Objective. To determine the frequency, clinical associations, and any major histocompatibility complex correlations of antifibrillarin antibodies in patients with systemic sclerosis (SSc).Methods. Antifibrillarin antibodies were determined by indirect immunofluorescence, immunoblotting, and immunoprecipitation, and HLA class I1 alleles by DNA oligotyping, in a large cohort of SSc patients.Results. Antifibrillarin was found in 8% of 335 SSc sera and was significantly more common in blacks (16%) than whites (S%), in males (33%) than females (14%), and in patients with cardiac, renal, or gut involvement. The HLA class I1 haplotype DRBZ *Z302, DQBZ*0604 was found significantly more frequently in SSc patients with antifibrillarin compared with racematched normal controls and 260 SSc patients without antifibrillarin. In addition, 1 or more of the HLA-DQB1
Objective. To examine interrelationships among myositis subsets, autoantibodies, and major histocompatibility complex (MHC) class 1 1 alleles across ethnic lines, and to localize genetic susceptibility (presence of HLA-DR versus DQ) to myositis within the MHC class 1 1 region.Methods. MHC class I1 alleles (HLA-DRBZ, DQM, and DQBI, detected by DNA oligotyping) and myositis-specific autoantibodies (MSA) were determined in 224 patients with various myositis syndromes, including 89 whites, 89 African-Americans, 25 MexicanAmericans, and 21 Japanese.Results. Anti-Jo-1 (histidyl-transfer RNA [tRNA] synthetase) and other MSAs (anti-PL-12, anti-PL-7, anti-OJ, anti-EJ, anti-KJ, anti-tRNA, and antisignal recognition particle) were equally distributed among the races, but occurred more often in patients with polymyositis (PM) than in those with dermatomyositis (DM) or other myositis syndromes. MSA frequencies were significantly positively associated with anti-Ro (SS-A) (P = 0.002), and significantly negatively associated with anti-U1 RNP (P = 0.003). Frequencies of the HLA-DRBI *0301 (DR3), DQAZ*0501, and DQBl*O2OISupported by grants from the Muscular Dystrophy Association, the RGK Foundation, NIH grants R-29AR-39325, AR-32214, and AI-27181, and medical research funds from (DQ2) alleles (and haplotype) were each increased in white patients with myositis, especially those with PM, but most strikingly in those with MSAs. However, in the other ethnic groups, except the Japanese group, only frequencies of HLA-DQAI *0501 and the structurally similar DQAI *0402 alleles were significantly increased. The presence of HLA-D@iI*0501 or *040I was most significantly associated with anti-Jo-1, anti-PLU, and other MSAs, compared with myositis patients without MSAs (P = 0.0008,Pc,, = 0.01, odds ratio [OR] = 3.7), and with normal, ethnically matched controls (P = 3 X lo-', P,,, = 1 x OR = 6.5). Among MSApositive patients who were negative for HLADQAl*O501 and *0401, including Japanese patients, the HLA-D&iI *OI02 and *OI03 alleles predominated. In addition, there appeared to be a negative association of the HLA-DR2 alleles (DRBI*I501 and *1503) with PM (P = 0.007, P,,, not significant, OR = 039), but not with DM or myositis overall.Conclusion. By transracial gene mapping, genetic susceptibility to anti-Jo-1 and other MSAs in patients with myositis can be localized within the MHC region to the HLA-DQ4I locus.Polymyositis (PM) and dermatomyositis (DM) are idiopathic inflammatory myopathies that are characterized clinically by proximal muscle weakness, elevations in the level of serum muscle enzymes, especially creatine kinase (CK), and typical abnormal findings on electromyography. Histopathologic analysis has revealed that affected skeletal muscles are infiltrated by inflammatory mononuclear cells, predominantly CDS+ T lymphocytes, and that those muscles show myofibril degeneration, regeneration, and/or necrosis. Similar clinical and histopathologic features of myositis have been observed in association with malignancies, other connective ti...
Nitrotyrosine is widely recognized as a surrogate marker of up-regulated inducible NO synthase expression at sites of inflammation. However, the potential immunogenicity of autologous proteins containing nitrotyrosine has not previously been investigated. Herein, we used the I-EK-restricted T cell epitope of pigeon/moth cytochrome c (PCC/MCC88–103) to assess the ability of T cells to recognize ligands containing nitrotyrosine. Substitution of the single tyrosine (Y97) in PCC/MCC88–103 with nitrotyrosine abrogates recognition by the MCC88–103-specific T cell hybridoma 2B4. CBA (H2K) mice immunized with MCC88–103 or nitrated MCC88–103 peptides produce T cell responses that are mutually exclusive. Transgenic mice that constitutively express PCC under the control of an MHC class I promoter are tolerant toward immunization with MCC88–103, but exhibited a robust immune response against nitrated MCC88–103. Analysis of T cell hybridomas specific for nitrated-MCC88–103 indicated that subtle differences in TCR VDJ gene usage are sufficient to allow nitrotyrosine-specific T cells to escape the processes of central tolerance.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.