Antibody responses toBorrelia burgdorferiin patients with antibiotic-refractory, antibiotic-responsive, or non-antibiotic-treated lyme arthritis

Pathogen-specific antibody responses need to be tightly regulated to generate protective but limit self-reactive immune responses. While loss of humoral tolerance has been associated with microbial infections, the pathways involved in balancing protective versus autoreactive antibody responses in humans are incompletely understood. Studies in classical mouse model systems have provided evidence that balancing of immune responses through inhibitory receptors is an important quality control checkpoint. Genetic differences between inbred mouse models and the outbred human population and allelic receptor variants not present in mice; however, argue for caution when directly translating these findings to the human system. By studying Borrelia burgdorferi infection in humanized mice reconstituted with human hematopoietic stem cells from donors homozygous for a functional or a non-functional FcγRIIb allele, we show that the human inhibitory FcγRIIb is a critical checkpoint balancing protective and autoreactive immune responses, linking infection with induction of autoimmunity in the human immune system.

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Human Lyme Arthritis and the Immunoglobulin G Antibody Response to the 37-Kilodalton Arthritis-Related Protein of Borrelia burgdorferi

Infection and Immunity ◽

10.1128/iai.73.5.2951-2957.2005 ◽

2005 ◽

Vol 73 (5) ◽

pp. 2951-2957 ◽

Cited By ~ 8

Author(s):

Carlos A. Salazar ◽

Monika Rothemich ◽

Elise E. Drouin ◽

Lisa Glickstein ◽

Allen C. Steere

Keyword(s):

Borrelia Burgdorferi ◽

Immunoglobulin G ◽

Erythema Migrans ◽

Total Duration ◽

Surface Protein ◽

Antibody Responses ◽

Lyme Arthritis ◽

Related Protein ◽

Serum Samples ◽

Igg Antibody

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.

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