Clinicopathological and prognostic characteristics of idiopathic membranous nephropathy with dual antigen positivity

Abstract

BackgroundIdiopathic membranous nephropathy (IMN) is the most common pathological type in adults with nephrotic syndrome. Many target antigens have been discovered. However, dual antigen-positive IMN patients are very rare, with only a few such cases being briefly described in various studies. There is no specific study on the clinicopathological and prognostic characteristics of dual antigen-positive IMN patients, and the disease characteristics of such patients remain unclear.MethodsImmunohistochemical staining of PLA2R, THSD7A, and NELL-1 was conducted on kidney tissue samples obtained from patients diagnosed with IMN. Simultaneously, the presence of corresponding serum antibodies was determined. Patients exhibiting positivity for dual antigens were included in the study, identified either through tissue staining or serum antibody detection. We retrospectively collected their clinical, pathological, and follow-up data and measured their serum antibody levels at multiple time points. Additionally, the same type of dual antigen-positive IMN cases reported in the literature were reviewed to extract clinical, pathological, and prognostic information. We compared the data for all of the above dual antigen-positive and PLA2R single-positive IMN cases at our center.ResultsWe identified 6 IMN patients with dual antigen positivity at our center, approximately 0.7% of whole MN series; the previous literature reports 43 IMN patients with dual antigen positivity, the proportion ranged from 0.2% to 2.8%. The IgG1 positivity rate in the renal tissue of the dual antigen-positive patients at our center was significantly lower than that of dual antigen-positive patients previously reported (16.7% vs. 100.0%, p=0.015), but there was no significant difference in clinical or prognostic aspects. Patients with dual antigen positivity reported at our center and in the literature were combined and compared with PLA2R single-positive IMN reported at our center. Compared with PLA2R single-positive IMN patients, dual antigen-positive IMN patients had a higher renal tissue IgG1 positivity rate (58.3% vs. 22.3%, p=0.016), and the time required to achieve remission was longer [13.5 (3.3,35.0) vs. 3.0 (1.0,8.0), p=0.052]. Overall, The changes in urine protein were consistent with the changes in serum PLA2R antibody levels in dual antigen-positive IMN patients.ConclusionsFor patients with primary membranous nephropathy who did not attain remission following prolonged treatment, multiple target antigen staining should still be actively performed, even with positivity for the PLA2R target antigen.

The Prevalence, Characteristics, and Putative Mechanisms of Dual Antigen-Positive Membranous Nephropathy: The Underestimated Condition

“…Serum anti-NELL1 antibodies are detected in patients with NELL1-associated MN [ 25 ]. A recent interesting study, which performed immunostaining for PLA 2 R, THSD7A, and NELL1 in the renal tissue and evaluated the corresponding circulating antibodies, reported the clinicopathological information of “dual antigen-positive” MN [ 26 ]. In the study, the proportion of patients with MN showing dual antigen positivity, defined as positive glomerular deposits and/or circulating antibodies, was approximately 0.7%, and these cases consisted of “PLA 2 R and THSD7A dual-positive cases” and “PLA 2 R and NELL1 dual-positive cases”.…”

“…First, the serological diagnosis could change depending on the timing of sample collection for analysis; this case might have been diagnosed as PLA 2 R-associated MN if a serological approach alone was performed at the later disease phase. Second, serum PLA 2 R antibody has been reported to directly induce structural changes in and the apoptosis of podocytes [ 46 ], and its level has been proposed as a useful marker to predict the disease activity of MN [ 3 ], even in patients with dual antigen-positive MN [ 26 ]. However, the clinical course of this case suggests that the significance of serum PLA 2 R antibodies in patients with dual antigen-positive MN should be re-evaluated in future studies involving a larger number of participants.…”