C3 Glomerulonephritis and Neuromyelitis Optica in a Patient with Systemic Lupus Erythematosus (SLE)/Sjogren Overlap Syndrome

Introduction: C3 glomerulopathy (C3G) that includes dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are rare glomerular disorders triggered by dysregulation of the alternative complement pathway with an estimated incidence of 2-3 cases per million. We describe a rare case of C3GN and neuromyelitis optica in a patient with known SLE/Sjogren overlap syndrome. Case Description: 51-year-old African-American female with SLE/Sjogren overlap syndrome presented with proteinuric AKI on CKD and newly diagnosed transverse myelitis. Baseline Cr 0.8 mg/dL. Labs on admission: Cr 1.7 mg/dL, Sr albumin 2.8 g/dL, UPCR 5511 mg/g, urinalysis revealed acanthocytes. C3 152, C4 38, ANA 1:320 [speckled], ds-DNA (-), SSA > 150, SSB 106, NMO/AQP4 (+) at 1:10000. Rest of serological workup negative. No e/o infection. Kidney USG unremarkable. Kidney biopsy - LM: 35 glomeruli, no segmental or global sclerosis. Glomeruli normal, no endocapillary hypercellularity noted. IFTA <5%. Mild to moderate arterial and arteriolar sclerosis. IF: Fine granular reactivity for C3 [3+] along capillaries and in mesangium that are chunky. Rest of immunoreactants negative. Pronase IF negative. EM: Few scattered medium to large-sized electron dense deposits present in the mesangium and paramesangial area. Alternative complement pathway functional panel revealed low APFA and Fb levels and elevated C5 levels. C3GN genetic panel revealed a VUS in the THBD and MPLA gene. Patient received repeated doses of rituximab and has attained complete remission of proteinuria and resolution of AKI. Discussion: C3GN affecting younger patients usually are mediated by genetic abnormalities of the alternative complement pathway. In addition to renal manifestations, a number of other extra-renal manifestations have also been associated with C3G including retinal involvement [drusen] and lipodystrophy, particularly in DDD. To date, concomitant NMO (+) transverse myelitis presenting concomitantly with C3GN has not been described. It remains unclear if the C3G-dominant immune complex-mediated glomerulonephritis was precipitated by the underlying SLE/Sjogren overlap syndrome.