Statistics and Epidemiology Branch, Walter Reed Army Institute of Research, Silver Spring, MD.
Department of Biostatistics, UCLA Fielding School of Public Health, Los Angeles, CA.
Cancer Epidemiol Biomarkers Prev. 2023 Feb 6;32(2):233-241. doi: 10.1158/1055-9965.EPI-22-0247.
To examine the contribution of B-cell activation molecules to B-cell follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL), a prospective study was conducted using pre-diagnosis serial serum samples from the US Department of Defense Serum Repository.
Each case (n = 142 FL, n = 211 DLBCL) was matched to two controls on age, gender, race, military branch, and blood collection dates. Immune activation molecules (IL1β, IL2, IL4, IL5, IL6, IL10, IL12, CXCL13, IL8, TNFα, IFNγ, GM-CSF, VEGF, sCD30, IgE) were quantified using ELISA or multiplex immunometric (Luminex) assay. Longitudinal data were analyzed using linear mixed modeling. As serial specimens were collected over several years before diagnosis, we evaluated the temporal dynamics of these markers.
Increased serum levels of sCD30, CXCL13, and to a lesser extent IL10, were associated with both FL and DLBCL in cases compared with controls, with a median follow-up of 5.5 years from the earliest specimen collection to diagnosis date. Significant increasing sCD30 and CXCL13 trajectories for FL and DLBCL subtypes were noted starting at the earliest time points and with IL10 levels increasing significantly at time points closer to diagnosis.
These results suggest that sCD30, CXCL13, and IL10 may contribute to the etiology of FL and DLBCL and are potential biomarkers for these non-Hodgkin lymphoma subtypes.
The increasing trajectories of the B-cell activation molecules, sCD30, CXCL13, and to a lesser extent IL10, may indicate early disease-induced effects or reflect the chronic stimulation of B-cells that promotes the development of FL and DLBCL subtypes.
为了研究 B 细胞激活分子对滤泡性淋巴瘤（FL）和弥漫性大 B 细胞淋巴瘤（DLBCL）的贡献，我们在美国国防部血清库中进行了一项前瞻性研究，使用了诊断前的系列血清样本。
每位病例（FL 组 n=142，DLBCL 组 n=211）均与年龄、性别、种族、军种和采血日期匹配的 2 位对照相匹配。使用 ELISA 或多重免疫荧光（Luminex）检测法检测免疫激活分子（IL1β、IL2、IL4、IL5、IL6、IL10、IL12、CXCL13、IL8、TNFα、IFNγ、GM-CSF、VEGF、sCD30、IgE）。使用线性混合模型分析纵向数据。由于在诊断前的几年中采集了一系列血清样本，我们评估了这些标志物的时间动态。
与对照相比，FL 和 DLBCL 病例的血清 sCD30、CXCL13 和 IL10 水平升高，中位随访时间为最早采集样本至诊断日期的 5.5 年。FL 和 DLBCL 亚型的 sCD30 和 CXCL13 轨迹显著增加，最早时间点开始注意到，而 IL10 水平在更接近诊断的时间点显著增加。
这些结果表明，sCD30、CXCL13 和 IL10 可能有助于 FL 和 DLBCL 的病因学，并且是这些非霍奇金淋巴瘤亚型的潜在生物标志物。
B 细胞激活分子 sCD30、CXCL13 和 IL10 的增加轨迹可能表明早期疾病诱导的影响，或反映促进 FL 和 DLBCL 亚型发展的 B 细胞的慢性刺激。
