Ooms Mark, Strom Alexander, Strassburger Klaus, Menart Barbara, Leslie Richard D, Schloot Nanette C
Institute for Clinical Diabetology, Leibniz Center for Diabetes Research at Heinrich-Heine-University, Duesseldorf, Germany.
Clinic and Policlinic for Oral and Maxillofacial Surgery, University Hospital Aachen, Aachen, Germany.
Diabetes Metab Res Rev. 2021 Oct;37(7):e3431. doi: 10.1002/dmrr.3431. Epub 2021 Jan 16.
Immune-mediated type 1 diabetes (T1D) in adulthood and latent autoimmune diabetes in adults (LADA) share similar pathological mechanisms but differ clinically in disease progression. The aim of this study was to acquire insights into spontaneous and stimulated chemokine secretion of immune cells in different diabetes types.
We investigated in vitro spontaneous, mitogen (PI) and antigen (HSP60, p277, pGAD, pIA2) stimulated chemokine secretion of leucocytes from patients with T1D (n = 32), LADA (n = 22), type 2 diabetes (T2D; n = 49), and glucose-tolerant individuals (n = 13). Chemokine concentration in supernatants was measured for CCL2 (MCP-1), CXCL10 (IP10) and CCL5 (RANTES) using a multiplex bead array assay.
Spontaneous secretion of CCL2 and CCL5 were higher in LADA compared to T1D and T2D (all p < 0.05) while CXCL10 was similar in the groups. Mitogen-stimulated secretion of CCL2 in LADA was lower compared to T1D and T2D (all p < 0.05) while CXCL10 and CCL5 were similar in all groups. Upon stimulation with pIA2 the secretion of CCL2 in LADA was lower compared to T2D (p < 0.05). Spontaneous CXCL10 secretion in LADA was positively associated with body mass index (r = 0.35; p = 0.0035) and C-peptide (r = 0.30; p = 0.009).
Chemokine secretion is altered between different diabetes types. Increased spontaneous secretion of CCL2 and CCL5 and decreased secretion of CCL2, upon stimulation with PI and pIA2, in LADA compared to T1D and T2D could reflect altered immune responsiveness in LADA patients in association with their slower clinical progression compared to insulin dependence.
成年期免疫介导的1型糖尿病（T1D）和成人隐匿性自身免疫性糖尿病（LADA）具有相似的病理机制，但在疾病进展的临床特征上有所不同。本研究旨在深入了解不同类型糖尿病中免疫细胞自发和受刺激后的趋化因子分泌情况。
我们研究了T1D患者（n = 32）、LADA患者（n = 22）、2型糖尿病（T2D；n = 49）和糖耐量正常个体（n = 13）白细胞在体外自发、有丝分裂原（PI）和抗原（HSP60、p277、pGAD、pIA2）刺激下的趋化因子分泌情况。使用多重微珠阵列分析法测量上清液中CCL2（MCP-1）、CXCL10（IP10）和CCL5（RANTES）的趋化因子浓度。
与T1D和T2D相比，LADA中CCL2和CCL5的自发分泌更高（所有p < 0.05），而CXCL10在各组中相似。与T1D和T2D相比，LADA中有丝分裂原刺激的CCL2分泌较低（所有p < 0.05），而CXCL10和CCL5在所有组中相似。在用pIA2刺激后，LADA中CCL2的分泌低于T2D（p < 0.05）。LADA中CXCL10的自发分泌与体重指数呈正相关（r = 0.35；p = 0.0035）和C肽呈正相关（r = 0.30；p = 0.009）。
不同类型糖尿病之间趋化因子分泌存在改变。与T1D和T2D相比，LADA中CCL2和CCL5自发分泌增加，在用PI和pIA2刺激后CCL2分泌减少，这可能反映了LADA患者免疫反应性的改变，与其相对于胰岛素依赖型患者较慢的临床进展相关。
