Transcriptional changes that characterize the immune reactions of leprosy.

Leprosy morbidity is increased by two pathologic immune reactions, reversal reaction (RR) and erythema nodosum leprosum (ENL). To discover host factors related to immune reactions, global transcriptional profiles of PBMC were compared between 11 RR, 11 ENL, and 19 matched control patients, with confirmation with qPCR. Encoded proteins were investigated in skin biopsies using immunohistochemistry. There were 275 genes differentially expressed in RR and 517 genes differentially expressed in ENL on the microarray. Pathways analysis showed immunity-related pathways represented in RR and ENL transcriptional profiles, with the "Complement and Coagulation" pathway common to both. IFN- γ was identified as a significant upstream regulator of the expression changes for RR and ENL. Immunohistochemical staining of skin lesions showed increased C1q in both RR and ENL. These data suggest a previously under-recognized role for complement in the pathogenesis of both RR and ENL and propose new hypotheses for reaction pathogenesis.