FALSE POSITIVE ANTI-GBM ANTIBODIES IN A PATIENT WITH BOVINE BIOPROSTHESIS PRESENTING WITH PULMONARY HAEMORRHAGE: A CASE REPORT

Anti–glomerular basement membrane (anti-GBM) disease is a rare autoimmune disorder characterised by antibodies directed against the α3 chain of type IV collagen, leading to rapidly progressive glomerulonephritis and, in some cases, life- threatening pulmonary haemorrhage. Diagnosis primarily relies on serological enzyme immunoassays (EIA), which demonstrate high sensitivity and specificity. However, false-positive results have been reported following exposure to bovine-derived surgical materials such as prosthetic valves or adhesives. We report a rare case of false-positive anti-GBM serology following bovine aortic valve implantation, adding to the emerging evidence of diagnostic interference likely secondary to antibody cross-reactivity with α3(IV)NC1 antigens.

A man in his 50s presented with exertional haemoptysis six months after aortic valve replacement using a bovine pericardial bio-prosthesis (Avalus). CT thorax showed patchy ground-glass opacities in the right upper lobe, consistent with intrapulmonary haemorrhage. Urinalysis showed no haemoproteinuria and renal biomarkers remained within normal range. Serology revealed a markedly elevated anti-GBM antibody titre (399 CU, FEIA using BIO-­FLASH®). In view of persistent pulmonary haemorrhage and the risk of isolated pulmonary anti-GBM disease, empirical treatment with plasma exchange, intravenous methylprednisolone, and cyclophosphamide was commenced, while awaiting confirmatory testing. The incongruity between preserved renal function and aberrant serological findings introduced diagnostic ambiguity, and the challenge of determining the appropriateness of treating with potentially lifesaving high-risk immunosuppressive therapy.

Indirect Immunofluorescence (IIF) using frozen section of primate kidney as substrate, which is historically used for qualitative detection, did not show linear IgG deposition, confirming a false-positive result. Additional immunological panel with contrasting enzyme immunoassays revealed weakly positive MPO and strongly positive double-stranded DNA antibodies, as well as positive extractable nuclear antigens (Ro52, Ro60), strongly suggestive of an atypical immune response. Follow-up imaging demonstrated persistent periaortic inflammatory changes. PET-CT showed increased uptake around the aortic graft, consistent with a postoperative inflammatory or infective process, likely triggering antibody cross-reactivity. Broncho-alveolar lavage showed haemosiderin laden macrophages consistent with alveolar haemorrhage. As the renal function was normal, with Serum Creatinine consistently < 90 umol/L, a kidney biopsy was not indicated.

This case highlights the diagnostic challenge of interpreting anti-GBM serology in patients with bovine-derived prosthetic materials. Cross-reactivity between antibodies generated against xenoantigenic bovine proteins and recombinant human α3(IV)NC1 antigens used in FEIA assays can lead to false-positive results. Reliance on serology alone may result in unnecessary immunosuppression and associated morbidity. Clinicians should recognize that bovine bio-prostheses can induce cross-reactive antibodies, producing false-positive anti-GBM serology. Confirmatory testing and multidisciplinary correlation are essential.