Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA.
Cytokine. 2012 Dec;60(3):882-9. doi: 10.1016/j.cyto.2012.08.028. Epub 2012 Sep 23.
Abnormal immune function is a key factor in predisposition to non-Hodgkin lymphoma (NHL). We evaluated the association of 30 cytokines individually and as a profile with diffuse large B-cell (DLBCL) and follicular (FL) lymphomas.
We used a multiplexed assay to measure 30 cytokine concentrations in pre-treatment serum in a case-control study of 234 FL, 188 DLBCL, and 400 control participants. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for age and sex, and polytomous regression was used to evaluate heterogeneity between FL and DLBCL. Principal components analysis (PCA) was used to assess cytokine profiles associated with FL and DLBCL.
In single cytokine modeling, we found that 12 of the 30 circulating serum cytokines were significantly (P<0.05) associated with FL and/or DLBCL after accounting for multiple testing (q<0.05). Soluble IL-2R (sIL-2R) had the strongest association with both FL (OR=6.0 for highest versus lowest tertile, 95% CI 3.8-9.5; p-trend=1.8 × 10(-21)) and DLBCL (OR=7.6, 95% CI 4.5-13.1; p-trend=7.2 × 10(-20)). IL1RA and IL-12p40 also showed similar associations for DLBCL and FL. In contrast, HGF, MIG, and MIP-1α had a stronger association with DLBCL compared to FL, and IL-6, IL-8, IL-10, IFN-γ, IP-10, and VEGF were only statistically significantly associated with DLBCL after accounting for multiple testing. However, in PCA modeling, a cytokine profile based on sIL-2R, IL-1RA, MIG, IP-10, IL-8, and IL-12p40 explained most of the variability between controls and both FL and DLBCL.
We identified some cytokines unique to DLBCL, but overall cytokine associations were more similar than distinct for DLBCL and FL. While these data are limited by concerns of reverse causality, they do suggest cytokines and cytokine profiles that can be prioritized in future studies.
异常的免疫功能是非霍奇金淋巴瘤（NHL）易感性的一个关键因素。我们评估了 30 种细胞因子单独作为一个谱与弥漫性大 B 细胞（DLBCL）和滤泡性（FL）淋巴瘤的关联。
我们使用一种多重分析方法来测量 234 例 FL、188 例 DLBCL 和 400 例对照参与者治疗前血清中的 30 种细胞因子浓度。使用条件逻辑回归估计调整年龄和性别后的比值比（OR）和 95%置信区间（CI），并使用多元回归评估 FL 和 DLBCL 之间的异质性。主成分分析（PCA）用于评估与 FL 和 DLBCL 相关的细胞因子谱。
在单细胞因子建模中，我们发现 30 种循环血清细胞因子中有 12 种在考虑到多次检验（q<0.05）后与 FL 和/或 DLBCL 显著相关（P<0.05）。可溶性白细胞介素-2 受体（sIL-2R）与 FL（最高与最低三分位组的比值比[OR]为 6.0，95%CI 为 3.8-9.5；p 趋势=1.8×10(-21))和 DLBCL（OR 为 7.6，95%CI 为 4.5-13.1；p 趋势=7.2×10(-20))均有最强的关联。IL1RA 和 IL-12p40 也与 DLBCL 和 FL 有类似的关联。相比之下，HGF、MIG 和 MIP-1α 与 DLBCL 的关联强于 FL，而 IL-6、IL-8、IL-10、IFN-γ、IP-10 和 VEGF 仅在考虑到多次检验后才与 DLBCL 有统计学显著关联。然而，在 PCA 建模中，基于 sIL-2R、IL-1RA、MIG、IP-10、IL-8 和 IL-12p40 的细胞因子谱解释了对照组与 FL 和 DLBCL 之间的大部分可变性。
我们确定了一些与 DLBCL 独特相关的细胞因子，但总的来说，DLBCL 和 FL 的细胞因子关联更相似而不是不同。尽管这些数据受到反向因果关系的限制，但它们确实表明可以在未来的研究中优先考虑细胞因子和细胞因子谱。
