Lymphoproliferative Responses to Borrelia burgdorferi in Patients With Erythema Migrans, Acrodermatitis Chronica Atrophicans, Lymphadenosis Benigna Cutis, and Morphea

Abstract

Specific humoral and cell-mediated immune responses play an important role in the pathogenesis of Lyme borreliosis. Several previous studies demonstrated that a specific cellular immune response to Borrelia burgdorferi can occur independently of a diagnostic humoral response. Little is known about T-cell reactivities against B burgdorferi in early and late cutaneous manifestations of Lyme borreliosis. We studied the lymphoproliferative response of peripheral blood mononuclear cells to B burgdorferi antigen from 99 patients (25 with erythema migrans, 16 with acrodermatitis chronica atrophicans, 13 with lymphadenosis benigna cutis, and 45 with localized scleroderma) and 21 control subjects. The results are expressed as a stimulation index (SI) (mean count per minute of triplicate cultures with stimulant divided by mean count per minute without stimulant). The serum samples from all patients and control subjects were tested for antibodies to B burgdorferi by indirect immunofluorescence assay. The 21 healthy seronegative controls had an SI of 3.3 +/- 2.0 (mean +/- SD). Compared with that of control subjects, the SIs were significantly elevated in patients with erythema migrans (9.8 +/- 9.1), acrodermatitis chronica atrophicans (11.8 +/- 8.2), and lymphadenosis benigna cutis (7.2 +/- 6.2). The 45 patients with localized scleroderma had elevated proliferative responses, with an SI of 6.5 +/- 7.3, but these responses did not significantly differ from those of controls. Elevated titers of antibodies to B burgdorferi were present in six (24%) of 25 patients with erythema migrans, five (38%) of 13 patients with lymphadenosis benigna cutis, and 13 (29%) of 45 patients with localized scleroderma. All 16 patients with acrodermatitis chronica atrophicans had markedly elevated antibody titers. Our findings show that a significant lymphoproliferative response to B burgdorferi occurs in the majority of patients with cutaneous manifestations of Lyme borreliosis. The lymphocyte proliferation assay may be of diagnostic value in patients in whom Lyme borreliosis is strongly clinically suspected and who have nondiagnostic levels of antibodies against B burgdorferi.