Stiff-man syndrome (SMS) is a rare disorder of the central nervous system 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 titers 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, although usually at a lower titer and with a different 
reaction pattern than patients with SMS. To investigate the immunogenetic basis 
of SMS, we HLA-typed 18 patients with the disease. Seventy-two percent carried 
the DQB1*0201 allele (13 of 18, P = 0.02 vs. 18 of 48 controls), indicating that 
SMS is associated with this allele. DQB1*0201 is also a susceptibility allele 
for IDDM and other autoimmune diseases. Patients with SMS carried the 
IDDM-protective DQB1*0602 allele and other sequence-related DQB1*06 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 DQB1*06 allele were 
diabetic in contrast to only 2 of 10 (20%) with a DQB1*06 allele (P = 0.08), 
suggesting that the presence of DQB1*0602 or other DQB1*06 alleles may be 
associated with a reduced prevalence of diabetes among patients with SMS.