Department of Pediatrics, Government Medical College (GMC), Srinagar, India.
Clinical Immunology & Rheumatology Division, Department of Pediatrics, Khyber Medical Institute, Srinagar, India.
J Clin Immunol. 2023 Dec 22;44(1):17. doi: 10.1007/s10875-023-01633-1.
Inherited deficiencies of CD40 and CD40 ligand (CD40L) reflect the crucial immunological functions of CD40-CD40L interaction/signaling. Although numerous studies have provided a detailed description of CD40L deficiency, reports of CD40 deficiency are scarce. Herein, we describe the characteristics of all reported patients with CD40 deficiency.
The PubMed, Embase and Web of Science databases were searched for relevant literature published till 7th August 2023. Study deduplication and identification of relevant reports was performed using the online PICO Portal. The data were extracted using a pre-designed data extraction form and the SPSS software was used for analysis.
Systematic literature review revealed 40 unique patients with CD40 deficiency. Respiratory tract and gastrointestinal infections were the predominant clinical manifestations (observed in 93% and 57% patients, respectively). Sclerosing cholangitis has been reported in nearly one-third of patients. Cryptosporidium sp. (29%) and Pneumocystis jirovecii (21%) were the most common microbes identified. Very low to undetectable IgG levels and severely reduced/absent switch memory B cells were observed in all patients tested/reported. Elevated IgM levels were observed in 69% patients. Overall, splice-site and missense variants were the most common (36% and 32%, respectively) molecular defects identified. All patients were managed with immunoglobulin replacement therapy and antimicrobial prophylaxis was utilized in a subset. Hematopoietic stem cell transplantation (HSCT) has been performed in 45% patients (curative outcome observed in 73% of these patients). Overall, a fatal outcome was reported in 21% patients.
We provide a comprehensive description of all important aspects of CD40 deficiency. HSCT is a promising curative treatment option for CD40 deficiency.
CD40 和 CD40 配体（CD40L）的遗传性缺陷反映了 CD40-CD40L 相互作用/信号的关键免疫功能。尽管许多研究已经详细描述了 CD40L 缺乏，但 CD40 缺乏的报道很少。在此，我们描述了所有报道的 CD40 缺乏患者的特征。
在 PubMed、Embase 和 Web of Science 数据库中搜索截至 2023 年 8 月 7 日发表的相关文献。使用在线 PICO 门户进行研究去重和相关报告的识别。使用预设计的数据提取表提取数据，并使用 SPSS 软件进行分析。
系统文献综述共发现 40 例独特的 CD40 缺乏患者。呼吸道和胃肠道感染是最主要的临床表现（分别见于 93%和 57%的患者）。近三分之一的患者报告有硬化性胆管炎。已鉴定的最常见微生物包括 Cryptosporidium sp.（29%）和 Pneumocystis jirovecii（21%）。所有接受检测/报告的患者均观察到极低至无法检测到的 IgG 水平和严重减少/缺失的转换记忆 B 细胞。69%的患者观察到 IgM 水平升高。总体而言，剪接位点和错义变异分别是最常见的（分别为 36%和 32%）分子缺陷。所有患者均接受免疫球蛋白替代治疗，部分患者采用抗菌药物预防。45%的患者进行了造血干细胞移植（HSCT）（这些患者中有 73%观察到治愈结果）。总体而言，21%的患者报告了致命结局。
我们全面描述了 CD40 缺乏的所有重要方面。HSCT 是 CD40 缺乏的一种有前途的治愈治疗选择。
