Temporal correlation of antibody responses to different epitopes of the human La autoantigen.

Clair, E. William St.; Burch, James A.; Ward, Michael M.; Keene, Jack D.; Pisetsky, David S.

doi:10.1172/jci114467

Cited by 33 publications

(9 citation statements)

References 32 publications

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“…Firstly, anti-scRNP antibodies are predominantly of the IgG1 subclass, suggesting a T cell dependent (antigen driven) mechanism [11][12][13]. Secondly, epitope-mapping studies of Ro/SS-A and La/SS-B autoantigens have yielded results compatible with a sequence of events whereby the autoantigens themselves serve as driving force behind the initiation of the autoimmune response [14][15][16]. Thirdly, human specific epitopes have been unequivocally demonstrated on the La/SS-B protein [17].…”

Section: Introductionmentioning

confidence: 99%

Production of anti-Ro/SS-A and anti-La/SS-B Autoantibodies is Closely Coordinated in Systemic Lupus Erythematosus and Independent of anti-dsDNA Production

Meilof

Veldhoven

Swaak³

et al. 1997

Journal of Autoimmunity

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Autoimmune diseases such as Sjögren's Syndrome and systemic lupus erythematosus (SLE) are characterized by serum autoantibodies against protein components of small cytoplasmic ribonucleoproteins (scRNPs). The origin and regulation of these anti-Ro/SS-A and anti-La/SS-B antibodies is not well understood. Regular co-occurrence of these two autoantibodies in humans together with murine studies on antibody responses against scRNPs after immunization suggest a role for scRNPs as common antigen. We sought additional evidence for this hypothesis in a longitudinal serological study of patients with SLE. Quantitative measurement of the antibody responses against Ro/SS-A and La/SS-B proteins and for comparison to dsDNA in 852 serum samples was performed. These samples were collected from nine patients during an average observation period of more than 10 years. A significant and strong correlation between the two anti-scRNP responses emerged during 90% of follow-up. In contrast, correlation of anti-scRNP with anti-dsDNA responses was remarkably absent in the same patients. Our results confirm the unique relationship between anti-Ro/SS-A and anti-La/ SS-B responses and could thus be interpreted as support for a model wherein induction and perpetuation of autoantibody production is dependent on scRNPs containing both proteins as antigen.

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Section: Introductionmentioning

confidence: 99%

Production of anti-Ro/SS-A and anti-La/SS-B Autoantibodies is Closely Coordinated in Systemic Lupus Erythematosus and Independent of anti-dsDNA Production

Meilof

Veldhoven

Swaak³

et al. 1997

Journal of Autoimmunity

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“…G. Tzioufas et al Their results did not lead to a clear definition of B cell epitopes of La/SSB protein, since they were only assigned to long stretches of polypeptides. It was shown, however, that antibodies to La/SSB, binding to a given B cell epitope, did not react with antibodies directed to other epitopes, suggesting that an anti-La/SSB response comprises independent anti-La/SSB antibody populations [32]. These observations strongly suggest that the production of anti-La/SSB antibodies is attributable to an antigen-driven process.…”

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confidence: 96%

Fine specificity of autoantibodies to La/SSB: epitope mapping, and characterization

Tzioufas

Yiannaki

Sakarellos‐Daitsiotis

et al. 1997

Clinical and Experimental Immunology

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SUMMARYThe B cell epitope mapping of La/SSB was performed using 20 mer synthetic peptides overlapping by eight amino acids covering the whole sequence of the protein. IgG, purified from sera of five patients with systemic lupus erythematosus (SLE) and four sera from patients with primary Sjögren's syndrome (pSS) were tested against the overlapping synthetic peptides. Peptides highly reactive with purified IgG were those spanning the regions 145-164, 289-308, 301-320 and 349-368 364 . Predicted features and molecular similarities of the defined epitopes were investigated using protein databases. The La epitope 147 HKAFKGSI 154 presented 83·3% similarity with the 139 HKGFKGVD 146 region of human myelin basic protein (MBP) and 72% similarity with the fragment YKNFKGTI of human DNA topoisomerase II. Peptides corresponding to these sequences cross-reacted with anti-La/SSB antibodies. Sixty-three sera with anti-La/SSB antibodies from patients with pSS or SLE, 35 sera without anti-La/SSB antibodies from patients with SS or SLE and 41 sera from age/sex-matched healthy blood donors were tested against biotinylated synthetic epitope analogues in order to determine their sensitivity and specificity for the detection of anti-La/SSB antibodies. Anti-La/SSB were detected with various frequencies ranging from 20% to epitope 147 HKAFKGSI 154 to 100% to epitope 349 GSGKGKVQGKKTKF 364 . The overall sensitivity and specificity using all assays with the synthetic peptides were found to be 93·6% and 85·6%, respectively. In conclusion, antibodies to La/SSB constitute a heterogeneous population, directed against different linear B cell epitopes of the molecule. The epitope 147 HKAFKGSI 154 presents molecular similarity with fragments of two other autoantigens, i.e. human MBP and DNA topoisomerase II. Finally, synthetic epitope analogues exhibit high sensitivity and specificity for the detection of anti-La/SSB antibodies.

