To describe the presentation of renal dysfunction and peripheral neuropathy associated with contactin-1 IgG seropositivity.

Only a few cases of contactin-1 IgG autoimmune nodopathy and concurrent nephrotic syndrome have been reported.

We retrospectively reviewed contactin-1 IgG-seropositive cases evaluated at Mayo clinic for neuropathy and/or renal dysfunction.

Of ten contactin-1 IgG seropositive cases identified, six had neuro-renal syndrome (polyradiculoneuropathy and renal involvement).  Four of six were males, and median age was 68 years (range 33-75). All patients were diagnosed with neuropathy prior to detection of renal dysfunction. Neuropathy symptom onset to nadir was 5 months (range 1-9 months). Four patients were monophasic while two had a relapsing course. Three patients had sensory-predominant presentations, while three had progressive asymmetric quadriparesis due to severe polyradiculoneuropathy. Sensory ataxia and pseudoathetosis were present in all but one case, and four patients required a wheelchair at disease nadir. Renal presentation was nephrotic syndrome (proteinuria n=5; hypoalbuminemia n=5; edema n=3; hypercholesterolemia/hypertriglyceridemia n=5), while creatinine was normal (n=4) or only mildly elevated (n=2). Renal biopsies performed in 4 cases showed membranous nephropathy (n=4) with immunofluorescence showing prominent IgG glomerular capillary wall staining, mainly of the IgG4 subclass (n=3). Mass spectrometry of immune complexes recovered from biopsy tissue of a patient revealed contactin-1. Nephropathy worsening was concurrent with neuropathy relapses in all cases; however, one patient had an isolated renal relapse 8 years later. Five patients demonstrated neurologic stabilization or improvement following immunotherapy, but two patients remained wheelchair bound (median follow-up time 19 months). Renal outcomes including proteinuria and hypoalbuminemia improved/stabilized in three patients treated with rituximab.

Renal dysfunction is common among patients with contactin-1 IgG associated autoimmune nodopathy.  These patients often have evidence of proteinuria, but creatine levels are usually normal. Similar to neuropathy, renal dysfunction also responds favorably to B-cell depleting therapies.