Plasmablasts as a biomarker for IgG4-related disease, independent of serum IgG4 concentrations.
Plasmablasts as a biomarker for IgG4-related disease, independent of serum IgG4 concentrations.
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DOI：
10.1136/annrheumdis-2014-205233
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发表时间：
2015-01
影响因子：
27.4
通讯作者：
Stone JH
中科院分区：
文献类型：
--
作者：
Wallace ZS;Mattoo H;Carruthers M;Mahajan VS;Della Torre E;Lee H;Kulikova M;Deshpande V;Pillai S;Stone JH
我们研究了循环总血浆和IgG4+血浆母细胞作为IgG4相关疾病（IgG4- rd）诊断和疾病活动性的生物标志物的效用。我们评估了活动性、未经治疗、活检证实的IgG4-RD影响一系列器官的患者。流式细胞术检测外周血中CD19lowCD38+CD20−CD27+细胞和CD19lowCD38+CD20−CD27+IgG4+细胞的总浆母细胞计数和IgG4+细胞计数。用浊度法测定血清IgG4浓度。我们将37名IgG4-RD患者与35名对照组进行比较，其中包括健康个体（n=14）和治疗前患有其他炎症性疾病的患者（n=21）。igg4 - rd患者的平均年龄为59岁，68%为男性。14名患者（38%）有三个或更多器官受累。与未治疗的疾病对照组（中位数：592/mL，范围：19 - 4294 /mL， P<0.001）和健康对照组（中位数：94/mL，范围：1-653 /mL， P<0.001）相比，IgG4-RD患者的总浆母细胞计数显著升高（中位数：4698 /mL，范围：610 - 79524 /mL）。13例IgG4- rd患者（36%）血清IgG4浓度正常（平均：60 mg/dL；范围：5-123 mg/dL；正常：<135 mg/dL）。然而，在血清IgG4浓度正常的亚组中，中位血浆母细胞计数并未显著低于血清IgG4浓度升高的亚组：分别为3,784/mL和5,155/mL （P=0.242）。在12例接受利妥昔单抗（RTX）治疗的患者中，疾病爆发期间血浆单抗的中位水平为6,356/mL（范围：1,123-41,589 /mL），缓解期间降至1,419/ mL（范围：386/mL - 4,150/mL） （P<0.01）。即使在血清IgG4浓度正常的患者中，循环浆母细胞活性IgG4- rd升高。质母细胞计数是一种潜在的有用的生物标志物，用于诊断，评估治疗反应，并确定再次治疗患者的时间。
We examined the utility of circulating total and IgG4+ plasmablasts as biomarkers of diagnosis and disease activity in IgG4-related disease (IgG4-RD). We evaluated patients with active, untreated, biopsy-proven IgG4-RD affecting an array of organs. Flow cytometry was used to measure total plasmablast and IgG4+ plasmablast counts by gating peripheral blood for CD19lowCD38+CD20−CD27+cells and CD19lowCD38+CD20−CD27+IgG4+cells. Serum IgG4 concentrations were measured by nephelometry. We compared 37 IgG4-RD patients to 35 controls, including healthy individuals (n=14) and patients with other inflammatory diseases prior to treatment (n=21). TheIgG4-RD patients’ mean age was 59, and 68% were male. Fourteen patients (38%) had three or more organs involved. The IgG4-RD patients had substantially elevated total plasmablast counts (median: 4,698/mL; range: 610–79,524/mL) compared to both untreated disease controls (median: 592/mL; range: 19–4,294/mL;P<0.001) and healthy controls (median: 94/mL; range: 1–653/mL; P<0.001). Thirteen IgG4-RD patients (36%) had normal serum IgG4 concentrations (mean: 60 mg/dL; range: 5–123 mg/dL; normal: <135 mg/dL). However, the median plasmablast count was not significantly lower in that subset with normal serum IgG4 concentrations compared to those with elevated serum IgG4: 3,784/mL versus 5,155/mL, respectively (P=0.242). Among the 12 rituximab (RTX)-treated patients, the median plasmablast level during disease flare was 6,356/mL (range: 1,123–41,589/mL), declining to 1,419/ml (range: 386/mL–4,150/mL) during remission (P<0.01). Circulating plasmablasts are elevated in active IgG4-RD, even in patients with normal serum IgG4 concentrations. Plasmablast counts are a potentially useful biomarker for diagnosis, assessing response to treatment, and determining the time to re-treat patients.