Revealing disease subtypes and heterogeneity in common variable immunodeficiency through transcriptomic analysis

Kienzler, A. K., Hargreaves, C. E. & Patel, S. Y. The role of genomics in common variable immunodeficiency disorders. Clin. Exp. Immunol. 188(3), 326–332 (2017).Article 
PubMed 

Google Scholar 
Ahn, S. & Cunningham-Rundles, C. Role of B cells in common variable immune deficiency. Expert Rev. Clin. Immunol. 5(5), 557–564 (2009).Article 
PubMed 
PubMed Central 

Google Scholar 
Chapel, H. et al. Common variable immunodeficiency disorders: Division into distinct clinical phenotypes. Blood 112(2), 277–286 (2008).Article 
PubMed 

Google Scholar 
Resnick, E. S. & Cunningham-Rundles, C. The many faces of the clinical picture of common variable immune deficiency. Curr. Opin. Allergy Clin. Immunol. 12(6), 595–601 (2012).Article 
PubMed 

Google Scholar 
Bonilla, F. A. et al. International consensus document (ICON): Common variable immunodeficiency disorders. J. Allergy Clin. Immunol. In Pract. 4(1), 38–59 (2016).Article 

Google Scholar 
Bogaert, D. J. et al. Genes associated with common variable immunodeficiency: One diagnosis to rule them all?. J. Med. Genet. 53(9), 575–590 (2016).Article 
PubMed 

Google Scholar 
Tseng, C.-W. et al. The incidence and prevalence of common variable immunodeficiency disease in Taiwan, a population-based study. PLoS One 10(10), e0140473 (2015).Article 
PubMed 
PubMed Central 

Google Scholar 
Lougaris, V. & Plebani, A. The genetic heterogeneity of common variable immunodeficiency (CVID). Immunol. Genet. J., 1–14 (2020).Liu, G. et al. Identification of candidate disease genes in patients with common variable immunodeficiency. Quant. Biol. 7(3), 190–201 (2019).Article 
ADS 

Google Scholar 
Warnatz, K. et al. Severe deficiency of switched memory B cells (CD27(+)IgM(-)IgD(-)) in subgroups of patients with common variable immunodeficiency: A new approach to classify a heterogeneous disease. Blood 99(5), 1544–1551 (2002).Article 
PubMed 

Google Scholar 
Warnatz, K. et al. Severe deficiency of switched memory B cells (CD27+ IgM− IgD−) in subgroups of patients with common variable immunodeficiency: A new approach to classify a heterogeneous disease. Blood J. Am. Soc. Hematol. 99(5), 1544–1551 (2002).
Google Scholar 
Piqueras, B. et al. Common variable immunodeficiency patient classification based on impaired B cell memory differentiation correlates with clinical aspects. J. Clin. Immunol. 23, 385–400 (2003).Article 
PubMed 

Google Scholar 
Wehr, C. et al. The EUROclass trial: Defining subgroups in common variable immunodeficiency. Blood J. Am. Soc. Hematol. 111(1), 77–85 (2008).MathSciNet 

Google Scholar 
Alharbi, F. & Vakanski, A. Machine learning methods for cancer classification using gene expression data: A review. Bioengineering 10(2), 173 (2023).Article 
PubMed 
PubMed Central 

Google Scholar 
Padroni, L. et al. Identifying MicroRNAs suitable for detection of breast cancer: A systematic review of discovery phases studies on MicroRNA expression profiles. Int. J. Mol. Sci. 24(20), 15114 (2023).Article 
PubMed 
PubMed Central 

Google Scholar 
Tulsyan, S. et al. A systematic review with in silico analysis on transcriptomic profile of gallbladder carcinoma. Semin. Oncol. 47(6), 398–408 (2020).Article 
PubMed 

Google Scholar 
Gutierrez-Camino, A. et al. miRNA deregulation in childhood acute lymphoblastic leukemia: A systematic review. Epigenomics 12(1), 69–80 (2020).Article 
PubMed 

Google Scholar 
De Felice, B. et al. Differently expressed microRNA in response to the first Ig replacement therapy in common variable immunodeficiency patients. Sci. Rep. 10(1), 21482 (2020).Article 
ADS 
PubMed 
PubMed Central 

Google Scholar 
Babaha, F. et al. Evaluation of miR-210 expression in common variable immunodeficiency: Patients with unsolved genetic defect. Allergol. Immunopathol. 49(2), 84–93 (2021).Article 

