Müller-Deile Janina, Jaremenko Christian, Haller Hermann, Schiffer Mario, Haubitz Marion, Christiansen Silke, Falk Christine, Schiffer Lena
Department of Nephrology and Hypertension, Friedrich-Alexander-University (FAU) Erlangen-Nuremberg, 91054 Erlangen, Germany.
Institute for Nanotechnology and Correlative Microscopy eV, INAM, 91301 Forchheim, Germany.
J Clin Med. 2021 Jun 19;10(12):2715. doi: 10.3390/jcm10122715.
ANCA-associated vasculitis (AAV) is a rare small vessel disease characterized by multi-organ involvement. Biomarkers that can measure specific organ involvement are missing. Here, we ask whether certain circulating cytokines and chemokines correlate with renal involvement and if distinct cytokine/chemokine patterns can differentiate between renal, ear/nose/throat, joints, and lung involvement of AAV.
Thirty-two sets of Birmingham vasculitis activity score (BVAS), PR3-ANCA titers, laboratory marker, and different cytokines were obtained from 17 different patients with AAV. BVAS, PR3-ANCA titers, laboratory marker, and cytokine concentrations were correlated to different organ involvements in active AAV.
Among patients with active PR3-AAV (BVAS > 0) and kidney involvement we found significant higher concentrations of chemokine ligand (CCL)-1, interleukin (IL)-6, IL21, IL23, IL-28A, IL33, monocyte chemoattractant protein 2 (MCP2), stem cell factor (SCF), thymic stromal lymphopoietin (TSLP), and thrombopoietin (TPO) compared to patients without PR3-ANCA-associated glomerulonephritis. Patients with ear, nose, and throat involvement expressed higher concentrations of MCP2 and of the (C-X-C motif) ligand-12 (CXCL-12) compared to patients with active AAV and no involvement of these organs.
We identified distinct cytokine patterns for renal manifestation and for ear, nose and throat involvement of PR3-AAV. Distinct plasma cytokines might be used as non-invasive biomarkers of organ involvement in AAV.
抗中性粒细胞胞浆抗体相关性血管炎（AAV）是一种罕见的小血管疾病，其特征为多器官受累。目前尚缺乏能够衡量特定器官受累情况的生物标志物。在此，我们探讨某些循环细胞因子和趋化因子是否与肾脏受累相关，以及不同的细胞因子/趋化因子模式能否区分AAV的肾脏、耳鼻喉、关节和肺部受累情况。
从17例不同的AAV患者中获取了32组伯明翰血管炎活动评分（BVAS）、蛋白酶3-抗中性粒细胞胞浆抗体（PR3-ANCA）滴度、实验室指标以及不同的细胞因子。将BVAS、PR3-ANCA滴度、实验室指标和细胞因子浓度与活动性AAV的不同器官受累情况进行相关性分析。
在活动性PR3-AAV（BVAS>0）且有肾脏受累的患者中，我们发现与无PR3-ANCA相关性肾小球肾炎的患者相比，趋化因子配体（CCL）-1、白细胞介素（IL）-6、IL21、IL23、IL-28A、IL33、单核细胞趋化蛋白2（MCP2）、干细胞因子（SCF）、胸腺基质淋巴细胞生成素（TSLP）和血小板生成素（TPO）的浓度显著更高。与活动性AAV但无这些器官受累的患者相比，有耳鼻喉受累的患者表达的MCP2和（C-X-C基序）配体-12（CXCL-12）浓度更高。
我们确定了PR3-AAV肾脏表现以及耳鼻喉受累的不同细胞因子模式。不同的血浆细胞因子可能用作AAV器官受累的非侵入性生物标志物。
