The association of serum interleukin-6 levels with clinical outcomes in antineutrophil cytoplasmic antibody-associated vasculitis.,Journal of Autoimmunity

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The association of serum interleukin-6 levels with clinical outcomes in antineutrophil cytoplasmic antibody-associated vasculitis.
Journal of Autoimmunity ( IF 7.9 ) Pub Date : 2019-07-15 , DOI: 10.1016/j.jaut.2019.07.001
Alvise Berti ₁ , Roscoe Warner ₂ , Kent Johnson ₂ , Divi Cornec ₁ , Darrell R Schroeder ₁ , Brian F Kabat ₁ , Carol A Langford ₃ , Cees G M Kallenberg ₄ , Philip Seo ₅ , Robert F Spiera ₆ , E William St Clair ₇ , Fernando C Fervenza ₁ , John H Stone ₈ , Paul A Monach ₉ , Ulrich Specks ₁ , Peter A Merkel ₁₀ ,

Affiliation

OBJECTIVE To investigate serum IL-6 (sIL-6) levels during active disease, complete remission (CR), and relapse in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), and to explore the association of changes in sIL-6 with clinical outcomes. METHODS sIL-6 levels were measured at baseline and longitudinally over 18 months, in 78 patients with AAV enrolled in a randomized controlled trial comparing treatment with either rituximab (RTX) or cyclophosphamide (CYC)/azathioprine (AZA). Outcome variables included baseline clinical features, ANCA specificity, disease activity (active disease versus CR), time to relapse events, B cell repopulation, and ANCA titer increases. RESULTS At baseline, sIL6 levels were detectable in 81% of patients; 73% (n = 57) of subjects were proteinase 3 (PR3)-ANCA positive, sIL-6 levels were higher in subjects with PR3-ANCAs and positively correlated with their levels (rs = 0.36,p < 0.01), but not with levels of myeloperoxidase (MPO)-ANCA (rs = -0.17,p = 0.47). Higher baseline sIL-6 levels were associated with PR3-ANCA positivity, fever, pulmonary nodules/cavities, conductive deafness, and absence of urinary red blood cell casts (p < 0.05). Baseline sIL6 levels did not predict CR at month 6 (p = 0.71), and the median sIL-6 level declined from baseline with induction therapy, regardless of CR achievement. An increase in sIL-6 during CR was a predictor for subsequent severe relapse in RTX-treated patients (hazard ratio (HR):7.24,p = 0.01), but not in CYC/AZA-treated patients (HR:0.62,p = 0.50). In contrast, a sIL-6 increase did not predict B cell repopulation or ANCA titer increase in either treatment arm (p > 0.05). CONCLUSION At baseline, sIL-6 concentrations correlate with PR3-ANCA titers and are associated with specific clinical manifestations of AAV. Baseline sIL6 concentrations do not predict CR at 6 months, but the increase in sIL-6 concentrations during CR is associated with subsequent severe relapse among RTX-treated patients. Further investigation into the mechanistic role of IL6 in AAV might lead to identifying this pathway as a potential therapeutic target in this disease.

中文翻译：

血清白细胞介素 6 水平与抗中性粒细胞胞浆抗体相关性血管炎临床结果的关联。

目的探讨抗中性粒细胞胞浆抗体（ANCA）相关性血管炎（AAV）疾病活动期、完全缓解（CR）和复发期间血清IL-6（sIL-6）水平，并探讨sIL-6变化之间的关联。与临床结果。方法在一项随机对照试验中，对 78 名 AAV 患者进行基线测量和 18 个月内的纵向 sIL-6 水平测量，该试验比较了利妥昔单抗 (RTX) 或环磷酰胺 (CYC)/硫唑嘌呤 (AZA) 的治疗。结果变量包括基线临床特征、ANCA 特异性、疾病活动性（活动性疾病与 CR）、复发事件时间、B 细胞再增殖和 ANCA 滴度增加。结果在基线时，81% 的患者可检测到 sIL6 水平；73% (n = 57) 的受试者为蛋白酶 3 (PR3)-ANCA 阳性，PR3-ANCA 受试者的 sIL-6 水平较高，并与其水平呈正相关 (rs = 0.36，p < 0.01)，但与髓过氧化物酶 (MPO)-ANCA 水平（rs = -0.17，p = 0.47）。较高的基线 sIL-6 水平与 PR3-ANCA 阳性、发热、肺结节/空洞、传导性耳聋和尿红细胞管型缺失相关（p < 0.05）。基线 sIL6 水平并不能预测第 6 个月时的 CR (p = 0.71)，并且无论是否达到 CR，诱导治疗后中位 sIL-6 水平均较基线有所下降。CR 期间 sIL-6 的增加是 RTX 治疗患者随后严重复发的预测因子（风险比 (HR)：7.24，p = 0.01），但 CYC/AZA 治疗患者则不然（HR：0.62，p = 0.01） 0.50）。相反，sIL-6 的增加并不能预测任一治疗组中 B 细胞的重新增殖或 ANCA 滴度的增加 (p > 0.05)。结论在基线时，sIL-6 浓度与 PR3-ANCA 滴度相关，并且与 AAV 的特定临床表现相关。基线 sIL6 浓度不能预测 6 个月时的 CR，但 CR 期间 sIL-6 浓度的增加与 RTX 治疗患者随后的严重复发相关。进一步研究 IL6 在 AAV 中的机制作用可能会确定该通路作为该疾病的潜在治疗靶点。

更新日期：2019-11-18

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