Albano-Aluquin Shirley, Malysz Jozef, Aluquin Vincent R, Ratnam Manohar, Olsen Nancy
Penn State Hershey College of MedicineHershey PA, USA.
Wayne State University School of MedicineDetroit MI, USA.
Am J Clin Exp Immunol. 2017 Dec 20;6(6):107-114. eCollection 2017.
Giant cell arteritis (GCA) is a chronic vasculitis of large and medium vessels in which no targetable biomarkers exist to allow selective treatment, predict disease activity and monitor therapeutic responses. The accessibility of the temporal artery (TA) for biopsy allows morphologic studies to characterize macrophages and T cells in the microenvironment of the arterial wall. We evaluated the expression of folate receptor beta (FRB), a candidate diagnostic/therapeutic biomarker, compared its expression with key macrophage markers and correlated it with GCA severity.
Formalin-fixed paraffin-embedded tissue sections were examined from 6 patients with GCA and 2 controls. Immunohistochemistry was performed using FRB, ETB, CD68 and CD3 antibodies to evaluate for activated macrophages and T cells, assess FRB distribution along the intima, media and adventitial layers and composition of inflammatory infiltrates. We compared the expression of FRB, ETB and CD68 in GCA versus negative controls and in severe (with visual loss) versus mild (without visual loss) disease.
In GCA, moderate to severe inflammation was accompanied by >90% destruction of the internal elastic lamina. Macrophages comprised 36.3 ± 4.1% while CD3+ lymphocytes accounted for 61.7 ± 4.1% of total leukocytes. FRB was selectively expressed in macrophages and localized to the adventitia. GCA patients had marginally increased median FRB (9.8 cells/hpf vs. 0; p=0.095), ETB (20.5 vs. 0; p=0.095) and CD68 (38.8 vs. 5; p=0.071) expression versus controls. ETB was found in endothelial cells, smooth muscle cells and macrophages in intima/media. FRB positively correlated with ETB (r=0.90; p-0.037) and CD68 levels (r=0.90; p=0.037). ETB expression positively correlated with CD68 (r=1.0; p<0.0001). There was no difference in FRB between severe and mild GCA.
FRB is a potential diagnostic and therapeutic biomarker with restricted expression in GCA macrophages. FRB+ macrophages localized to the adventitia and their expression correlated with ETB and CD68 macrophages, suggesting that they contribute to GCA pathogenesis.
巨细胞动脉炎（GCA）是一种大中血管的慢性血管炎，目前尚无可用于选择性治疗、预测疾病活动和监测治疗反应的靶向生物标志物。颞动脉（TA）易于进行活检，这使得形态学研究能够对动脉壁微环境中的巨噬细胞和T细胞进行特征描述。我们评估了叶酸受体β（FRB）作为一种候选诊断/治疗生物标志物的表达情况，将其表达与关键巨噬细胞标志物进行比较，并将其与GCA的严重程度相关联。
对6例GCA患者和2例对照的福尔马林固定石蜡包埋组织切片进行检查。使用FRB、ETB、CD68和CD3抗体进行免疫组织化学，以评估活化的巨噬细胞和T细胞，评估FRB沿内膜、中膜和外膜层的分布以及炎症浸润的组成。我们比较了GCA与阴性对照以及重度（有视力丧失）与轻度（无视力丧失）疾病中FRB、ETB和CD68的表达。
在GCA中，中度至重度炎症伴有内弹性膜>90%的破坏。巨噬细胞占白细胞总数的36.3±4.1%，而CD3+淋巴细胞占61.7±4.1%。FRB在巨噬细胞中选择性表达，并定位于外膜。与对照组相比，GCA患者的FRB（9.8个细胞/hpf对0；p=0.095）、ETB（20.5对0；p=0.095）和CD68（38.8对5；p=0.071）表达略有增加。ETB在内膜/中膜的内皮细胞、平滑肌细胞和巨噬细胞中发现。FRB与ETB（r=0.90；p=0.037）和CD68水平（r=0.90；p=0.037）呈正相关。ETB表达与CD68呈正相关（r=1.0；p<0.0001）。重度和轻度GCA之间的FRB没有差异。
FRB是一种潜在的诊断和治疗生物标志物，在GCA巨噬细胞中表达受限。FRB+巨噬细胞定位于外膜，其表达与ETB和CD68巨噬细胞相关，表明它们参与了GCA的发病机制。