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“…The use of small length antigenic peptides to detect anti-La/ SSB antibodies has been tested in a few previous studies. The failure of binding of anti-La/SSB human positive sera to synthetic La peptides reported previously [26] was probably due to an incomplete survey of sequential epitopes, excluding peptides that we found to be reactive. These four antigenic La peptides proved to be very sensitive and highly specific using the ELISA and dot blot.…”

Section: Discussionmentioning

confidence: 52%

The value of synthetic linear epitope analogues of La/SSB for the detection of autoantibodies to La/SSB; specificity, sensitivity and comparison of methods

Yiannaki

Tzioufas

Bachmann

et al. 1998

Clinical and Experimental Immunology

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In a previous study it was shown that La/SSB contains four linear epitopes, p147-154, p291-302, p301-318 and p349-364. The aim of the present study was to investigate the value of the synthetic epitope analogues of the La/SSB autoantigen for the detection of antibodies to La/SSB, in comparison with recombinant La and fragments of this protein. A total of 122 sera with anti-La/SSB activity, from patients with primary Sjögren's syndrome (pSS) or systemic lupus erythematosus (SLE), were tested in various peptide-based assays. In addition, 62 sera from pSS or SLE patients with other autoantibody specificities and 95 sera from healthy individuals were used as controls. The autoantibody specificity was identified by counter immunoelectrophoresis and immunoblot. The peptide-based ELISA assays presented sensitivities ranging from 78% to 88-8% and specificities from 69% to 94-3%. Dot blot assays exhibited sensitivities ranging from 93-6% to 97%, but remarkably lower specificities from 56% to 88%. The most sensitive and specific peptide 349GSGKGKVQFQGKKTKF364 was synthesized and attached on a tetramer sequential oligopeptide carrier SOC4 and used for immunoassay development. Assays based on the recombinant native La protein, the La-C terminal (215 aa), and the N-terminal of La with a mutation at base pair 640 (nine adenines instead of eight) were also developed and compared with the SOC4 peptide-based assay. Of anti-La-positive sera, 88.1% were reactive with both the synthetic peptide SOC4-(349-364aa) and the recombinant La protein. Eighty-three percent of sera were reactive with the La N-terminus and 67.8% of sera were reactive with the La C-terminus. Using sera that were anti-Ro-positive but anti-La-negative, 37% were reactive with the recombinant protein, 26% with the La N-terminus, 33% with the La C-terminus and only 11 % with the synthetic peptide. Our results suggest that the synthetic peptide epitopes exhibit high sensitivity and specificity for the detection of anti-La/ SSB antibodies in ELISA and dot blot techniques. The peptide SOC4-(349-364aa) has the same sensitivity for the detection of anti-La/SSB antibodies as the recombinant protein.

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Temporal correlation of antibody responses to different epitopes of the human La autoantigen.

Cited by 33 publications

References 32 publications

Production of anti-Ro/SS-A and anti-La/SS-B Autoantibodies is Closely Coordinated in Systemic Lupus Erythematosus and Independent of anti-dsDNA Production

Production of anti-Ro/SS-A and anti-La/SS-B Autoantibodies is Closely Coordinated in Systemic Lupus Erythematosus and Independent of anti-dsDNA Production

Fine specificity of autoantibodies to La/SSB: epitope mapping, and characterization

The value of synthetic linear epitope analogues of La/SSB for the detection of autoantibodies to La/SSB; specificity, sensitivity and comparison of methods

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