Human antibody responses to VlsE antigenic variation protein of Borrelia burgdorferi

VlsE is a 35-kDa surface-exposed lipoprotein of Borrelia burgdorferi that w as shown previously to undergo antigenic variation through segmental recomb ination of silent vis cassettes with vlsE during experimental mouse infecti ons. Previous data had indicated that sera from North American Lyme disease patients and experimentally infected animals contained antibodies reactive with VlsE, In this study, sera from patients with Lyme disease, syphilis, and autoimmune conditions as well as from healthy controls were examined fo r reactivity with VlsE by Western blotting and enzyme-linked immunosorbent assay (ELISA). Strong Western blot reactivity to a recombinant VlsE cassett e region protein was obtained consistently with Lyme disease sera. Although sera from Lyme disease patients also reacted with a band corresponding to VlsE in B. burgdorferi B31-5A3, interpretation was complicated by low level s of VlsE expression in in vitro-cultured B, burgdorferi and by the presenc e of comigrating bands. An ELISA using recombinant VlsE was compared with a n ELISA using sonically disrupted B, burgdorferi as the antigen. For a tota l of 93 Lyme disease patient sera examined, the VlsE ELISA yielded sensitiv ities of 63% for culture-confirmed erythema migrans cases and 92% for later stages, as compared to 61 and 98%, respectively, for the "whole-cell" ELIS A, The specificities of the two assays with healthy blood donor sera were c omparable, but the VlsE ELISA was 90% specific with sera from syphilis pati ents, compared to 20% specificity for the whole-cell ELISA with this group. Neither assay showed reactivity with a panel of sera from 20 non-lyme dise ase arthritis patients or 20 systemic lupus erythematosus patients. Our res ults indicate that VlsE may be useful in the immunodiagnosis of Lyme diseas e and may offer greater specificity than ELISAs using whole B. burgdorferi as the antigen.