Department of Nephrology and Blood Purification, Kidney Disease Center, Tokyo Medical University Hachioji Medical Center, 1163 Tatemachi, Hachioji, Tokyo, 193-0998, Japan.
BMC Nephrol. 2022 Feb 5;23(1):56. doi: 10.1186/s12882-022-02684-z.
To date, a few case reports have described the association between poststreptococcal acute glomerulonephritis (PSAGN) and hemolytic anemia/thrombocytopenia, both with or without a pathology similar to that of thrombotic microangiopathy (TMA). However, the detailed mechanism leading to the complication of TMA in PSAGN patients remains to be clarified. In contrast, infection with neuraminidase-producing Streptococcus pneumoniae is a well-known cause of TMA, and it has been reported that transient positivity of the direct Coombs test is observed in up to 90% of such patients.
A 44-year-old man was hospitalized for acute nephritic syndrome 3 weeks after developing pharyngitis. PSAGN was suspected owing to a low complement C3, increased antistreptolysin-O and serum creatinine (5.46 mg/dL), and hematuria/proteinuria. The throat antigen test for group A Streptococcus was positive. He developed hemolytic anemia with thrombocytopenia from hospital day 9. TMA was suspected owing to minimal coagulation abnormalities. ADAMTS-13 activity was normal, whereas the direct Coombs test was transiently positive. Renal biopsy demonstrated glomerular endocapillary proliferation without crescents, but with severe tubulitis and peritubular capillaritis on light microscopy. Immunofluorescence demonstrated C3 deposition along the glomerular capillary walls, and many subepithelial humps were observed on electron microscopy. The deposition of nephritis-associated plasmin receptor (NAPlr), a nephritogenic protein of Streptococcus pyogenes, was observed only in glomeruli. Thus, the histological diagnosis was typical PSAGN, but with atypical severe tubulointerstitial lesions. A positive direct Coombs test is often observed in pneumococcal TMA patients, which is attributed to the exposure of Thomsen-Friedenreich (T) antigen by neuraminidase. As Streptococcus pyogenes is one of the neuraminidase-producing bacteria other than Streptococcus pneumoniae, T-antigen exposure was analyzed in the renal tissue of this patient using labelled peanut lectin as a probe, which has strong and specific binding affinity for T-antigen. Exposure of T-antigen was found on tubular epithelial cells and small vessels in the tubulointerstitial area, but not in the glomeruli of this patient.
These findings suggest that 2 pathogenic proteins of Streptococcus pyogenes, i.e., NAPlr and neuraminidase, induced glomerular lesions of PSAGN and tubulointerstitial inflammation with TMA, respectively, resulting in severe acute kidney injury in this patient.
迄今为止，已有少数病例报告描述了链球菌后急性肾小球肾炎（PSAGN）与溶血性贫血/血小板减少症之间的关联，这些病症既有表现为血栓性微血管病（TMA）的，也有不表现为 TMA 的。然而，导致 PSAGN 患者发生 TMA 这一并发症的详细机制仍有待阐明。相比之下，感染具有神经氨酸酶的肺炎链球菌是 TMA 的一个已知病因，据报道，高达 90%的此类患者的直接抗人球蛋白试验呈一过性阳性。
一名 44 岁男性因咽炎发作后 3 周出现急性肾炎综合征而住院。由于补体 C3 降低、抗链球菌溶血素 O 和血清肌酐（5.46mg/dL）升高以及血尿/蛋白尿，疑诊 PSAGN。咽拭子 A 组链球菌抗原检测阳性。从住院第 9 天起，患者出现溶血性贫血伴血小板减少症。由于存在轻微的凝血异常，怀疑发生 TMA。ADAMTS-13 活性正常，但直接抗人球蛋白试验呈一过性阳性。光镜下，肾脏活检显示肾小球毛细血管内增生，但无新月体形成，而小管炎和小管间毛细血管炎严重。免疫荧光显示肾小球毛细血管壁有 C3 沉积，电镜下观察到许多上皮下驼峰。在该患者的肾小球中观察到肾炎相关纤溶酶受体（NAPlr）的沉积，NAPlr 是酿脓链球菌的一种致肾炎蛋白。因此，组织学诊断为典型的 PSAGN，但伴有非典型的严重肾小管间质病变。肺炎球菌 TMA 患者常出现直接 Coombs 试验阳性，这归因于神经氨酸酶暴露了 Thomsen-Friedenreich（T）抗原。由于酿脓链球菌是除肺炎链球菌以外的具有神经氨酸酶的细菌之一，因此使用标记过的花生凝集素作为探针分析了该患者肾组织中的 T 抗原，花生凝集素对 T 抗原具有很强的特异性结合亲和力。在该患者的肾小管间质区域的肾小管上皮细胞和小血管中发现 T 抗原暴露，但在肾小球中未发现。
这些发现表明，酿脓链球菌的 2 种致病蛋白，即 NAPlr 和神经氨酸酶，分别诱导 PSAGN 的肾小球病变和 TMA 的肾小管间质炎症，导致该患者发生严重的急性肾损伤。
