The changing landscape of autoantibody testing in myasthenia gravis in the setting of novel drug treatments

Abstract

Acquired myasthenia gravis (MG) is an autoimmune disease targeting the specific proteins in the postsynaptic muscle membrane. 50% of ocular and 80% of generalized MG have acetylcholine receptor antibodies (AChR Abs). 1-10% of MG patients have antibodies against muscle-specific kinase (MuSK), and 2-50 % of seronegative MG cases have antibodies against lipoprotein-receptor-related protein4 antibodies (LRP4 Abs). Serological testing is crucial for diagnosing and determining the appropriate therapeutic approach for MG patients. The radioimmunoprecipitation assay (RIPA) method is a historical standard test for detecting the AChR Abs and MuSK Abs. While it has nearly 100% specificity in the AChR Abs detection, its sensitivity is between 50--92%. The sensitivity and specificity of RIPA for detecting MuSK Abs is much lower. The fixed and live Cell-Based assays (f-CBA and L- CBA) have higher sensitivity than RIPA. With advancements in the serological diagnosis and management of MG, we now recommend a complete reflex testing algorithm on the first pretreatment sample of a suspected MG patient, starting with the binding and blocking assays for AChR Abs by RIPA and/ or f-CBA. If AChR Ab is negative, then reflex to MuSK Abs by RIPA and/ or CBAs. If AChR and MuSK Abs are negative, then use clustered L-CBA by request.

Keywords: Acetylcholine receptor; Fixed Cell-Based assay; Lipoprotein-receptor-related protein 4 antibodies; Live Cell-Based assay; Muscle-specific kinase (MuSK); Myasthenia Gravis; RIPA.