A Rare Case of Seronegative Lupus Nephritis Presenting as Immune Complex Diffuse Glomerulonephritis

Lupus nephritis (LN) is a well-characterized renal manifestation of systemic lupus erythematosus (SLE), typically supported by serologic markers such as antinuclear antibody (ANA) and anti-double stranded deoxyribonucleic acid (anti-dsDNA). However, seronegative presentations remain rare and diagnostically elusive, particularly when renal involvement precedes other systemic features. We report a case of a 31-year-old male with type 1 diabetes who presented with progressive anasarca, dyspnea, and a diffuse non-blanching rash. Laboratory evaluation revealed nephrotic-range proteinuria, hypoalbuminemia, and elevated serum creatinine. Despite strong clinical suspicion, comprehensive autoimmune serologies, including ANA, anti-dsDNA, extractable nuclear antigen (ENA) panel, and anti-neutrophil cytoplasmic antibodies (ANCA), were negative. Renal biopsy demonstrated diffuse proliferative glomerulonephritis with a full house immunofluorescence pattern, including granular capillary wall staining for immunoglobulin G, A, and M (IgG, IgA, and IgM), complement 1q (C1q), and complement 3 (C3). These findings, in the absence of secondary causes such as infection, paraproteinemia, or cryoglobulinemia, supported a diagnosis of seronegative lupus nephritis. The patient was initiated on corticosteroids and mycophenolate mofetil, with resolution of edema and stabilization of renal function. This case highlights the diagnostic significance of renal biopsy in seronegative LN. The presence of a full house immune complex deposition pattern should prompt consideration of LN regardless of serologic status. While rare, seronegative LN underscores the limitations of relying solely on serologies for diagnosis and reinforces the central role of histopathology in complex glomerular disease. In patients presenting with immune complex-mediated glomerulonephritis and absent serologic markers, seronegative lupus nephritis should remain on the differential. Renal biopsy not only establishes diagnosis but also guides timely immunosuppressive therapy critical to preserving renal function.