Renal Expression of Annexin A1 Is Associated With the Severity of Renal Injury in Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis.

Renal Expression of Annexin A1 Is Associated With the Severity of Renal Injury in Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis.
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膜联蛋白 A1 的肾表达与抗中性粒细胞胞质自身抗体相关性血管炎肾损伤的严重程度相关

DOI:
10.3389/fmed.2022.769813
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发表时间:
2022
影响因子:
3.9
通讯作者:
--
中科院分区:
医学3区
文献类型:
--
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越来越多的研究表明,中性粒细胞活化在抗神经细胞胞浆抗体(ANCA)相关性血管炎(AAV)发病机制中的重要性。以往的研究表明,膜联蛋白A1(ANXA 1)抑制中性粒细胞的募集、跨内皮迁移和呼吸爆发,并诱导中性粒细胞凋亡。本研究旨在研究ANXA 1的血浆和肾脏水平以及它们与AAV患者疾病严重程度的相关性。31例活动期AAV患者和35例缓解期AAV患者被招募。免疫组化法检测ANXA 1在肾组织中的表达。免疫荧光双标法检测ANXA 1与肾脏固有细胞和浸润细胞的共定位。ELISA法测定血浆ANXA 1水平。进一步分析血浆和肾脏ANXA 1水平与临床病理参数的相关性。活动性AAV患者的ANXA 1血浆水平显著高于缓解期AAV患者和健康对照组。ANXA 1在活动性AAV患者中的肾脏表达显著高于健康对照和疾病对照。免疫荧光双标法显示ANXA 1在AAV患者肾小球内皮细胞、系膜细胞、足细胞、近端肾小管上皮细胞、中性粒细胞、单核/巨噬细胞和T细胞中均有表达。肾小球中ANXA 1的平均光密度与AAV患者肾活检时的血清肌酐水平(r =-0.491,P = 0.005)和eGFR(r = 0.492,P = 0.005)以及肾标本中新月体的比例(r =-0.423,P = 0.018)相关。肾功能完全恢复的AAV患者肾小球ANXA 1的表达显著高于肾功能部分恢复的AAV患者。在AAV患者中,肾脏ANXA 1的表达与肾损伤的严重程度相关。
Increasing studies demonstrated the importance of activation of neutrophils in the pathogenesis of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). Previous studies showed that annexin A1 (ANXA1) inhibited the recruitment, transendothelial migration and respiratory burst of neutrophils and induced apoptosis of neutrophils. The current study aimed to investigate the plasma and renal levels of ANXA1 as well as their association with the disease severity in AAV patients. Thirty-one AAV patients in active stage and 35 AAV patients in remission stage were recruited. The expression of ANXA1 in renal specimens was assessed by immunohistochemistry. The co-localization of ANXA1 with renal intrinsic and infiltrating cells was detected by double immunofluorescence. The plasma levels of ANXA1 were determined by ELISA. The association of plasma and renal levels of ANXA1 with clinicopathological parameters was further analyzed. Plasma levels of ANXA1 were significantly higher in active AAV patients than those in AAV patients in remission as well as healthy controls. The renal expression of ANXA1 was significantly higher in active AAV patients than in healthy controls and disease controls. Double immunofluorescence assay showed that ANXA1 was expressed in glomerular endothelial cells, mesangial cells, podocytes, proximal tubular epithelial cells, neutrophils, monocytes/macrophages and T cells in AAV patients. The mean optical density of ANXA1 in glomeruli was correlated with serum creatinine levels (r = −0.491, P = 0.005) and eGFR (r = 0.492, P = 0.005) at renal biopsy and the proportion of crescents (r = −0.423, P = 0.018) in renal specimens of AAV patients. The expression of ANXA1 in glomeruli of AAV patients achieving complete renal recovery was significantly higher than those achieving partial renal recovery. In AAV patients, the renal expression of ANXA1 was associated with the severity of renal injury.
DOI: 10.1093/oxfordjournals.ndt.a027086
发表时间: 1996-10-01
影响因子: 6.1
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发表时间: 2019-10-01
影响因子: 4.4
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