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HLA Class I (hla + class_i)
Terms modified by HLA Class I Selected AbstractsJuvenile idiopathic arthritis and HLA Class I and Class II interactions and age-at-onset effectsARTHRITIS & RHEUMATISM, Issue 6 2010Jill A. Hollenbach Objective The aim of this study was to quantitate risk and to examine heterogeneity for HLA at high resolution in patients with the most common subtypes of juvenile idiopathic arthritis (JIA), IgM rheumatoid factor,negative polyarticular JIA and oligoarticular JIA. Use of 4-digit comprehensive HLA typing enabled great precision, and a large cohort allowed for consideration of both age at disease onset and disease subtype. Methods Polymerase chain reaction,based high-resolution HLA typing for class I and class II loci was accomplished for 820 patients with JIA and 273 control subjects. Specific HLA epitopes, potential interactions of alleles at specific loci and between loci (accounting for linkage disequilibrium and haplotypic associations), and an assessment of the current International League of Associations for Rheumatology classification criteria were considered. Results An HLA,DRB1/DQB1 effect was shown to be exclusively attributable to DRB1 and was similar between patients with oligoarticular JIA and a younger subgroup of patients with polyarticular JIA. Furthermore, patients with polyarticular JIA showed age-specific related effects, with disease susceptibility in the group older than age 6 years limited to an effect of the HLA,DRB1*08 haplotype, which is markedly different from the additional susceptibility haplotypes, HLA,DRB1*1103/1104, found in the group with oligoarticular JIA and the group of younger patients with polyarticular JIA. Also in contrast to findings for oligoarticular JIA, patients with polyarticular arthritis had no evidence of an HLA class I effect. Markers associated with a reduced risk of disease included DRB1*1501, DRB1*0401, and DRB1*0701. DRB1*1501 was shown to reduce risk across the whole cohort, whereas DRB1*0401 and DRB1*0701 were protective for selected JIA subtypes. Surprisingly, the disease predisposition mediated by DPB1*0201 in individuals without any disease-predisposing DRB1 alleles was great enough to overcome even the very strong protective effect observed for DRB1*1501. Conclusion Inherited HLA factors in JIA show similarities overall as well as differences between JIA subtypes. [source] Extensive HLA class I allele promiscuity among viral CTL epitopesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2007Nicole Frahm Abstract Promiscuous binding of T helper epitopes to MHC class II molecules has been well established, but few examples of promiscuous class I-restricted epitopes exist. To address the extent of promiscuity of HLA class I peptides, responses to 242 well-defined viral epitopes were tested in 100 subjects regardless of the individuals' HLA type. Surprisingly, half of all detected responses were seen in the absence of the originally reported restricting HLA class I allele, and only 3% of epitopes were recognized exclusively in the presence of their original allele. Functional assays confirmed the frequent recognition of HLA class I-restricted T cell epitopes on several alternative alleles across HLA class I supertypes and encoded on different class I loci. These data have significant implications for the understanding of MHC class I-restricted antigen presentation and vaccine development. [source] The impact of HLA-A and -DRB1 on age at onset, disease course and severity in Scandinavian multiple sclerosis patientsEUROPEAN JOURNAL OF NEUROLOGY, Issue 8 2007C. Smestad The human leucocyte antigen (HLA) class II haplotype DRB1*15,DQB1*06 (DR15,DQ6) is associated with susceptibility to multiple sclerosis (MS), and HLA class I associations in MS have also been reported. However, the influence of HLA class I and II alleles on clinical phenotypes in MS has not yet been completely studied. This study aimed at evaluating the impact of HLA-A and -DRB1 alleles on clinical variables in Scandinavian MS patients. The correlation between HLA-A or -DRB1 alleles and age at onset, disease course and Multiple Sclerosis Severity Score (MSSS) were studied in 1457 Norwegian and Swedish MS patients by regression analyses and Kruskal,Wallis rank sum test. Presence of HLA-DRB1*15 was correlated with younger age at onset of disease (corrected P = 0.009). No correlation was found between HLA-A and the variables studied. This study analysed the effect of HLA-A on clinical variables in a large Scandinavian sample set, but could not identify any significant contribution from HLA-A on the clinical phenotype