[1345] Increased CXCL10 Is Associated with Reversal Reaction in Leprosy

DM Scollard, A Martinez, M Chaduvula, N Fowlkes, I Nath, B Stryjewska, DL Williams. National Hansen's Disease Programs, Baton Rouge, LA; Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil; LEPRA- Blue Peter Research Centre, Hyderabad, India; Louisiana State University, Baton Rouge

Background: The normally indolent course of leprosy is complicated in many patients by an acute, systemic inflammatory syndrome termed 'Reversal Reaction' (RR) that is a major cause of neuritis and other morbidity in leprosy. RR appears to be a spontaneous enhancement of cellular immunity, but the mechanisms underlying this clinical syndrome are unknown and no laboratory tests are available to diagnose or monitor it.
Design: Sereum was collected monthly x 12 from 20 patients in India who had borderline leprosy (10BT and 10 BL) and who had RR at some time during their course, and from 20 similar patients who did not have RR. Serum CXCL10 levels were assayed by ELISA. Real-time quantitative PCR was performed on paired skin biopsies taken before and during RR, from 7 patients in the United States. Immunohistochmical staining was performed on paraffin sections of the same paired biopsies, using antibodies to CXCL10 and its receptor, CXCR3.
Results: Measurements of serum ELISA levels of CXCL10 in sequential, monthly specimens from 20 borderline (BL and BT) patients revealed significantly elevated levels of this chemokine associated with RR (p = 0.03). Real-time quantitative PCR revealed elevated expression of CXCL10 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 both of these molecules throughout the infiltrate.
Conclusions: 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.
Category: Infections

Monday, March 9, 2009 1:00 PM

Poster Session II # 192, Monday Afternoon