ArticleThe Journal of allergy and clinical immunology2018
Plasma cell deficiency in human subjects with heterozygous mutations in Sec61 translocon alpha 1 subunit (SEC61A1).
Article in The Journal of allergy and clinical immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 81 citations in OpenAlex.
- Identification of a Novel De Novo Heterozygous SEC61A1 Variant in a Patient With Severe Congenital Neutropenia.Molecular genetics & genomic medicine · 2026Article
- Rules of Engagement for Components of Membrane Protein Biogenesis at the Human Endoplasmic Reticulum.International journal of molecular sciences · 2025Review
- Single-cell transcriptomic profiling reveals dysregulation of B-cell subset function in patients with chronic hepatitis B.Hepatology international · 2025Article
- Toward Understanding the Mechanism of Client-Selective Small Molecule Inhibitors of the Sec61 Translocon.Journal of molecular recognition : JMR · 2025Review
- Exploring Monogenic, Polygenic, and Epigenetic Models of Common Variable Immunodeficiency.Human mutation · 2025Review
- Exploring the ER channel protein Sec61: recent advances in pathophysiological significance and novel pharmacological inhibitors.Frontiers in pharmacology · 2025Review
- Role of Sec61α2 Translocon in Insulin Biosynthesis.Diabetes · 2024Article
- Revealing disease subtypes and heterogeneity in common variable immunodeficiency through transcriptomic analysis.Scientific reports · 2024Article
- Hypoaldosteronism due to a novel SEC61A1 variant successfully treated with fludrocortisone.Clinical kidney journal · 2024Article
- Comparative analysis of SEC61A1 mutant R236C in two patient-derived cellular platforms.Scientific reports · 2024Article
- Clinical and experimental treatment of primary humoral immunodeficiencies.Clinical and experimental immunology · 2024Review
- Review
- Characterizing CD38 expression in terminally differentiated B cells using variable lymphocyte receptor B tetramers.Frontiers in immunology · 2024Article
- Quantitative Mass Spectrometry Characterizes Client Spectra of Components for Targeting of Membrane Proteins to and Their Insertion into the Membrane of the Human ER.International journal of molecular sciences · 2023Review
- Improved approaches to channel capacity estimation discover compromised GPCR signaling in diverse cancer cells.iScience · 2023Article
- SEC-seq: association of molecular signatures with antibody secretion in thousands of single human plasma cells.Nature communications · 2023Article
- Interstitial Deletion of 3q21 in a Kuwaiti Child with Multiple Congenital Anomalies-Expanding the Phenotype.Genes · 2023Article
- Wnt inhibitors reduce the unfolded protein response and enhance bortezomib-induced cell death in multiple myeloma.Blood advances · 2023Article
- Gene expression networks and functionally enriched pathways involved in the response of domestic chicken to acute heat stress.Frontiers in genetics · 2023Article
- Collagen Synthesis as a Prominent Process During the Interval between Two Laser Sessions.Journal of lasers in medical sciences · 2023Article
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Authors and funding
28 authors at 10 institutions in 5 countries.
Funding
Abstract
backgroundPrimary antibody deficiencies (PADs) are the most frequent primary immunodeficiencies in human subjects. The genetic causes of PADs are largely unknown. Sec61 translocon alpha 1 subunit (SEC61A1) is the major subunit of the Sec61 complex, which is the main polypeptide-conducting channel in the endoplasmic reticulum membrane. SEC61A1 is a target gene of spliced X-box binding protein 1 and strongly induced during plasma cell (PC) differentiation.
objectiveWe identified a novel genetic defect and studied its pathologic mechanism in 11 patients from 2 unrelated families with PADs.
methodsWhole-exome and targeted sequencing were conducted to identify novel genetic mutations. Functional studies were carried out ex vivo in primary cells of patients and in vitro in different cell lines to assess the effect of SEC61A1 mutations on B-cell differentiation and survival.
resultsWe investigated 2 families with patients with hypogammaglobulinemia, severe recurrent respiratory tract infections, and normal peripheral B- and T-cell subpopulations. On in vitro stimulation, B cells showed an intrinsic deficiency to develop into PCs. Genetic analysis and targeted sequencing identified novel heterozygous missense (c.254T>A, p.V85D) and nonsense (c.1325G>T, p.E381*) mutations in SEC61A1, segregating with the disease phenotype. SEC61A1-V85D was deficient in cotranslational protein translocation, and it disturbed the cellular calcium homeostasis in HeLa cells. Moreover, SEC61A1-V85D triggered the terminal unfolded protein response in multiple myeloma cell lines.
conclusionWe describe a monogenic defect leading to a specific PC deficiency in human subjects, expanding our knowledge about the pathogenesis of antibody deficiencies.
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