PMID- 17177971 OWN - NLM STAT- MEDLINE DCOM- 20070329 LR - 20181113 IS - 0009-9104 (Print) IS - 1365-2249 (Electronic) IS - 0009-9104 (Linking) VI - 147 IP - 1 DP - 2007 Jan TI - Spreading of antibody reactivity to non-thyroid antigens during experimental immunization with human thyroglobulin. PG - 120-7 AB - Intermolecular spreading of antibody reactivity has been implicated in the evolution of autoimmune disease. In this study, spreading of antibody reactivity to non-thyroid autoantigens after experimental immunization with thyroglobulin (Tg) was investigated. For this purpose, two rabbits were injected with human Tg six times (stages 1-6) every 3 weeks. Animals were also bled before priming. Antisera were tested by enzyme-linked immunosorbent assay (ELISA) for reactivity to several non-thyroid antigens: bovine serum albumin (BSA), native DNA (nDNA), human myosin, human globular (G) and filamentous (F) actin and porcine tubulin. Tg-immunized animals developed the following serological reactivity pattern: (a) high reactivity to myosin from stage 2 onward, (b) significant reactivity to F-actin, remaining high up to stage 6, (c) reactivity to BSA with a peak at stage 3, (d) a small increase of reactivity to G-actin at stage 3 and (e) no increase of reactivity to nDNA and tubulin. The study of affinity-purified anti-Tg antibodies and the use of competitive assays revealed that reactivity to F-actin was not due to cross-reaction with Tg. On the contrary, reactivity to myosin during the first stages of immunization was due to cross-reaction with Tg, while at stage 6 it became myosin-specific. Reactivity to BSA at stage 3 was also due to cross-reaction with Tg. We conclude that at least part of the induced anti-Tg antibodies may result from the expansion of B cell clones producing polyreactive natural autoantibodies, and polyreactivity of anti-Tg antibodies during the first stages of Tg-immunization may be responsible for the intermolecular spreading of antibody response. FAU - Thrasyvoulides, A AU - Thrasyvoulides A AD - Laboratory of Immunology, Department of Biochemistry, Hellenic Pasteur Institute, Athens, Greece. FAU - Liakata, E AU - Liakata E FAU - Lymberi, P AU - Lymberi P LA - eng PT - Journal Article PL - England TA - Clin Exp Immunol JT - Clinical and experimental immunology JID - 0057202 RN - 0 (Actins) RN - 0 (Antibodies) RN - 0 (Antigens) RN - 0 (Autoantibodies) RN - 0 (Epitopes) RN - 0 (anti-thyroglobulin) RN - 27432CM55Q (Serum Albumin, Bovine) RN - 9010-34-8 (Thyroglobulin) RN - EC 3.6.4.1 (Myosins) SB - IM MH - Actins/immunology MH - Animals MH - Antibodies/*blood MH - Antibody Formation MH - Antibody Specificity MH - Antigens/*immunology MH - Autoantibodies/blood MH - Cross Reactions MH - Enzyme-Linked Immunosorbent Assay/methods MH - Epitopes MH - Humans MH - Immunization/methods MH - Immunosorbent Techniques MH - Myosins/immunology MH - Protein Conformation MH - Rabbits MH - Serum Albumin, Bovine/immunology MH - Thyroglobulin/*pharmacology PMC - PMC1810443 EDAT- 2006/12/21 09:00 MHDA- 2007/03/30 09:00 PMCR- 2008/01/01 CRDT- 2006/12/21 09:00 PHST- 2006/12/21 09:00 [pubmed] PHST- 2007/03/30 09:00 [medline] PHST- 2006/12/21 09:00 [entrez] PHST- 2008/01/01 00:00 [pmc-release] AID - CEI3246 [pii] AID - 10.1111/j.1365-2249.2006.03246.x [doi] PST - ppublish SO - Clin Exp Immunol. 2007 Jan;147(1):120-7. doi: 10.1111/j.1365-2249.2006.03246.x.