Geographic clustering of an outer surface protein A mutant of Borrelia burgdorferi. Possible implications of multiple variants for Lyme disease persistence

DNA sequences encoding full-length outer surface protein (Osp) A were ampli fied from four joint fluid samples over 4.5 months from a patient with chro nic Lyme arthritis, with a variant from wild type only found in sample 3. R ather than a mutation in vivo, these findings suggested a mixed infection i n which Borrelia containing the wild-type and mutant ospA were waxing and w aning in the patient's joint. If so, we reasoned that the mutant should be present in the community. We therefore took the novel epitope resulting fro m the mutation, expressed as a fusion protein in Escherichia coli, and perf ormed Western blots on 80 high-titred stored sera; however, all except that of our index patient were negative. We then collected 36 stored sera from patients with Lyme disease residing within 10 miles of where the index pati ent had lived. An additional two sera from this circumscribed area were pos itive (P = 0.038). These findings show that results from single samples can be misleading, and suggest that the OspAs expressed in force late in Lyme arthritis are the same ones introduced initially into the host. Moreover, t hey allow a speculative mechanism for disease persistence not previously co nsidered, in which antigenically distinct B. burgdorferi variant proteins p resent themselves serially to the immune system.