Reversal reaction in leprosy is associated with increased CXCL10 production

Abstract

Leprosy usually follows an indolent course, but is complicated in many patients by a systemic inflammatory syndrome termed 'Reversal Reaction' (RR) that appears to be a spontaneous enhancement of cellular immunity. RR is a major cause of neuritis and other morbidity in leprosy, but the mechanisms underlying this clinical syndrome are unknown, and no laboratory tests are available to diagnose or monitor it. Real-time quantitative PCR revealed elevated expression of CXCL10 mRNA in skin biopsies during RR compared to pre-RR biopsies in 7/7 patients. Immunohistochemical staining of skin biopsies did not identify an increase in the number of leukocytes strongly positive for CXCL10 or its receptor, CXCR3, but suggested an overall increase in staining for CXCL10. Measurements of serum levels of CXCL10 by ELISA in sequential, monthly specimens from 20 borderline (BL and BT) patients revealed significantly elevated levels of this chemokine associated with RR (p = 0.03). Together, these findings suggest that increased CXCL10 is a characteristic of cutaneous and systemic manifestations of RR. These findings may offer new possibilities for laboratory support in the diagnosis and monitoring of RR, and suggest that studies of the regulation of CXCL10 may provide further insight into the mechanisms responsible for this complication of leprosy.