Borrelia burgdorferi -specific IgA in Lyme Disease

Abstract

The laboratory diagnosis of Lyme disease is currently dependent on the detection of IgM and IgG antibodies against Borrelia burgdorferi, the causative agent of the disease. The significance of serum IgA against B. burgdorferi remains unclear. The production of intrathecal IgA has been noted in patients with the late Lyme disease manifestation, neuroborreliosis, but production of antigen-specific IgA during early disease has not been evaluated. In the current study, we assessed serum IgA binding to the B. burgdorferi peptide antigens, C6, the target of the FDA-cleared C6 EIA, and FlaB(211-223)-modVlsE(275-291), a peptide containing a Borrelia flagellin epitope linked to a modified VlsE sequence, in patients with early and late Lyme disease. Specific IgA was detected in 59 of 152 serum samples (38.8%) from early Lyme disease patients. Approximately 50% of early Lyme disease patients who were seropositive for peptide-specific IgM and/or IgG were also seropositive for peptide-specific IgA. In a subpopulation of patients, high peptide-specific IgA could be correlated with disseminated disease, defined as multiple erythema migrans lesions, and neurological disease complications. These results suggest that there may be an association between elevated levels of antigen-specific IgA and particular disease manifestations in some patients with early Lyme disease.

Immune Response to Borrelia: Lessons from Lyme Disease Spirochetes

“…Characteristics of the antibody response to B. burgdorferi Serum antibodies to B. burgdorferi are of the IgM, IgG and IgA isotypes in humans, with IgA responses most prevalent in early Lyme borreliosis in patients presenting with EM (Steere et al, 1979;D'Arco et al, 2017). IgM and IgG responses have been detected in the serum of 30-80% of patients at the initial visit (Aguero-Rosenfeld et al, 1996;Barbour et al, 2008;Tjernberg et al, 2009), which in the case of patients presenting with EM, is usually within the first 10-14 days after a tick bite.…”

Ticks and Tick-Borne Diseases of Livestock in the Middle East and North Africa: A Review

“…This is a zoonotic disease transmitted by hard ticks of the genus Ixodes [ 256 , 257 ] and most common in temperate forested regions of North America, Europe and Asia [ 258 ]. Globally, Lyme disease is caused by some members of the B. burgdorferi sensu lato (s.l.)…”

Single-cell immunophenotyping of the skin lesion erythema migrans identifies IgM memory B cells

“…The B cells in the EM lesion of this subject possessed the highest fraction of IgG-switched receptors among memory B cells, and the highest fraction of IgA-switched receptors among plasma cells, as well as the highest mean SHM for IgA-switched receptors among plasma cells. IgA-serum reactivity to Bb has been observed in up to a third of subjects with early disease and IgA-positive subjects were more likely to have disseminated disease (48). More extensive studies are warranted to determine whether a reduced T cell response and low frequency of unmutated IgM antigen-presenting memory B cells, as seen in the subject with disseminated disease in our study, represents a suboptimal skin immune response that is permissive to Bb dissemination.…”

“…IgA-serum reactivity to B . burgdorferi has been observed in up to a third of subjects with early disease and IgA-positive subjects were more likely to have disseminated disease ( 48 ). More extensive studies are warranted to determine whether a reduced T cell response and low frequency of unmutated IgM antigen-presenting memory B cells, as seen in the subject with disseminated disease in our study, represent a suboptimal skin immune response that is permissive to B .…”