Unveiling a Novel Co-occurrence: CIDP and NELL-1 Membranous Nephropathy

Dear Editor,

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated neuropathy with emerging antibody-defined subtypes, including anti-CNTN1, anti-Caspr1, anti-NF155, and anti-pan-neurofascin nodopathies.¹ Membranous nephropathy (MN), another autoimmune condition, involves podocyte-targeting antibodies, most commonly against PLA2R, but also THSD7A, NELL-1, EXT1/EXT2, and Sema3B.² Rare cases suggest a pathophysiological link between CIDP and MN, particularly in patients with anti-CNTN1 antibodies.³ However, the coexistence of CIDP with NELL-1-positive MN is exceedingly rare.

We present a 35-year-old female with no prior co-morbidities who presented with tingling sensations in her bilateral feet and hands for 4 months, which gradually progressed to her bilateral knees and elbows over 2 months, respectively. Neurological examination revealed distal weakness in bilateral ankles (MRC 3/5), wrist (MRC 4/5), and small muscles of the hands. Deep tendon reflexes were sluggish with absent ankle reflex, glove-and-stocking sensory loss, and positive Romberg’s sign. Nerve conduction studies revealed a sensory-motor polyradiculoneuropathy with evidence of demyelination. MRI spine screening was normal. Cerebrospinal fluid analysis revealed albuminocytologic dissociation, consistent with CIDP. She was treated with intravenous immunoglobulins (IVIG) followed by oral steroids in view of partial improvement of symptoms.

While on prednisolone 5 mg once daily, 2 months later, she developed anasarca. There was no history of alternative drug or fairness cream usage. On evaluation, she had nephrotic-range proteinuria (4 g/day) with hypoalbuminemia (serum albumin 2.2 g/dL) [Table 1]. An extensive workup for secondary causes, including autoimmunity, infections, malignancy, and paraproteinemia, was done and ruled out. Kidney biopsy revealed membranous glomerulopathy. Notably, PLA2R, THSD7A, and Sema3B were negative, but NELL-1 staining was positive on immunohistochemistry. She was managed conservatively with telmisartan (80 mg) once daily; she attained complete remission at the 2-month follow-up.

While NELL-1 MN has been associated with malignancy in some studies,⁴ no neoplastic cause was found in the index case, suggesting possible autoimmune overlap. We advocate for increased awareness and routine use of expanded antigen panels in MGN diagnosis.