The p41 is a very important protein that has been found in bacterial flagellum including Borrelia burgdorferi. Flagellin p41 plays an essential role in bacterial invasion of the host tissue. IgM/IgG antibodies, against the protein of Borrelia burgdorferi, are the most detectable antibodies in the serum of patients with Lyme borreliosis. However, the p41 IgG antibodies have also been found in some healthy control serums. The p41 shares amino acid homology with other flagellated microorganisms and can explain the presence of these antibodies in healthy control serum by cross-reactivity with other flagellated bacteria. Thus, the specificity of serological tests involves p41 as the only diagnostic tool for Lyme borreliosis. Nevertheless, several cases of neuroborreliosis, with no known history of tick bites and persistently negative serological and PCR tests, have been described.
In studies, a patient with a previous history of lymphoma demonstrated symptoms of meningoencephalitis and has been misdiagnosed for suspected lymphoma relapse. However, no signs of malignancy were found, and PCR tests for Borrelia and other infections have been negative. The serological test has shown positivity for p41 IgG antibodies only and has been identified as negative for Lyme borreliosis. After two months, this patient was finally diagnosed with neuroborreliosis. Based on this incident, the role of p41 (flagellin) IgG antibodies became equivocal two months after initial testing. This case has demonstrated the difficulty of diagnosing the disease in immunocompromised patients. In other known cases, two young men had some health problems for approximately two years. They were both diagnosed with Lyme disease. However, their test results came back positive only for IgG p41 antibodies and were dismissed by doctors due to a lack of other specific Lyme disease antibodies. According to the CDC and LabCore explanation of the results, IgG/IgM p41 antibodies in Lyme Disease Western Blot assays can be related to other spirochetal diseases that cross-react with autoimmune diseases or other infections. Lastly, there was a case with a young girl who was suffering from very serious neurological symptoms and had been misdiagnosed because only a p41 AB band showed up on her test results for Lyme disease. All these cases demonstrate the difficulty of diagnosing Lyme disease or neuroborreliosis in some patients, including severely immunocompromised patients. The unknown history of tick bites, health issues, atypical symptoms, and low sensitivity of the tests limited Lyme disease diagnostics in this specific patient category. Thus, the diagnosis of Lyme disease/neuroborreliosis must be considered whenever neurological symptoms are present in a patient.
Recently it was demonstrated that in Lyme disease patients serum CD4/CD8 ratios correlate with high-level IgG p41 antibodies.