Characteristics and Prognostic Value of Tertiary Lymphoid Organs in Membranous Nephropathy: A Retrospective Study

Abstract

BackgroundTertiary lymphoid organs play an essential role in the inflammation of the kidney. The clinical association between TLOs and membranous nephropathy (MN) is not clear yet.MethodsConsecutive patients with the histologically confirmed membranous nephropathy in Tongji Hospital from July 19, 2012, to September 26, 2019, were included in this study. TLOs in renal biopsy tissues were detected by periodic acid–Schiff-stained and immunohistochemistry. Logistic regression was performed to evaluate the correlations of TLOs and clinical features of patients with MN. Kaplan–Meier analysis was utilized to examine the relationship between TLOs and remission of proteinuria.ResultsA total of 442 patients with MN were included in this study, of which the average age was 46.4 years old, and 58.8% were male. Moreover, 33% of patients with MN had TLOs in this study. The median value of proteinuria among patients with MN with TLOs was 4.9 g/24 h, which was much greater than no-TLOs ones (3.2 g/24 h, p < 0.001). Moreover, the patients with TLOs had higher serum creatinine and lower serum albumin. The severity of clinical features among the patients with MN aggravated with the increase in the grade of TLOs. In addition, the patients who had TLOs were more likely to be positive of anti-phospholipase A2 receptor autoantibodies. Meanwhile, the patients without TLOs showed significantly higher complete remission and total remission of proteinuria.ConclusionIn this study, we demonstrated that TLOs were common among patients with MN. Moreover, the patients with MN with TLOs showed a worse clinical manifestation and an outcome compared with the patients without TLOs.

Integrative profiling of untreated primary membranous nephropathy at the single-cell transcriptome level

“…In addition, T cells and macrophages are the main infiltrating cells in PMN [ 52 , 53 ]. For example, in some patients, even tertiary lymphoid structure could be observed which were associated with the severity of clinical features [ 54 ]. T cells and myeloid cells were the dominant immune cells, which was also found in the report of Xu et al.…”

The roles of tertiary lymphoid structures in chronic diseases

“…Kidney. TLSs can be induced in CKDs, including IgA nephropathy [158][159][160] , lupus nephritis 65 , IgG4-related kidney diseases 161 , interstitial nephritis 162,163 , membranous nephropathy 164 and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis 165,166 as well as in kidney allografts 37,39,44,[167][168][169][170] . Clinical studies have demonstrated that TLS formation is associated with poor kidney outcomes in these diseases (Supplementary Table 2).…”

“…Studies in patients with IgA nephropathy have reported that TLSs were detected in 30-40% of participants and were associated with higher levels of serum creatinine, proteinuria and blood pressure, greater severity of glomerulonephritis and future disease progression [158][159][160] . A study in patients with membranous nephropathy reported that TLSs were detected in 34.2% of participants and were associated with higher levels of serum creatinine, proteinuria and blood pressure, lower serum albumin concentrations and lower remission rates 164 . Notably, a higher proportion of patients with membranous nephropathy who had renal TLSs had anti-PLA2R autoantibodies than those without TLSs (72.5% versus 47.4%) 164 .…”

“…A study in patients with membranous nephropathy reported that TLSs were detected in 34.2% of participants and were associated with higher levels of serum creatinine, proteinuria and blood pressure, lower serum albumin concentrations and lower remission rates 164 . Notably, a higher proportion of patients with membranous nephropathy who had renal TLSs had anti-PLA2R autoantibodies than those without TLSs (72.5% versus 47.4%) 164 . However, most of these studies were observational and the cellular and molecular characteristics of TLSs as well as the mechanisms that underlie the observed associations remain unclear.…”