Cellular and molecular aspects of Lyme arthritis

Abstract

Lyme disease is a multisystem illness initiated upon infection with the spirochete Borrelia burgdorferi. Whereas the majority of patients who develop Lyme arthritis may be successfully treated with antibiotic therapy, about 10% go on to develop arthritis which persists for months to years, despite antibiotic therapy. Development of what we have termed treatment-resistant Lyme arthritis has previously been associated with both the presence of particular major histocompatibility complex class II alleles and immunoreactivity to the spriochetal outer surface protein A (OspA). Recently, we showed that patients with treatment-resistant Lyme arthritis, but not patients with other forms of arthritis, generate synovial fluid T cell responses to an immunodominant epitope of OspA and a highly homologous region of the human-lymphocyte-function-associated antigen-1alphaL chain. Identification of a bacterial antigen capable of propagating an autoimmune response against a self-antigen provides a model of molecular mimicry in the pathogenesis of treatment-resistant Lyme arthritis.

Serum Levels of Interleukin-18 (IL-18), Interleukin-1β (IL-1β), its Soluble Receptor sIL-1RII and C-reactive Protein (CRP) in Patients with Lyme Arthritis

“…arthritis which lasts for more than 1 year in spite of antibiotic treatment [27], the determination of IL-18 may have a prognostic value. It is suggested that this form of LA has an autoimmunological ethiology [35]. Leukocyte functionassociated antigen-1 (LFA-1) was identified as a potential autoantigen in this form of LA [27].…”

“…It enables APC to present LFA-1 to immunocompetent cells and initiate the development of arthritis even after the pathogen was eliminated by antibiotic treatment. Immunocompetent cells in response to the interaction with LFA-1 secrete proinflammatory cytokines, which could be responsible for the damage of joints [35]. So the elevated serum level of IL-18 observed in patients with LA could be a predictor of treatment -resistant LA development, especially in patients with HLA DRB1 antigens, and a high ratio of anti-OspA IgG [35,36], but none of patients included in our study developed treatment-resistant LA as evaluated by clinical examination.…”

An Enhanced ELISPOT Assay for Sensitive Detection of Antigen-Specific T Cell Responses to Borrelia burgdorferi

“…Only a fraction of these cases are being diagnosed and treated, due to an unclear history, equivocal manifestations, inaccurate or insensitive laboratory clinical tests, and underreporting [5]. These undiagnosed and untreated patients may develop chronic infection or late stage Lyme disease such as chronic Lyme arthritis [6,7] and chronic Lyme neuroborreliosis [8,9] which can be devastating in some cases. …”

Prevention of Lyme Disease and Other Tick-Borne Infections

“…There were several factors involved in the lack of sales including the expense, the need for frequent revaccination and widely publicized concerns about a potential relationship with the development of autoimmune arthritis in patients with a specific HLA haplotype (DRB 0401) ref. A region of OspA that spans the amino acid residues 165–173 (OspA 165–173 ) was postulated to be a molecular mimic of human leukocyte function associated antigen - 1 αL326–345 (LFA-1) capable of inducing proliferation of autoreactive T cells [53, 54]. However, since then, multiple lines of evidence have not supported this hypothesis and molecular mimicry of LFA-1 is no longer felt to be a mechanism of antibiotic resistant Lyme arthritis, although other cross-reactions with OspA cannot be ruled out [55].…”