Non-Full House Membranous Lupus Nephritis Represents a Clinically Distinct Subset

Abstract

Key Points Non-full house (NFH) membranous lupus nephritis (MLN) is a minor subset of all MLN cases.Patients with NFH MLN tend to be older when diagnosed with systemic lupus erythematosus, undergo first renal biopsy at an older age, and have fewer extrarenal systemic manifestations.Lower load of C3 glomerular deposits seen in NFH MLN biopsies suggests attenuation of complement-mediated injury, which may have wider systemic implications. Background Renal involvement in systemic lupus erythematosus (SLE) is a key predictor of morbidity and mortality. Immunofluorescence (IF) staining of glomeruli is typically positive for IgG, IgA, IgM, C3, and C1q—the full house (FH) pattern. However, a subset of patients with membranous lupus nephritis (MLN) have a Non-FH (NFH) IF pattern more typical of idiopathic membranous nephropathy. Methods From a multi-institutional cohort of 113 MLN cases, we identified 29 NFH MLN biopsies. NFH MLN was defined by IF criteria: ≥1+ glomerular capillary loop IgG staining and<1+ IgA, IgM, and C1q. FH MLN was defined as ≥1+ staining for all five antibodies. Intermediate (Int) cases did not meet criteria for FH or NFH. We compared the pathological and clinical characteristics and outcomes among patients with FH, NFH, and Int IF patterns on kidney biopsy. Results NFH MLN represents a subset of MLN biopsies (13.4%). Compared with patients with FH MLN, patients with NFH MLN were older at SLE diagnosis (29 versus 22.5 years), had a longer time to initial kidney biopsy (8 versus 3.16 years), and had fewer SLE manifestations (2.5 versus 3.36 involved systems). NFH MLN biopsies showed lower C3 IF intensity (1.16+ versus 2.38+). Int biopsies had findings intermediate between those of NFH and FH groups. Conclusions NFH IF pattern defines a small subset of MLN biopsies and appears to be associated with milder clinical manifestations and slower disease progression. Less robust C3 deposition in NFH MLN may suggest a pathophysiology distinct from that of FH MLN.