Preferential recognition of the phosphorylated major linear B-cell epitope of La/SSB 349-368aa by anti-La/SSB autoantibodies from patients with systemic autoimmune diseases

被引：29

作者：

Terzoglou, A. G. ^{[1
]}

Routsias, J. G. ^{[1
]}

Avrameas, S. ^{[1
]}

Moutsopoulos, H. M. ^{[1
]}

Tzioufas, A. G. ^{[1
]}

机构：

[1] Univ Athens, Dept Pathophysiol, Sch Med, Athens 11527, Greece

来源：

CLINICAL AND EXPERIMENTAL IMMUNOLOGY | 2006年 / 144卷 / 03期

关键词：

B-cell epitopes; autoantibodies; La/SSB; Sjogren's syndrome; posttranslational modifications;

D O I：

10.1111/j.1365-2249.2006.03088.x

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Sera from patients with primary Sjogren Syndrome (pSS) or Systemic Lupus Erythematosus (SLE) often contain autoantibodies directed against La/SSB. The sequence 349-368aa represents the major B-cell epitope of La/SSB, also it contains, at position 366, a serine aminoacid residue which constitutes the main phosphorylation site of the protein. In this study we investigated the differential recognition of the 349-368aa epitope and its phosphorylated form by antibodies found in sera from patients with systemic autoimmune diseases. Peptides corresponding to the sequence of the unphosphorylated (pep349-368aa) and the phosphorylated form (pep349-368aaPh) of the La/SSB epitope 349-368aa, as well as to a truncated form spanning the sequence 349-364aa and lacking the phosphorylation site (pep349-364aa), were synthesized. Sera from 53 patients with pSS and SLE with anti-La/SSB specificity, 30 patients with pSS and SLE without anti-La/SSB antibodies, 25 patients with rheumatoid arthritis and 32 healthy individuals were investigated by ELISA experiments. Autoantibodies to pep349-368aaPh were detected in sera of anti-La/SSB positive patients with a higher prevalence compared to the pep349-368aa (66% versus 45%). Pep349-368aaPh inhibited the antibody binding almost completely (92%), while pep349-368aa inhibited the binding only partially (45%). Anti-La/SSB antibodies presented a higher relative avidity for the phosphorylated than the unphosphorylated peptide. Immunoadsorbent experiments using the truncated peptide pep349-364aa indicated that the flowthrough showed a selective specificity for pep349-368aaPh, while the eluted antibodies reacted with both peptide analogues of the La/SSB epitope. These data suggest that sera from pSS and SLE patients with anti-La/SSB reactivity possess autoantibodies that bind more frequently and with a higher avidity to the phosphorylated major B-cell epitope of the molecule.

引用

页码：432 / 439

页数：8