Defects in plasma cell differentiation are associated with primary immunodeficiency in human subjects

• Published in: Journal of allergy and clinical immunology Vol. 141; no. 4; pp. 1217 - 1219
• Main Authors: Pan-Hammarström, Qiang, Abolhassani, Hassan, Hammarström, Lennart
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2018; Elsevier Limited
• Subjects: common variable immunodeficiency; Defects; Diabetes; Disease; Genes; Glaucoma; Human subjects; Immunodeficiency; Infections; Mutation; Plasma; Plasma cell; Polypeptides; Primary immunodeficiencies; primary immunodeficiency diseases; Proteins; primary immunodeficiency diseases; Plasma cell; common variable immunodeficiency
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2017.10.025

In this issue of the Journal, Schubert et al6 describe a potential new gene defect (heterozygous mutations in SEC61 translocon alpha 1 subunit [SEC61A1]) associated with reduced terminal plasma cell differentiation (both in vivo and in vitro) in 2 unrelated families with hypogammaglobulinemia and severe recurrent respiratory tract infections yet with normal peripheral blood subpopulations of B and T cells. [...]either such genetic defects have not yet been identified in human subjects or their relation to plasma cell function has not been specified/studied. [...]the mutations identified in the SEC61A1 gene by Schubert et al6 represent the first genetic defect that specifically affects the plasma cell compartment. [...]ER stress has been postulated to play a mechanistic role in other human diseases (eg, diabetes mellitus, glaucoma, neurodegenerative diseases, ischemia-reperfusion injury, glioblastoma, multiple myeloma, and carcinomas).12 Pilot trials have suggested that treatment with sodium phenylbutyrate can alleviate symptoms in selected diseases, including glaucoma (mouse)13 and lipid-induced insulin resistance and β cell dysfunction (human subjects).14 Thus it would be of potential interest to examine the therapeutic effects of this drug in cells from patients with SEC61A1 mutations.