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Autoimmune Disorders (autoimmune + disorders)
Kinds of Autoimmune Disorders Selected AbstractsThe oral mucosa as a therapeutic target for xerostomiaORAL DISEASES, Issue 8 2008WR Thelin Autoimmune disorders, medical interventions, and aging are all known to be associated with salivary gland hypofunction, which results in the uncomfortable feeling of dry mouth (xerostomia) and significantly diminished oral health. The current therapeutic regimen includes increasing oral hydration using over-the-counter oral comfort agents and the use of systemic cholinergic drugs to stimulate salivary output. However, these approaches produce very transient relief or are associated with uncomfortable side-effects. Thus, new treatments that provide long-lasting relief from discomfort and improve oral health with minimal side-effects would benefit the therapy of this disease. The processes that mediate fluid loss from the oral cavity, such as the absorption of fluid from the oral mucosa, represent novel therapeutic targets for xerostomia. Preventing fluid absorption from the oral cavity is predicted to improve oral hydration and alleviate the clinical symptoms and discomfort associated with dry mouth. Furthermore, therapeutic strategies that prevent fluid absorption should complement current approaches that increase salivary output. This review discusses the current understanding of oral fluid balance and how these processes may be manipulated to provide relief for those suffering from dry mouth. [source] Clinical aspects of neuromuscular transmission disordersACTA NEUROLOGICA SCANDINAVICA, Issue 2006Amelia Evoli Autoimmune disorders of neuromuscular transmission are caused by antibodies (abs) directed against membrane proteins at the motor end-plate. Myasthenia gravis (MG) is due, in most cases, to abs against the nicotinic acetylcholine receptor (AChR). Anti-AChR-positive MG actually includes different disease entities: weakness can be confined to extrinsic ocular muscles or can be generalized; patients with generalized MG (G-MG) can be subdivided on the basis of age of onset, HLA association and thymic pathology. About 15% of G-MG patients are anti-AChR-negative; in a proportion of these cases serum abs against the muscle- specific kinase (MuSK) are found. Anti-MuSK-positive MG is characterized by predominant involvement of bulbar muscles and very low frequency of thymic pathology. The Lambert-Eaton myasthenic syndrome (LEMS) is caused by abs against voltage-gated calcium channels at nerve terminal. LEMS is characterized by muscle weakness and autonomic disturbances and it is paraneoplastic in over 50% of the cases. In neuromyotonia and cramp-fasciculation syndrome, that are thought to be due to anti-voltage-gated potassium channel abs, signs of peripheral nerve hyperexcitability can be associated with CNS features. [source] The islet autoantibody titres: their clinical relevance in latent autoimmune diabetes in adults (LADA) and the classification of diabetes mellitusDIABETIC MEDICINE, Issue 2 2008A. W. Van Deutekom Abstract Latent autoimmune diabetes in the adult (LADA) is a slowly progressive form of autoimmune diabetes, characterized by diabetes-associated autoantibody positivity. A recent hypothesis proposes that LADA consists of a heterogeneous population, wherein several subgroups can be identified based on their autoimmune status. A systematic review of the literature was carried out to appraise whether the clinical characteristics of LADA patients correlate with the titre and numbers of diabetes-associated autoantibodies. We found that the simultaneous presence of multiple autoantibodies and/or a high-titre anti-glutamic acid decarboxylase (GAD),compared with single and low-titre autoantibody,is associated with an early age of onset, low fasting C-peptide values as a marker of reduced pancreatic B-cell function, a high predictive value for future insulin requirement, the presence of other autoimmune disorders, a low prevalence of markers of the metabolic syndrome including high body mass index, hypertension and dyslipidaemia, and a high prevalence of the genotype known to increase the risk of Type 1 diabetes. We propose a more continuous classification of diabetes mellitus, based on the finding that the clinical characteristics gradually change from classic Type 1 diabetes to LADA and finally to Type 2 diabetes. Future studies should focus on determining optimal cut-off points of anti-GAD for differentiating clinically relevant diabetes mellitus subgroups. [source] Soluble hemoglobin,haptoglobin scavenger receptor CD163 as a lineage-specific marker in the reactive hemophagocytic syndromeEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2005Dominik J. Schaer Abstract:, Reactive hemophagocytic syndrome (RHS) is a disease of overwhelming macrophage activity triggered by infection, malignancy or autoimmune disorders. Currently used laboratory markers for the quantitative assessment of monocyte/macrophage activation lack lineage-restricted expression patterns and thus specificity. Serum levels of the macrophage specific scavenger receptor CD163 were detemined by enzyme-linked immunosorbent assay (ELISA) and were found to be highly increased in patients with RHS (median 39.0 mg/L). Significantly lower levels were determined in patients with sepsis (median 9.1 mg/L), acute mononucleosis (median 8.2 mg/L), Leishmania infection (median 6.7 mg/L) and healthy controls (median 1.8 mg/L). Follow-up of patients with a relapsing course of the disease revealed close correlations of sCD163 with clinical disease activity, serum ferritin and other markers of macrophage activity. Large sinusoidal accumulations of CD163 expressing macrophages actively engaged in phagocytosis of blood cells were detected in spleen sections of RHS patients. Our data suggests sCD163 to be a macrophage-specific marker in patients with disorders of inappropriate macrophage