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At least 181 records · Page 10Linked to original sources
PubMed2006

Anti-interleukin-6 monoclonal antibody inhibits autoimmune responses in a murine model of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease resulting from dysregulation of the immune system. Interleukin-6 (IL-6) is a multifunctional cytokine produced by macrophages, monocytes and T and B cells. It stimulates B-cell differentiation/maturation, immunoglobulin secretion, and T-cell functions. Elevated levels of IL-6 in serum, urine and renal glomeruli were detected in patients with active SLE and in murine models of SLE. Our study investigated the role of IL-6 in an SLE-like disease in New Zealand Black/White (NZB/W) F1 mice by administration of an anti-murine IL-6 monoclonal antibody (mAb). Intraperitoneal administration of the anti-IL-6 mAb suppressed the production of anti-dsDNA autoantibody. B-cell proliferation induced by anti-IgM and anti-CD40 was lower in the anti-IL-6 mAb-treated mice, ex vivo studies demonstrated that anti-IL-6 mAb treatment inhibited anti-dsDNA production. Anti-CD3-induced T-cell proliferation and mixed lymphocyte reactions were inhibited by anti-IL-6 mAb treatment, indicating a partial down-regulation of T cells. Histological analysis showed that treatment with anti-IL-6 mAb prevented the development of severe kidney disease. These results suggest that treatment with anti-IL-6 mAb has a beneficial effect on autoimmunity in murine SLE and that autoreactive B cells may be the primary target for anti-IL-6 mAb treatment; its effect on autoreactive T cells is also indicated.

Animals↗
PubMed1981

Gene(s) at I-A subregion controls the autoimmune response to thyroglobulin in mice.

Immunization of mice with thyroglobulin emulsified in Freund's complete adjuvant produces autoimmune thyroiditis, characterized by antibodies to thyroglobulin and infiltration of the thyroid with mononuclear cells. Some strains of mice are low and others are high responders to thyroglobulin. The immune response as reflected especially in the magnitude of the thyroid infiltration, is controlled by gene(s) within the H-2 locus. Previous attempts to map the Ir gene(s) for thyroglobulin (Ir-Tg) showed that it could be assigned to either the K or I-A subregion of H-2. An H-2 recombinant strain of mice, B10.MBR (H-2bq1), in which the H-2K is derived from the H-2b haplotype and which carries the I-Ak allele(s), was immunized with thyroglobulin. B10.MBR mice were high responders to thyroglobulin in contrast to C57BL/6 mice, which have both the H-2K and I-A from the H-2b haplotype and were low responders. This suggests that Ir-Tg, which controls the severity of autoimmune thyroiditis, maps within the I-A subregion, similar to gene(s) controlling the susceptibility to experimental myasthenia gravis.

Animals↗
PubMed1998

Experimental autoimmune prostatitis: in vivo induction of the autoimmune response to lymphocytic soluble factors. Alterations at the endocrine metabolism level.

PROBLEM: In rats, immunization with male accessory gland (MAG) extract promotes experimental autoimmune vesicle prostatitis. A specific mononuclear cell-mediated immune response and prostate androgen metabolism impairment in MAG-immunized rats were observed. The possibility that lymphocytic soluble factors (SoFs) can regulate the local steroid metabolism in these rats directly was studied. We investigated whether the SoFs released by MAG-sensitized lymphocytes are capable of modifying the prostatic androgen metabolism and whether they induce histologic lesions "in vivo" when they are inoculated, carried by liposomes, into untreated rats. METHOD OF STUDY: "In vitro" enzymatic [3H]-5 alpha-dihydrotestosterone bioconversion and histologic studies were performed with prostates from SoF-treated rats (LK rats). The obtained 3 alpha/beta-hydroxysteroid-oxidoreductase activities showed that LK rat values were significantly lower than in controls: 79.0 +/- 2.5 vs 158.7 +/- 10.2 pmol/min/mg protein, respectively (P < 0.01). RESULTS: In the histologic studies, LK rat prostates showed focalized mononuclear infiltrates of various degrees, whereas control rats showed non-atypic modification of the gland. CONCLUSION: These results indicate that SoFs (probably total lymphokines) contribute significantly to the pathogenesis of experimental autoimmune prostatitis, involving a biochemical relationship between immune reaction and the androgenic enzymatic inhibition in the prostate.

Animals↗
PubMed2003

Treatment of corticosteroid-responsive autoimmune inner ear disease with methotrexate: a randomized controlled trial.

