The insulin-dependent diabetes mellitus-associated ICA 105 autoantigen in stiff-man syndrome in patients

Gianvito Martino, L. M E Grimaldi, Elena Bazzigaluppi, Nadia Passini, Francesco Sinigaglia, Lars Rogge

Research output: Contribution to journalArticlepeer-review

Abstract

The pathogenetic role of anti-glutamic acid decarboxylase (GAD) antibodies found in up to 60% of patients with stiff-man syndrome (SMS) is still controversial. GAD, in fact, is also one of the major target antigens of insulin-dependent diabetes mellitus (IDDM), a disease affecting one third of anti-GAD antibody-positive patients with SMS. To better define the role of autoimmunity in SMS we looked for molecular and immunological evidence of an autoimmune recognition of a second IDDM-associated autoantigen, the pancreatic 37/40 kDa IDDM-autoantigen, whose gene called ICA 105 has been recently cloned. By Northern blot analysis we found that tissue distribution of human ICA 105 is restricted to pancreas and brain and within the central nervous system (CNS) its distribution is similar to GAD. We also measured anti-ICA 105 antibodies in 11 SMS patients and 56 control patients with other neurological diseases (OND). Anti-ICA 105 antibodies were found in 4/11 (36%) patients with SMS (a frequency similar to that of anti-GAD-antibodies in our SMS population) but in only 2/56 (3%) patients with OND (P <0.001). Anti-ICA 105 and anti-CAD antibodies were associated in 3/4 (75%) patients with SMS but in none of the 2 anti-ICA 105 antibody-positive OND patients. Among anti-ICA 105 antibody-positive patients with SMS, only 1 suffered also from IDDM. In contrast, the only 2 anti-ICA 105 antibody-positive patients with OND had IDDM. Our results indicate that ICA 105 represents another putative neuroendocrine autoantigen in SMS. The presence of circulating anti-GAD and/or anti-ICA 105 antibodies might help the diagnosis of SMS. The absence, however, of antibodies recognising specific CNS autoantigens (e.g. GAD, ICA 105) does not rule out SMS.

Original languageEnglish
Pages (from-to)129-134
Number of pages6
JournalJournal of Neuroimmunology
Volume69
Issue number1-2
DOIs
Publication statusPublished - Sep 1996

Keywords

  • glultamic-acid decarboxylase
  • ICA 105
  • insulin-dependent diabetes mellitus
  • stiff-man syndrome

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Clinical Neurology
  • Neurology

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