Characterization of Thyroglobulin-Directed and Polyreactive Catalytic Antibodies in Autoimmune Disease

Sudhir Paul, Lan Li, Ravishankar Kalaga, James O'Dell, Robert E. Dannenbring, Susan Swindells, Steven Hinrichs, Patrizio Caturegli, Noel R. Rose

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64 Scopus citations


Polyreactive and thyroglobulin (Tg)-directed proteolytic activities present in the serum IgG of healthy controls and patients with autoimmune disease were studied by electrophoretic separation of 125I-labeled Tg reaction products and spectrofluorometric measurement of Pro-Phe-Arg-methylcoumarinamide cleavage at the Arg-methylcoumarinamide bond. A decrease of the polyreactive proteolytic activity accompanying an increase of the Tg-cleaving activity in IgG from autoimmune thyroiditis (ATh) and systemic lupus erythematosus (SLE) patients was evident. The Tg, a known target of autoimmune reactions in ATh, was cleaved at lower levels by Abs from patients with this disease than from SLE patients. The Tg-cleaving and Tg-binding activities of the autoantibody preparations were not correlated. Enhanced rates of cleavage at saturating substrate concentrations (Vmax), not increased Tg-binding affinities, were evident in IgG preparations with the greatest Tg-cleaving activity. Similarly, diminution of the polyreactive proteolytic activity in IgG from the autoimmune disease patients was due to decreased Vmax values, not decreased substrate-binding affinities. No cleavage of Tg by IgG from subjects with HIV-1 infection, or from mice hyperimmunized with an albumin-hapten conjugate was evident, suggesting that generation of Tg-cleaving Abs does not accompany V region affinity maturation in response to unrelated Ags. These observations establish Tg as a target of catalytic autoantibodies in SLE and ATh, suggest a transition from polyreactive proteolytic activity to autoantigen-directed activity in autoimmune disease, and open the possibility that combining site chemical reactivity is a factor driving the expression of catalytic activity by autoantibodies.

Original languageEnglish (US)
Pages (from-to)1530-1536
Number of pages7
JournalJournal of Immunology
Issue number3
StatePublished - Aug 1 1997

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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