IgA Antibody Responses to Borrelia Burgdorferi and Three Specific Autoantigens in Patients With Lyme Disease: Correlations With Cytokine Mediators and Disease Duration

Abstract

The aim of this research was to investigate IgA antibody responses to Borrelia burgdorferi and 3 related autoantigens in patients with early manifestations of Lyme disease, including those with erythema migrans (EM) and in those with antibiotic-responsive and antibiotic-refractory Lyme arthritis (LA), a late disease manifestation. IgA antibody responses were then correlated with levels of innate, Th1 and Th17 inflammatory mediators and with arthritis duration. As determined by ELISA, serum levels of IgA antibodies to B. burgdorferi were highest in patients with LA, and these responses were still higher in joint fluid in those with antibiotic-responsive arthritis, suggesting local production of these antibodies in synovial tissue. In contract, IgA autoantibody responses to the 3 autoantigens, endothelial cell growth factor (ECGF) and matrix metalloproteinase-10 (MMP-10), and apolipoprotein B-100 (apoB-100) were similar or greater in serum than in joint fluid, both in response and refractory groups, suggestive of production at extra-articular sites. Serum IgA antibody responses to B. burgdorferi in patients with EM correlated directly with the levels of Th17-associated cytokines, whereas IgA responses to the spirochete in joint fluid in patients with refractory LA correlated inversely with the Th17-associated cytokine levels. Furthermore, IgA antibody responses to the 3 autoantigens correlated directory with the duration of arthritis in patients with refractory LA. Thus, in patients with EM or LA, IgA antibody responses to B. burgdorferi would appear to play a role in fighting the infection, but IgA responses to the 3 autoantigens appear to be a marker for prolonged arthritis that persists after spirochetal killing with antibiotic therapy.