Unique Case of IgM Nephropathy with Monoclonal Immune Deposits Attributed to Anti-Myelin-Associated Glycoprotein (MAG) Antibody

Introduction: Anti-MAG antibodies usually cause neurological symptoms, characterized as distal demyelinating symmetric neuropathy. This presentation is considered a monoclonal gammopathy. IgM nephropathy, on the other hand, is a disease not fully defined and sometimes encompassed within Minimal Change Disease (MCD), FSGS and/or MPGN processes. Here we present a unique case of IgM nephropathy attributed to anti-MAG antibodies. Case Description: A 52-year-old woman with past medical history of rheumatoid arthritis, hypothyroidism, pulmonary embolisms, fibromyalgia, migraines, and Hepatitis B infection. She presented to the hospital due to weight gain, flank pain, bilateral leg edema, shortness of breath and hypertension. Eventually found to have nephrotic range proteinuria with peak random urinary protein to creatinine ratio of 9 mg/mg. Had a kidney biopsy done with findings consistent with IgM nephropathy, described as granular mesangial IgM deposition with extensive foot process effacement of >90%, with 1/24 globally sclerotic glomerulus. She was started on ACE-I with significant improvement in proteinuria, with UPCR decreasing to 2.6 after 3 weeks, but persistence of edema. Months later, neurology workup of peripheral neuropathy eventually demonstrated anti-MAG IgM antibodies at 1,570 TU (<1000 TU), and joint decision was to start treatment with rituximab. Other serologies were significant only for high IgM cardiolipin antibody at 22.9 MPL (<12 MPL). She had another admission for continued edema and hypertension with worsening UPCR, and rituximab was started as inpatient. Anti-MAG ab decreased quickly to undetectable levels, although cardiolipin ab remained high at 20.6 MPL. Now, more than a year after rituximab was started, her nephrotic syndrome has resolved, her latest UPCR is undetectable (<0.13 mg/mg), and MAG antibodies have been undetectable. Her neuropathy persists. Discussion: IgM nephropathy is an undefined disease process, and treatment is often steroid-based. Although IgM is abundant and many conditions may lead to elevated IgM levels and some to IgM nephropathy, this is the first described case, to our knowledge, of IgM nephropathy attributed to anti-myelin-associated glycoprotein antibodies. In this case, rituximab was an effective treatment for this patient’s nephropathy.