Google Scholar 
Park, J. et al. Interferon signature in the blood in inflammatory common variable immune deficiency. PloS One 8(9), e74893 (2013).Article 
ADS 
PubMed 
PubMed Central 

Google Scholar 
Rodríguez-Ubreva, J. et al. Single-cell atlas of common variable immunodeficiency shows germinal center-associated epigenetic dysregulation in B-cell responses. Nat. Commun. https://doi.org/10.1038/s41467-022-29450-x (2022).Article 
PubMed 
PubMed Central 

Google Scholar 
Lunshof, J. E. et al. Personal genomes in progress: From the human genome project to the personal genome project. Dialog. Clin. Neurosci. 12(1), 47–60 (2010).Article 

Google Scholar 
Khan, M.F., et al. An IoMT-enabled smart healthcare model to monitor elderly people using machine learning technique. Comput. Intell. Neurosci. 2021 (2021).Akshay, A. et al. Machine learning-based classification of transcriptome signatures of non-ulcerative bladder pain syndrome. Int. J. Mol. Sci. 25(3), 1568 (2024).Article 
PubMed 
PubMed Central 

Google Scholar 
Zarei Ghobadi, M. et al. Exploration of blood− derived coding and non-coding RNA diagnostic immunological panels for COVID-19 through a co-expressed-based machine learning procedure. Front. Immunol. 13, 1001070 (2022).Article 
PubMed 
PubMed Central 

Google Scholar 
Swanson, K. et al., From patterns to patients: Advances in clinical machine learning for cancer diagnosis, prognosis, and treatment. Cell (2023).Daamen, A. R. et al., Classification of COVID-19 patients into clinically relevant subsets by a novel machine learning pipeline using transcriptomic features. Int. J. Mol. Sci. 24(5), 2023.Peng, X. P., Caballero-Oteyza, A. & Grimbacher, B. Common variable immunodeficiency: More pathways than roads to Rome. Annu. Rev. Pathol. 18, 283–310 (2023).Article 
PubMed 

Google Scholar 
Yazdani, R. et al. Comparison of various classifications for patients with common variable immunodeficiency (CVID) using measurement of B-cell subsets. Allergol. Immunopathol. (Madr) 45(2), 183–192 (2017).Article 
PubMed 

Google Scholar 
Aggarwal, V. et al. Recent advances in elucidating the genetics of common variable immunodeficiency. Genes. Dis. 7(1), 26–37 (2020).Article 
PubMed 

Google Scholar 
Akshay, A. et al., Machine learning-based classification of transcriptome signatures of non-ulcerative bladder pain syndrome. Int. J. Mol. Sci. 25(3), 2024.Grimbacher, B. et al. Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency. Nat. Immunol. 4(3), 261–268 (2003).Article 
PubMed 

Google Scholar 
Castigli, E. et al. TACI is mutant in common variable immunodeficiency and IgA deficiency. Nat. Genet. 37(8), 829–834 (2005).Article 
PubMed 

Google Scholar 
van Zelm, M. C. et al. Human CD19 and CD40L deficiencies impair antibody selection and differentially affect somatic hypermutation. J. Allergy Clin. Immunol. 134(1), 135–144 (2014).Article 
PubMed 

Google Scholar 
Warnatz, K. et al. B-cell activating factor receptor deficiency is associated with an adult-onset antibody deficiency syndrome in humans. Proc. Natl. Acad. Sci. U. S. A. 106(33), 13945–13950 (2009).Article 
ADS 
PubMed 
PubMed Central 

Google Scholar 
Kuijpers, T. W. et al. CD20 deficiency in humans results in impaired T cell-independent antibody responses. J. Clin. Invest. 120(1), 214–222 (2010).Article 
PubMed 

Google Scholar 
van Zelm, M. C. et al. CD81 gene defect in humans disrupts CD19 complex formation and leads to antibody deficiency. J. Clin. Invest. 120(4), 1265–1274 (2010).Article 
PubMed 
PubMed Central 

Google Scholar 
Thiel, J. et al. Genetic CD21 deficiency is associated with hypogammaglobulinemia. J. Allergy Clin. Immunol. 129(3), 801-810.e6 (2012).Article 
PubMed 