activation. [source] Activating and inhibitory Fc, receptors can differentially modulate T cell-mediated autoimmunityEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2008Mirentxu Abstract The molecular bases responsible for the loss of T cell tolerance to myelin antigens leading to the onset of multiple sclerosis remain obscure. It has been shown that balanced signaling through activating and inhibitory receptors is critical for the maintenance of tolerance to self antigens in autoimmune disorders. However, although Fc,R have been shown to influence experimental autoimmune encephalomyelitis (EAE) development, their role during pathogenesis remains controversial. Here we have evaluated whether relative expression of activating (Fc,RIII) and inhibitory (Fc,RIIb) Fc,R can modulate myelin-specific T cell response, as well as the susceptibility to develop EAE in mice. While Fc,RIIb,/, mice showed a significant increase in EAE severity, an Fc,RIII deficiency protected mice from disease. In addition, Fc,RIIb,/, mice showed enhanced activation of myelin-specific effector T cells, which were significantly more effective at causing EAE in adoptive transfer experiments than were T cells from wild-type mice. In contrast, Fc,RIII,/, mice showed a significantly reduced activation of myelin-specific T cells and these cells failed to adoptively transfer EAE. Consistently, increased expansion of regulatory T cells (Treg) during EAE was observed only for Fc,RIII,/, mice, which were able to suppress disease when adoptively transferred to recipient mice. These findings suggest that the balance between activating and inhibitory Fc,R signaling can contribute to the maintenance of T cell tolerance to myelin antigens and modulate EAE progression. [source] Development of nephritis but not sialadenitis in autoimmune-prone BAFF transgenic mice lacking marginal zone B cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2006Carrie Abstract B cell-activating factor belonging to the TNF family (BAFF) is a B cell survival factor required for B cell maturation. BAFF transgenic (Tg) mice develop autoimmune disorders characterized by autoantibody production, which leads to nephritis and salivary gland destruction (sialadenitis), features reminiscent of systemic lupus erythematosus and Sjögren's syndrome (SS), respectively. Disease in BAFF Tg mice correlates with the expansion of the marginal zone (MZ) B cell compartment and the abnormal presence of MZ-like B cells in the blood, LN and inflamed salivary glands, suggesting a role for these cells in BAFF-induced autoimmunity. Lymphotoxin-, (LT,)-deficient mice show disrupted splenic architecture, lack MZ B cells and some peripheral LN, and are unable to mount T cell-dependent immune responses. BAFF Tg mice lacking LT, (LT,,-BTg) retained these defects, yet still developed nephritis associated with the presence of B-1 B cells in the kidneys. However, in contrast to old BAFF Tg mice, aging LT,,-BTg mice no longer developed sialadenitis. Thus, autoimmune disorders in BAFF Tg mice are possibly events coordinated by MZ and B-1 B cells at separate anatomical sites. [source] Elevated cerebrospinal fluid adiponectin and adipsin levels in patients with multiple sclerosis: a Finnish co-twin studyEUROPEAN JOURNAL OF NEUROLOGY, Issue 2 2010A. Hietaharju Background and purpose:, The aim of this study was to investigate the levels of three adipocytokines: leptin, adiponectin and adipsin, in serum and cerebrospinal fluid (CSF) of twins discordant for multiple sclerosis (MS). Adipose tissue is an important component connecting immune system and several tissues and organs including CNS. Fat cells produce adipocytokines, which seem to have a role in various autoimmune disorders including MS. Methods:, Plasma samples were collected from twelve twins and CSF samples from four twins discordant for MS. The concentrations of interleukine (IL)-6, adiponectin, adipsin and leptin in plasma and CSF samples were determined by enzyme immuno assay. Results:, A significant difference was seen in the adipocytokine levels in CSF samples. Twins with MS had higher concentrations of adiponectin (P = 0.039) and adipsin (P = 0.039), than their asymptomatic co-twins. Conclusion:, As adiponectin and adipsin levels in CSF did not correlate with their levels in plasma, it seems that there could be a secondary intrathecal synthesis of these adipocytokines in MS. [source] Insight into the molecular mechanisms of glucocorticoid receptor action promotes identification of novel ligands with an improved therapeutic indexEXPERIMENTAL DERMATOLOGY, Issue 8 2006Heike Schäcke Abstract:, Glucocorticoids are highly effective in the therapy of inflammatory and autoimmune disorders. Their beneficial action is restricted because of their adverse effects upon prolonged usage. Topical glucocorticoids that act locally have been developed to significantly reduce systemic side effects. Nonetheless, undesirable cutaneous effects such as skin atrophy persist from the use of topical glucocorticoids. There is therefore a high medical need for drugs as effective as glucocorticoids but with a reduced side-effect profile. Glucocorticoids function by binding to and activating the glucocorticoid receptor that positively or negatively regulates the expression of specific genes. Several experiments suggest that the negative regulation of gene expression by the glucocorticoid receptor accounts for its anti-inflammatory action. This occurs through direct or indirect binding of the receptor to transcription factors such as activator protein-1, nuclear factor- ,B or interferon regulatory factor-3 that are already bound to their regulatory sites. The positive action of the receptor occurs through homodimer binding of the receptor to discrete nucleotide sequences and this possibly contributes to some of the adverse effects of the hormone. Glucocorticoid receptor ligands that promote the negative regulatory action of the receptor with reduced positive