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Logo of arthresbiomed central web sitesearch.manuscript submission.see also journal with issn 1478-6354registration.reference to the article.journal front page.
 
Arthritis Res. 2001; 3(Suppl A): P071.
Published online Jan 26, 2001. doi:  10.1186/ar240
PMCID: PMC3273277
Study of the anti-idiotypic resonse to anti-LA/SSB autoantibodies using complementary peptides to B- and T-cell epitopes of La/SSB
JG Routsias,1 E Touloupi,1 A Moulia,2 M Sakarellos-Daitsiotis,2 H Dotsika,3 C Sakarellos,2 HM Moutsopoulos,1 and AG Tzioufas1
1Department of Pathophysiology, University of Athens, Greece
2Department of Organic Chemistry, University of Ioannina, Greece
3Hellenic Pasteur Institute, Athens, Greece
Supplement
21st European Workshop for Rheumatology Research
Conference
21st European Workshop for Rheumatology Research
1-4 March 2001
Vienna, Austria
Received January 15, 2001
 
Autoantibodies to La/SSB are found in sera of patients with primary Sjogren's Syndrome (pSS) and Systemic Lupus Erythematosus (SLE). A large body of these autoantibodies are directed towards discrete linear epitopes comprising the sequences 289-308 aa and 349-364 aa. Several previous studies have shown that in the sequence 289-308 aa resides also a T-cell epitope. Based on "molecular recognition" theory, complementary peptides cpep289-308 and cpep349-364, derived by anti-parallel readings of the non-coding strand of La/SSB DNA encoding epitopes 289-308 and 349-364 respectivelly, were synthesized. Complementary peptides cpep289-308 and cpep349-364 presented inverted hydrophobicity profiles, compared with sense peptides and recognized by 28% and 51% of anti-La/SSB positive sera respectively. F(ab')2 fragments were prepared after pepsin enzymatic degradation of affinity purified anti-pep and anti-cpep specific IgG. Anti-pep IgG found to specific recognize anti-cpep F(ab')2 fragment and vice versa, suggesting an idiotype - antiidiotype relation. Homologous inhibition with soluble anti-pep or anti-cpep F(ab')2 further confirmed this relation. In addition soluble pep, cpep or recombinant La/SSB inhibited (65%-85%) anti-pep and anti-cpep interaction indicating that the idiotype is located within the antigen binding site of anti-La/SSB antibodies. Anti-pep349-364 antibodies, purified from different patient sera were all found to recognize the same anti-cpep F(ab')2 suggesting that a common idiotype exists. Immunizations of BALB-c non-autoimmune mice with pep289-308 produced anti-pep289-308 followed by the production of anti-cpep289-308 antibodies 10 days later. In a similar manner immunization with cpep289-308 led to the appearance of anti-cpep289-308 followed by the formation of anti-pep289-308 antibodies. In conclusion, antibodies to B-cell epitopes of La/SSB contain in their antigen binding site a common idiotype which can be detected using complementary peptides to these epitopes. Antibodies to La/SSB epitopes are target of an anti-idiotypic response against this common idiotype. Manipulation of this Id - anti-Id network may provide potential insights into the understanding of the molecular mechanisms for autoantibody production and therapeutic approaches.
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