Division of Nephrology, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
Department of Applied Biochemistry, Tokai University, Hiratsuka, Kanagawa, Japan.
Nephrol Dial Transplant. 2018 May 1;33(5):832-840. doi: 10.1093/ndt/gfx235.
The M-type phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) were identified as intrinsic antigens in primary membranous nephropathy (MN). Complement activation via the lectin pathway in intrinsic antigen-related MN is still unclear.
We retrospectively enrolled 60 primary Japanese MN patients and detected activated complement pathways by staining complement proteins in glomerular deposition. According to the findings of PLA2R and THSD7A staining in glomeruli, they were classified into intrinsic antigen-related or -unrelated MN. We evaluated clinicopathological characteristics and predictors of clinical outcomes in intrinsic antigen-related MN.
Thirty-nine (65%) patients had PLA2R in glomerular deposits and two (3.3%) patients had THSD7A. One of them had both PLA2R and THSD7A (double positive). Forty patients were classified into the intrinsic antigen-related group. The other 20 patients were negative for both antigens (unrelated group). The prevalence and staining intensity of mannose-binding lectin (MBL) deposits were much higher in the intrinsic antigen-related group [55% versus 20%, P < 0.010, 1.0 (interquartile range 1.0-2.0) versus 1.0 (0.0-1.0), P = 0.01, respectively]. The staining intensity of MBL in glomeruli also correlated with the IgG4 staining intensity. In intrinsic antigen-related MN, MBL staining intensity was an unfavorable predictor for remission of proteinuria [hazard ratio (HR) 0.40, P < 0.01] and renal dysfunction (HR 3.81, P = 0.01) in Cox proportional hazards analysis. Moreover, the glomerular MBL-positive group showed more severe interstitial fibrosis and worse clinical outcomes.
Intrinsic antigen-related MN was more strongly associated with complement activation by the lectin pathway, which may contribute to a less favorable clinical outcome.
M 型磷脂酶 A2 受体（PLA2R）和血小板反应蛋白-1 型结构域包含 7A（THSD7A）被鉴定为原发性膜性肾病（MN）中的固有抗原。固有抗原相关 MN 中补体通过凝集素途径的激活仍不清楚。
我们回顾性纳入 60 例日本原发性 MN 患者，并通过染色肾小球沉积中的补体蛋白检测激活的补体途径。根据肾小球 PLA2R 和 THSD7A 染色结果，将其分为固有抗原相关或无关 MN。我们评估了固有抗原相关 MN 的临床病理特征和临床结局预测因素。
39 例（65%）患者肾小球沉积物中有 PLA2R，2 例（3.3%）患者有 THSD7A。其中 1 例为 PLA2R 和 THSD7A 双阳性。40 例患者被归入固有抗原相关组。另 20 例患者两种抗原均为阴性（无关组）。固有抗原相关组甘露聚糖结合凝集素（MBL）沉积物的患病率和染色强度明显更高[55%比 20%，P < 0.010，1.0（四分位间距 1.0-2.0）比 1.0（0.0-1.0），P = 0.01]。肾小球 MBL 染色强度也与 IgG4 染色强度相关。在固有抗原相关 MN 中，MBL 染色强度是蛋白尿缓解[风险比（HR）0.40，P < 0.01]和肾功能不全（HR 3.81，P = 0.01）的不良预测因子。此外，肾小球 MBL 阳性组表现出更严重的间质纤维化和更差的临床结局。
固有抗原相关 MN 与补体通过凝集素途径的激活相关性更强，这可能导致更不利的临床结局。