regulatory function should therefore show improved therapeutic potential. A complete separation of the positive from the negative regulatory activities of the receptor has so far not been possible because of the interdependent nature of the two regulatory processes. Nevertheless, considerable improvement in the therapeutic action of glucocorticoid receptor ligands is being achieved through the use of key molecular targets for screening novel glucocorticoid receptor ligands. [source] Themes of liver transplantation,HEPATOLOGY, Issue 6 2010Thomas E. Starzl Liver transplantation was the product of five interlocking themes. These began in 1958-1959 with canine studies of then theoretical hepatotrophic molecules in portal venous blood (Theme I) and with the contemporaneous parallel development of liver and multivisceral transplant models (Theme II). Further Theme I investigations showed that insulin was the principal, although not the only, portal hepatotrophic factor. In addition to resolving long-standing controversies about the pathophysiology of portacaval shunt, the hepatotrophic studies blazed new trails in the regulation of liver size, function, and regeneration. They also targeted inborn metabolic errors (e.g., familial hyperlipoproteinemia) whose palliation by portal diversion presaged definitive correction with liver replacement. Clinical use of the Theme II transplant models depended on multiple drug immunosuppression (Theme III, Immunology), guided by an empirical algorithm of pattern recognition and therapeutic response. Successful liver replacement was first accomplished in 1967 with azathioprine, prednisone, and antilymphoid globulin. With this regimen, the world's longest surviving liver recipient is now 40 years postoperative. Incremental improvements in survival outcome occurred (Theme IV) when azathioprine was replaced by cyclosporine (1979), which was replaced in turn by tacrolimus (1989). However, the biologic meaning of alloengraftment remained enigmatic until multilineage donor leukocyte microchimerism was discovered in 1992 in long-surviving organ recipients. Seminal mechanisms were then identified (clonal exhaustion-deletion and immune ignorance) that linked organ engraftment and the acquired tolerance of bone marrow transplantation and eventually clarified the relationship of transplantation immunology to the immunology of infections, neoplasms, and autoimmune disorders. With this insight, better strategies of immunosuppression have evolved. As liver and other kinds of organ transplantation became accepted as healthcare standards, the ethical, legal, equity, and the other humanism issues of Theme V have been resolved less conclusively than the medical-scientific problems of Themes I-IV. HEPATOLOGY 2010 [source] Photoprotein aequorin as a novel reporter for SNP genotyping by primer extension,application to the variants of mannose-binding lectin gene,HUMAN MUTATION, Issue 3 2006Panayotis G. Zerefos Abstract Mannose-binding lectin (MBL) is a key component of the innate immune system, and its deficiency is associated with increased susceptibility to various infections and autoimmune disorders. Since several nucleotide variations in the mannose-binding lectin 2 gene (MBL2) have been associated with the functional deficiency of MBL, there is a growing need to screen its allelic variants and develop genotyping methods for MBL2. In this context we propose a rapid, robust, cost-efficient, and automatable method for detecting all known allelic variants of MBL2. This report introduces for the first time the photoprotein aequorin as a reporter in genotyping by primer extension (PEXT) reactions. The method involves a single PCR amplification of a genomic region that spans all six variant nucleotide sites, i.e., three structural mutations in exon 1 (c.154C>T, pArg52Cys; c.161A>G, p.Gly54Asp; and c.170A>G, p.Gly57Glu), two single nucleotide polymorphisms (SNPs) at positions c.,619G>C and c.,290G>C (promoter region), and one SNP at position c.,66C>T of the 5, untranslated region. PCR is followed by PEXT reactions for each site. Biotin-dUTP is incorporated in the extended primer. The genotyping primers contain a poly(dA) segment at their 5, end. The products are captured by hybridization on the surface of microtiter wells that are coated with a poly(dT)-albumin. The extended primers only are detected by reaction with a streptavidin-aequorin conjugate. The bound photoprotein aequorin is measured within 3,sec by simply adding Ca2+. We carried out extensive optimization studies of the PEXT reaction and genotyped the six nucleotide variant sites using blood specimens from 27 normal DNA samples. The results of the proposed method agreed entirely with the sequencing data. Hum Mutat 27(3), 279,285, 2006. © 2006 Wiley-Liss, Inc. [source] The role of BAFF in immune function and implications for autoimmunityIMMUNOLOGICAL REVIEWS, Issue 1 2005Susan L. Kalled Summary:, BAFF [B-cell activating factor belonging to the tumor necrosis factor (TNF) family] is a ligand that is required for peripheral B-cell survival and homeostasis. In addition to mediating B-cell survival, BAFF also regulates expression of certain B-cell-surface proteins, such as CD21/35. BAFF deficiency results in a reduced number of peripheral B cells and a diminished ability to mount robust humoral immune responses. Overexpression of BAFF has been linked to murine and human autoimmunity, and recent data provide clues as to how excess BAFF may allow the emergence of autoreactive B cells. In vivo animal testing with BAFF inhibitors has generated exciting data that support the pathway as a target for modulating B cells. The role of BAFF in B-cell biology, T-cell biology, and autoimmunity is discussed, as well as current efforts to develop BAFF inhibitors for clinical testing in autoimmune disorders. [source] T-cell reconstitution without T-cell immunopathology in two models of T-cell-mediated tissue destructionIMMUNOLOGY, Issue 2 2009Pablo