Significance of KM55 immunohistochemical staining in the diagnosis and prognosis of IgA nephropathy

Abstract

Background: Galactose-deficient IgA1 (Gd-IgA1) plays a crucial role in IgA nephropathy (IgAN).The monoclonal antibody KM55 has emerged as a simplified method for detecting Gd-IgA1; however, the clinicopathological significance of immunohistochemistry for Gd-IgA1 remains under-explored. This study evaluated the prognostic and clinicopathological significance of KM55 immunohistochemistry in IgAN. Methods: A total of 114 native kidney biopsies showing at least mild mesangial IgA positivity on immunofluorescence were retrospectively analyzed. Patients were categorized as having IgAN or non-IgAN diseases. The KM55 immunohistochemical staining was graded as 0, 1+, 2+, 3+, or 4+. Data on Oxford classification, laboratory parameters, and renal outcomes were collected. Results: The IgAN group showed significantly higher KM55 scores than the non-IgAN group (median: 3 vs. 1; p < .001). IgAN cases were further stratified into KM55-high (>= 3+, n = 38) and-low groups (<= 2+, n = 37). The KM55-high group had significantly higher diastolic blood pressure, blood urea nitrogen, creatinine, urine protein/creatinine ratio, and Oxford mesangial hypercellularity scores, along with lower estimated glomerular filtration rate (eGFR) and serum albumin. Cox analysis revealed significantly poorer outcomes in the KM55-high group for chronic kidney disease stage 4 (p = .015), end-stage renal disease (p = .024), and 75% eGFR decline (p = .016). Conclusions: Mesangial Gd-IgA1 deposition graded by KM55 immunohistochemistry may be a useful adjunct for IgAN diagnosis and a potential prognostic biomarker.