A Rare Case of Atypical IgA-Mediated Anti-GBM Disease with ANCA-Associated Glomerulonephritis

Introduction: Atypical anti-GBM has been used to describe seronegative cases of anti-GBM disease and constitutes up to 10% of anti-GBM cases. Patients can have milder symptoms and atypical pathological findings, such as linear deposition of IgA or IgM. Current conventional assays are unable to detect these classes of immunoglobulin. Approximately 30% of anti-GBM glomerulonephritis (GN) cases have concomitant ANCA GN. However, coexisting atypical anti-GBM and ANCA GN is very rare. We present the first case of seronegative atypical IgA-mediated anti-GM with MPO-ANCA GN. Case Description: The patient is a 64-year-old male with a history of well-controlled type 2 diabetes. Two months prior, he developed myalgias and unintentional weight loss after a COVID-19 infection. He was diagnosed with polymyalgia rheumatica and treated with prednisone 20 mg/day. Initially, myalgias improved but symptoms recurred when the dose was reduced to 5 mg/day. At a subsequent visit, he endorsed a new cough, and his BP was elevated at 164/94 mmHg. Laboratories showed creatinine (Cr) 2.01 mg/dl, CRP 64.0 mg/l, normal C3 and C4 complement, P-ANCA 1:320, MPO >134.0 U/ml and negative anti-GBM. Monoclonal protein was negative with normal kappa/lambda ratio. Urinalysis showed RBC 17/hpf without RBC casts, UACR 142 mg/g and UPCR 0.39 g/g. Kidney biopsy showed focal necrotizing and crescentic glomerulonephritis in 23% of glomeruli with a vasculitis lesion in one artery and no significant fibrosis. Immunofluorescence showed linear GBM staining for IgA (3+), kappa (1+) and lambda (2+). Overall results were consistent with atypical anti-GBM and ANCA-GN. He was started on methylprednisolone 500 mg x 3 days and plasmapheresis (PLEX) for 5 days until Cr improved (as serologic levels of IgA anti-GBM were unavailable to guide the duration of PLEX). He then started oral cyclophosphamide. At 3-month follow-up, he felt better with improved energy. Cr improved to 1.45 mg/dl. MPO titer decreased to 2.0 U/ml with normal ESR and CRP. UA showed resolution of hematuria. Discussion: Atypical anti-GBM may present with ANCA-GN. Treatment with cyclophosphamide and PLEX can improve kidney outcomes in these patients.