Penaloza-MacMaster Summary Antigen-specific T cells play a pivotal role in adaptive immune responses. However, they also contribute to the progression of a variety of diseases including autoimmune disorders, graft rejection and graft-versus-host disease (GVHD). Non-specific immune-ablation treatments compromise the ability of the host to respond to infection, whereas the selective removal of epitope-specific T cells could theoretically ameliorate T-cell-mediated pathology while preserving the rest of the host immune function. In this study we investigated whether it is possible to destroy specific unwanted antigen-specific T cells by incubating polyclonal T-cell populations with major histocompatibility complex (MHC) tetramers that are conjugated to the ribosomal-inactivating toxin, saporin. This strategy resulted in a dramatic reduction in the number of targeted antigen (Ag)-specific CD8 T cells with no observable bystander toxicity in vitro. Moreover, in a model of transferable T-cell-dependent neurological disease induced by intracerebral (i.c.) lymphocytic choriomeningitis virus (LCMV) infection, the targeted killing of LCMV-specific CD8 T cells extended the survival of mice or fully prevented their death, depending on the dose of cells transferred. In addition, the tetramer, saporin conjugate also reduced liver damage in a model of donor T-cell-mediated hepatic destruction. These data provide a proof of principle that MHC tetramers could be exploited for the elimination or clinical manipulation of T-cell responses by linking effector molecules (a toxin in this case) to MHC tetramers. Also, the results suggest that it may be feasible to remodel T-cell responses, especially in immunocompromised hosts who receive adoptive cell transfers with many potential alloreactive cells. [source] Role of functional polymorphisms of NRAMP1 gene for the development of Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 10 2008Maria Gazouli PhD Abstract Background: Crohn's disease (CD) is characterized by chronic activation of macrophages. Natural resistance-associated macrophage protein 1 (NRAMP1) gene exerts many pleiotropic effects on macrophage functions. Hence, NRAMP1 may be also involved in the resistance to intracellular pathogens, and this effector of the innate immunity might be involved in CD pathogenesis. Polymorphic alleles at the NRAMP1 locus have been previously associated with susceptibility both to the putative infectious agents and to autoimmune disorders. Based on these indications, in the present study we investigate its candidacy as a genetic determinant for CD in a Greek population in an association-based study, comparing frequencies of 274 CD patients to these of 200 healthy control subjects. Methods: The 5,(GT)n promoter polymorphism and 9 either single nucleotide (SNPs) or insertion/deletion type polymorphisms were genotyped across the NRAMP1 gene. Reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry were performed in order to investigate the NRAMP1 mRNA levels in RNA isolated from biopsies of CD patients as well as protein expression in tissues. Results: Three NRAMP1 polymorphisms [5,(GT)n, D543N, and INT4G/C] were significantly associated with CD. Consistent with previous autoimmune disease studies, allele 3 at the functional 5,(GT)n promoter region repeat polymorphism, was significantly associated with CD when compared to healthy controls (odds ratio 1.50; 95% confidence interval [CI]: 1.16,1.95; P = 0.002). Interestingly, we observed that CD patients homozygous for allele 3 expressed higher NRAMP1 mRNA levels compared to carriers of allele 2. Furthermore, the protein levels of allele 3 carriers in tissues were also elevated compared to those of allele 2 carriers. Based on these data we can speculate that overrepresentation of allele 3 in CD patients could lead to hyperactivation of bowel-wall macrophages that are chronically exposed to lipopolysaccharide and this could subsequently cause the autoimmune-like phenotype characteristic of CD. Conclusions: Collectively, our data indicate that genetic polymorphisms of NRAMP1 might be associated with susceptibility to CD. (Inflamm Bowel Dis 2008) [source] The non-Hodgkin lymphomas: A review of the epidemiologic literatureINTERNATIONAL JOURNAL OF CANCER, Issue S12 2007Dominik D. Alexander Abstract The non-Hodgkin lymphomas (NHL) are a heterogeneous group of B-cell and T-cell neoplasms that arise primarily in the lymph nodes. NHL incidence rates in the US doubled between about 1970 and 1990, and stabilized during the 1990s. NHL accounts for ,3.4% of cancer deaths in the US. Although some of the observed patterns in NHL have been related to HIV/AIDS, these conditions cannot fully explain the magnitude of the changes; neither do changes in classification systems nor improved diagnostic capabilities. Studies of occupational and environmental exposures (e.g., pesticides, solvents) have produced no consistent pattern of significant positive associations. Inverse associations with ultraviolet radiation exposure and alcohol and fish intake, and positive associations with meat and saturated fat intake have been reported in several studies; additional studies are needed to confirm or refute these associations. Family history of NHL or other hematolymphoproliferative cancers and personal history of several autoimmune disorders are associated with increased risk of NHL, but are not likely to account for a large proportion of cases. HIV and other infectious agents, such as human herpesvirus 8 and Epstein,Barr, appear to be associated with differing types of NHL, such as some B-cell lymphomas. Future epidemiologic studies should evaluate associations by NHL type, enhance exposure information collected, and elucidate factors that may identify susceptible (or resistant) subpopulations because of genetic, immunologic or other characteristics. The extent to which the etiology of NHL types may differ is important to resolve in ongoing and