in MS. However, associations between HLA-DRB1*15 and age at onset of MS were reproduced in this extended Scandinavian MS cohort. [source] IDENTIFYING COEVOLUTIONARY PATTERNS IN HUMAN LEUKOCYTE ANTIGEN (HLA) MOLECULESEVOLUTION, Issue 5 2010Xiaowei Jiang The antigenic peptide, major histocompatibility complex molecule (MHC; also called human leukocyte antigen, HLA), coreceptor CD8, or CD4 and T-cell receptor (TCR) function as a complex to initiate effectors' mechanisms of the immune system. The tight functional and physical interaction among these molecules may have involved strong coevolution links among domains within and between proteins. Despite the importance of unraveling such dependencies to understand the arms race of host,pathogen interaction, no previous studies have aimed at achieving such an objective. Here, we perform an exhaustive coevolution analysis and show that indeed such dependencies are strongly shaping the evolution and probably the function of these molecules. We identify intramolecular coevolution in HLA class I and II at domains important for their immune activity. Most of the amino acid sites identified to be coevolving in HLAI have been also detected to undergo positive Darwinian selection highlighting therefore their adaptive value. We also identify coevolution among antigen-binding pockets (P1-P9) and among these and TCR-binding sites. Conversely to HLAI, coevolution is weaker in HLAII. Our results support that such coevolutionary patterns are due to selective pressures of host,pathogen coevolution and cooperative binding of TCRs, antigenic peptides, and CD8/CD4 to HLAI and HLAII. [source] Loss of heterozygosity on chromosome 6 in HPV-16 positive cervical carcinomas carrying the DRB1*1501-DQB1*0602 haplotypeGENES, CHROMOSOMES AND CANCER, Issue 4 2004Hugo Arias-Pulido High-risk human papillomaviruses (HPVs), specifically HPV-16 and -18, have been associated with the development of carcinoma in situ (CIS) and of invasive cervical cancer (CC). However, only a small fraction of HPV-infected women will show signs of disease progression, suggesting that other factors in the carcinogenic pathway are needed. We previously demonstrated that human leukocyte antigen (HLA) DRB1*1501-DQB1*0602 (high risk) was associated with the development of CIS and CC tumors in HPV-16-positive patients. To characterize the molecular changes that could be relevant to tumor progression, we compared the extent of loss of heterozygosity (LOH) on chromosome 6 in HPV-16-positive CIS patients who were carriers of high-risk and neutral HLA haplotypes. CIS and CC cases demonstrated similar LOH patterns. A wide range of LOH frequencies was found at 6p (10,53%) and 6q (5,28%) in CIS cases, suggesting that LOH is an early event in the carcinogenic process. A comparative analysis of LOH frequencies in the high-risk versus the neutral HLA haplotypes showed a statistically significant difference in the extent of LOH at 6p24,p25 (58.6% versus 25.8%; P = 0.018) and at 6p21.3 (79.3% versus 35.5%; P = 0.001), a region that contains the HLA complex. LOH at this region could affect genes encoding HLA class I,II molecules, as well as factors responsible for the assembly, transport, and stable expression of HLA molecules. These losses may be a reflection of both an abnormal immune response and a general genome-wide instability resulting from virus persistence. © 2004 Wiley-Liss, Inc. [source] Specific human leukocyte antigen class I and II alleles associated with hepatitis C virus viremia,,§HEPATOLOGY, Issue 5 2010Mark H. Kuniholm Studies of human leukocyte antigen (HLA) alleles and their relation with hepatitis C virus (HCV) viremia have had conflicting results. However, these studies have varied in size and methods, and few large studies assessed HLA class I alleles. Only one study conducted high-resolution class I genotyping. The current investigation therefore involved high-resolution HLA class I and II genotyping of a large multiracial cohort of U.S. women with a high prevalence of HCV and HIV. Our primary analyses evaluated associations between 12 HLA alleles identified through a critical review of the literature and HCV viremia in 758 HCV-seropositive women. Other alleles with >5% prevalence were also assessed; previously unreported associations were corrected for multiple comparisons. DRB1*0101 (prevalence ratio [PR] = 1.7; 95% confidence interval [CI] = 1.1,2.6), B*5701 (PR=2.0; 95% CI = 1.0,3.1), B*5703 (PR = 1.7; 95% CI = 1.0,2.5), and Cw*0102 (PR = 1.9; 95% CI = 1.0,3.0) were associated with the absence of HCV RNA (i.e., HCV clearance), whereas DRB1*0301 (PR = 0.4; 95% CI = 0.2,0.7) was associated with HCV RNA