Removal Kinetics of Antibodies Against Glutamic Acid Decarboxylase by Various Plasmapheresis Modalities in the Treatment of Neurological Disorders

Abstract

Plasmapheresis is one of the acute treatment modalities for neurological disorders associated with antibodies against glutamic acid decarboxylase (anti-GAD). However, there is little information about the removal kinetics of anti-GAD by various plasmapheresis modalities. Here, we investigated the removal rate of anti-GAD and fibrinogen (Fib) by immunoadsorption (IA), plasma exchange using a conventional plasma separator (OP-PE), and plasma exchange using a high cut-off selective membrane plasma separator (EC-PE) in two cases of anti-GAD-associated neurological diseases. In case 1, IA and OP-PE were used, and the percent reductions were as follows: anti-GAD: 38.2% and 69.1% and Fib: 67.7% and 68.2%, respectively. In case 2, OP-PE and EC-PE were used, and the percent reductions were as follows: anti-GAD: 65.8% and 48.5% and Fib: 68.5% and 19.8%, respectively. OP-PE could remove anti-GAD more efficiently than IA. Further, EC-PE could maintain coagulation factors such as Fib better than IA and OP-PE. It is important to select the appropriate plasmapheresis modality on the basis of the removal kinetics.

Removal Characteristics of Immunoglobulin G Subclasses by Conventional Plasma Exchange and Selective Plasma Exchange

“…We have previously reported that in the antibodies against glutamic acid decarboxylase (anti‐GAD) associated neurological disorders, the mean percent reduction by PE was as follows: IgG, 69.1% and anti‐GAD, 65.8%, when the mean processed volume was 0.94 PV (corresponding to 3.16 L). Moreover, the mean percent reduction by SePE was as follows: IgG, 51.2% and anti‐GAD, 48.5%, when the mean processed volume was 1.06 PV (corresponding to 3.73 L) . In both PE and SePE, the removal ratio of IgG and anti‐GAD were also similar.…”

“…However, the reduction of coagulation factors such as FXIII and Fib was higher in PE than in SePE, and thus, the risk of bleeding was also higher in PE. The mean percent reduction of Fib as well as IgG was approximately 69% by PE, and the mean percent reduction of Fib by IA was about 68%, but the mean percent reduction of Fib by SePE was only 20% . Therefore, SePE can be relatively safe to be performed on a daily basis compared with PE and IA.…”

“…We have previously reported that the sieving coefficients (SC) of immunoglobulin G (IgG) and fibrinogen (Fib) using EC‐4A were 0.5 and 0, respectively . Moreover, when we performed SePE using the EC‐4A in which 1.06 plasma volume (PV) was replaced with albumin (Alb) solution during the treatment of immunological disorders, the mean percent reductions in IgG and Fib were 51.2% and 19.8%, respectively . SePE can be considered a useful treatment option for the removal of IgG in immunological disorders while retaining coagulation factors such as Fib.…”

Removal Characteristics of Immunoadsorption with the Tryptophan‐Immobilized Column Using Conventional and Selective Plasma Separators in the Treatment of Myasthenia Gravis

“…The adsorption ability of IM‐TR against AChRAb and antiganglioside antibodies was higher than that of IgG . However, the GADAb reduction rate was similar to that of IgG in IA . Although it is important to clarify the IgG subclass distribution of autoantibodies, the adsorption ability by immunoadsorption is not determined by only IgG subclass distribution.…”

“…IM‐TR yielded an adsorption rate of 91.3% with AChRAb in vitro, indicating a high adsorption capability . However, it could also adsorb >90% of fibrinogen in vitro , and the percentage reduction of fibrinogen in one session of IA has been reported to be approximately 67.7% when the processed plasma volume (PPV) was 2 L . Thus, frequent IA can induce hypofibrinogenemia.…”