Case Report
Treatment of life threatening autoimmune disease following Covid-19 vaccination has used a polypharmacy approach, directed at clearance and reduced production of autoantibodies. For example, IgA producing Beta cells in the gut play a key role in reducing inflammation (Rojas et al, 2019). In people treated for multiple sclerosis (MS), rituximab lowers immune B cell counts and reduces autoantibodies and autoimmune disease. The treatment relieved inflammation and reduced the risk of relapse. However, the drug, atacicept, that destroys even more B cells than does rituximab had the opposite effect to rituximab, triggering relapses. The evidence suggests that rituximab was efficacious because it destroyed the particular B cells that make the inflammation-causing immunoglobulin G antibodies. However, atacicept destroyed a different population of B cells found predominantly in the lining of the gut. These B cells, activated by bacteria, produce interleukin 10 (IL-10) that reduce inflammation. These gut-microbe-activated B cells may have been reducing MS symptoms through IL-10 activation, and therefore, the gut B cells destroyed by atacicept needed to be preserved by using rituximab. And we know that gut-associated IgA+ B cells and plasma cells traffic to the CNS and are part of the disease sequalae in MS (Probstel et al, 2020). However, rituximab doesn’t stop the actions of intracellular autoantibodies that affect many targets and cause many symptoms of autoimmune disease (Burbello et al, 2021), including targeting the cytoplasmic domain of the β4 integrin subunit in epithelial and mucosal cells (Bhol et al, 2000). Importantly, rituximab targets the CD20 antigen on B-cells, but not all B-cells express CD20 (Kuijpers et al, 2010), and therefore autoantibodies can still be produced by these non-CD20 B-cells. Perhaps these non-CD20 B-cells release autoantibodies that target intracellular targets. CD-20 appears to be regulated in B-cells (Pavlasova and Mraz, 2020), and therefore during conditions of an autoimmune response, may be down regulated in those cells releasing intracellular autoantibodies. These monoclonal antibody therapeutics have significant negative side effects, including that some patients will never regain their B-cell compartment (Stensland et al, 2021).
As explained by Murphy and Longo (2021) a specific type of autoantibody is called an anti-idiotype. or antigen-binding domains, of some of the resulting anti-idiotype (or “Ab2”) antibodies that are specific for Ab1 can structurally resemble that of the original antigens themselves. Thus, the Ab2 antigen-binding region can potentially represent an exact mirror image of the initial targeted antigen in the Ab1 response, and Ab2 antibodies have even been examined for potential use as a surrogate for the antigen in vaccine studies. However, as a result of this mimicry, Ab2 antibodies also have the potential to bind the same receptor that the original antigen was targeting. Ab2 antibodies binding to the original receptor on normal cells therefore have the potential to mediate profound effects on the cell that could result in pathological changes, particularly in the long term — long after the original antigen itself has disappeared. Ab2 antibodies can mediate the neurological effects of SARS-CoV-2 infection or vaccines, because ACE2 is expressed in neural cells, including neurons (Doobay et al, 2007), and the specific neuropathological effects of SARS-CoV-2 infection, and the similarity of these effects to Ab2-mediated neurological effects observed in other viral models.