Science News: Impaired B Cell Expression of the Inhibitory Fcγ Receptor IIB in Myasthenia Gravis

Submitted by: Raymond Rosales, MD, PhD
Edited by: Eman Tawfik, MD

Keller CW, Chuquisana O, Derdelinckx J, et al. Impaired B cell expression of the inhibitory Fcγ receptor IIB in myasthenia gravis. Ann Neurol. 2022;92(6):1046-1051. doi:10.1002/ana.26507

Summary: Myasthenia gravis (MG) is an autoimmune disease in which pathogenic immunoglobulin G antibodies (Abs) bind to acetylcholine receptors (AChR) (or to functionally related molecules at the neuromuscular junction). B cell expression of the inhibitory immunoglobulin G receptor, Fc-gamma receptor (FcγR) IIB, maintains peripheral immune tolerance, and its absence renders B cells hyper-responsive to auto-antigen. In this study, the authors report that FcγRIIB expression levels are substantially reduced in B lineage cells derived from immunotherapy-naïve patients with ACHR-AB+ early-onset MG. In contrast, genetic variants associated with impaired FcγRIIB expression are not enriched in MG, indicating posttranscriptional dysregulation. The authors suggest that FcγRIIB-targeting therapies could have therapeutic benefits in AChR-Ab+ MG.

Comments:

1. The present study provides evidence for lower expression of the inhibitory FcγRIIB on B lineage cells in AChR-Ab+ patients with early-onset MG.
2. The present results warrant further investigations; for example, to correlate FcγRIIB expression profiles with clinical disease severity parameters in larger cohorts of MG subtypes.
3. The unique inhibitory features of the B cell inhibitory Fcγ R can be exploited by novel therapeutic platforms, such as B-specific Abs, which crosslink the Fcγ RIIB with BCR complex-associated molecules, such as CD19 or CD79B. These strategies were found to highly effective in suppressing humoral autoimmunity and disease development in animal models.