future studies. © 2007 Wiley-Liss, Inc. [source] Livedoid vasculopathy and hypercoagulability in a patient with primary Sjögren's syndromeINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 4 2007Raquel Cardoso MD Background, A 31-year-old woman presented with a 5-year history of painful ulcerations, palpable purpura, porcelain-white atrophic scars of the malleolar region and dorsal aspect of the feet, livedo reticularis on the limbs, arthralgia, xerophthalmia, and xerostomia. Methods, Skin biopsy revealed vessel wall hyalinization and thrombosis of the microvasculature with a very scarce dermal inflammatory infiltrate. Biopsy of the oral mucosa showed mononuclear infiltration of an intralobular duct of a salivary gland. Results, Laboratory studies, including autoantibodies and inflammation markers, were normal, except for a positive rheumatoid factor. Coagulation screening revealed C677T methylenetetrahydrofolate reductase (MTHFR) mutation, with a normal serum homocysteine. The patient was treated with oral methylprednisolone (32 mg/day with progressive reduction) and enoxaparin (20 mg/day subcutaneously), with complete ulcer healing within 4 months. Conclusion, Livedoid vasculitis or vasculopathy has not been referred to previously in association with Sjögren's syndrome, but may be associated with other autoimmune disorders and anomalies of coagulation, namely factor V Leiden mutation, protein C deficiency, and MTHFR mutation, associated or not with hyperhomocysteinemia, a condition that seems to confer an increased risk of recurrent arterial and venous thrombosis. We stress the importance of anticoagulant therapy for ulcer healing and for the prevention of other thrombotic events. [source] Compound KIR - HLA genotype analyses in the Iranian population by a novel PCR,SSP assayINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 3 2010N. Tajik Summary Natural killer (NK) cells eliminate infected and transformed cells while still are self-tolerant. Interactions of the independently segregating Killer cell immunoglobulin-like receptors (KIR) and human leucocyte antigens (HLA) loci play a critical role in NK cell regulation. Different compound KIR-HLA genotypes can impart different thresholds of activation to the NK-cell repertoire and such genotypic variation has been found to confer altered risk in a number of human diseases including viral infections, autoimmune disorders, reproduction abnormalities and cancers. In this study, we presented a novel combined KIR-HLA polymerase chain reaction,sequence-specific primers genotyping assay for simultaneous determination of KIR genes and their three major HLA class I ligand groups (C1, C2, and Bw4). Moreover, known inhibitory and activating KIR + HLA (iKIR + HLA: 2DL2/3 + C1, 2DL1 + C2, 3DL1 + Bw4; and aKIR + HLA: 2DS2 + C1, 2DS1 + C2, 3DS1 + Bw4) combinations as well as co-inheritance of aKIR genes and iKIR + HLA pairs were analysed in a total of 200 unrelated healthy Iranian individuals. All tested subjects had at least one of the three iKIR + HLA pairs and the frequencies of various inhibitory combinations in the study group were: 31.5%, three iKIR + HLA pairs, 53.5%, two iKIR + HLA pairs, and 15%, 0ne iKIR + HLA pair. Furthermore, we revealed that majority of Iranians (69%) carry compound genotypes with greater number of inhibitory pairings than activating combinations (iKIR + HLA > aKIR + HLA). Conversely, iKIR + HLA < aKIR (45%) was dominant genotype in the study group. We conclude that selective evolutionary pressure has propensity to maintain KIR-HLA genotypes with more inhibitory combinations to guarantee self-tolerance. In contrast, existence of activating KIR genes without normal endogenous ligands, potentially arms the NK population for competent immunosurveillance and stronger defense against infections. [source] Protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene R620W variant and sporadic idiopathic hypoparathyroidism in Asian IndiansINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 4 2006D. Ray Summary Recently, a gain of function variant C1858T of the lymphoid-specific protein tyrosine phosphatase non-receptor (LYP, PTPN22) gene has been reported to be associated with several autoimmune disorders including Graves' disease, type 1 diabetes, rheumatoid arthritis and vitiligo. The present study was carried out in 80 patients with sporadic idiopathic hypoparathyroidism (SIH) [43 males and 37 females, mean ± SD age and duration of symptoms 32.5 ± 14.1 years and 6.7 ± 7.2 years (range 1 day to 35 years), respectively] and 193 healthy controls (male : female ratio 91:102, mean ± SD age, 43.1 ± 11.6 years) to assess association of 1858T allele with the disease. Polymerase chain reaction,restriction fragment length polymorphism analysis was performed to genotype C1858T variant. The frequency of occurrence of 1858T allele was 4/160 (2.5%) in SIH and 5/386 (1.3%) in the control alleles (odds ratio 1.95, 95% CI 0.51,7.37). Thus, the present study reveals that 1858T allele is rare (1.3%) in Asian Indians. The trend of higher prevalence of 1858T allele in patients with SIH needs to be studied further in other population with higher rate of the allele to support the autoimmune basis of the disease. [source] Evans' syndrome following autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphomaINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 4 2004K. Kamezaki Summary A 34-year-old woman with non-Hodgkin's lymphoma received high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT). She developed Evans' syndrome, the association of immune thrombocytopenia and autoimmune hemolytic anemia, 49 days after transplantation. Multiple autoimmune disorders may occur concurrently after autologous PBSCT. [source] Profile of opportunistic infections among patients on immunosuppressive medicationINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 3 2006Srinivas REDDY Abstract Background:, The widespread use of immunosuppressives