Early mortality in sickle cell disease (SCD) is attributed to increased infections due to loss of splenic function. Marginal zone B cells are important for initial opsonization of pathogens and can be absent in spleen histopathology in SCD. The frequency of unswitched memory B cells (UMBC), the circulating correlate of marginal zone B cells, reflects the immunologic function of the spleen. We hypothesized that asplenia in SCD is associated with alterations in the peripheral blood lymphocyte population and explored whether UMBC deficiency was associated with a clinical phenotype. We analyzed B cell subsets and clinical history for 238 children with SCD and 63 controls. The median proportion of UMBCs was lower in children with SCD compared with controls (4.7% vs. 6.6%, p < .001). Naïve B cells were higher in SCD compared with controls (80.6 vs. 76.3%, respectively, p = .02). UMBC frequency declined by 3.4% per year increase in age in SCD (95% CI: 2%, 4.7%, p < .001), but not in controls. A majority of children in all cohorts had an IgM concentration in the normal range for age and there were no differences between groups (p = .13). Subjects developed titers adequate for long-term protection to fewer serotypes in the polysaccharide vaccine than controls (14.7 vs. 19.4, p < .001). In this cohort, bacteremia was rare and specific clinical complications were not associated with UMBC proportion. In summary, UMBC deficiency occurs in SCD and is associated with age. Future studies should investigate B cell subsets prospectively and identify the mechanism of B cell loss in the spleen.

中文翻译：

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镰状细胞病儿童未转换记忆 B 细胞缺陷及肺炎球菌多糖疫苗的反应


镰状细胞病 (SCD) 的早期死亡归因于脾功能丧失导致的感染增加。边缘区 B 细胞对于病原体的初始调理作用很重要，并且在 SCD 的脾脏组织病理学中可能不存在。未转换记忆 B 细胞 (UMBC) 是边缘区 B 细胞的循环相关物，其频率反映了脾脏的免疫功能。我们假设 SCD 中的无脾与外周血淋巴细胞群的改变有关，并探讨 UMBC 缺陷是否与临床表型相关。我们分析了 238 名 SCD 儿童和 63 名对照儿童的 B 细胞亚群和临床病史。与对照组相比，SCD 儿童 UMBC 的中位比例较低（4.7% vs. 6.6%，p < .001）。与对照组相比，SCD 中的初始 B 细胞含量更高（分别为 80.6% 和 76.3%，p = .02）。随着 SCD 年龄的增加，UMBC 频率每年下降 3.4%（95% CI：2%、4.7%，p < .001），但在对照组中则不然。所有队列中的大多数儿童的 IgM 浓度均在正常年龄范围内，并且组间没有差异 (p = .13)。与对照组相比，受试者对多糖疫苗中较少的血清型产生了足够的长期保护滴度（14.7 vs. 19.4，p < .001）。在该队列中，菌血症很少见，并且特定的临床并发症与 UMBC 比例无关。总之，UMBC 缺乏症发生在 SCD 中，并且与年龄有关。未来的研究应该前瞻性地研究 B 细胞亚群并确定脾脏中 B 细胞丢失的机制。