Google Scholar 
Lopez-Herrera, G. et al. Deleterious mutations in LRBA are associated with a syndrome of immune deficiency and autoimmunity. Am. J. Hum. Genet. 90(6), 986–1001 (2012).Article 
PubMed 
PubMed Central 

Google Scholar 
Chen, K. et al. Germline mutations in NFKB2 implicate the noncanonical NF-κB pathway in the pathogenesis of common variable immunodeficiency. Am. J. Hum. Genet. 93(5), 812–824 (2013).Article 
PubMed 
PubMed Central 

Google Scholar 
Salzer, E. et al. Early-onset inflammatory bowel disease and common variable immunodeficiency-like disease caused by IL-21 deficiency. J. Allergy Clin. Immunol. 133(6), 1651–9.e12 (2014).Article 
PubMed 

Google Scholar 
Tuijnenburg, P. et al. Loss-of-function nuclear factor κB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency in Europeans. J. Allergy Clin. Immunol. 142(4), 1285–1296 (2018).Article 
PubMed 
PubMed Central 

Google Scholar 
Kuehn, H. S. et al. Loss of B cells in patients with heterozygous mutations in IKAROS. N. Engl. J. Med. 374(11), 1032–1043 (2016).Article 
PubMed 
PubMed Central 

Google Scholar 
Keller, M. D. et al. Mutation in IRF2BP2 is responsible for a familial form of common variable immunodeficiency disorder. J. Allergy Clin. Immunol. 138(2), 544-550.e4 (2016).Article 
PubMed 
PubMed Central 

Google Scholar 
Schubert, D. et al. Plasma cell deficiency in human subjects with heterozygous mutations in Sec61 translocon alpha 1 subunit (SEC61A1). J Allergy Clin Immunol 141(4), 1427–1438 (2018).Article 
PubMed 

Google Scholar 
Wang, L. et al. Functions and molecular mechanisms of Deltex family ubiquitin E3 ligases in development and disease. Front. Cell. Dev. Biol. 9, 706997 (2021).Article 
PubMed 
PubMed Central 

Google Scholar 
Camacho-Ordonez, N. et al., Integrated multi-omics analyses of NFKB1 patients B cells points towards an up regulation of NF-κB network inhibitors (2022).Stuchlý, J. et al. Common variable immunodeficiency patients with a phenotypic profile of immunosenescence present with thrombocytopenia. Sci. Rep. 7, 39710 (2017).Article 
ADS 
PubMed 
PubMed Central 

Google Scholar 
Feng, Q. et al. CDC42EP3 promotes colorectal cancer through regulating cell proliferation, cell apoptosis and cell migration. Cancer Cell. Int. 21(1), 169 (2021).Article 
PubMed 
PubMed Central 

Google Scholar 
Chemnitz, J. et al. The acidic protein rich in leucines Anp32b is an immunomodulator of inflammation in mice. Sci. Rep. 9(1), 4853 (2019).Article 
ADS 
PubMed 
PubMed Central 

Google Scholar 
Kim, S. et al. PubChem 2023 update. Nucleic Acids Res. 51(D1), D1373–D1380 (2023).Article 
PubMed 

Google Scholar 
Tomar, N. & De, R. K. A model of an integrated immune system pathway in Homo sapiens and its interaction with superantigen producing expression regulatory pathway in Staphylococcus aureus: Comparing behavior of pathogen perturbed and unperturbed pathway. PLoS One 8(12), e80918 (2013).Article 
ADS 
PubMed 
PubMed Central 

Google Scholar 
Zhu, J. et al. RPL21 interacts with LAMP3 to promote colorectal cancer invasion and metastasis by regulating focal adhesion formation. Cell. Mol. Biol. Lett. 28(1), 31 (2023).Article 
PubMed 
PubMed Central 

Google Scholar 
Zhuang, X. et al. Development of a novel immune infiltration-related diagnostic model for Alzheimer’s disease using bioinformatic strategies. Front. Immunol. 14, 1147501 (2023).Article 
PubMed 
PubMed Central 

Google Scholar 
Squires, R., et al., Influenza life cycle. Reactome Curated Knowl. Biol. Pathw. 21 (2007).Paquin-Proulx, D. et al. Inversion of the Vδ1 to Vδ2 γδ T cell ratio in CVID is not restored by IVIg and is associated with immune activation and exhaustion. Medicine (Baltimore) 95(30), e4304 (2016).Article 
PubMed 