in treating systemic autoimmune disorders has resulted in opportunistic infections (OIs) following such therapy. Current data regarding the possibility of infection due to these drugs or from the primary disease, per se, is conflicting. Objectives:, We aimed to analyse the profile of patients requiring hospitalization for OIs among those being treated with glucocorticoids and other immunosuppressive agents as part of management of systemic autoimmune disorders and to analyse the host factors in relation to OIs. Method:, In this descriptive analysis, all patients hospitalized the Postgraduate Institute of Medical Education and Research, Chandigarh, India, under medicinal units for OIs that occurred following and during treatment with corticosteroids and other immunosuppressive agents for treatment of systemic autoimmune disorders from February 2002 to January 2003, were studied. All hospitalized patients received antibiotics according to the nature of infection and sensitivity reports. All relevant clinical details were recorded in a standard pro forma. Descriptive statistics were used. The Institute Ethics Committee's permission was secured prior to study commencement. Results:, Nineteen patients (16 female) were admitted because of OIs. Their mean age (± SD) was 37.32 (± 19.9) years. Ten patients had systemic lupus erythematosus (SLE), two had SLE with overlap, five had rheumatoid arthritis, and one each had vasculitis and scleroderma with polymyositis. There were 28 infections. One (5.3%) patient had four infections, one (5.3%) had three, six (31.6%) had two, nine (47.4%) had one, and in two (10.5%) patients the infection was not localized. Of the 19 cases, 10 (52.6%) received > 10 mg of prednisolone each day (median = 1130 mg). The remaining nine (47.4%) were on < 10 mg prednisolone each day (median = 880 mg). Methylprednisolone was given to two (6.3%) patients. Bacteria accounted for most of the infections. There were two fungal infections and one patient each with tuberculosis and peritonitis. Infections occurred predominantly in the chest, urine and skin. Septicemia was diagnosed in three patients. There were two deaths, one each with SLE and rheumatoid arthritis. Conclusion:, Since infections can occur at low doses of corticosteroids, we suggest that these disorders may be, per se, responsible for an increased risk of infection. [source] Adverse drug reactions to biologicsJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 6 2010Kathrin Scherer Summary The use of biologics has rapidly expanded since the introduction of the first diagnostic antibodies; they are now widely employed in oncology, autoimmune disorders, inflammatory diseases and transplantation medicine. Their widespread use has resulted in an increase in adverse drug reactions. Adverse effects result from both direct pharmacological actions and immunological actions, as well as through induction of a specific immune response. The nomenclature, particularly of the monoclonal antibodies, identifies the target structure and organ as well as the species of origin, which then helps predict their effects and antigenic properties. Depending on the extent of foreign protein, anti-allotypic or anti-idiotypic antibodies with or without neutralizing properties may be induced. Adverse drug reactions from biologics often depend on the target and may be explained by activation or inhibition of particular cytokine pathways. Adverse drug reactions are classified by their pathomechanism, which enhances understanding of the pathogenesis and facilitates both allergologic diagnostic measures and planning of premedication in future treatments. This review emphasizes immunostimulatory and hypersensitivity reactions. [source] Lymphocytapheresis in the treatment of psoriasis vulgaris ,,JOURNAL OF CLINICAL APHERESIS, Issue 3 2006Giancarlo Maria Liumbruno Abstract Psoriasis is a common autoimmune chronic inflammatory skin disease that affects approximately 2% of the world's population; fundamental for its immunopathogenic mechanism is secretion of type 1 (Th1) cytokines by T cells and their activation. Since cytapheresis has been widely applied to autoimmune disorders, emphasizing the recently reported results of granulocyte and monocyte adsorption apheresis in psoriasis, a small series of psoriasis vulgaris (PV) patients underwent lymphocytapheresis (LCA) with the aim to remove lymphocytes. Five patients were submitted to weekly LCA. The severity of the disease had been evaluated through psoriasis area and severity index (PASI) score before LCA and one week after the last apheresis. PASI score before: patient A: 66; patient B: 33; patient C: 50; patient D: 56; patient E: 29. All the patients showed improvement of skin lesions. PASI score after LCA: patient A: 24; patient B: 8; patient C: 5; patient D: 36; patient E: 2.1. No side effects linked to apheresis were reported. LCA seems to produce interesting results in PV, and PASI improvement related to apheresis is clinically significant. Further studies to address its mechanism of action and potential long-term side effects are needed. It could become a valuable therapeutic alternative or a complementary tool, which might even be used to reduce the dosages of conventional pharmacological therapies adopted for this chronic disease. J. Clin. Apheresis 2006. © 2006 Wiley-Liss, Inc. [source] Improved treatment of sudden hearing loss by specific fibrinogen aphaeresisJOURNAL OF CLINICAL APHERESIS, Issue 2 2004Heidrun Ullrich Abstract The etiology of sudden sensorineural hearing loss is still unclear and is thought to result from disturbances of microcirculation, infectious causes, or autoimmune disorders. So far standard therapy did not show clear improvement over spontaneous remission rate, which is assumed to be about 50% [Nakashima et al., Acta. Otolaryngol. Stockh. 514:14,16, 1994; Schuknecht and Donovan, Arch. Otorhinolaryngol. 243:1,15, 1986; Harris and Sharp, Laryngoscope 100:516,524, 1990; Mayot et al., Clin. Immunol. Immunopath. 