Human Lyme arthritis and the immunoglobulin G antibody response to the 37-kilodalton arthritis-related protein of Borrelia burgdorferi

Abstract

In Borrelia burgdorferi-infected C3H-scid mice, antiserum to a differentially expressed, 37-kDa spirochetal outer-surface protein, termed arthritis-related protein (Arp), has been shown to prevent or reduce the severity of arthritis. In this study, we determined the immunoglobulin G (IgG) antibody responses to this spirochetal protein in single serum samples from 124 antibiotic-treated human patients with early or late manifestations of Lyme disease and in serial serum samples from 20 historic, untreated patients who were followed longitudinally from early infection through the period of arthritis. These 20 patients were representative of the spectrum of the severity and duration of Lyme arthritis. Among the 124 antibiotic-treated patients, 53% with culture-proven erythema migrans (EM) had IgG responses to recombinant glutathione S-transferase (GST)-Arp, as did 59% of the patients with facial palsy and 68% of those with Lyme arthritis. In addition, 75 to 80% of the 20 past, untreated patients had reactivity with this protein when EM was present, during initial episodes of joint pain, or during the maximal period of arthritis. There was no association at any of these three time points between GST-Arp antibody levels and the severity of the maximal attack of arthritis or the total duration of arthritis. Thus, after the first several weeks of infection, 60 to 80% of patients had IgG antibody responses to GST-Arp, but this response did not correlate with the severity or duration of Lyme arthritis.

FIG. 1.

IgG antibody responses to GST-Arp are shown (A) in single serum samples from 124 antibiotic-treated patients with erythema migrans, facial palsy, or Lyme arthritis and (B) in serial serum samples from 20 past, untreated patients who were followed longitudinally from early infection when EM was present, through initial episodes of joint pain, and during the maximal period of arthritis. The bars show the median values in the patients' responses (in panel A, healthy [normal] control subjects, 0.02; acute erythema migrans, 0.06; convalescent erythema migrans, 0.1; facial paralysis, 0.25; arthritis, 0.19; in panel B, erythema migrans, 0.17; initial joint pain, 0.25; maximal arthritis, 0.26).

FIG. 2.

The clinical courses and IgG antibody responses to GST-Arp and whole-cell Borrelia sonicate are shown in four representative patients. Patient 1, who had three brief episodes of arthritis, had a strong response to GST-Arp early in the illness, which declined after the first attack, but the response increased again during the subsequent episodes of arthritis. Patient 2 had strong reactivity with GST-Arp prior to the onset of arthritis, and this response declined throughout the subsequent four attacks of arthritis. Patient 3, who had more prolonged arthritis, had no reactivity with GST-Arp at any time in the illness. In contrast, patient 4, who also had prolonged attacks of arthritis, had marked reactivity with GST-Arp throughout the illness. In patients 1 and 4, the responses to GST-Arp sometimes decreased along with attacks of arthritis. However, reactivity with Borrelia sonicate also declined at these times, and thus, this pattern was not specific for GST-Arp. The gray area shows the range in seven healthy (normal) control subjects used to calibrate the ELISA.

FIG. 3.

Correlation of the IgG antibody responses to GST-Arp during erythema migrans, early arthralgia, or maximal arthritis with the severity and duration of arthritis. At each of these three time points, there was no association between the antibody levels to GST-Arp and the severity of duration of arthritis. Coef, coefficient.