Google Scholar 
Viallard, J. F. et al. Gammadelta T lymphocytosis associated with granulomatous disease in a patient with common variable immunodeficiency. Clin. Infect. Dis. 35(12), e134–e137 (2002).Article 
PubMed 

Google Scholar 
Barba-Aliaga, M. & Alepuz, P. Role of eIF5A in mitochondrial function.Int. J. Mol. Sci. 23(3), (2022).Schäfer, B. et al. Inhibition of multidrug-resistant HIV-1 by interference with cellular S-adenosylmethionine decarboxylase activity. J. Infect. Dis. 194(6), 740–750 (2006).Article 
PubMed 

Google Scholar 
de Almeida, O. P. Jr. et al. Hypusine modification of the ribosome-binding protein eIF5A, a target for new anti-inflammatory drugs: Understanding the action of the inhibitor GC7 on a murine macrophage cell line. Curr. Pharm. Des. 20(2), 284–292 (2014).Article 
PubMed 

Google Scholar 
Puleston, D. J. et al. Polyamines and eIF5A hypusination modulate mitochondrial respiration and macrophage activation. Cell. Metab. 30(2), 352-363.e8 (2019).Article 
PubMed 
PubMed Central 

Google Scholar 
Tan, T. C. J. et al. Translation factor eIF5a is essential for IFNγ production and cell cycle regulation in primary CD8(+) T lymphocytes. Nat. Commun. 13(1), 7796 (2022).Article 
ADS 
PubMed 
PubMed Central 

Google Scholar 
Hu, H. et al. Systematic mutational analysis of human neutrophil α-defensin HNP4. Biochimica et Biophysica Acta (BBA) Biomembranes 1861(4), 835–844 (2019).Article 
PubMed 

Google Scholar 
Wu, Z. et al. Human neutrophil α-defensin 4 inhibits HIV-1 infection in vitro. FEBS Lett. 579(1), 162–166 (2005).Article 
PubMed 

Google Scholar 
Zhou, Q. et al. Comparative transcriptome analysis of peripheral blood mononuclear cells in hepatitis B-related acute-on-chronic liver failure. Sci. Rep. 6, 20759 (2016).Article 
ADS 
PubMed 
PubMed Central 

Google Scholar 
Villanueva, E. et al. Netting neutrophils induce endothelial damage, infiltrate tissues, and expose immunostimulatory molecules in systemic lupus erythematosus. J. Immunol. 187(1), 538–552 (2011).Article 
MathSciNet 
PubMed 

Google Scholar 
Tseng, C. C. et al., Next-generation sequencing profiles of the methylome and transcriptome in peripheral blood mononuclear cells of rheumatoid arthritis. J. Clin. Med. 8(9) (2019).Rohde, G. et al. CXC chemokines and antimicrobial peptides in rhinovirus-induced experimental asthma exacerbations. Clin. Exp. Allergy 44(7), 930–939 (2014).Article 
PubMed 
PubMed Central 

Google Scholar 
He, T., Xia, Y. & Yang, J. Systemic inflammation and chronic kidney disease in a patient due to the RNASEH2B defect. Pediatr. Rheumatol. 19(1), 9 (2021).Article 

Google Scholar 
Branco, A. C. C. C., Rogers, L. M. & Aronoff, D. M. Folate receptor beta signaling in the regulation of macrophage antimicrobial immune response: A scoping review. Biomed. Hub 9(1), 31–37 (2024).Article 
PubMed 
PubMed Central 

Google Scholar 
Fabregat, A. et al. Reactome diagram viewer: Data structures and strategies to boost performance. Bioinformatics (Oxford, England) 34(7), 1208–1214 (2018).PubMed 

Google Scholar 
Williams, C. G. et al. An introduction to spatial transcriptomics for biomedical research. Genome Med. 14(1), 68 (2022).Article 
PubMed 
PubMed Central 

Google Scholar 
Ahmed, Z. et al. Human gene and disease associations for clinical-genomics and precision medicine research. Clin. Transl. Med. 10(1), 297–318 (2020).Article 
PubMed 
PubMed Central 

Google Scholar 
Mathur, S. & Sutton, J. Personalized medicine could transform healthcare. Biomed. Rep. 7(1), 3–5 (2017).Article 
PubMed 
PubMed Central 

Google Scholar 

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