CONTEXT: A number of therapies have been proposed for the long-term management of corticosteroid-responsive, rapidly progressive, bilateral sensorineural hearing loss (autoimmune inner ear disease [AIED]). Methotrexate has emerged as the benchmark agent but has not been rigorously evaluated for hearing improvement in patients with AIED. OBJECTIVE: To assess the efficacy of long-term methotrexate in maintaining hearing improvements achieved with glucocorticoid (prednisone) therapy in patients with AIED. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled trial conducted from February 3, 1998, to November 5, 2001, of 67 patients with rapidly progressive, bilateral sensorineural hearing loss at 10 tertiary care centers in the United States. INTERVENTION: Randomization to either oral methotrexate (15 to 20 mg/wk; n = 33) or placebo (n = 34), in combination with an 18-week prednisone taper. Follow-up examinations, including audiometric evaluation, were performed at 4, 8, 12, 24, 36, 48, and 52 weeks, or until hearing loss was documented. MAIN OUTCOME MEASURE: Maintenance of hearing improvement achieved from prednisone treatment. RESULTS: Sixty-seven patients (57.8%) enrolled in the prednisone challenge experienced hearing improvement. Twenty-five patients (37%) experienced hearing improvements in both ears. Of the individuals who reached study end points, 24 (80%) of 30 end points were because of measured hearing loss in the methotrexate group and 29 (93.5%) of 31 end points were because of measured hearing loss in the placebo group (P =.15). Methotrexate was no more effective than placebo in maintaining the hearing improvement achieved with prednisone treatment (hazard ratio, 1.31; 95% confidence interval, 0.79-2.17; P =.30). CONCLUSION: Methotrexate does not appear to be effective in maintaining the hearing improvement achieved with prednisone therapy in patients with AIED.

Audiometry↗
PubMed2003

Autoimmune response in cartilage-delivered peptides in a patient with osteoarthritis.

Whatever the initiating factor of osteoarthritis (OA), the process ultimately unmasks the immunogenic determinants of chondrocytes, proteoglycans and collagens, which then triggers autoimmune reactions. Although the precise mechanism of the immune responses in the pathogenesis of OA requires further investigation, here I postulate that the presence of autoimmunity to cartilage components has an important role in the process of cartilage degradation in OA. Current studies strongly suggest that a immunoregulatory therapeutic strategy should be established.

Editorial↗
PubMed1997

Autoimmune responses against acetylcholine receptor: T and B cell collaboration and manipulation by synthetic peptides.

Myasthenia gravis (MG) and experimental autoimmune MG (EAMG) are induced by antibodies (Abs) against self acetylcholine receptor (AChR). We have mapped the T and B cell epitopes on AChR alpha subunit in human MG and in EAMG-susceptible (C57BL/6, B6) and nonsusceptible mouse strains. A T-cell epitope within residues alpha 146-162 (P14) of Torpedo californica (t)AChR plays an important role in EAMG pathogenesis of the auto Ab-induced disease. P14-specific T cell (P14Th) lines from tAChR-primed B6 mice activated, in vivo and in vitro, tAChR-primed B cells that secreted anti-AChR Abs directed against four other regions on the tAChR alpha-chain, but not against P14 itself. P14Th cells are pathogenic because they help B cells that make Abs against a conserved tAChR region (t alpha 122-150) involved in ACh binding. These Abs cross-react with region alpha 122-150 of mouse (m)AChR, thereby disrupting its normal physiological function. Thus, a T cell epitope not recognized by Abs plays an active role in B cell responses against other epitopes on the protein. We have found that in B6, the MHC region 62-76 of I-A beta(b) is involved in the presentation of P14 to T cells. Anti-peptide Abs, prepared in BALB/c, were found to inhibit in vitro the proliferation of P14-specific T-cells. Furthermore, this MHC peptide elicited Abs in B6 mice and we are investigating whether immunization of B6 with this peptide, before priming with tAChR, would suppress in vivo the T-cell response to the epitope in P14. Thus, these preliminary results would suggest that immunization with the MHC peptide might be employed for control of the autoimmune disease.

Amino Acid Sequence↗
PubMed1993

Autoimmune responses as assessed by hypergammaglobulinemia and the presence of autoantibodies in patients with chronic hepatitis C.

