Abolhassani Hassan, Caballero-Oteyza Andres, Yang Mingyu, Proietti Michele, Delavari Samaneh, Maffucci Patrick, Schäffer Alejandro A, Boisson Bertrand, Casanova Jean-Laurent, Rezaei Nima, Pan-Hammarström Qiang, Cunningham-Rundles Charlotte, Hammarström Lennart, Grimbacher Bodo
Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
J Hum Immun. 2025 Nov 3;1(4). doi: 10.70962/jhi.20250016. Epub 2025 Aug 19.
Predominantly antibody deficiency (PAD) is the most prevalent form of human inborn errors of immunity (IEI). PAD is characterized by recurrent bacterial infections, immune dysregulation, and impaired immunoglobulin production. A monogenic cause of PAD can be identified in about 20% of cases. Approximately 10% of patients carry heterozygous mutations in the tumor necrosis factor receptor superfamily member 13B gene (), encoding the B cell surface protein TACI. Heterozygous variants in are not sufficient to cause PAD, as approximately 1% of the healthy population carries one of these variants. To identify additional genetic contributors to the immune defect in these individuals, we examined the exomes of 161 PAD patients with rare-damaging variants in . We identified (i) biallelic mutations in , (ii) the HLA-class II marker (DPA1*03), and (iii) multiple single nucleotide polymorphisms in known B-cell related genes, as additional genetic risk factors. Moreover, pathogenic mutations in other known IEI genes were presented in 16% of patients with heterozygous variants.
主要抗体缺陷（PAD）是人类遗传性免疫缺陷（IEI）中最常见的形式。PAD的特征是反复发生细菌感染、免疫失调和免疫球蛋白产生受损。约20%的病例可确定PAD的单基因病因。约10%的患者在肿瘤坏死因子受体超家族成员13B基因（）中携带杂合突变，该基因编码B细胞表面蛋白TACI。由于约1%的健康人群携带这些变体之一，因此中的杂合变体不足以导致PAD。为了确定这些个体免疫缺陷的其他遗传因素，我们检查了161例在中携带罕见有害变体的PAD患者的外显子组。我们确定了（i）中的双等位基因突变，（ii）HLA-II类标记（DPA1*03），以及（iii）已知B细胞相关基因中的多个单核苷酸多态性，作为额外的遗传风险因素。此外，16%携带杂合变体的患者中存在其他已知IEI基因的致病突变。