68:41,45, 1993; Gussen, Ann. Otol. Rhinol. Laryngol. 85:94,100, 1976]. Elevated blood viscosity due to high fibrinogen levels is supposed to cause decreased cochlear blood flow and thus initiate sudden hearing loss. The specific lowering of fibrinogen immediately decreases plasma viscosity exactly to the desired extent and should lead to improved cochlear blood flow [Suckfüll et al., Acta. Otolaryngol 119:763,766, 1999; Suckfüll, Lancet 360:1811,1817, 2002; Walch et al., Laryngol. Rhino. Otol. 75:641,645, 1996; Suckfüll et al., Otol. Neurotol. 23:309,311, 2002]. In a prospective uncontrolled pilot study on 36 patients with unilateral sudden onset sensorineural hearing loss (SHL) we tried to establish that 1,3 specific fibrinogen aphaereses alone improve recovery of hearing and that it is possible to lower fibrinogen to the target of 80,100 mg/dl without important side effects. Pure tone audiometry was carried out immediately before and after each aphaeresis as well as at 2 and 4 weeks and 6 months after treatment. Sixteen patients recovered spontaneously before undergoing fibrinogen adsorption. All 20 aphaeresis patients improved during immunoadsorption; in 60% of patients auditory thresholds returned to normal after the first immunoadsorption and treatment could be discontinued, in another 20% of patients complete recovery was reached after 4 weeks. The mean plasma fibrinogen concentration of the 20 patients before the first aphaeresis session was 308.1 ± 51.5 mg/dl. Immediately after the first treatment session, the fibrinogen concentration was lowered to 100.7 ± 25.3 mg/dl (P < 0.001). The second and third sessions also showed highly significant reductions in plasma fibrinogen. No important side effects were seen. In conclusion, specific fibrinogen adsorption is a promising new treatment modality that should be tested in a prospective, randomized controlled trial in patients with sudden hearing loss. J. Clin. Apheresis 19:71,78, 2004. © 2004 Wiley-Liss, Inc. [source] Signal transduction and functional changes in neutrophils with agingAGING CELL, Issue 4 2004Tamas Fulop Summary It is well known that the immune response decreases during aging, leading to a higher susceptibility to infections, cancers and autoimmune disorders. Most widely studied have been alterations in the adaptive immune response. Recently, the role of the innate immune response as a first-line defence against bacterial invasion and as a modulator of the adaptive immune response has become more widely recognized. One of the most important cell components of the innate response is neutrophils and it is therefore important to elucidate their function during aging. With aging there is an alteration of the receptor-driven functions of human neutrophils, such as superoxide anion production, chemotaxis and apoptosis. One of the alterations underlying these functional changes is a decrease in signalling elicited by specific receptors. Alterations were also found in the neutrophil membrane lipid rafts. These alterations in neutrophil functions and signal transduction that occur during aging might contribute to the significant increase in infections in old age. [source] Sudden Cardiac Death due to Giant Cell Inflammatory Processes,JOURNAL OF FORENSIC SCIENCES, Issue 4 2007Rebecca A. Hamilton M.D. Abstract:, Granulomatous inflammation of the myocardium may occur in a number of systemic disease processes including those with infectious etiologies such as fungal, mycobacterial and parasitic infections, as well as hypersensitivity reactions, and rarely autoimmune disorders. In many of these disorders, giant cells are components of the inflammatory infiltrate. Systemic granulomatous processes of unknown pathogenesis, most notably sarcoidosis, may also be associated with involvement of the myocardium. Occasionally, these disorders are associated with sudden death due to pathologic involvement of the heart. In contrast, giant cell myocarditis, also known as idiopathic myocarditis, a rare, frequently fulminant and fatal disorder of unknown etiology, is isolated to the heart and lacks systemic involvement. This disorder is most commonly diagnosed at autopsy. We present two cases in which sudden death resulted from a giant cell inflammatory process affecting the myocardium. Both individuals lacked antemortem diagnoses and collapsed at their respective places of employment. These cases compare and contrast the clinical and pathologic issues involved in the differential diagnoses of the subgroup of sudden cardiac deaths resulting from giant cell inflammatory processes that affect the myocardium, as well as the value of histologic examination and immunohistochemical studies. [source] Autoimmune and inflammatory disorders and risk of malignant lymphomas , an updateJOURNAL OF INTERNAL MEDICINE, Issue 6 2008K. E. Smedby Abstract. As specific autoimmune disorders now constitute established risk factors for malignant lymphomas, we describe this association. We review reported risk levels, risk determinants, lymphoma subtypes and biological mechanisms in autoimmunity/inflammation, emphasizing on recent findings. Whilst numerous reports describe average lymphoma risks in large patient groups, there's a recent shift of focus to risk determinants and the role of inflammatory activity. Studies highlight associations with diffuse large B-cell lymphoma, apart from lymphoma development in target organs of inflammation. Future studies of high-risk patient subsets using detailed assessments of autoimmunity/inflammation and lymphoma may give important clues to lymphomagenesis. [source] Immunomodulation by mesenchymal stem cells and clinical experienceJOURNAL OF INTERNAL MEDICINE, Issue 5 2007K. Le Blanc Abstract Mesenchymal stem cells (MSCs) from adult marrow can differentiate in vitro and in vivo into various cell types, such as bone, fat and cartilage. MSCs preferentially home to damaged tissue and may