positivity. DQB1*0301 was also associated with the absence of HCV RNA but only among HIV-seronegative women (PR = 3.4; 95% CI = 1.2,11.8). Each of these associations was among those predicted. We additionally studied the relation of HLA alleles with HCV infection (serostatus) in women at high risk of HCV from injection drug use (N = 838), but no significant relationships were observed. Conclusion: HLA genotype influences the host capacity to clear HCV viremia. The specific HLA associations observed in the current study are unlikely to be due to chance because they were a priori hypothesized. (HEPATOLOGY 2010.) [source] E5 protein of human papillomavirus type 16 selectively downregulates surface HLA class IINTERNATIONAL JOURNAL OF CANCER, Issue 2 2005G. Hossein Ashrafi Abstract Papillomaviruses have evolved mechanisms that result in escape from host immune surveillance. The E5 protein is expressed early in papillomavirus infection in the deep layers of the infected epithelium. It is localized to the Golgi apparatus (GA) and endoplasmic reticulum. The E5 protein of bovine papillomavirus (BPV) impairs the synthesis and stability of major histocompatibility (MHC) class I complexes and prevents their transport to the cell surface due to retention in the GA. Here we show that human papillomavirus type 16 (HPV-16) E5 also causes the retention of MHC (HLA) class I complexes in the GA and impedes their transport to the cell surface, which is rescued by treatment with interferon. Unlike BPV E5, HPV-16 E5 does not affect the synthesis of HLA class I heavy chains or the expression of the transporter associated with antigen processing TAP. These results show that downregulation of surface MHC class I molecules is common to both BPV and HPV E5 proteins. Moreover, we determined that HPV-16 E5 downregulates surface expression of HLA-A and HLA-B, which present viral peptides to MHC class I-restricted cytotoxic T lymphocytes (CTLs), but not the natural killer (NK) cell inhibitory ligands HLA-C and HLA-E. Selective downregulation of cell surface HLA class I molecules may allow the virus to establish infection by avoiding immune clearance of virus-infected cells by both CTLs and NK cells. [source] Small interfering RNA (siRNA) inhibits the expression of the Her2/neu gene, upregulates HLA class I and induces apoptosis of Her2/neu positive tumor cell linesINTERNATIONAL JOURNAL OF CANCER, Issue 1 2004Aniruddha Choudhury Abstract Silencing of a specific mRNA using double stranded RNA oligonucleotides represents one of the newest technologies for suppressing a specific gene product. Small interfering RNA (siRNA) are 21 nucleotides long, double stranded RNA fragments that are identical in sequence to the target mRNA. We designed 3 such siRNA against the Her2/neu (HER2) gene. The HER2 gene is known to play an important role in the oncogenesis of several types of cancers, such as breast, ovarian, colon and gastric cancers. Introduction of the siRNA into HER2 positive tumor lines in vitro greatly reduced the cell surface expression of the HER2 protein. Concurrently, a range of effects on cell physiology, such as growth inhibition or apoptosis, was observed. The expression of HLA class I was observed to be upregulated when HER2 was silenced with siRNA. Treatment of SKBr3 and MCF7/HER2 tumor cell lines with the HER2 siRNA resulted in growth arrest of cells in the late G1/S-phase. Our results suggest that siRNA may be an effective method of abrogating the effect of HER2 in tumorigenesis. © 2003 Wiley-Liss, Inc. [source] HLA allele and haplotype frequencies in the Albanian population and their relationship with the other European populationsINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 6 2009G. Sulcebe Summary Human leucocyte antigen (HLA) alleles are very interesting markers in identifying population relationships. Moreover, their frequency distribution data are important in the implementation of donor,recipient registry programs for transplantation purposes and also in determining the genetic predisposition for many diseases. For these reasons, we studied the HLA class I and II allele and haplotype frequencies in 160 healthy, unrelated Albanian individuals originating from all regions of the country. The HLA genotyping was performed through a 2-digit resolution SSOP method. The data were analysed with Arlequin and Phylip programs. No deviation was found from the Hardy,Weinberg equilibrium. A total of 17 A*, 30 B*, 12 Cw*, 13 DRB1* and 5 DQB1* alleles were identified. The six most frequent HLA-A-B-DRB1 haplotypes were A*02,B*18,DRB1*11 (5.60%), A*02,B*51,DRB1*16 (4.74%), A*01,B*08,DRB1*03 (3.48%), A*24,B*35,DRB1*11 (2.77%), A*02,B*51,DRB1*13 (2.21%), A*24,B*35,DRB1*14 (1.89%). Interestingly, 12 HLA-A-B-Cw-DRB1-DQB1 haplotypes occurred at a frequency >1%. When compared with the other populations, a close relationship was found with North Greek, Bulgarian, Macedonian, Romanian, Turkish, Cretan, Serbian, Croatian and Italian populations. A higher differentiation in allele frequency level was found with Western Europe populations. These data are the first report of HLA allele and haplotype distribution in an Albanian population inside this country. When compared with other populations, their distribution frequencies show close similarities with neighbouring populations of the entire Balkan area. [source] MICA and MICB microsatellite alleles in HLA extended haplotypesINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 5 2001E. Bolognesi Summary The present study is a contribution to the definition of the linkage disequilibrium relationship of MICA and MICB with adjacent loci and to the characterization of extended HLA haplotypes. These issues are of importance for the identification of disease associations and for a better definition of donor,recipient compatibility in bone-marrow grafts through the typing of haplospecific markers. The distribution of the five alleles of MICA and the 13 alleles of MICB microsatellites, located, respectively, in MICA transmembrane exon 5 and in MICB intron 1, was examined in 133 healthy Italian individuals previously typed for HLA class I, class II and complement loci and for the TNFa microsatellite. The MICB microsatellite was also analysed in 49 HTCLs for which MICA typing was already available. Very strong linkage disequilibria with HLA-B and TNFa were detected in the Italian population for both MICA and MICB microsatellite alleles, in spite of the high mutability rate of the larger MICB alleles. Some strong associations were also detected between MICB and DRB1. The strongest associations (P < 0.001, D, > 0.7) were those of MICA-A4 with HLA-B18, B27 and TNFa1, MICA-A5 with HLA-B35, B61 and B62, MICA-A5.1 with HLA-B7, B8, B13, B63 and MICB-CA24, MICA-A6 with HLA-B51, MICA-A9 with HLA-B39, B57 and TNFa2, MICB-CA14 with HLA-B14, B27 and TNFa1, MICB-CA15 with HLA-B52, TNFa4 and TNFa13, MICB-CA17 with HLA-B7 and TNFa11, MICB-CA18 with HLA-B13 and TNFa7, MICB-CA22 with HLA-B57, and MICB-CA24 with HLA-B8 and TNFa2. From pairwise associations in the random panel and results for the homozygous cell lines it was possible to deduce the MICA and MICB microsatellite alleles present in many of the well-known Caucasoid extended haplotypes. [source] Lack of association between HLA genotype and chronic fatigue syndromeINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 3 2001J. A. Underhill Summary Although the aetiology of chronic fatigue syndrome is controversial, evidence that infective agents including viruses may have a role in the development of the condition has led to studies seeking an association with the immunomodulatory HLA genes. In the present study, we sought to extend previous work using a well-characterized patient group and modern HLA genotyping techniques. Fifty-eight patients were phenotyped for HLA A and B by microcytotoxicity and genotyped for HLA DRB, DQB and DPB by PCR oligoprobing, and the frequencies of antigens so assigned were compared with those from a control group of 134. No significant differences in HLA frequencies were found between patient and control groups. Thus, this study does not confirm previous findings of an HLA association with chronic fatigue syndrome, suggesting that neither presentation of viral antigen by HLA class I nor antigen processing genes in the HLA region is a major contributory factor in the development of the disease. [source] A HCMV pp65 polypeptide promotes the expansion of CD4+ and CD8+ T cells across a wide range of HLA specificitiesJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 8b 2009Maurizio Provenzano Abstract Human cytomegalovirus (HCMV) can cause life-threatening disease in infected hosts. Immunization with human leukocyte antigen (HLA)-restricted immunodominant synthetic peptides and adoptive transfer of epitope-specific T cells have been envisaged to generate or boost HCMV-specific cellular immunity, thereby preventing HCMV infection or reactivation. However, induction or expansion of T cells effective against HCMV are limited by the need of utilizing peptides with defined HLA restrictions. We took advantage of a combination of seven predictive algorithms to identify immunogenic peptides of potential use in the prevention or treatment of HCMV infection or reactivation. Here we describe a pp65-derived peptide (pp65340,355, RQYDPVAALFFFDIDL: