Neuropsychiatric systemic lupus erythematosus is associated with imbalancein interleukin 10 promoter haplotypes

Objective-To investigate the association of interleukin 10 (IL10) promoter polymorphisms and neuropsychiatric manifestations of systemic lupus erythem atosus (SLE). Methods-IL10 haplotypes of 11 healthy volunteers were cloned to confirm tha t in the Dutch population, only the three common haplotypes (-1082/-819/-59 2) GCC, ACC and ATA exist. The IL10 promoter polymorphisms of 92 SLE patien ts and 162 healthy controls were determined. The medical records of the SLE patients were screened for the presence of neuropsychiatric involvement. Results-All cloned haplotypes were either GCC, ACC or ATA. Forty two SLE pa tients had suffered from neuropsychiatric manifestations (NP-SLE). In NP-SL E patients, the frequency of the ATA haplotype is 30% versus 18% in the con trols and 17% in the non-NP-SLE group (odds ratios 1.9, p=0.02, and 2.1, p= 0.04, respectively), whereas the GCC haplotype frequency is lower in the NP -SLE group compared with controls and non-NP-SLE patients (40% versus 55% a nd 61%, odds ratios 0.6, p=0.02 and 0.4 p=0.006). The odds ratio for the pr esence of NP-SLE is inversely proportional to the number of GCC haplotypes per genotype when the NP-SLE group is compared with non-NP-SLE patients. Conclusions-The IL10 locus is associated with neuropsychiatric manifestatio ns in SLE. This suggests that IL10 is implicated in the immunopathogenesis of neuropsychiatric manifestations in SLE.