have therapeutic potential. In vitro data suggest that MSCs have low inherent immunogenicity as they induce little, if any, proliferation of allogeneic lymphocytes. Instead, MSCs appear to be immunosuppressive in vitro. They inhibit T-cell proliferation to alloantigens and mitogens and prevent the development of cytotoxic T-cells. In vivo, MSCs prolong skin allograft survival and have several immunomodulatory effects, which are presented and discussed in the present study. Possible clinical applications include therapy-resistant severe acute graft-versus-host disease, tissue repair, treatment of rejection of organ allografts and autoimmune disorders. [source] Parvovirus B19 nonstructural (NS1) protein as a transactivator of interleukin-6 synthesis: Common pathway in inflammatory sequelae of human parvovirus infections?JOURNAL OF MEDICAL VIROLOGY, Issue 2 2002Leslie Ann Mitchell PhD Abstract This review focuses on the role that human parvovirus B19 nonstructural (NS1) protein as a transactivator of the proinflammatory cytokine, interleukin-6 (IL-6), might play in triggering the multiparametric inflammatory outcomes of B19 infection. Parvovirus B19 is a ubiquitous virus, and it is often expressed during conditions of immunodepression including that induced by long-term chemotherapy, viral infection (HIV, HTLV-1), or genetic immunodeficiency disorders. Through NS1 expression, B19 may contribute to the immune dysregulation associated with these disorders, or serve as a cofactor in enhancing retroviral replication. Hence, NS1 transactivation of proinflammatory cytokine promoters such as IL-6 may be pivotal in triggering the various inflammatory and autoimmune disorders that have been linked to parvovirus B19 infections. J. Med. Virol. 67:267,274, 2002. © 2002 Wiley-Liss, Inc. [source] Autoimmunity as an aetiological factor in vitiligoJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 7 2007N Rezaei Abstract Vitiligo is a common dermatological disorder characterized by the presence on the skin of depigmented macules resulting from the destruction of cutaneous melanocytes. Autoimmunity is an important hypothesis with regard to vitiligo aetiology and the evidence for autoimmune responses being involved in the pathogenesis of this disorder will be discussed in the present review. All immune system compartments, including innate and adaptive immunity have been implicated in vitiligo development. Particularly relevant are autoantibodies and autoreactive T cells in vitiligo patients that have cytotoxic effects upon pigment cells. Furthermore, predisposition to vitiligo appears to be associated with certain alleles of the major histocompatibility complex class II antigens as well as with other autoimmune-susceptibility genes. Moreover, the association of vitiligo with autoimmune disorders, the animal models of the disease, and the positive response to immunosuppressive therapeutic agents emphasize the role of autoimmunity in the development of this disorder. [source] Interaction between psychiatric and autoimmune disorders in coeliac disease patients in the Northeastern United StatesALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2009S. GARUD Summary Background, Previous studies yielded conflicting results regarding the presence of an association between coeliac disease (CD) and psychiatric disorders including depression. This association has not been studied in the United States. Aim, To determine the prevalence of psychiatric and autoimmune disorders in patients with CD in the US compared with control groups. Methods, In a case control study, the prevalence of psychiatric and autoimmune disorders was compared in 600 CD patients, 200 irritable bowel syndrome (IBS) patients and 200 healthy controls. Results, The prevalence of depression in CD was 17.2% and was similar to that in IBS (18.5%, P = 0.74) and controls (16.0%, P = 0.79). Among CD patients, type I diabetes mellitus (DM) was identified as a significant risk factor for depression (P < 0.01) with 37% of patients with both CD and type I DM having clinical depression. Conclusion, The prevalence of depression in CD is similar to that in other chronic gastrointestinal diseases and healthy controls. However, there is a markedly elevated risk of depression in patients with both type I DM and CD. Differing rates of type 1 DM among coeliac populations may account for disparity in published rates of depression in patients with CD. [source] Hepatitis C virus-related extra-hepatic disease , aetiopathogenesis and managementALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2004J. Medina Summary Hepatitis C virus infection is often associated with extra-hepatic manifestations, secondary to the elicitation of autoimmune reactions, generalized deposition of immune complexes and lymphoproliferative disorders. The most clearly established associations are those linking chronic hepatitis C with mixed cryoglobulinaemia (and the related glomerulonephritis and cutaneous vasculitis), as well as with the presence of autoantibodies. Less well-documented disorders include non-Hodgkin's lymphoma, thrombocytopenia, sialadenitis, thyroid disease, lichen planus, porphyria cutanea tarda, rheumatoid disorders and neurological disorders. Extra-hepatic manifestations are most frequent in patients of female sex, advanced age, long-lasting infection and cirrhosis. Optimal treatment strategies should be based on the predominant manifestation of the disease. In the case of autoimmune disorders not clearly attributable to the viral infection, corticosteroids may be the most effective option. Interferon-, alone or in combination with ribavirin may be indicated for those disorders related to immune complex deposition, such as mixed cryoglobulinaemia, although relapses of extra-hepatic signs often occur on discontinuation of treatment. In some cases, interferon-, may induce or exacerbate some extra-hepatic manifestations. [source] | |||||||||||||||||||||||||||||||||||||