CASPASE-12 (CASP12) modulates inflammation by down-regulating inflammatory cytokines. CASP12 is a risk factor for sepsis in persons of African ancestry, as the functional CASP12 allele is present in about 20% of persons of African descent. Nearly all other human populations lack a functional CASP12 gene. Systemic lupus erythematosus (SLE) is a serious and complex autoimmune disease affecting multiple organ systems and is most common in African-American (AA) women. To determine if CASP12 may be protective against SLE, 596 AA SLE patients and 296 healthy controls from the Lupus Family Registry and Repository were genotyped for CASP12. Serum from 30 patients and controls was assayed by antibody arrays for 23 inflammatory cytokines and chemokines. There was a significant association between CASP12 and protection against serositis. CASP12 homozygosity was seen only in controls, and CASP12 was only in female, but not male patients without serositis compared to those with serositis. In male patients, CASP12 was protective against the development of arthritis. Expression of the Mig chemokine was statistically different between patients and controls, independent of genotype. No influence of CASP12 genotype was seen upon serum cytokine levels in patients vs controls. The results indicate that CASP12 is protective against lupus serositis and arthritis in AA patients, with possible gender influences for both. In addition, chemokines may contribute to the pathogenesis of SLE.
- Copyright © 2013 by The American Association of Immunologists, Inc.