Early-onset ankylosing spondylitis is associated with a functional MICA polymorphism

Major histocompatibility complex (MHC) class I chain-related A (MICA) molecules deliver activating signals through the NKG2D receptor expressed on the surface of natural killer (NK), CD8alphabeta and gammadelta T cells, and the MICA gene is polymorphic. The recently described MICA amino acid substitution at position 129 (MICA-129) seems to affect its binding to NKG2D. We investigated whether this dimorphism (MICA-129met [methionine] and MICA-129val [valine]) is associated with susceptibility to ankylosing spondylitis (AS) in a cohort of Algerian patients stratified according to their HLAB27 status and the age of onset of the disease. DNA from 129 patients and 76 healthy individuals were analyzed to determine the HLA-B generic type as well as MICA-129 polymorphism. Statistical analysis revealed: (1) a weaker association between AS and HLA-B27 in Algerians than in that reported for European patients (63% versus 80-90%), suggesting a possible influence of other genetic/environmental determinants in the studied population and (2) an association between MICA-129 met/met genotype and juvenile AS (p = 0.02) independent of HLA-B27 status. These data suggest a potential role for a functionally relevant MICA gene polymorphism in autoimmune/inflammatory disease susceptibility.