THE INSULIN-DEPENDENT DIABETES MELLITUS-ASSOCIATED ICA-105 AUTOANTIGEN IN STIFF-MAN SYNDROME PATIENTS

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