Pediatrics Clinic and "A. Nocivelli" Institute for Molecular Medicine, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili of Brescia, Brescia, Italy.
Pediatric Hematology Oncology Unit, Department of Pediatrics, University of Milano Bicocca, MBBM Foundation, Monza, Italy.
J Clin Immunol. 2022 Feb;42(2):365-374. doi: 10.1007/s10875-021-01169-2. Epub 2021 Nov 20.
Jacobsen syndrome (JS) is a rare form of genetic disorder that was recently classified as a syndromic immunodeficiency. Available detailed immunological data from JS patients are limited.
Clinical and immunological presentation of twelve pediatric patients with JS by means of revision of clinical records, flow cytometry, real-time PCR, and lymphocyte functional testing were collected.
Recurrent infections were registered in 6/12 patients (50%), while bleeding episodes in 2/12 (16.7%). White blood cell and absolute lymphocyte counts were reduced in 8/12 (66.7%) and 7/12 (58.3%) patients, respectively. Absolute numbers of CD3 and CD4 T cells were reduced in 8/12 (66.7%) and 7/12 (58.3%), respectively. Of note, recent thymic emigrants (RTE) were reduced in all tested patients (9/9), with T-cell receptor excision circle analysis (TRECs) showing a similar trend in 8/9 patients; naïve CD4 T cells were low only in 5/11 patients (45.4%). Interestingly, B-cell counts, IgM memory B cells, and IgM serum levels were reduced in 10/12 (83.3%) patients. Natural killer (NK) cell counts were mostly normal but the percentages of CD16CD56 cells were expanded in 7/7 patients tested. The observed immunological alterations did not correlate with patients' age. Finally, responses to proliferative stimuli were normal at presentation for all patients, although they may deteriorate over time.
Our data suggest that patients affected with JS may display important numeric and maturational alterations in the T-, B-, and NK-cell compartments. These findings suggest that JS patients should be regularly monitored from an immunological point of view.
雅各布森综合征（JS）是一种罕见的遗传疾病，最近被归类为综合征免疫缺陷。目前可用的 JS 患者详细免疫学数据有限。
通过复习临床记录、流式细胞术、实时 PCR 和淋巴细胞功能检测，收集了 12 例儿科 JS 患者的临床和免疫学表现。
6/12 例（50%）患者出现反复感染，2/12 例（16.7%）患者出现出血事件。白细胞和绝对淋巴细胞计数减少见于 8/12（66.7%）和 7/12（58.3%）患者，分别为 8/12（66.7%）和 7/12（58.3%）患者。绝对 CD3 和 CD4 T 细胞计数减少见于 8/12（66.7%）和 7/12（58.3%）患者。值得注意的是，所有检测患者的近期胸腺迁出细胞（RTE）均减少，T 细胞受体切除环分析（TRECs）在 8/9 例患者中显示出类似趋势；仅 5/11 例（45.4%）患者幼稚 CD4 T 细胞减少。有趣的是，10/12（83.3%）例患者的 B 细胞计数、IgM 记忆 B 细胞和 IgM 血清水平降低。自然杀伤（NK）细胞计数大多正常，但在 7/7 例检测的患者中，CD16+CD56+细胞的比例扩大。观察到的免疫改变与患者年龄无关。最后，所有患者在出现时对增殖刺激的反应均正常，尽管随着时间的推移可能会恶化。
我们的数据表明，JS 患者可能在 T、B 和 NK 细胞亚群中表现出重要的数量和成熟改变。这些发现表明 JS 患者应从免疫学角度定期监测。