RQY16-mer), characterized by peculiar features. First, RQY-16mer is able to stimulate HCMV pp65 specific responses in both CD4+ and CD8+ T cells, restricted by a wide range of HLA class I and II determinants. Second, RQY-16mer is able to induce an unusually wide range of effector functions in CD4+ T cells, including proliferation, killing of autologous HCMV-infected target cells and cytokine production. Third, and most importantly, the RQY-16mer is able to stimulate CD4+ and CD8+ T-cell responses in pharmacologically immunosuppressed patients. These data suggest that a single reagent might qualify as synthetic immunogen for potentially large populations exposed to HCMV infection or reactivation. [source] Psoriasis vulgaris and human leukocyte antigensJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 3 2007FF Cassia Abstract Background, Psoriasis vulgaris is a skin disease with a complex immunological and genetic background, triggered by environmental factors. The association of human leukocyte antigens (HLA) and psoriasis has long been reported on population and familial studies. Objectives, To review and discuss studies on psoriasis vulgaris and HLA, in Caucasian and non-Caucasian populations. Methods, The major population studies on psoriasis vulgaris and the associated HLA antigens and alleles are described and discussed based on a review of the current literature. Results, Population studies demonstrate the presence of different HLA specificities as well as extended haplotypes in patients with psoriasis, when compared to controls. Some alleles occur in a lower frequency in patients with psoriasis, indicating they could be protection alleles. In all studies which HLA class I was typed, Cw6 or Cw*0602 was present in a significant frequency in patients with psoriasis, mainly when early onset and positive family history were considered. HLA-DRB1*0701 was also present in a higher frequency in patients in different populations. Conclusions, Different antigens and alleles from both HLA classes I and II were seen in a significantly higher frequency in patients with psoriasis vulgaris. HLA Cw*0602 and DRB1*0701 were represented in different reports, and the former was related mainly to psoriasis type I. [source] HLA DRB1*15-DPB1*05 haplotype: a susceptible gene marker for isocyanate-induced occupational asthma?ALLERGY, Issue 7 2006S.-H. Kim Background:, There has been no study for evaluating the associations of human leukocyte antigen (HLA) class I and II alleles with toluene diisocyanate (TDI)-induced asthma in an Asian population. Objective:, The aim of this study was to investigate a susceptible or protective marker of HLA class I and II alleles in TDI-induced asthma. Methods:, Fifty-five patients with TDI-induced asthma patients (group I) showing positive responses on TDI bronchoprovocation test, 47 asymptomatic exposed subjects (group II) and 95 unexposed healthy nonatopic controls (group III) were enrolled in our study. HLA class I and II genotyping was done by the direct DNA sequencing method. Results:, The allelic frequency of C*09 (15.5%) was significantly higher in group I than in group III (6.8%, P = 0.019), but this statistical significance disappeared after correction was made for multiple comparisons. On two-locus and three-locus haplotype analysis, the allelic frequency of HLA DRB1*15-DPB1*05 in group I (10.6%) was significantly higher than that of group II (0%, P = 0.001) and group III (2.5%, P = 0.003). The allelic frequencies of HLA A*02-DRB1*15, A*02-DQB1*06, B*62-C*09 and A*02-DRB1*15-DQB1*06 were significantly higher in group I (8.5%, 10.3%, 8.2% and 6.8%, respectively) than those allelic frequencies of group III (1.3%, P = 0.002; 1.6%, P = 0.001; 0.6%, P < 0.0001; 0%, P < 0.0001, respectively). The allelic frequencies of HLA DQB1*06-DPB1*05 and DRB1*15-DQB1*06-DPB1*05 were significantly higher in group I (16.0% and 10.5%) than those in group II (2.5%, P = 0.001; 0%, P = 0.001), while the frequencies of DRB1*09-DPB1*05 and DRB1*09-DQB1*0303-DPB1*05 were significantly lower in group I (0% and 0%) than those of group II (7.4%, P = 0.004; 7.5%, P = 0.004). These differences remained statistically significant even after the correction for multiple comparisons. Conclusions:, The HLA haplotype DRB1*15-DPB1*05 can be a susceptibility gene marker for the development of TDI-induced asthma among the exposed workers in the Korean population. [source] Increased Ig-null B lymphocytes in the peripheral blood of pediatric solid organ transplant recipients with elevated Epstein-Barr viral loadsPEDIATRIC TRANSPLANTATION, Issue 3 2009Elizabeth Schauer Abstract:, In this study, the characteristics of Ig-null