Grados Aurélie, Ebbo Mikael, Piperoglou Christelle, Groh Matthieu, Regent Alexis, Samson Maxime, Terrier Benjamin, Loundou Anderson, Morel Nathalie, Audia Sylvain, Maurier François, Graveleau Julie, Hamidou Mohamed, Forestier Amandine, Palat Sylvain, Bernit Emmanuelle, Bonotte Bernard, Farnarier Catherine, Harlé Jean-Robert, Costedoat-Chalumeau Nathalie, Vély Frédéric, Schleinitz Nicolas
AP-HM, Service de Médecine Interne, Hôpital de la Timone, Marseille, France; Aix-Marseille Université, CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy, Marseille, France.
Aix-Marseille Université, CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy, Marseille, France; AP-HM, Service d'Immunologie, Hôpital de la Conception, Marseille, France.
Front Immunol. 2017 Mar 13;8:235. doi: 10.3389/fimmu.2017.00235. eCollection 2017.
IgG4-related disease (IgG4-RD) is a fibro-inflammatory disorder involving virtually every organ with a risk of organ dysfunction. Despite recent studies regarding B cell and T cell compartments, the disease's pathophysiology remains poorly understood. We examined and characterized subsets of circulating lymphocytes in untreated patients with active IgG4-RD. Twenty-eight consecutive patients with biopsy-proven IgG4-RD were included in a prospective, multicentric study. Lymphocytes' subsets were analyzed by flow cytometry, with analysis of T1/T2/T17, T cells, and cytokine release by peripheral blood mononuclear cells. Results were compared to healthy controls and to patients with primary Sjögren's syndrome. Patients with IgG4-RD showed an increase of circulating T regulatory, T2, T17, and CD4CXCR5PD1 T cell subsets. Accordingly, increased levels of IL-10 and IL-4 were measured in IgG-RD patients. T increase was characterized by the specific expansion of T2 (CCR6CXCR3), and to a lesser extent of T17 (CCR6CXCR3) cells. Interestingly, CD4CXCR5PD1 T cells normalized under treatment. IgG4-RD is characterized by a shift of circulating T cells toward a T2/T2 and T17/T17 polarization. This immunological imbalance might be implicated in the disease's pathophysiology. Treatment regimens targeting such T cells warrant further evaluation.
IgG4相关疾病（IgG4-RD）是一种纤维炎症性疾病，几乎累及每个器官，存在器官功能障碍风险。尽管最近有关于B细胞和T细胞亚群的研究，但该疾病的病理生理学仍知之甚少。我们对未经治疗的活动性IgG4-RD患者的循环淋巴细胞亚群进行了检测和表征。一项前瞻性、多中心研究纳入了28例经活检证实为IgG4-RD的连续患者。通过流式细胞术分析淋巴细胞亚群，分析外周血单个核细胞的T1/T2/T17、T细胞及细胞因子释放情况。将结果与健康对照以及原发性干燥综合征患者进行比较。IgG4-RD患者循环中的调节性T细胞、T2细胞、T17细胞和CD4CXCR5PD1 T细胞亚群增加。相应地，在IgG-RD患者中检测到IL-10和IL-4水平升高。T细胞增加的特征是T2（CCR6CXCR3）细胞特异性扩增，T17（CCR6CXCR3）细胞扩增程度较小。有趣的是，CD4CXCR5PD1 T细胞在治疗后恢复正常。IgG-RD的特征是循环T细胞向T2/T2和T17/T17极化转变。这种免疫失衡可能与该疾病的病理生理学有关。针对此类T细胞的治疗方案值得进一步评估。
