Nephrotic Syndrome in CASPR2 Antibody Syndromes: Two Cases with Neuro-Renal Manifestations

Contactin-associated protein-like 2 (CASPR2) antibody syndromes, ranging from Isaac’s to Morvan syndrome, are well recognized for their neurological manifestations, but renal involvement is rarely reported. We describe two patients with biopsy-proven membranous nephropathy who developed nephrotic syndrome in the setting of CASPR2 autoimmunity. A 38-year-old female with Isaac’s syndrome showed limited steroid response but improved neurologically and renally after plasmapheresis, while a 58-year-old male with Morvan syndrome and chronic MN changes responded only after plasmapheresis following steroids and rituximab. These cases highlight a rare neuro-renal overlap in VGKC-complex autoimmunity, where treatment directed primarily at neurological disease resulted in parallel renal remission, underscoring the importance of early biopsy and antibody-targeted therapy.