Immunological Investigations ( IF 2.9 ) Pub Date : 2020-10-13 , DOI: 10.1080/08820139.2020.1829638 Niusha Sharifinejad 1, 2 , Gholamreza Azizi 2 , Nasrin Behniafard 3 , Majid Zaki-Dizaji 4 , Mahnaz Jamee 1, 2 , Reza Yazdani 5 , Hassan Abolhassani 6 , Asghar Aghamohammadi 5
ABSTRACT
Background
Protein kinase C is a family of serine/threonine kinases that play a key role in the adaptive immune cell signaling, as well as regulation of growth, apoptosis, and differentiation of a variety of cell types. Patients homozygous for a null mutation of the Protein Kinase C Delta (PRKCD) gene, present clinical feature of immune dysregulation with susceptibility to Epstein-Barr virus infection. However, a minority of patients present the autoimmune lymphoproliferative syndrome (ALPS).
Methods
The data were collected by direct interview and examining the patient’s clinical record. Whole-exome sequencing was performed to detect the underlying genetic mutation in the patient. We also conducted electronic searches for ALPS-like reported patients in PubMed, Web of Science, and Scopus databases.
Results
In this study, we reported a 13-year-old boy who presented with autoimmunity, lymphoproliferation, recurrent pneumonia, cardiomyopathy, and dermatological manifestations. An elevation of double-negative T cells, CD8+ T cells, serum IgG level, as well as a reduction in NK cells, was observed in the patient. A homozygous frameshift mutation (c.1293_1294insA) in exon 13 of the PRKCD gene was confirmed. The literature search showed 39 ALPS-like patients with monogenic defects which only six (15.3%) of them were due to PRKCD genes.
Conclusion
PRKCD should be considered in the context of ALPS clinical manifestations with prominent dermatological involvements.
中文翻译:
自身免疫性淋巴增生综合征样疾病中的蛋白激酶 C-Delta 缺陷:伊朗国家登记处的首例病例和文献回顾
摘要
背景
蛋白激酶 C 是丝氨酸/苏氨酸激酶家族,在适应性免疫细胞信号传导以及多种细胞类型的生长、凋亡和分化的调节中起关键作用。蛋白激酶 C Delta (PRKCD)基因的无效突变纯合子患者呈现免疫失调的临床特征,易感染 Epstein-Barr 病毒。然而,少数患者会出现自身免疫性淋巴组织增生综合征 (ALPS)。
方法
通过直接访谈和检查患者的临床记录收集数据。进行全外显子组测序以检测患者潜在的基因突变。我们还在 PubMed、Web of Science 和 Scopus 数据库中对报告的类似 ALPS 的患者进行了电子搜索。
结果
在这项研究中,我们报告了一名 13 岁男孩,他出现自身免疫、淋巴组织增生、复发性肺炎、心肌病和皮肤病表现。在患者中观察到双阴性 T 细胞、CD8 + T 细胞、血清 IgG 水平升高,以及 NK 细胞减少。证实了 PRKCD 基因外显子 13 中的纯合移码突变 (c.1293_1294insA)。文献检索显示 39 例 ALPS 样患者存在单基因缺陷,其中仅 6 例(15.3%)是由于 PRKCD 基因所致。
结论
PRKCD 应在具有突出皮肤病学受累的 ALPS 临床表现的背景下考虑。