A Shadow Actor: Double-Positive Glomerulonephritis with Serologically Negative Anti-Glomerular Basement Membrane

Introduction: Anti-glomerular basement membrane disease is a rare renal-pulmonary syndrome in which serological antibodies are pivotal in achieving an accurate diagnosis. These antibodies target the glomerular basement membrane, leading to kidney damage and pulmonary hemorrhage. The presence of anti-gbm antibodies carry a sensitivity of 93% and specificity of 97% for diagnosis with a negative predictive value of 99.4%. In this exceptionally rare case, we report a patient with abnormal renal function to have serologically negative anti-GBM. Case Description: The patient was admitted for acute kidney injury, and he was administered IV fluids without any improvement in kidney function. Given the lack of response to fluid resuscitation combined with imaging without a reversible etiology, the patient’s acute kidney injury intrinsic in etiology. Due to his active urinary sediment, laboratory investigation for a cause of glomerulonephritis was initiated. The pertinent labs were: anti-GBM: <0.02, P and C anca: normal, SPEP and UPEP negative, and urine protein/creatinine ratio: >3. Unfortunately, there was no improvement in creatinine after IV steroids and renal biopsy was performed, which showed diffuse crescentic and necrotizing glomerulonephritis, while immunofluorescent imaging revealed linear IgG deposition consistent with anti-glomerular basement membrane disease (p-anca seropositive). Given the diagnosis, the patient was transferred to a tertiary care center to undergo plasmapheresis. Discussion: Collagen type IV is the most common protein present in our basement membranes. Among the six distinct alpha chains, alpha-chain 3 is specifically found in the kidney, lungs, and cochlea. Specifically, the Ea epitope on the third alpha-chain is most associated with anti-GBM disease. Lower concentration of anti-GBM auto-antibodies may result from lower specificity of the typical Ea antigen or due to the immune system generating a broader spectrum of autoantibodies, thereby reducing the affinity to the GBM antibodies. There is a possibility that the patient might have an antibody to an epitope other alpha3(IV)N1 that can elicit an autoimmune response.