Phenotype, Severity, and Therapy of Patients With LRP4 Antibody-Associated Myasthenia Gravis in the German Myasthenia Gravis Registry.

Abstract

Lipoprotein receptor-related protein 4 antibody-positive myasthenia gravis (LRP4-Ab-positive MG) is a rare serologic subgroup with poorly defined clinical phenotype. This study investigated demographics, clinical features, treatments, and disease burden of LRP4-Ab-positive MG against other antibody-defined subgroups. Patients from the prospective longitudinal German MG registry tested for LRP4, AChR, and MuSK Abs were grouped and analyzed for symptoms, treatment, and disease burden scores (for example, Myasthenia Gravis Activities of Daily Living [MG-ADL] and Myasthenia Gravis Quality-of-Life 15-item revised version scale [MG-Qol15r]). Among 3,319 patients, 1,432 (43.1%, median age 54, 57.4% female) had complete antibody testing: 4.8% of these were LRP4-Ab-positive (2.4% single-positive; 2.4% LRP4/AChR-Ab-double-positive), 63.6% AChR-Ab-positive, 2.4% MuSK-Ab-positive, 0.8% MuSK/AChR-Ab-double-positive, and 28.4% triple seronegative. LRP4-Ab-single-positive patients reported high symptom rates, and all LRP4-Ab-positive patients showed high rates of escalation (e.g., rituximab) and rescue therapies (e.g., IVIG). Linear mixed-effects models revealed greater disease burden in LRP4-Ab-single-positive patients vs all other subgroups (e.g., vs AChrR-Ab-positive: MG-ADL -2.5 points [95% CI -3.9 to -1.2]; MG-Qol15r -8.4 [95% CI -13.3 to -3.4]). Conversely, LRP4/AChR-Ab-double-positive patients showed burden and treatment patterns comparable with other subgroups. LRP4-Ab-single-positive MG represents a distinct phenotype characterized by high disease burden and treatment needs. By contrast, LRP4/AChR-Ab-double-positive MG phenotypes align more closely with other MG subgroups. German clinical trial registry (drks.de), DRKS00024099, first patient enrolled: February 4, 2019.