SERA OF LEPROSY PATIENTS WITH TYPE-2 REACTIONS RECOGNIZE SELECTIVE SEQUENCES IN MYCOBACTERIUM-LEPRAE RECOMBINANT LSR PROTEIN

Type 2 reactions (erythema nodosum leprosum [ENL]) are episodic, react ional states causing significant morbidity in lepromatous leprosy pati ents, With a view to defining the immunological differences between th e stable and reactional forms of lepromatous leprosy, we determined an tibody responses to LSR, a recombinant protein of Mycobacterium leprae previously described by us (S. Laal, Y. D. Sharma, H. K. Prasad, A. M urtaza, S. Singh, S. Tangri, R. S. Mishra, and I. Nath, Proc. Natl. Ac ad. Sci. USA 88:1054-1058, 1991), as well as to 10- to 15-mer overlapp ing peptides synthesized on the basis of the LSR amino acid sequence. We report here the selective recognition of B cell epitopes by sera fr om patients with ENL as compared with a control group with nonreaction al lepromatous leprosy. Peptides 2 and 3, with the sequences GVTYEIDLT NKNAA and IDLTNKNAAKLRGD, respectively, were recognized by >95% of ser a from patients with active ENL. Peptide 3 in addition showed reactivi ty with sera taken from 91.6% of lepromatous leprosy patients who were apparently stable but who were recorded to have had ENL several weeks before or after the sample collection. The core sequence IDLTNKNAA co mmon to both these peptides may be a major target of humoral responses in ENL. In addition, the RGD motif at the C terminus appeared to infl uence the antigenicity of peptide 3 in enzyme-linked immunosorbent ass ay. It would appear that humoral responses during ENL are directed to selective antigenic determinants of the leprosy bacillus. The use of s uch serological markers to identify lepromatous leprosy patients with a high risk for developing ENL would be of clinical and predictive val ue.