B cells in high viral load carriers were examined by four-color flow cytometry. The frequency of Ig-null B cells in patients with high, low or undetectable virus loads was found that while patients with a high load had more Ig-null cells, these cells were also present in the low and undetectable load groups. As Ig-null cells from patients with no viral load were EBV-negative, EBV infection was not absolutely required for the generation or survival of Ig-null cells. Ig-null cells were CD19+, sIg - , CD5,, CD10,, CD27,, CD23,, CD38,, and CD69, with variable surface expression of CD20 and CD40. Ig-null cells did not have a proliferating cell phenotype (Ki67 - ) and a high proportion were HLA class I - and class II - . Virus copy number in CD19+ Ig-null cell populations may be much higher than in CD19+ Ig+ cell populations. EBV infected Ig-null cells were common in blood specimens from pediatric solid organ transplant recipients and infected Ig-null cells may pose potential problems for immunotherapies that target infected B cells directly. [source] Analysis of the HLA class I associated peptide repertoire in a hepatocellular carcinoma cell line reveals tumor-specific peptides as putative targets for immunotherapyPROTEOMICS - CLINICAL APPLICATIONS, Issue 3 2007Iñaki Alvarez Abstract HLA class I molecules present peptides on the cell surface to CD8+ T cells. The repertoire of peptides that associate to class I molecules represents the cellular proteome. Therefore, cells expressing different proteomes could generate different class I-associated peptide repertoires. A large number of peptides have been sequenced from HLA class I alleles, mostly from lymphoid cells. On the other hand, T cell immunotherapy is a goal in the fight against cancer, but the identification of T cell epitopes is a laborious task. Proteomic techniques allow the definition of putative T cell epitopes by the identification of HLA natural ligands in tumor cells. In this study, we have compared the HLA class I-associated peptide repertoire from the hepatocellular carcinoma (HCC) cell line SK-Hep-1 with that previously described from lymphoid cells. The analysis of the peptide pool confirmed that, as expected, the peptides from SK-Hep-1 derive from proteins localized in the same compartments as in lymphoid cells. Within this pool, we have identified 12 HLA class I peptides derived from HCC-related proteins. This confirms that tumor cell lines could be a good source of tumor associated antigens to be used, together with MS, to define putative epitopes for cytotoxic T cells from cancer patients. [source] HLA Class I Antibodies Provoke Graft Arteriosclerosis in Human Arteries Transplanted into SCID/Beige MiceAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009S. Galvani Antibodies toward HLA class I and/or MICA are commonly observed in transplanted patients suffering from allograft arteriosclerosis, also called chronic vascular rejection (CVR). The relative importance of cellular versus humoral alloreactivity for CVR is still disputed. We demonstrate that antibodies toward HLA class I provoke lesions typical for CVR in human arteries in vivo in the absence of cellular immunity. To show this, we grafted segments of human mesenteric arteries from 8 deceased organ donors into 36 immunodeficient SCID/beige mice in the infrarenal aortic position. Three mice died postoperatively. The remaining 33 mice received weekly i.v. injections of either a monoclonal antibody toward HLA class I, toward MICA or an irrelevant monoclonal antibody. At sacrifice after 6 weeks, mice receiving the HLA antibody showed a significant neointimal thickening in the grafted artery due to smooth muscle cell (SMC) proliferation while control mice receiving anti-MICA or irrelevant antibody showed little or no thickening. Whereas antibodies toward HLA class I were mitogenic to SMC in vitro, those directed toward MICA did not have any effect. Humoral alloreactivity toward HLA may thus play a causal role for the development of CVR and this opens new possibilities for the treatment of CVR. [source] Evidence for Humoral Rejection of a Pancreatic Islet Graft and Rescue with Rituximab and IV Immunoglobulin TherapyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009L. Kessler We describe the decline in islet function, in relation to HLA sensitization, in an islet transplant recipient and the recovery of this function after treatment with anti-CD20 monoclonal antibody and IV immunoglobulins. A 51-year-old woman with type 1 diabetes received one intraportal islet infusion. Following this transplantation, she became insulin independent. A search for HLA antibodies by using an ELISA