Cross-Reactive Results in Serological Tests for Borreliosis in Patients with Active Viral Infections

Abstract

Currently, serological tests for Lyme disease (LD), routinely performed in laboratories following the European Concerted Action on Lyme Borreliosis recommendations as part of two-stage diagnostics, are often difficult to interpret. This concerns both the generation of false positive and negative results, which frequently delay the correct diagnosis and implementation of appropriate treatment. The above problems result from both morphological and antigenic variability characteristics for the life strategy of the spirochete Borrelia burgdorferi sensu lato, a complicated immune response, and imperfections in diagnostic methods. The study aimed to check the reactivity of sera from 69 patients with confirmed infection with Epstein–Barr virus (EBV), cytomegalovirus (CMV) and BK virus (BKV) with Borrelia antigens used in serological tests: indirect immunofluorescence (IIFT), enzyme-linked immunosorbent (ELISA) and immunoblot (IB). In the group of patients infected with EBV, the highest percentage of positive/borderline anti-Borrelia IgM and IgG results was obtained in the following tests: IIFT (51.9% for IgM, 63.0% for IgG), ELISA (22.2% for IgM, 29.6% for IgG) and IB (11.1% for IgM, 7.4% for IgG). In the group of CMV-infected patients, the highest percentage of positive/borderline anti-Borrelia IgM results were obtained in the following tests: IB (23.1%), IIFT (15.4%) and ELISA (7.7%), while in the IgG class in the IIFT (15.4%), IB (11.5%) and ELISA (3.9%) tests. In the group of patients infected with BKV, the highest percentage of positive/borderline anti-Borrelia IgM results was obtained in the following tests: IIFT (25.0%), IB (25.0%) and ELISA (3.9%), and in the IgG class in the tests: IB (50.0%), IIFT (6.2%) and ELISA (6.2%). The native flagellin (p41) and OspC proteins were the most frequently detected Borrelia antigens in all studied groups of patients in both classes of antibodies. Similar to other authors, the study confirmed the fact that serological tests used in the diagnosis of LD have a high potential to generate false positive results in patients with active viral infections, which may be related to cross-reacting antibodies appearing during the most common polyclonal activation of T/B lymphocytes, activated by viral superantigens.

Seroprevalence of Toxoplasma gondii and Borrelia burgdorferi infections in patients with multiple sclerosis in Poland

“…A more important problem than lower sensitivity is low test specificity, particularly in the case of IgM antibody 53 . It cannot be excluded that immunomodulation leading, among others, to lymphocytes B proliferation may be also the cause of not only equivocal results, but also false-positive results, and that the predictive value of diagnostic tests in these cases may be lower 52 . Diagnostic parameters of individual methods depend on the patient's clinical condition, infectious and non-infectious comorbidities 53 .…”

“…All doubtful results were noted in MS patients with IMD treatment. Serological screening tests used in the diagnosis of B. burgdorferi infection have a significant potential to generate false positive and equivocal results in patients with immunological disorders and viral infections which may be related to the cross-reactions occurring during polyclonal activation of B cells 52 , 53 . A more important problem than lower sensitivity is low test specificity, particularly in the case of IgM antibody 53 .…”

Could the Optiplex <i>Borrelia</i> assay replace the traditional, two-step method of diagnosing Lyme disease?

“…In this situation, choosing an optimal antigen pattern for diagnostic tests seems to be problematic. Taking the above into account, the diagnostic methods used in detecting LD should be selected to carry the lowest risk of false-positive or negative results [2][3][4]. Currently, the diagnostics of choice are serological assays, which rely on the detection of anti-Borrelia antibodies in the IgM and IgG classes.…”

Epitope Mapping of BmpA and BBK32 Borrelia burgdorferi Sensu Stricto Antigens for the Design of Chimeric Proteins with Potential Diagnostic Value

“…The frequent nonspecific reactions were the reason for the introduction of the two-step serodiagnostic test, as ELISA alone was not sufficiently specific. The introduction of a second-stage WB test improved the specificity of diagnostics but also significantly increased its costs. ,, …”

“…The introduction of a second-stage WB test improved the specificity of diagnostics but also significantly increased its costs. 5,9,10 The use of recombinant proteins is a potential solution to the problems of Lyme disease serodiagnosis. At present, they are the main form of antigens used in commercial WB (EUROLINE Borrelia-RN-AT (Euroimmun), recomLine Borrelia IgG/IgM (Microgen)).…”