Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Clinic of Medicine, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
Akademiskt Specialistcentrum, Centrum för Diabetes, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Cytokine. 2022 Mar;151:155792. doi: 10.1016/j.cyto.2022.155792. Epub 2022 Jan 20.
Cytokines and chemokines participate in autoimmune processes at cellular targets which include insulin-producing beta cells. To which extent such participation is reflected in the circulation has not been conclusively resolved.
We compared the time course of cytokines/chemokines in Latent Autoimmune Diabetes in Adults (LADA) patients heterogeneous for high or low autoimmune activity as determined by levels of antibodies against glutamic acid decarboxylase (GADA).
Serum samples to be measured were from a two-armed randomized controlled trial (RCT) in 68 LADA patients. The study encompassed 21 months with C-peptide as primary endpoint. We measured 27 immune mediators at baseline, at 9 and at 21 months (end of study). Results of measurements were analyzed by multiple linear regression.
At baseline, a high body mass index (BMI) (>26 kg/m) was associated with elevated levels of the interleukins (IL) IL-1 beta, IL-1ra, IL-2, IL-5, IL-6 and IL-13. Treatment during RCT (sitagliptin vs. insulin) did not affect the time course (21 months) of levels of cytokines/chemokines (by univariate analyses). However, levels of the cytokines IL-1ra and IL-1 beta decreased significantly (p < 0.04 or less) in patients with high vs. low GADA when adjusted for BMI, age, gender (male/female), treatment (insulin/sitagliptin) and study site (Norwegian/Swedish).
In LADA, high levels of GADA, a proxy for high autoimmune activity and linked to a decline in C-peptide, was associated with a decrease of selected cytokines over time. This implies that the decline of IL-1ra and IL-1 beta in the circulation reflects autoimmune activity and beta cell demise in LADA.
细胞因子和趋化因子参与细胞靶点的自身免疫过程，其中包括产生胰岛素的β细胞。这种参与在多大程度上反映在循环中尚未得到明确解决。
我们比较了谷氨酸脱羧酶（GADA）抗体水平高低不同的成人隐匿性自身免疫性糖尿病（LADA）患者的细胞因子/趋化因子的时间进程。
用于测量的血清样本来自一项 68 例 LADA 患者的两臂随机对照试验（RCT）。该研究包括 21 个月的 C 肽作为主要终点。我们在基线、9 个月和 21 个月（研究结束时）测量了 27 种免疫介质。通过多元线性回归分析测量结果。
基线时，高体重指数（BMI）（>26 kg/m）与白细胞介素（IL）IL-1β、IL-1ra、IL-2、IL-5、IL-6 和 IL-13 水平升高有关。RCT 期间的治疗（西格列汀与胰岛素）并未影响细胞因子/趋化因子的时间进程（21 个月）（通过单变量分析）。然而，当调整 BMI、年龄、性别（男性/女性）、治疗（胰岛素/西格列汀）和研究地点（挪威/瑞典）时，高 GADA 水平（高自身免疫活性的代表）的患者的细胞因子 IL-1ra 和 IL-1β 水平显著下降（p<0.04 或更低）。
在 LADA 中，高 GADA 水平，即高自身免疫活性的代表，与 C 肽下降有关，与随时间推移选择细胞因子的下降有关。这意味着循环中 IL-1ra 和 IL-1β 的下降反映了 LADA 中的自身免疫活性和β细胞死亡。
