A Case of NELL-1 Associated Membranous Nephropathy and Guillain-Barré Syndrome

Introduction: Recent studies have identified shared or cross-reactive autoantigens—such as contactin-1 (CNTN1) and neural epidermal growth factor-like 1 (NELL-1)—as contributors to the pathogenesis of both peripheral neuropathies and membranous nephropathy (MN). While the association between MN and chronic inflammatory demyelinating polyneuropathy (CIDP) is increasingly recognized, the co-occurrence of MN with acute inflammatory demyelinating polyradiculoneuropathy (AIDP), the most common subtype of Guillain-Barré Syndrome (GBS) in the United States, remains rare. Here, we report a unique case of simultaneous onset of AIDP and nephrotic syndrome (NS), with renal biopsy findings consistent with MN characterized by NELL-1–positive, IgG1-dominant deposits. Case Description: A 45-year-old Hispanic woman with a recent diagnosis of Bell’s palsy—treated with a prednisone taper—presented with a two-week history of ascending paresthesia and progressive weakness. Initial laboratory evaluation revealed a normal serum creatinine and a urinalysis notable for 3+ proteinuria. A 24-hour urine collection confirmed nephrotic-range proteinuria, with a total of 4.9 g/day. Electromyography demonstrated findings consistent with a subacute polyneuropathy with demyelinating features, consistent with AIDP. Renal biopsy showed segmental granular deposits of IgG, C3, and kappa and lambda light chains on immunofluorescence (IF). Serologic testing was negative for anti-PLA2R antibodies. IF analysis showed no co-localization of IgG4 with PLA2R; however, there was positive co-localization of IgG1 with NELL-1. The patient was treated with IVIG at 2 g/kg over three days, which provided minimal symptomatic improvement, and was started on Losartan. Discussion: Although the mainstays of AIDP/GBS management are IVIG and plasma exchange, there is limited evidence to guide treatment in cases of concurrent AIDP and MN. Moreover, the use of rituximab in immune-mediated neuropathies is only supported by data from patients with CIDP, where small studies and systematic reviews suggest possible benefit in refractory cases. This case highlights the potential pathogenic role of NELL-1 as a shared autoantigen contributing to simultaneous involvement of neural and glomerular tissues. Further investigation is needed to elucidate the underlying immunologic mechanisms and to guide therapeutic strategies and long-term outcomes.