Dear Mariane Stefani and colleagues,

I have just read with interest your work on Tregs and Th-17 cytokines in leprosy. I think this is a very interesting and important aspect of the immunopathogenesis of leprosy reaction states. However I have some concerns regarding the control group. I think that the name “reaction-free patients” is misleading. In fact, according to the authors, the control group was made mostly (~2/3) of patients who have had a reaction episode, either T1R or T2R, and have been treated (MDT plus immunosuppression with corticosteroids up to 1 mg/Kg and/or thalidomide). Based on that, the observation that the “control group” had less inflamatory cells and cytokines in the lesions is rather expected, since they are mostly treated patients (some of them probably with regressive lesions after a mean of 9 or 12 months of MDT+ several months of immunosuppression). The potent immunosupressors are purposely used to decrease the infiltration of inflammatory cells and cytokines. I thus think that the comparison between reactional lesions and treated or regressive lesions is not quite meaningful, at least immunologically speaking.
In addition I believe that the heterogeneous nature of the control group makes difficult immunological comparisons with other groups, since it comprised the above mentioned 2/3 of immuno-manipulated reactional leprosy patients and 1/3 of non-immuno-manipulated, non-reactional leprosy patients (they developed the reaction later on). That’s the reason we compared in our study (cited by the authors, ref. 19), we compared patients undergoing a moderate/severe reaction episode with patients without previous reaction and without immunomanipulation. One of the limitations of our work is the low number of patients evaluated, and so far we would like to see if our results could be replicated by other groups. I think that a meaningful comparison in Stefani 's group nice work, would be that between the reaction patients and those who did not develop reaction at any time, even though in this case it leads to a smaller control group.

Sincerely yours

Gil Benard
Tropical Medicine Institute
São Paulo