PDF(Pubmed)
Abstract：
Growing evidence links immunological responses to Multiple sclerosis (MS), but specific immune factors are still unclear.
Mendelian randomization (MR) was performed to investigate the association between peripheral hematological traits, MS risk, and its severity. Then, further subgroup analysis of immune counts and circulating cytokines and growth factors were performed.
MR revealed higher white blood cell count (OR [95%CI] = 1.26 [1.10,1.44], P = 1.12E-03, P adjust = 3.35E-03) and lymphocyte count (OR [95%CI] = 1.31 [1.15,1.50], P = 5.37E-05, P adjust = 3.22E-04) increased the risk of MS. In further analysis, higher T cell absolute count (OR [95%CI] = 2.04 [1.36,3.08], P = 6.37E-04, P adjust = 2.19E-02) and CD4+ T cell absolute count (OR [95%CI] = 2.11 [1.37,3.24], P = 6.37E-04, P adjust = 2.19E-02), could increase MS risk. While increasing CD25++CD4+ T cell absolute count (OR [95%CI] = 0.75 [0.66,0.86], P = 2.12E-05, P adjust = 1.72E-03), CD25++CD4+ T cell in T cell (OR [95%CI] = 0.79[0.70,0.89], P = 8.54E-05, P adjust = 5.29E-03), CD25++CD4+ T cell in CD4+ T cell (OR [95%CI] = 0.80[0.72,0.89], P = 1.85E-05, P adjust = 1.72E-03), and CD25++CD8+ T cell in T cell (OR [95%CI] = 0.68[0.57,0.81], P = 2.22E-05, P adjust = 1.72E-03), were proved to be causally defensive for MS. For the disease severity, the suggestive association between some traits related to CD4+ T cell, Tregs and MS severity were demonstrated. Moreover, elevated levels of IL-2Ra had a detrimental effect on the risk of MS (OR [95%CI] = 1.22 [1.12,1.32], P = 3.20E-06, P adjust = 1.34E-04).
This study demonstrated a genetically predicted causal relationship between elevated peripheral immune cell counts and MS. Subgroup analysis revealed a specific contribution of peripheral immune cells, holding potential for further investigations into the underlying mechanisms of MS and its severity.
Mendelian randomization (MR) was performed to investigate the association between peripheral hematological traits, MS risk, and its severity. Then, further subgroup analysis of immune counts and circulating cytokines and growth factors were performed.
MR revealed higher white blood cell count (OR [95%CI] = 1.26 [1.10,1.44], P = 1.12E-03, P adjust = 3.35E-03) and lymphocyte count (OR [95%CI] = 1.31 [1.15,1.50], P = 5.37E-05, P adjust = 3.22E-04) increased the risk of MS. In further analysis, higher T cell absolute count (OR [95%CI] = 2.04 [1.36,3.08], P = 6.37E-04, P adjust = 2.19E-02) and CD4+ T cell absolute count (OR [95%CI] = 2.11 [1.37,3.24], P = 6.37E-04, P adjust = 2.19E-02), could increase MS risk. While increasing CD25++CD4+ T cell absolute count (OR [95%CI] = 0.75 [0.66,0.86], P = 2.12E-05, P adjust = 1.72E-03), CD25++CD4+ T cell in T cell (OR [95%CI] = 0.79[0.70,0.89], P = 8.54E-05, P adjust = 5.29E-03), CD25++CD4+ T cell in CD4+ T cell (OR [95%CI] = 0.80[0.72,0.89], P = 1.85E-05, P adjust = 1.72E-03), and CD25++CD8+ T cell in T cell (OR [95%CI] = 0.68[0.57,0.81], P = 2.22E-05, P adjust = 1.72E-03), were proved to be causally defensive for MS. For the disease severity, the suggestive association between some traits related to CD4+ T cell, Tregs and MS severity were demonstrated. Moreover, elevated levels of IL-2Ra had a detrimental effect on the risk of MS (OR [95%CI] = 1.22 [1.12,1.32], P = 3.20E-06, P adjust = 1.34E-04).
This study demonstrated a genetically predicted causal relationship between elevated peripheral immune cell counts and MS. Subgroup analysis revealed a specific contribution of peripheral immune cells, holding potential for further investigations into the underlying mechanisms of MS and its severity.
