antigen-presenting Cells in Pregnant and Non-pregnant Human MyometriumAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2010Marina Ivanisevic Citation Ivanisevic M, Segerer S, Rieger L, Kapp M, Dietl J, Kämmerer U, Frambach T. Antigen-presenting cells in pregnant and non-pregnant human myometrium. Am J Reprod Immunol 2010; 64: 188,196 Problem, Inflammatory cells play a crucial role in human parturition. Different populations of leucocytes invade the reproductive tract. Numerous studies have described the decidual immune cell population in pregnant and non-pregnant endometrium. However, little is known about the presence of immune cells in human myometrium. Method of study, We herein analysed a spectrum of immune cells in human myometrium comparing tissue samples from non-pregnant (n = 8) and pregnant (n = 10) uteri. Applying immunohistochemistry with a panel of antibodies specific for T cells, monocytes, natural killer cells, B cells and antigen-presenting cells (CD4, CD8, CD14, CD15, CD16, CD19, CD56, CD68, CD83, HLA-DR, DC-Sign, mast cell tryptase), we characterized the immune cell population of human myometrium. Results, A significantly higher number of CD14, CD15, CD16, DC-SIGN as well as CD4-positive cells were found in myometrium of pregnant compared to non-pregnant uteri, while mast cells were significantly reduced in pregnant myometrium. Conclusion, All markers found increased in pregnant myometrium indicate monocyte/macrophage lineage cells and thus suggest a possible involvement of these cells in healthy pregnancy maintenance. Monocytes/macrophages might produce a microenvironment that permits a controlled invasion of trophoblast cells into the myometrium while preventing a rejection of the semiallogenic conceptus and providing an important barrier against invading pathogenes. [source] Elevated NK Cell Cytotoxicity, CD158a Expression in NK Cells and Activated T Lymphocytes in Peripheral Blood of Women with IVF FailuresAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2010Viktor P. Chernyshov Citation Chernyshov VP, Sudoma IO, Dons'koi BV, Kostyuchyk AA, Masliy YV. Elevated NK cell cytotoxicity, CD158a expression in NK cells and activated T lymphocytes in peripheral blood of women with IVF failures. Am J Reprod Immunol 2010; 64: 58,67 Problem, The aim of this study was to evaluate the role of elevated natural killer cytotoxicity (NKc) in women with multiple implantation failures (IF) in vitro fertilization,embryo transfer (IVF,ET) cycles. Methods of study, Seventy-nine antiphospholipid antibodies-negative women with IF including 33 women with elevated NKc were selected for investigation. K-562 cell line was used to evaluate NKc. Lymphocyte subsets, intracellular cytokines [interferon (IFN)-,, interleukin (IL)-4, tumour necrosis factor, IL-10], expression of activating markers [CD69, human leukocyte antigen (HLA)-DR], CD8, KIR (CD158a), CD95, and chemokine receptors (CXCR3, CCR4) were estimated by flow cytometry. Results, In women with IF, levels of NKc were higher than in IVF successful women. IF was associated with higher expression of CD8, CD158a, and HLA-DR in NK cells, activating markers in T lymphocytes, and lower levels of CCR4+ and IL-4+ T lymphocyte subsets. Predictive value of single elevated NKc for IVF success was 0.85, but addition of two other abnormal parameters resulted in its decrease to <0.39. Conclusions, Elevated NKc is negative factor, though not critical for implantation in IVF cycles. Immune mechanism of IVF failure includes not only elevated NKc but also some other factors, such as elevated expression of CD8 and CD158a on NK cells, T lymphocyte activation, and diminished T helper 2 parameters. [source] | |||||||||||||||||||||||||||||||