Anti-Ro(SSA) autoantibodies are associated with T cell receptor beta genes in systemic lupus erythematosus patients.

Frank, Mark Barton; McArthur, Robert A.; Harley, JB; Fujisaku, Atsushi

doi:10.1172/jci114430

Cited by 71 publications

(29 citation statements)

References 24 publications

(37 reference statements)

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“…In addition, vesicular stomatitis virus, through its G protein, is known to be capable of generating HLA class II restricted T-lymphocyte responses (33). This is compatible with the known HLA class II and T-lymphocyte receptor associations with the anti-Ro/SSA autoimmune response (1,(3)(4)(5).…”

supporting

confidence: 83%

“…The presence of anti-Ro/SSA autoantibodies is associated with powerful genetic effects at the HLA-DQ and the T-cell receptor f chain genes (3)(4)(5). These results, along with the greater antigenicity of the human form of Ro/SSA (6), implicate the particular human Ro/SSA autoantigen, histocompatibility molecules, and T-cell receptors in the molecular control of this autoimmune response.…”

mentioning

confidence: 99%

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Autoantigenicity of Ro/SSA antigen is related to a nucleocapsid protein of vesicular stomatitis virus.

Scofield

Harley

1991

Proc. Natl. Acad. Sci. U.S.A.

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107

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The fine specificit of a reference human anti-Ro/SSA autoantibody-containing serum has been analyzed by using sequential overlapping octapeptides from the human 60-kDa Ro/SSA antigen. From preliminary data, the most antigenic octapeptide in the carboxyl-terminal 120 amino acid residues of Ro/SSA shares seven ofeight amino acids with the nucleocapsid (N) protein from the Indiana serotype of vesicular stomatitis virus. A sequence comparison of Ro/SSA and N has unexpectedly revealed six small peptides shared by Ro/SSA and N. Fine specificity analysis with 531 octapeptides from the Ro/SSA sequence demonstrates that five of the six shared small peptides are bound by anti-Ro/SSA (P = 0.00017). A more powerful association is not present in 12,476 protein sequences similarly evaluated. In addition, the inclusion of single-residue gaps in Ro/SSA enlarges the sequence similarity of Ro/SSA and N for three of the five small shared antigenic peptides. This additional level of sequence similarity between Ro/SSA and N is unlikely to be the result of chance (P < 0.0002). While a number of models may explain these data, including independent immune responses to N and

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supporting

confidence: 83%

mentioning

confidence: 99%

Autoantigenicity of Ro/SSA antigen is related to a nucleocapsid protein of vesicular stomatitis virus.

Scofield

Harley

1991

Proc. Natl. Acad. Sci. U.S.A.

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107

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“…Weaker associations have been described for anti-U 1 RNP/Sm with the DR4 antigen in SLE patients (25,26). Finally, a recent report describes a T cell receptor p chain polymorphism which is associated with anti-Ro/SS-A alone, but not with anti-Ro/SS-A plus anti-LdSS-B in SLE patients (27). Thus, the results described in this paper are consistent with important roles of class 11, T cell receptor, and V region genes that are inherited in the germline and determine antibody specificity.…”

Section: Discussionmentioning

confidence: 95%

Serologic studies of monozygotic twins with systemic lupus erythematosus

Reichlin

Harley

Lockshin

1992

Arthritis & Rheumatism

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Objective. The goal of these studies was to assess the role of genetic factors and disease expression in the pattern and titer of autoantibodies to several RNA protein antigens in patients with systemic lupus erythematosus (SLE) by studying identical twins concordant and discordant for disease expression. Methods. Autoantibodies to Ro/SS‐A, La/SS‐B, U1 RNP, and Sm were measured by quantitative enzyme‐linked immunosorbent assay using affinity‐purified antigens. Results. Detailed serologic studies were performed in 7 pairs of identical twins, 3 of whom were concordant and 4 of whom were discordant for disease expression. Autoantibody titers were higher in affected than in unaffected twins from discordant pairs, but in 3 of 4 pairs, the profile of anti—RNA proteins (e.g., Ro/SS‐A, La/SS‐B, U1 RNP, and Sm) was virtually identical. In the SLE pairs concordant for disease expression, the autoantibody titers were very similar, as were the anti—RNA protein profiles. When the identical twins were matched by sex, race, and age to pairs of nontwin SLE patients, the 6 white twins shared an average of 2.5 (± 1.05 SD) anti—RNA proteins, while the control SLE pairs shared only 0.33 (± 0.82), P < 0.01 (t = 4.0, P < 0.01). In addition, in the white SLE twins, all had elevated levels of anti—U1 RNP while in white nontwin SLE patients, the frequency of anti—U1 RNP was 30%. Conclusion. These data point to a dominant role for genetic factors in the determination of specific autoantibody profiles.

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“…Autoantibodies to Ro/SSA are associated with particular HLA serotypes and gene markers in these patients (I 1, 68-71). We have recently reported T cell receptor restriction fragment length proteins which are associated with the presence of anti-Ro/SSA antibodies (72). Since the antigenic portion of these complexes resides in the polypeptide, differences in the presence of particular anti-Ro/SSA antibodies between patients may be based on the ability of that patient's immune system to process and recognize epitopes which are unique to each form of the Ro/SSA polypeptides.…”

Section: Resultsmentioning

confidence: 99%

Protein heterogeneity in the human Ro/SSA ribonucleoproteins. The 52- and 60-kD Ro/SSA autoantigens are encoded by separate genes.

Itoh¹,

Itoh²,

Frank³

1991

J. Clin. Invest.

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174

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Two cDNA clones encoding the 52-kD form of a protein present in human Ro/SSA ribonucleoprotein complexes were cloned from a X gtl1 human thymocyte cDNA library. These clones reacted with lupus patient sera which had anti-52-kD Ro/SSA antibodies, and with affinity-purified anti-52-kD Ro/ SSA antibodies. Moreover, affinity-purified antibodies isolated from isopropyl-l-D-thiogalactopyranoside-induced proteins of these clones reacted only with the 52-kD protein of lymphocytes in Western blots and precipitated Ro/SSA hY RNAs, confirming that the clones encode a 52-kD Ro/SSA antigen.The

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Anti-Ro(SSA) autoantibodies are associated with T cell receptor beta genes in systemic lupus erythematosus patients.

Cited by 71 publications

References 24 publications

Autoantigenicity of Ro/SSA antigen is related to a nucleocapsid protein of vesicular stomatitis virus.

Autoantigenicity of Ro/SSA antigen is related to a nucleocapsid protein of vesicular stomatitis virus.

Serologic studies of monozygotic twins with systemic lupus erythematosus

Protein heterogeneity in the human Ro/SSA ribonucleoproteins. The 52- and 60-kD Ro/SSA autoantigens are encoded by separate genes.

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