We investigated autoimmunity, as assessed by hypergammaglobulinemia and the presence of autoantibodies including anti-nuclear antibodies (ANA) and anti-liver membrane antibodies (LMA), in 149 patients with chronic hepatitis C, 55 patients with chronic hepatitis B and 11 patients with autoimmune hepatitis. There was no significant difference in the incidence of these autoantibodies between chronic hepatitis C and chronic hepatitis B. Nine patients with chronic hepatitis C satisfied the serological criteria of autoimmune hepatitis (ANA positive and gammaglobulin or serum IgG greater than 2500 mg/dl), but none of the patients with chronic hepatitis B met the criteria. This suggests that autoimmunity is greater in chronic hepatitis C than in chronic hepatitis B. Of the 9 patients with chronic hepatitis C, all 4 patients tested for human leukocyte antigen (HLA) phenotype had HLA-DR4, which is known to be associated with autoimmune hepatitis in Japanese patients. We believe that hepatitis C virus (HCV) infection enhances the initiation and perpetuation of autoimmunity in susceptible individuals.

Adult↗
PubMed2005

Visualizing regulatory T cell control of autoimmune responses in nonobese diabetic mice.

The in vivo mechanism of regulatory T cell (T(reg) cell) function in controlling autoimmunity remains controversial. Here we have used two-photon laser-scanning microscopy to analyze lymph node priming of diabetogenic T cells and to delineate the mechanisms of T(reg) cell control of autoimmunity in vivo. Islet antigen-specific CD4(+)CD25(-) T helper cells (T(H) cells) and T(reg) cells swarmed and arrested in the presence of autoantigens. These T(H) cell activities were progressively inhibited in the presence of increasing numbers of T(reg) cells. There were no detectable stable associations between T(reg) and T(H) cells during active suppression. In contrast, T(reg) cells directly interacted with dendritic cells bearing islet antigen. Such persistent T(reg) cell-dendritic cell contacts preceded the inhibition of T(H) cell activation by dendritic cells, supporting the idea that dendritic cells are central to T(reg) cell function in vivo.

Adoptive Transfer↗
PubMedDate not supplied

Spectrum of autoimmune responses in systemic vasculitis.

Growing evidence supports the inclusion of primary forms of systemic vasculitis within the category of autoimmune diseases. Thus their association with a family of autoantibodies, related to their specificity or neutrophil cytoplasm antigens, has been identified and the role these autoantibodies play in pathogenesis is now being explored. Different members of the autoantibody family have now been characterised in terms of their molecular specificity and the isotype of immunoglobulin of which they are composed. These properties may be a useful adjunct in the classification of systemic vasculitis (see table I). It is the purpose of this review to put a perspective on the specificity and pathogenicity of autoantibodies found in patients with systemic vasculitis and to outline new strategies for the treatment of these conditions, based on the involvement of autoimmune mechanisms in the development of these disorders.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2002

Autoimmune responses in patients with linear IgA bullous dermatosis: both autoantibodies and T lymphocytes recognize the NC16A domain of the BP180 molecule.

Linear IgA bullous disease (LABD) is an autoimmune skin disease characterized by subepidermal blisters and IgA autoantibodies directed against the epidermal basement membrane zone (BMZ) of the skin. Various antigens have been identified as targets of IgA autoantibodies including BP180, a type II glycoprotein that spans the BMZ and lamina lucida. Previously, we have identified a subset of LABD patients whose sera contained IgA antibodies against the 16th noncollagenous (NC16A) domain of BP180. NC16A was previously shown to harbor epitopes that are recognized by both autoantibodies and T cells from patients with bullous pemphigoid and herpes gestationis and is thought to be associated with the development of these immunobullous diseases. The aim of this study was to determine whether T lymphocytes from LABD patients with anti-NC16A IgA autoantibodies respond to epitopes in the same region of the BP180 protein. Indeed, of the four LABD patients in our study, all had T cells that specifically proliferated in response to NC16A. Moreover, two subfragments of NC16A were identified as the predominant targets of LABD T cells. Further analysis of T cell lines and clones derived from these patients revealed that these cells express a CD4 memory T cell phenotype and secrete a Th1/Th2 mixed-cytokine profile, characteristics similar to those of T cells in bullous pemphigoid patients. Our data suggest that the BP180 protein, typically the NC16A region, is the common target of both cellular and humoral immune responses in some LABD patients. This information helps to further elucidate the autoimmune mechanisms in this disease.

Antigens, CD↗