Polyspecific antibodies without persisting antigen in multiple sclerosis, neurolupus and Guillain-Barré syndrome: immune network connectivity in chronic diseases

Abstract

The polyspecific antibody synthesis in multiple sclerosis (MS) gained diagnostic relevance with the frequent combination of measles-, rubella-and varicella zoster antibodies (MRZ-antibody reaction) but their pathophysiological role remains unknown. This review connects the data for intrathecal polyspecific antibody synthesis in MS and neurolupus with observations in the blood of patients with Guillain-Barré syndrome (GBS). Simultaneously increased antibody and autoantibody titers in GBS blood samples indicate that the polyspecific antibodies are based on a general property of an immune network, supported by the deterministic day-to-day concentration variation of antibodies in normal blood. Strongly correlated measles-and rubella-antibody variations point to a particular connectivity between the MRZ antibodies. The immune network, which provides serological memory in the absence of an antigen, implements the continuous change of the MRZ pattern in blood, not followed by the earlier immigrated B cells without corresponding connectivity in the brain. This may explain the different antibody patterns in cerebrospinal fluid, aqueous humor and blood of the individual MS patient. A complexity approach must implement a different view on causation in chronic diseases and causal therapies.Keywords: cerebrospinal fluid; autoimmune diseases; antibodies; M,R,Z-antibody reaction; multiple sclerosis; Guillain-Barré syndrome, neurolupus. RESUMOA síntese de anticorpos poliespecíficos em esclerose múltipla (EM) ganhou relevância diagnóstica com a combinação frequente de anticorpos contra sarampo, rubéola e varicela-zoster (reação de anticorpos MRZ), mas seu papel fisiopatológico permanece desconhecido. Esta revisão relaciona os dados da síntese intratecal de anticorpos poliespecíficos em EM e Neurolupus com observações no sangue de pacientes com síndrome de Guillain Barré (SGB). Simultaneamente, os títulos aumentados de anticorpos e autoanticorpos em amostras de sangue de SGB indicam que os anticorpos poliespecíficos se baseiam numa propriedade geral de uma rede imunitária, suportada pela variação determinística da concentração diária de anticorpos no sangue normal. As variações fortemente correlacionadas de anticorpos contra sarampo e rubéola apontam para uma conectividade particular entre os anticorpos MRZ. A rede imunitária, que fornece memória sorológica na ausência de um antígeno, implementa a mudança contínua do padrão MRZ no sangue, não seguida pelas células B que imigraram anteriormente sem conectividade no cérebro. Isto pode explicar os diferentes padrões de anticorpos no LCR, humor aquoso e sangue do paciente individual de EM. Uma abordagem complexa deve implementar uma visão diferente sobre a causalidade em doenças crônicas e terapias causais.

G1m1 predominance of intrathecal virus‐specific antibodies in multiple sclerosis

“…In a majority of MS patients, antibody‐secreting cells are present in the central nervous system, and locally produced immunoglobulin G (IgG) can be detected in the cerebrospinal fluid (CSF) as oligoclonal bands (OCB) 3. Curiously, an intrathecal humoral immune response targeting commonly encountered viruses, including measles, rubella, and varicella zoster virus (VZV) can be observed in most MS patients, as opposed to patients with other neuroinflammatory diseases 4, 5, 6, 7, 8. These antibodies constitute a minor fraction of the intrathecally synthesized antibodies and are believed to be irrelevant to the pathophysiology of MS 7.…”

“…Curiously, an intrathecal humoral immune response targeting commonly encountered viruses, including measles, rubella, and varicella zoster virus (VZV) can be observed in most MS patients, as opposed to patients with other neuroinflammatory diseases 4, 5, 6, 7, 8. These antibodies constitute a minor fraction of the intrathecally synthesized antibodies and are believed to be irrelevant to the pathophysiology of MS 7. In contrast, no consensus has been found regarding an MS‐specific target of the major oligoclonal IgG fractions.…”

Estimation of intrathecal IgG synthesis: simulation of the risk of underestimation

“…GBS is not usually considered to be associated with ITS 42. OCB are sometimes reported but are identical between blood and CSF (type 4, indicating passive transfer) 43.…”

Chronic Diseases with Delayed Onset After Vaccinations and Infections. A Complex Systems Approach to Pathology and Therapy

“…The observation of an intrathecal antibody synthesis is not sufficient for the indication of an infection, as we learned from the polyspecific antibodies in MS (2,5,6). Nevertheless for the presence of an antibody species in the chronic diseases, the body must have had the contact with the real antigen.…”

“…-3 in less then 1% of the MS cases) and a low frequency of increased cell counts (> 35/µL only in 3% of the MS cases) in addition to the polyspecific measles-, rubella-, varicella zoster-(MRZ) antibody reaction in up to 94% of MS patients (2,5). In these cases the immune reaction cannot be questioned, however, the cause is unknown.…”