摘要：
■越来越多的证据将免疫反应与多发性硬化症（MS）联系起来，但具体的免疫因子尚不清楚。
■孟德尔随机化(MR)是为了研究外周血液学特征之间的关联，MS风险，及其严重程度。然后，我们对免疫计数和循环细胞因子和生长因子进行了进一步的亚组分析.
■MR显示白细胞计数较高（OR[95CI]=1.26[1.10,1.44]，P=1.12E-03，P调整=3.35E-03）和淋巴细胞计数（OR[95CI]=1.31[1.15,1.50]，P=5.37E-05，P调整=3.22E-04）增加MS的风险。在进一步分析中，较高的T细胞绝对计数(OR[95CI]=2.04[1.36,3.08]，P=6.37E-04，P调整=2.19E-02）和CD4+T细胞绝对计数（OR[95CI]=2.11[1.37,3.24]，P=6.37E-04,P调整=2.19E-02),可能会增加MS风险。当增加CD25++CD4+T细胞绝对计数时（OR[95CI]=0.75[0.66,0.86]，P=2.12E-05,P调整=1.72E-03),T细胞中的CD25++CD4+T细胞（OR[95CI]=0.79[0.70,0.89]，P=8.54E-05,P调整=5.29E-03),CD4+T细胞中的CD25++CD4+T细胞（OR[95CI]=0.80[0.72,0.89]，P=1.85E-05,P调整=1.72E-03),T细胞中的CD25++CD8+T细胞（OR[95CI]=0.68[0.57,0.81]，P=2.22E-05,P调整=1.72E-03),被证明对MS具有因果关系。对于疾病的严重程度，与CD4+T细胞相关的一些性状之间的暗示性关联，显示了Tregs和MS严重程度。此外，IL-2Ra水平升高对MS风险有不利影响（OR[95CI]=1.22[1.12,1.32]，P=3.20E-06,P调整=1.34E-04)。
这项研究证明了外周免疫细胞计数升高与MS之间存在遗传预测的因果关系。亚组分析显示外周免疫细胞的特定贡献，有可能进一步调查MS的潜在机制及其严重程度。
■孟德尔随机化(MR)是为了研究外周血液学特征之间的关联，MS风险，及其严重程度。然后，我们对免疫计数和循环细胞因子和生长因子进行了进一步的亚组分析.
■MR显示白细胞计数较高（OR[95CI]=1.26[1.10,1.44]，P=1.12E-03，P调整=3.35E-03）和淋巴细胞计数（OR[95CI]=1.31[1.15,1.50]，P=5.37E-05，P调整=3.22E-04）增加MS的风险。在进一步分析中，较高的T细胞绝对计数(OR[95CI]=2.04[1.36,3.08]，P=6.37E-04，P调整=2.19E-02）和CD4+T细胞绝对计数（OR[95CI]=2.11[1.37,3.24]，P=6.37E-04,P调整=2.19E-02),可能会增加MS风险。当增加CD25++CD4+T细胞绝对计数时（OR[95CI]=0.75[0.66,0.86]，P=2.12E-05,P调整=1.72E-03),T细胞中的CD25++CD4+T细胞（OR[95CI]=0.79[0.70,0.89]，P=8.54E-05,P调整=5.29E-03),CD4+T细胞中的CD25++CD4+T细胞（OR[95CI]=0.80[0.72,0.89]，P=1.85E-05,P调整=1.72E-03),T细胞中的CD25++CD8+T细胞（OR[95CI]=0.68[0.57,0.81]，P=2.22E-05,P调整=1.72E-03),被证明对MS具有因果关系。对于疾病的严重程度，与CD4+T细胞相关的一些性状之间的暗示性关联，显示了Tregs和MS严重程度。此外，IL-2Ra水平升高对MS风险有不利影响（OR[95CI]=1.22[1.12,1.32]，P=3.20E-06,P调整=1.34E-04)。
这项研究证明了外周免疫细胞计数升高与MS之间存在遗传预测的因果关系。亚组分析显示外周免疫细胞的特定贡献，有可能进一步调查MS的潜在机制及其严重程度。
