The relationship between humoral and cellular immunity to IA-2 in IDDM

Tamir M. Ellis, Desmond A. Schatz, Eric W. Ottendorfer, Michael S. Lan, Clive Wasserfall, Patricia J. Salisbury, Jin Xiong She, Abner L. Notkins, Noel K. Maclaren, Mark A. Atkinson

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Autoantibodies to the neuroendocrine protein insulinoma-associated protein 2 (IA-2), a member of the tyrosine phosphatase family, have been, observed in individuals with or at increased risk for IDDM. Because this disease is thought to result from a T-cell-mediated autoimmune destruction of the insulin-producing pancreatic β-cells, we analyzed humoral and cellular immune reactivity to this autoantigen to further define its role in the pathogenesis of IDDM. Peripheral blood mononuclear cells (PBMC) from individuals with newly diagnosed IDDM or at varying levels of risk for the disease were stimulated in vitro with the entire 42-kDa internal domain of IA-2 (amino acids 603-979), a series of control antigens (glutathionine-S- transferase, tetanus toxoid, Candida albicans, mumps, bovine serum albumin), and a mitogen (phytohemagglutinin). The frequency and mean stimulation index of PBMC proliferation against IA-2 was significantly higher in newly diagnosed IDDM subjects (14 of 33 [42%]; 3.8 ± 4.5 at 10 μg/ml) and autoantibody-positive relatives at increased risk for IDDM (6 of 9 [66%]; 3.9 ± 3.2) compared with autoantibody-negative relatives (1 of 15 [7%]; 1.8 ± 1.0) or healthy control subjects (1 of 12 [8%]; 1.5 ± 1.0). The frequencies of cellular immune reactivities to all other antigens were remarkably similar between each subject group. Sera from 58% of the newly diagnosed IDDM patients tested were IA-2 autoantibody positive. Despite investigations suggesting an inverse association between humoral and cellular immune reactivities against islet-cell-associated autoantigens, no such relationship was observed (r(s) = 0.18, P = 0.39) with respect to IA-2. These studies support the autoantigenic nature of IA-2 in IDDM and suggest the inclusion of cellular immune responses as an adjunct marker for the disease.

Original languageEnglish (US)
Pages (from-to)566-569
Number of pages4
JournalDiabetes
Volume47
Issue number4
DOIs
StatePublished - 1998
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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