Tarzi R M, Liu J, Schneiter S, Hill N R, Page T H, Cook H T, Pusey C D, Woollard K J
Renal and Vascular Inflammation Section, Department of Medicine, Imperial College London, London, UK.
Clin Exp Immunol. 2015 Jul;181(1):65-75. doi: 10.1111/cei.12625.
Monocyte subsets with differing functional properties have been defined by their expression of CD14 and CD16. We investigated these subsets in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) and determined their surface expression of ANCA autoantigens. Flow cytometry was performed on blood from 14 patients with active AAV, 46 patients with AAV in remission and 21 controls. The proportion of classical (CD14(high) CD16(neg/low)), intermediate (CD14(high) CD16(high)) and non-classical (CD14(low) CD16(high)) monocytes and surface expression levels of CD14 and CD16 were determined, as well as surface expression of proteinase 3 (PR3) and myeloperoxidase (MPO) on monocyte subsets. There was no change in the proportion of monocytes in each subset in patients with AAV compared with healthy controls. The expression of CD14 on monocytes from patients with active AAV was increased, compared with patients in remission and healthy controls (P < 0.01). Patients with PR3-ANCA disease in remission also had increased monocyte expression of CD14 compared with controls (P < 0.01); however, levels in patients with MPO-ANCA disease in remission were lower than active MPO-ANCA patients, and not significantly different from controls. There was a correlation between CD14 and both PR3 and MPO expression on classical monocytes in AAV patients (r = 0.79, P < 0.0001 and r = 0.42, P < 0.005, respectively). In conclusion, there was an increase in monocyte CD14 expression in active AAV and PR3-ANCA disease in remission. The correlation of CD14 expression with ANCA autoantigen expression in AAV may reflect cell activation, and warrants further investigation into the potential for increased CD14 expression to trigger disease induction or relapse.
具有不同功能特性的单核细胞亚群已通过其CD14和CD16的表达来定义。我们在抗中性粒细胞胞浆抗体(ANCA)相关性血管炎(AAV)中研究了这些亚群,并确定了它们表面ANCA自身抗原的表达情况。对14例活动性AAV患者、46例缓解期AAV患者和21名对照者的血液进行了流式细胞术检测。测定了经典型(CD14(高)CD16(阴性/低))、中间型(CD14(高)CD16(高))和非经典型(CD14(低)CD16(高))单核细胞的比例以及CD14和CD16的表面表达水平,同时还测定了单核细胞亚群上蛋白酶3(PR3)和髓过氧化物酶(MPO)的表面表达情况。与健康对照相比,AAV患者各亚群中单核细胞的比例没有变化。与缓解期患者和健康对照相比,活动性AAV患者单核细胞上CD14的表达增加(P < 0.01)。缓解期PR3-ANCA疾病患者的单核细胞CD14表达也高于对照(P < 0.01);然而,缓解期MPO-ANCA疾病患者的水平低于活动性MPO-ANCA患者,且与对照无显著差异。AAV患者经典单核细胞上CD14与PR3和MPO表达之间存在相关性(r分别为0.79,P < 0.0001和r为0.42,P < 0.005)。总之,活动性AAV和缓解期PR3-ANCA疾病中单核细胞CD14表达增加。AAV中CD14表达与ANCA自身抗原表达的相关性可能反映细胞活化,值得进一步研究CD14表达增加引发疾病诱导或复发的可能性。