technique remained consistently negative for HLA class I and II. It was only 2 years after the islet transplantation that this search became positive against class II antigens, reaching a peak of reactivity concomitantly with the appearance of a deterioration of glucose control requiring low-dose insulin therapy. Luminex® screening and single-antigen assays then revealed the presence of both nondonor-specific and donor-specific antibodies against HLA class II molecules. This immunization, already present in the pretransplant serum, had increased during the 6 months preceding the clinical deterioration. Since these data nevertheless pointed to antibody-mediated rejection of the islet allograft, treatment with anti-CD20 monoclonal antibody and IV immunoglobulins was initiated. One month later, the search by ELISA for antibodies against HLA class II antigens became negative, the Luminex® tests normalizing more gradually. As the result of an improvement in glucose control, the patient was again insulin-free. [source] Susceptibility of Liver Allografts to High or Low Concentrations of Preformed Antibodies as Measured by Flow CytometryAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2001Juan C. Scornik Liver grafts are more resistant to damage by HLA antibodies than other organ allografts, but it is not clear if the antibodies are associated with graft rejection or graft loss, or if different antibody concentrations have different effects. To explore potential associations between antibody concentrations and outcome, preformed IgG antibodies against donor cells were quantified by flow cytometry in 465 consecutive liver transplant recipients. Antibody-positive patients were classified according to whether they had high or low antibody concentrations and analyzed for possible correlation with graft rejection or graft loss. The results showed that the incidence of rejection was not significantly different between antibody-positive and -negative patients. However, patients with high antibody concentrations had a higher incidence of steroid-resistant rejections (31% at 1 year) than patients with low antibody (4%) or no antibody (8%, p <,0.0004). These effects were mainly due to T-cell (HLA class I) antibodies. The overall incidence of rejection at 1 year was 69% for high antibody patients, 51% for patients with low antibodies and 53% for patients with no antibodies (p not significant). In an apparent paradox, antibody-positive patients underwent fewer early graft losses. Thus, the associations of preformed antibodies and outcome depend, on the one hand, on antibody concentrations, and on the other hand on whether the outcome measured is steroid-sensitive rejection, steroid-resistant rejection or graft survival. These complex interactions may explain the controversial results observed in previous studies. [source] Expression of toll-like receptor 3 and toll-like receptor 7 in muscle is characteristic of inflammatory myopathy and is differentially regulated by Th1 and Th17 cytokinesARTHRITIS & RHEUMATISM, Issue 7 2010A. Tournadre Objective To assess the expression of Toll-like receptor 3 (TLR-3) and TLR-7 in muscle tissue from patients with polymyositis (PM) and dermatomyositis (DM) and to investigate the function and regulation of TLR-3 in cultured muscle cells. Methods The expression of TLR-3, TLR-7, HLA class I, and CD56, a marker of immature myoblast precursors, was analyzed using immunohistochemistry. TLR-3 regulation and signaling were assessed in myoblasts and in differentiated myotubes with the TLR-3 agonist poly(I-C), necrotic myoblasts, and Th1 and Th17 cytokines, in the presence or absence of neutralizing anti,TLR-3 antibody. Levels of TLR-3 messenger RNA (mRNA) were quantified by reverse transcription,polymerase chain reaction. Levels of interleukin-6 (IL-6), CCL20, and IL-8 were determined by enzyme-linked immunosorbent assay. Results TLR-3 and TLR-7 were expressed in PM/DM tissues, but not in noninflammatory muscle tissues, and were primarily detected in inflammatory infiltrates, although a few muscle cells were also positive. These TLR-3, and TLR-7,positive fibers expressed high levels of CD56 and HLA class I antigens. A synergy between poly(I-C) and IL-17 was observed for the production of IL-6 and CCL20. Similarly, stimulation with necrotic myoblasts increased IL-6 production, and stimulation with necrotic myoblasts in combination with IL-17 further increased the induction of IL-6. TLR-3 blockade decreased the inducing effect of necrotic myoblasts and IL-17 on IL-6 production. Stimulation with interferon-, (IFN,) increased TLR-3 mRNA levels, but IL-17 down-regulated the inducing effect of IFN,. Conclusion