Effect of therapeutic plasma exchange on immunoglobulins in myasthenia gravis

Abstract

An integrated understanding of therapeutic plasma exchange (TPE) effects on immunoglobulins, autoantibodies, and natural or acquired (vaccine) protective antibodies in patients with autoimmune myasthenia gravis (MG) is lacking. Prior studies measured TPE effects in healthy volunteers or heterogeneous autoimmune diseases populations. We prospectively profiled plasma IgA, IgM, IgG, IgG subclasses (IgG1-4), acetylcholine receptor autoantibodies (AChR+), and protective antibodies in patients with AChR+ MG receiving TPE for an exacerbation. TPE was performed according to institutional practice and patients were profiled for up to 12 weeks. Ten patients were enrolled (median age=72.9 years; baseline MG-Composite=21; median TPE treatments=6 during their first course) and all improved. The maximum decrease in all immunoglobulins, including AChR autoantibodies, was achieved on the final day of the first TPE course (approximately 60–70% reduction). Three weeks post-TPE mean AChR autoantibody, total IgG, IgG1 and IgG2 titers were below the reference range and had not recovered to within 20% of baseline, whereas other measured immunoglobulins approached baseline values. We did not generally observe an “overshoot” of immunoglobulins above pre-TPE levels or accelerated recovery of pathologic AChR autoantibodies. Protective antibody profiles showed similar patterns as other IgGs and were detectable at levels associated with protection from infection. A slow return to baseline for IgGs (except IgG3) was observed, and we did not observe any obvious effect of concomitant medications on this recovery. Collectively, these findings enhance our understanding of the immunological effects of TPE and further supports the concept of rapid immunoglobulin depletion for the treatment of patients with MG.

Antagonism of the Neonatal Fc Receptor as an Emerging Treatment for Myasthenia Gravis

“…The available phase 1 and phase 2 clinical trial data for anti-FcRn monoclonal antibodies consistently demonstrate the ability to reduce and maintain total IgG and/or AChR autoantibodies at levels associated with efficacy for PLEX (5,36). In general, all of the available therapeutics reduce IgG levels by 60-80% from baseline at the doses studied, with modest effects on albumin.…”

“…In many cases it is also not a viable long term treatment given relatively common issues with intravenous access needed for the infusions or the need for a long-term indwelling line; subcutaneous administration may help alleviate those issues. TPE effectively lowers circulating IgG blood levels, including pathogenic autoantibodies, and provides proof of concept for the clinical effectiveness of lowering IgG levels to treat MG (4,5). One plasma volume exchange reduces serum immunoglobulin levels by 60% and total body immunoglobulin stores by 20% (6).…”

“…Five sessions of TPE can lower IgG and autoantibody levels by ∼75-80%. Recovery of IgG levels close to a baseline level occurs ∼6 weeks after a course of TPE (5). TPE has limitations as a maintenance treatment given intravenous access limitations and many centers perform the procedure using a central line.…”

Autoantibodies in acquired myasthenia gravis: Clinical phenotype and immunological correlation

“…16 Clinico-demographic details such as the age at onset, duration of illness, precipitating factors, presence and number of respiratory crises were noted. They included newly diagnosed patients as well as those patients who were being regularly followed up.…”

“…Patients who had received plasmapheresis and/or intravenous immunoglobulin in the preceding 4 weeks were excluded from the study since they have been shown to alter the antibody levels. 16 Clinico-demographic details such as the age at onset, duration of illness, precipitating factors, presence and number of respiratory crises were noted. The duration and nature of treatment received in the past were also noted.…”