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首页> 外文期刊>Modern Pathology >THSD7A staining of membranous glomerulopathy in clinical practice reveals cases with dual autoantibody positivity
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THSD7A staining of membranous glomerulopathy in clinical practice reveals cases with dual autoantibody positivity

机译：临床实践中THSD7A膜性肾小球病染色显示双抗体阳性的病例

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Thrombospondin type I domain-containing 7A (THSD7A) is a known antigenic target of autoantibodies leading to primary membranous glomerulopathy and was reported to account for ~10% of phospholipase A2 receptor (PLA2R)-negative membranous glomerulopathy. It has been proposed that PLA2R and THSD7A autoantibodies are mutually exclusive in membranous glomerulopathy. We validated an immunohistochemical assay to investigate for THSD7A-associated membranous glomerulopathy and utilized it in 258 consecutive native kidney biopsies, which showed membranous glomerulopathy in our laboratory, with the exception of membranous lupus nephritis. Membranous glomerulopathy stained positive for THSD7A-only in 7 (3%) cases, PLA2R-only in 141 (55%) cases, and showed dual positivity for THSD7A and PLA2R in 2 (1%) cases. Serologic testing for antibodies to PLA2R and THSD7A was performed in a subset of these patients. There was 100% correlation between positive THSD7A and/or PLA2R tissue staining and the presence of the corresponding autoantibodies in the serum including the two cases with dual positive THSD7A and PLA2R antibodies. We describe and provide a protocol for detection of THSD7A-associated membranous glomerulopathy in clinical practice. The cases with dual THSD7A and PLA2R positivity show that these autoantibodies are not mutually exclusive. They also emphasize the importance of using a panel-based approach when subtyping membranous glomerulopathy as a patient could conceptually be identified and treated based on anti-PLA2R titers, but still have anti-THSD7A antibodies driving persistent disease.
机译：含I型血小板反应蛋白域的7A（THSD7A）是导致原发性膜性肾小球病的自身抗体的已知抗原靶标，据报道约占磷脂酶A2受体（PLA2R）阴性的膜性肾小球病的约10％。已经提出，PLA2R和THSD7A自身抗体在膜性肾小球病中是互斥的。我们验证了一种免疫组织化学方法以研究与THSD7A相关的膜性肾小球病，并将其用于258例连续的自然肾脏活检中，该活检在我们的实验室中显示了膜性肾小球病，但膜性狼疮性肾炎除外。膜性肾小球病仅7例（3％）的THSD7A染色阳性，仅141例（55％）的PLA2R染色阳性，而2例（1％）的THSD7A和PLA2R呈双重阳性。在这些患者的一部分中进行了针对PLA2R和THSD7A抗体的血清学测试。 THSD7A和/或PLA2R组织染色阳性与血清中相应自身抗体的存在之间存在100％的相关性，其中包括两个具有双重阳性THSD7A和PLA2R抗体的病例。我们描述并提供在临床实践中检测与THSD7A相关的膜性肾小球病的协议。具有THSD7A和PLA2R双重阳性的病例表明，这些自身抗体不是相互排斥的。他们还强调在亚型膜性肾小球疾病分型时使用基于专家组的方法的重要性，因为可以从概念上根据抗PLA2R滴度确定并治疗患者，但仍具有驱动持续疾病的抗THSD7A抗体。

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