Abstract：
Granulomatosis with polyangiitis (GPA) is an autoimmune disorder characterized by recurrent relapses that can cause severe tissue damage and life-threatening organ dysfunction. Multiple immune cells and cytokines/chemokines are involved in the different stages of the disease. Immune profiling of patients may be useful for tracking disease activity, however, reliable immune signatures for GPA activity are lacking. In this study, we examined circulating immune profiles in GPA patients during active and remission disease states to identify potential immune patterns associated with disease activity. The distribution and phenotypic characteristics of major circulating immune cells, and the profiles of circulating cytokines/chemokines, were studied on cryopreserved peripheral blood mononuclear cells from GPA patients (active, n = 20; remission, n = 20) and healthy controls (n = 20) leveraging a 40-color optimized multicolor immunofluorescence panel (OMIP-69) and in serum using a 46-plex Luminex multiplex assay, respectively. Deep phenotyping uncovered a distinct composition of major circulating immune cells in active GPA and GPA in remission, with the most significant findings emerging within the monocyte compartment. Our detailed analysis revealed circulating monocyte diversity beyond the conventional monocyte subsets. We identified eight classical monocyte populations, two intermediate monocyte populations, and one non-classical monocyte population. Notably, active GPA had a higher frequency of CD45RA+CCR5+CCR6-CCR7+/lowCD127-HLA-DR+CD2- classical monocytes and a lower frequency of CD45RA-CCR5-/lowCCR6-CCR7-CD127-HLA-DR+CD2+/- classical monocytes, which both strongly correlated with disease activity. Furthermore, serum levels of CXCL1, CXCL2, and CCL20, all linked to monocyte biology, were elevated in active GPA and correlated strongly with disease activity. These findings shed light on the circulating immune profile of GPA and may lead to immune signature profiles for assessing disease activity. Monocytes in particular may be studied further as potential markers for monitoring GPA.
摘要：
肉芽肿性多血管炎（GPA）是一种自身免疫性疾病，其特征是复发性复发，可引起严重的组织损伤和危及生命的器官功能障碍。多种免疫细胞和细胞因子/趋化因子参与疾病的不同阶段。患者的免疫分析可能有助于追踪疾病活动，然而,缺乏针对GPA活性的可靠免疫特征。在这项研究中,我们检测了GPA患者在活动期和缓解期疾病状态下的循环免疫谱,以确定与疾病活动相关的潜在免疫模式.主要循环免疫细胞的分布和表型特征，和循环细胞因子/趋化因子的概况，对来自GPA患者的冷冻保存的外周血单核细胞进行了研究(活性，n=20；缓解，n=20）和健康对照（n=20）利用40色优化的多色免疫荧光面板（OMIP-69），并使用46-plexLuminex多重测定在血清中，分别。深层表型揭示了活跃GPA和缓解GPA中主要循环免疫细胞的独特组成，最重要的发现出现在单核细胞区室。我们的详细分析显示，循环单核细胞的多样性超出了常规单核细胞亚群。我们确定了八个经典的单核细胞群，两个中间单核细胞群，和一个非经典单核细胞群体。值得注意的是,活性GPA的CD45RA+CCR5+CCR6-CCR7+/lowCD127-HLA-DR+CD2-经典单核细胞的频率较高，CD45RA-CCR5-/lowCCR6-CCR7-CD127-HLA-DR+CD2+/-经典单核细胞的频率较低，两者都与疾病活动密切相关。此外，CXCL1、CXCL2和CCL20的血清水平都与单核细胞生物学有关，活跃的GPA升高，与疾病活动密切相关。这些发现揭示了GPA的循环免疫谱，并可能导致用于评估疾病活动的免疫特征谱。特别地,可以进一步研究单核细胞作为用于监测GPA的潜在标志物。
