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.