Polymyositis and Molecular Mimicry, a Mechanism of Autoimmunity

Walker, E J; Jeffrey, Peter D.

doi:10.1016/s0140-6736(86)92429-3

Cited by 69 publications

(23 citation statements)

References 11 publications

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“…Some hypotheses have been addressed to explain the causal role of EBV infection in the pathogenesis of PM/DM, including molecular mimicry, 35,38 EBV-induced expansion of autoreactive B cells, 39 and altered T cell response against EBV as shown in SLE. 40 The potential role of molecular mimicry as revealed by previous studies showed that histidyl-tRNA synthetase matches with the hypothetical EC-RF4 protein of EBV, 38 and alanyl-tRNA synthetase matches with BPLF1 protein of EBV.…”

Section: Discussionmentioning

confidence: 99%

Polymyositis/dermatomyositis and nasopharyngeal carcinoma: The Epstein–Barr virus connection?

Chen

Lan

et al. 2010

Journal of Clinical Virology

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Section: Discussionmentioning

confidence: 99%

Polymyositis/dermatomyositis and nasopharyngeal carcinoma: The Epstein–Barr virus connection?

Chen

Lan

et al. 2010

Journal of Clinical Virology

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“…The inciting antigen relevant to myositis may be intrinsic, i.e., the aminoacyl-tRNA synthetase itself, perhaps after an interaction with a virus that renders it immunogenic (12); or, particularly for the antibody to tRNAaIa, an antiidiotypic mechanism may pertain (54). Alternatively, a n as-yet-unidentified extrinsic protein, perhaps viral, may mimic specific aminoacyl-tRNA synthetases and cause an immune response via molecular mimicry (55).…”

Section: Discussionmentioning

confidence: 99%

HLA‐D Region genes associated with autoantibody responses to histidyl‐transfer RNA synthetase (Jo‐1) and other translation‐related factors in myositis

Goldstein

Duvic

Targoff

et al. 1990

Arthritis & Rheumatism

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Myositis has been associated with HLA-B8 and DR3, especially in white patients with polymyositis and serum anti-Jo-1 antibodies. Twenty-eight patients with myositis and serum translation-related autoantibodies anti-Jo-1, anti-PL-7, anti-PL-12, anti-KJ, and anti-SRP were studied for HLA class I1 specificities by Southern blotting with HLA-DRP, DQP, and D Q a probes. The association of HLA-DR3 (DRwl7) with anti-Jo-1 antibodies in white myositis patients was confirmed (P = 0.003, relative risk 8.9). However, HLA-DRw52 haplotypes, regardless of subtype, were present in all of the white and black patients with serum anti-Jo-1 and other translation-related autoantibodies. Moreover, one anti-Jo-1 positive patient had HLADRw8, an HLA-DRw52 haplotype on which the DRp3 gene has been partially deleted. No HLA-DQ specificity or allele was common to all patients. The HLA-DR3, DRS, DRw6, and DRw8 haplotypes, which bear the HLA-DRw52 specificity, share the most homology in the DRPl first hypervariable region at amino acid positions 9-13. Thus, this DRPl region appears to be the most likely candidate "epitope" for translation-related autoimmune responses in inflammatory myositis.Inflammatory myositis, particularly polymyositis in adults and dermatomyositis in children, has been associated with HLA-B8 and DR3 in white individuals (1,2). In an earlier study using serologic HLA typing (3), the specific subset of myositis patients with serum anti-histidyl-transfer RNA (tRNA) synthetase (antiJo-1) autoantibodies (4) had an even higher frequency of HLA-DR3 than myositis patients overall; all 11 patients with serum anti-Jo-1 antibodies had either HLA-DR3 and/or HLA-DRw6. It was hypothesized that this autoimmune response in myositis may be

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“…If, on the other hand, the synthetases share a common structure that the antibodies recognize, or that tends to make them antigenic, then other mechanisms, such as "molecular mimicry" (which has been suggested as a possible explanation for antisynthetases [28]), become more likely. The localization of the human his-tRNA and thr-tRNA synthetase genes (29), along with 2 other synthetases, to chromosome 5 , raises the possibility of evolutionary relatedness and makes such shared structures conceivable.…”

Section: Discussionmentioning

confidence: 99%

Antibody to threonyl–transfer rna synthetase in myositis sera

Targoff

Arnett

Reichlin

1988

Arthritis & Rheumatism

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The prevalence and clinical correlations of antithreonyl-transfer RNA synthetase (anti-PL-7), as well as the relationship of anti-PL-7 to anti-histidyl-transfer RNA synthetase (anti-Jo-1) were studied in 109 sera from patients with myositis. Inhibition of threonine aminoacylation was used to screen for anti-PL-7. Sera from 3 patients, 2 with polymyositis and 1 with polymyositisoverlap syndrome, and a fourth serum from a patient with dermatomyositis, which was previously found to contain anti-PL-7, inhibited >90% of activity (3.7% of 109 sera). All 4 sera reacted strongly in an enzyme-linked immunosorbent assay with enzyme that was either affinity purified with anti-PL-7 or was biochemically purified. There was no indication of crossreactivity by aminoacylation inhibition or, for most sera, by enzyme-linked immunosorbent assay. Anti-PL- 7 is an uncommon myositis-associated antibody that is independent of anti-Jo-1, but is directed at a functionally related enzyme.Polymyositis (PM) and dermatomyositis (DM) are associated with a high frequency of antinuclear and anticytoplasmic autoantibodies (1). Some of them, including anti-Jo-1 (2), anti-PM-Scl(3), and anti-Mi-2 (4), are found almost exclusively in serum from patients with myositis. The myositis-associated antibodies are distinguished by the great variety of specificities and by the relatively frequent association of their antigens with transfer RNA (tRNA) (5). Anti-Jo-1, the antibody most commonly found in myositis patients, is present in only 20% of all myositis patients (2) and in about 35% of its characteristic subgroup, adult PM (6). This antibody reacts with histidyl-tRNA (his-tRNA) synthetase (7), the enzyme that catalyzes the attachment of histidine to its cognate tRNA (aminoacylation of tRNAhis). Autoantibodies to 2 of the other aminoacyl-tRNA synthetases, threonyl-tRNA (thr-tRNA) synthetase (anti-PL-7) (5,8) and alanyl-tRNA synthetase (anti-PL-12) (9), have also been described, and their presence has been associated with myositis. Other antibodies directed at antigens associated with tRNA have been found in myositis sera, as demonstrated by the ability of these sera to immunoprecipitate tRNA (5,10,11), but the antigens have not been identified. Although antibodies to thr-tRNA synthetase and alanyl-tRNA synthetase and other tRNArelated proteins are uncommon, the association of the group as a whole with myositis seems to be important.Bernstein et a1 (lo), using immunoprecipitation with labeled HeLa cell extracts to detect the antibody, reported the presence of anti-PL-7 in the sera of 3% of

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Polymyositis and Molecular Mimicry, a Mechanism of Autoimmunity

Cited by 69 publications

References 11 publications

Polymyositis/dermatomyositis and nasopharyngeal carcinoma: The Epstein–Barr virus connection?

Polymyositis/dermatomyositis and nasopharyngeal carcinoma: The Epstein–Barr virus connection?

HLA‐D Region genes associated with autoantibody responses to histidyl‐transfer RNA synthetase (Jo‐1) and other translation‐related factors in myositis

Antibody to threonyl–transfer rna synthetase in myositis sera

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