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

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

Research output: Contribution to journalArticle

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Abstract

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
Volume159
Issue number3
StatePublished - Aug 1 1997

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Catalytic Antibodies
Thyroglobulin
Autoimmune Diseases
Autoimmune Thyroiditis
Immunoglobulin G
Systemic Lupus Erythematosus
Autoantibodies
Haptens
HIV Infections
HIV-1
Albumins

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Characterization of Thyroglobulin-Directed and Polyreactive Catalytic Antibodies in Autoimmune Disease. / Paul, Sudhir; Li, Lan; Kalaga, Ravishankar; O'Dell, James Robert; Dannenbring, Robert E.; Swindells, Susan; Hinrichs, Steven Heye; Caturegli, Patrizio; Rose, Noel R.

In: Journal of Immunology, Vol. 159, No. 3, 01.08.1997, p. 1530-1536.

Research output: Contribution to journalArticle

Paul, S, Li, L, Kalaga, R, O'Dell, JR, Dannenbring, RE, Swindells, S, Hinrichs, SH, Caturegli, P & Rose, NR 1997, 'Characterization of Thyroglobulin-Directed and Polyreactive Catalytic Antibodies in Autoimmune Disease', Journal of Immunology, vol. 159, no. 3, pp. 1530-1536.
Paul, Sudhir ; Li, Lan ; Kalaga, Ravishankar ; O'Dell, James Robert ; Dannenbring, Robert E. ; Swindells, Susan ; Hinrichs, Steven Heye ; Caturegli, Patrizio ; Rose, Noel R. / Characterization of Thyroglobulin-Directed and Polyreactive Catalytic Antibodies in Autoimmune Disease. In: Journal of Immunology. 1997 ; Vol. 159, No. 3. pp. 1530-1536.
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