PMID- 12892735 OWN - NLM STAT- MEDLINE DCOM- 20040406 LR - 20231213 IS - 0896-8411 (Print) IS - 0896-8411 (Linking) VI - 21 IP - 1 DP - 2003 Aug TI - Linear epitopes of two different autoantigens-La/SSB and myelin basic protein--with a high degree of molecular similarity, cause different humoral immune responses. PG - 47-57 AB - The region 147-154aa of La/SSB presents 83% sequence similarity with the 139-146aa region of the human myelin basic protein (MBP). The aim of this study was to investigate the prevalence and significance of antibodies against both epitopes in sera from patients with systemic autoimmune diseases, and to compare the humoral responses produced after rabbit immunization. Peptides 147-154aa of La/SSB and 139-146aa of the MBP were attached on tetrameric sequential oligopeptide carriers and used for immunizations of New Zealand White rabbits. Antibodies to immunizing peptides, as well as to the peptides corresponding to other previously defined La/SSB epitopes (289-308aa, 349-364aa), to the intact human MBP (hMBP) and to the recombinant human La/SSB (rechLa) proteins, were identified using specific ELISA assays. Sera from 45 patients with Sjogren's syndrome (pSS), 49 with Systemic Lupus Erythematosus (SLE), and 18 with Rheumatoid Arthritis (RA) were tested against the two peptides and the hMBP. Twenty-two per cent of sera from pSS patients, 27% of SLE patients, and none from RA sera reacted with the La epitope; 27% from pSS sera, 22% of SLE sera, and 17% of RA sera gave a positive reaction against the MBP peptide. Finally, 19% of pSS, 30% of SLE, and 38% of RA sera reacted with the hMBP. Thirty-five days after immunization of rabbits with the La epitope, antibodies were produced against all three La/SSB peptides, the MBP peptide, and the hMBP and rechLa proteins. Rabbits immunized with the MBP peptide produced antibodies against the immunizing peptide and the mimicking peptide of La shortly after immunization, whilst antibodies against the other La epitopes and the two intact proteins were produced later. Inhibition experiments in rabbit sera with high reactivity against hMBP, using the MBP peptide as inhibitor, revealed that 80% of serum reactivity was abolished. In conclusion, a significant proportion of human autoimmune sera reacted with both La and MBP derived peptides, as well as with hMBP. La 147-154aa peptide, when used for animal immunizations, induces a fast epitope spreading involving both La and MBP. In contrast, the mimicking MBP epitope induces a delayed response against the other La epitopes. Thus, despite the fact that these peptides present molecular similarity, they induce different immune responses. FAU - Terzoglou, Apostolos G AU - Terzoglou AG AD - Department of Pathophysiology, School of Medicine, University of Athens, 75 M. Asias st, 11527 Athens, Greece. FAU - Routsias, John G AU - Routsias JG FAU - Sakarellos, Constantinos AU - Sakarellos C FAU - Sakarellos-Daitsiotis, Maria AU - Sakarellos-Daitsiotis M FAU - Moutsopoulos, Haralampos M AU - Moutsopoulos HM FAU - Tzioufas, Athanasios G AU - Tzioufas AG LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Autoimmun JT - Journal of autoimmunity JID - 8812164 RN - 0 (Autoantigens) RN - 0 (Epitopes) RN - 0 (Myelin Basic Protein) RN - 0 (Peptides) RN - 0 (Ribonucleoproteins) SB - IM MH - Animals MH - Antibody Formation/*immunology MH - Autoantigens MH - Autoimmune Diseases/immunology MH - Epitopes/*immunology MH - Humans MH - Kinetics MH - Myelin Basic Protein/*immunology MH - Peptides/*immunology MH - Rabbits MH - Ribonucleoproteins/*immunology MH - SS-B Antigen EDAT- 2003/08/02 05:00 MHDA- 2004/04/07 05:00 CRDT- 2003/08/02 05:00 PHST- 2003/08/02 05:00 [pubmed] PHST- 2004/04/07 05:00 [medline] PHST- 2003/08/02 05:00 [entrez] AID - S0896841103000829 [pii] AID - 10.1016/s0896-8411(03)00082-9 [doi] PST - ppublish SO - J Autoimmun. 2003 Aug;21(1):47-57. doi: 10.1016/s0896-8411(03)00082-9.