Our findings indicate that TLR-3 and TLR-7 are expressed in inflammatory myopathic tissues, particularly in immature myoblast precursors. Necrotic muscle cells activate cytokine production, in part, through the TLR-3 pathway, with a differential regulatory effect of Th1 and Th17 cytokines. [source] Association between human demodicosis and HLA class ICLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 1 2003O. E. Akilov Summary Demodex folliculorum and D. brevis are obligatory parasites in hair follicles and in pilosebaceous glands of human skin. Although most people are infested with these mites, only a small number develop the clinical symptoms of skin demodicosis. The objective of this study was to determine the association between HLA specificity and demodicosis. Twenty-five patients with human demodicosis and 150 controls were typed for HLA-A, B, Bw, and Cw using the microlymphocytotoxicity method. The immune response was evaluated by identifying membrane markers of different immune cells using monoclonal antibodies. An association between the frequency of HLA Cw2 and Cw4 haplotypes and human demodicosis was established. The risk of developing clinical symptoms of this disease is 5.0 times higher for people with the Cw2 phenotype and 3.1 times higher for those with the Cw4 haplotype. Individuals who have the HLA A2 phenotype are 2.9 times more resistant to demodicosis. A positive correlation between demodicosis and the haplotypes A3-Cw4, A3-Cw2, A3-B17, A3-B35 and B35-Cw4 was found. In addition, an association between Cw2 and Cw4 alleles in the phenotype of patients with demodicosis and a decrease in the number of natural killer cells was found. [source] Anti-topoisomerase II , autoantibodies in systemic sclerosis,association with pulmonary hypertension and HLA-B35CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2000B. Grigolo We have previously detected autoantibodies against topoisomerase II , (anti-topo II ,) in sera from patients with idiopathic pulmonary fibrosis. To determine whether anti-topo II , is also present in systemic sclerosis (SSc) patients with pulmonary involvement, we screened sera from 92 patients and 34 healthy controls. Presence of anti-topo II , was investigated with respect to clinical and serological features, including the frequencies of HLA class I and II alleles. Anti-topo II , was detected in 20/92 (21.7%) patients. No association was found with either anti-topoisomerase I (Scl-70 or anti-topo I) or anti-centromere antibodies. However, anti-topo II , was associated with the presence of pulmonary hypertension (PHT) (as opposed to pulmonary fibrosis), and with a decrease of carbon monoxide diffusing capacity. Anti-topo II , was strongly associated with the presence of the class I antigen HLA-B35. No significant association was found with HLA class II antigens. HLA-B35 also turned out to be associated with the presence of PHT. These results indicate that in SSc patients, the presence of anti-topo II , is associated with PHT, and that the simultaneous presence of HLA-B35 seems to add to the risk of developing PHT. [source] Psoriasis vulgaris and human leukocyte antigensJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 3 2007FF Cassia Abstract Background, Psoriasis vulgaris is a skin disease with a complex immunological and genetic background, triggered by environmental factors. The association of human leukocyte antigens (HLA) and psoriasis has long been reported on population and familial studies. Objectives, To review and discuss studies on psoriasis vulgaris and HLA, in Caucasian and non-Caucasian populations. Methods, The major population studies on psoriasis vulgaris and the associated HLA antigens and alleles are described and discussed based on a review of the current literature. Results, Population studies demonstrate the presence of different HLA specificities as well as extended haplotypes in patients with psoriasis, when compared to controls. Some alleles occur in a lower frequency in patients with psoriasis, indicating they could be protection alleles. In all studies which HLA class I was typed, Cw6 or Cw*0602 was present in a significant frequency in patients with psoriasis, mainly when early onset and positive family history were considered. HLA-DRB1*0701 was also present in a higher frequency in patients in different populations. Conclusions, Different antigens and alleles from both HLA classes I and II were seen in a significantly higher frequency in patients with psoriasis vulgaris. HLA Cw*0602 and DRB1*0701 were represented in different reports, and the former was related mainly to psoriasis type I. [source] | |||||||||||||||||||||||||||||||