ASSOCIATION OF HLA-DQB1-ASTERISK-0201 WITH STIFF-MAN SYNDROME

Stiff-man syndrome (SMS) is a rare disorder of the central nervous sys tem of probable autoimmune origin. Patients with SMS often have other autoimmune diseases, in particular type I (insulin-dependent) diabetes mellitus (IDDM). Approximately 60% of patients with SMS have high tit ers of autoantibodies against the enzyme glutamic acid decarboxylase, Similar to SMS, the majority of patients with IDDM have autoantibodies against glutamic acid decarboxylase at or before diabetes onset, alth ough usually at a lower titer and with a different reaction pattern th an patients with SMS. To investigate the immunogenetic basis of SMS, w e HLA-typed 18 patients with the disease. Seventy-two percent carried the DQB10201 allele (13 of 18, P = 0.02 vs. 18 of 48 controls), indic ating that SMS is associated with this allele. DQB10201 is also a sus ceptibility allele for IDDM and other autoimmune diseases. Patients wi th SMS carried the IDDM-protective DQB10602 allele and other sequence -related DQB106 alleles with the same frequency observed in controls. In contrast, these alleles are rarely found in IDDM. Five of 8 (62.5% ) SMS patients lacking a DQB106 allele were diabetic in contrast to o nly 2 of 10 (20%) with a DQB106 allele (P = 0.08), suggesting that th e presence of DQB10602 or other DQB1*06 alleles may be associated wit h a reduced prevalence of diabetes among patients with SMS.