Serum IgA-Fibronectin Concentration and IgA Nephropathy Diagnosis in Adults With Glomerulonephritis: A Diagnostic Test Study

Abstract

To the Editor: Immunoglobulin A (IgA) nephropathy (IgAN) is a common form of primary glomerulonephritis (GN) worldwide, diagnosed using biopsy and direct immunofluorescence (IF) microscopy. In large population-based cohorts in which primary GN is diagnosed clinically, lack of a biopsy diagnosis of IgAN causes considerable challenges for management and prognosis. Finding a serologic test is especially important in places in which tissue diagnosis is not available. In the recent past, a few studies have shown a strong association of serum IgAfibronectin (IgAFn) complex level with IgAN. However, the studies lacked the robust diagnostic values needed for a dependable biomarker to predict IgAN in the absence of a kidney biopsy diagnosis. Glomerular mesangial area dominant or codominant deposits of IgA are the hallmark of IgAN. However, Fn is associated with the Fn-binding moiety of type V collagen in the mesangial area along with the IgA deposits. This plausible association between IgAN and IgAFn complex is represented in Fig S1. The objective of this study is to examine the diagnostic association of serum IgAFn levels with biopsy and IF-proven IgAN cases in patients with primary GN. This was a prospective double-blind study of a cohort of consecutive cases of de novo primary GN in adults in Postgraduate Hospital in Dhaka, capital of Bangladesh (Table S1). Figure 1 summarizes patient recruitment. Serum IgAFn and IF microscopy were done in separate institutions to maintain blindness, simulating a real-world experience (Table S2). Detailed methods, including participant selection, are provided in Item S1. Briefly, serum IgAFn level was measured using enzyme-linked immunosorbent assay using anti-Fn antibody and albumin (count 60 and count 0, respectively), before kidney biopsy and before immunotherapy was started if needed. Because this study was done as a part of routine clinical and laboratory procedures for clinical management and assays were run on residual samples, informed consent was not required based on local regulations. Extinction values (EVs; value at count 60 minus value at count 0) for the study cases (EVs cases) and the healthy controls (EVc controls) were measured simultaneously. A cutoff value of EVs cases 3 times or more of EVc controls was considered a diagnostic marker for seropositive IgAN cases (IgAFn positive). Other cases with a cutoff value less than 3 times were defined as seronegative (IgAFn negative; Table S3). The primary outcome of the study was the comparison of serum IgAFn cutoff value of 3 times or greater as a biomarker for IgAN against the gold-standard IF microscopy results. Secondary outcomes included