Reduction in CD4 central memory T-cell subset in costimulation modulator abatacept-treated patients with recent-onset type 1 diabetes is associated with slower C-peptide decline.
Reduction in CD4 central memory T-cell subset in costimulation modulator abatacept-treated patients with recent-onset type 1 diabetes is associated with slower C-peptide decline.
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DOI：
10.2337/db14-0047
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发表时间：
2014-10
期刊：
影响因子：
7.7
通讯作者：
Type 1 Diabetes TrialNet Abatacept Study Group
中科院分区：
文献类型：
--
作者：
Orban T;Beam CA;Xu P;Moore K;Jiang Q;Deng J;Muller S;Gottlieb P;Spain L;Peakman M;Type 1 Diabetes TrialNet Abatacept Study Group
我们先前报道，阿巴西普连续24个月的共刺激阻断显著减缓了诊断为1型糖尿病后β细胞功能的下降。在该研究的机制扩展中，我们通过流式细胞术评估了基线和治疗开始后3、6、12、24和30个月的外周血免疫细胞亚群（CD 4、CD 8-幼稚、记忆和活化亚群、髓样和浆细胞样树突状细胞、单核细胞、B淋巴细胞、CD 4 + CD 25 high调节性T细胞和不变NK T细胞），以发现治疗效果的生物标志物。使用多变量分析和纵向测量变量的滞后，我们在安慰剂组中进行了新的观察，即在前一次访视期间中央记忆（CM）CD 4 T细胞（CD 4 + CD 45 R 0 + CD 62 L+）的增加与随后访视时C肽下降显著相关。这些变化受到阿巴西普治疗的显著影响，阿巴西普治疗驱动CM CD 4 T细胞的外周收缩和幼稚（CD 45 R 0 − CD 62 L+）CD 4 T细胞的扩增，与C肽下降的速率显著减慢相关。研究结果表明，CM CD 4 T细胞的定量可以为1型糖尿病诊断后C肽下降提供替代免疫标志物，并且共刺激阻断可以通过调节该亚群发挥其有益的治疗作用。
We previously reported that continuous 24-month costimulation blockade by abatacept significantly slows the decline of β-cell function after diagnosis of type 1 diabetes. In a mechanistic extension of that study, we evaluated peripheral blood immune cell subsets (CD4, CD8-naive, memory and activated subsets, myeloid and plasmacytoid dendritic cells, monocytes, B lymphocytes, CD4+CD25high regulatory T cells, and invariant NK T cells) by flow cytometry at baseline and 3, 6, 12, 24, and 30 months after treatment initiation to discover biomarkers of therapeutic effect. Using multivariable analysis and lagging of longitudinally measured variables, we made the novel observation in the placebo group that an increase in central memory (CM) CD4 T cells (CD4+CD45R0+CD62L+) during a preceding visit was significantly associated with C-peptide decline at the subsequent visit. These changes were significantly affected by abatacept treatment, which drove the peripheral contraction of CM CD4 T cells and the expansion of naive (CD45R0−CD62L+) CD4 T cells in association with a significantly slower rate of C-peptide decline. The findings show that the quantification of CM CD4 T cells can provide a surrogate immune marker for C-peptide decline after the diagnosis of type 1 diabetes and that costimulation blockade may exert its beneficial therapeutic effect via modulation of this subset.
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影响因子：
168.9
作者：
Wherrett, Diane K.;Bundy, Brian;Becker, Dorothy J.;DiMeglio, Linda A.;Gitelman, Stephen E.;Goland, Robin;Gottlieb, Peter A.;Greenbaum, Carla J.;Herold, Kevan C.;Marks, Jennifer B.;Monzavi, Roshanak;Moran, Antoinette;Orban, Tihamer;Palmer, Jerry P.;Raskin, Philip;Rodriguez, Henry;Schatz, Desmond;Wilson, Darrell M.;Krischer, Jeffrey P.;Skyler, Jay S.
通讯作者：
Skyler, Jay S.
影响因子：
3.9
作者：
Scarsi, Mirko;Ziglioli, Tamara;Airo', Paolo
通讯作者：
Airo', Paolo
影响因子：
56.9
作者：
STILLER, CR;DUPRE, J;WOLFE, BMJ
通讯作者：
WOLFE, BMJ
影响因子：
12.8
作者：
Orban T;Farkas K;Jalahej H;Kis J;Treszl A;Falk B;Reijonen H;Wolfsdorf J;Ricker A;Matthews JB;Tchao N;Sayre P;Bianchine P
通讯作者：
Bianchine P
DOI：
10.4049/jimmunol.1100539
发表时间：
2011-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Herold KC;Pescovitz MD;McGee P;Krause-Steinrauf H;Spain LM;Bourcier K;Asare A;Liu Z;Lachin JM;Dosch HM;Type 1 Diabetes TrialNet Anti-CD20 Study Group
通讯作者：
Type 1 Diabetes TrialNet Anti-CD20 Study Group