Antibody Cross-Reactivity in Serodiagnosis of Lyme Disease

Abstract

Lyme disease is a tick-borne disease caused by spirochetes belonging to the Borrelia burgdorferi sensu lato complex. The disease is characterized by a varied course; therefore, the basis for diagnosis is laboratory methods. Currently, a two-tiered serological test is recommended, using an ELISA as a screening test and a Western blot as a confirmatory test. This approach was introduced due to the relatively high number of false-positive results obtained when using an ELISA alone. However, even this approach has not entirely solved the problem of false-positive results caused by cross-reactive antibodies. Many highly immunogenic B. burgdorferi s.l. proteins are recognized nonspecifically by antibodies directed against other pathogens. This also applies to antigens, such as OspC, BmpA, VlsE, and FlaB, i.e., those commonly used in serodiagnostic assays. Cross-reactions can be caused by both bacterial (relapsing fever Borrelia, Treponema pallidum) and viral (Epstein–Baar virus, Cytomegalovirus) infections. Additionally, a rheumatoid factor has also been shown to nonspecifically recognize B. burgdorferi s.l. proteins, resulting in false-positive results. Therefore, it is necessary to carefully interpret the results of serodiagnostic tests so as to avoid overdiagnosis of Lyme disease, which causes unnecessary implementations of strong antibiotic therapies and delays in the correct diagnosis.

Cross‐reaction mediated by distinct key amino acid combinations in the complementary‐determining region (CDR) of a monoclonal antibody

“…In our study, we focused on the H1‐74 mAb, targeting the influenza virus HA antigen, and its binding to two specific antigenic epitope peptides, 191‐LVLWGIHHP‐199 and 307‐LPFQNI‐312 10 . We combined bioinformatics analysis with the classical ELISA method to investigate the mechanism of antibody cross‐reaction 24,25 …”

“…10 We combined bioinformatics analysis with the classical ELISA method to investigate the mechanism of antibody cross-reaction. 24,25 In our comparison of the peptides 191-LVLWGIHHP-199 and 307-LPFQNI-312, we identified a common "LXXXXI" structure (Figure 1A), suggesting they might represent similar conformational epitopes. To explore if H1-74 mAb could bind to two distinct short peptides with different conformations, we created a new structure to replace the "LXXXXI" structure in LI-6.…”

Brazilian Borreliosis: An In-depth Review of Incidence, Diagnostic Challenges, and Awareness Efforts in Brazil

“…However, the persistence of IgM responses for years [88,91] and IgG poses challenges in distinguishing between active and inactive infections [82]. Moreover, IgM antibodies may have the potential to cross-react with antigens that are unrelated to Borrelia [92,93]. During the acute phase, IgA is produced, particularly in the cerebrospinal fluid [94][95][96].…”

Diagnostic Challenges of Lyme Co-infections: Lessons From a Lyme and Herpes Simplex Virus-1 (HSV-1) Cocktail

“…This can lead to misdiagnosis, with some studies reporting overdiagnosis based on serologic testing alone [ 5 ]. Antibiotic therapy remains the mainstay of treatment for Lyme disease [ 6 , 7 ].…”

“…This can lead to misdiagnosis, with some studies reporting overdiagnosis based on serologic testing alone [5]. Antibiotic therapy remains the mainstay of treatment for Lyme disease [6,7]. This case report describes a 55-year-old woman presenting with severe headaches, facial asymmetry, neck stiffness, nausea, and photophobia.…”