Caspase-12 and lupus: the curious case of the dog that didn't bark

CASPASE-12 (CASP12) has an anti-inflammatory function during infection, and is a risk factor for sepsis in African-Americans (AA).  To determine if CASP12 could be protective for systemic lupus erythematosus (SLE) in AA, we genotyped AA SLE patients and controls. We found that, at best, there was a weak association between CASP12 genotype with the absence of anti-dsDNA autoantibodies in SLE patients.  No effect was seen upon serum interleukin-1 beta levels, nor was any other protective effect noted for the CASP12 genotype, whether upon association with SLE, or any of the 11 American College of Rheumatology classification criteria.  We concluded that CASP12 genotype thus does not influence the phenotype of SLE in AA. This raises the issue as to why this protein would not play a more significant role in a chronic inflammatory disease process.