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Whole genome sequencing combined with functional immunological analyses has greatly improved diagnostics and guided therapy, leading to significantly better prognoses.<\/jats:p>","DOI":"10.61409\/v10250786","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T10:20:46Z","timestamp":1774952446000},"page":"1-8","source":"Crossref","is-referenced-by-count":0,"title":["Diagnostics of immunodeficiencies"],"prefix":"10.61409","author":[{"given":"Hans Jakob","family":"Hartling","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanne Hjort","family":"Baatrup","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jakob Thaning","family":"Bay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens Magnus","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristian","family":"Assing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanne V.","family":"Marquart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"40208","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"ref0","doi-asserted-by":"publisher","unstructured":"Kim VHD, Upton JEM, Derfalvi B et al. 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Cytometry B Clin Cytom. 2008;74(5):261-71. https:\/\/doi.org\/10.1002\/cyto.b.20432","DOI":"10.1002\/cyto.b.20432"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"Baessler A, Vignali DAA. T cell exhaustion. Annu Rev Immunol. 2024;42(1):179-206. https:\/\/doi.org\/10.1146\/annurev-immunol-090222-110914","DOI":"10.1146\/annurev-immunol-090222-110914"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"Brodszki N, Frazer-Abel A, Grumach AS et al. European Society for Immunodeficiencies (ESID) and European Reference Network on Rare Primary Immunodeficiency, Autoinflammatory and Autoimmune Diseases (ERN RITA) complement guideline: deficiencies, diagnosis, and management. J Clin Immunol. 2020;40(4):576-591. https:\/\/doi.org\/10.1007\/s10875-020-00754-1","DOI":"10.1007\/s10875-020-00754-1"},{"key":"ref24","unstructured":"Dansk Selskab for Klinisk Immunologi. Immundefekt: DSKIs udvalg for Diagnostisk Immunologi har udarbejdet nedenst\u00e5ende retningslinjer og dokumenter til udredning af prim\u00e6r immundysfunktion: oversigt over tilg\u00e6ngelige analyser og genpaneler, 2025. https:\/\/dski.dk\/immundefekt\/ (17. nov 2025)"},{"key":"ref25","doi-asserted-by":"publisher","unstructured":"M\u00f8rup SB, Nazaryan-Petersen L, Gabrielaite M et al. Added value of reanalysis of whole-exome and whole-genome sequencing data from patients suspected of primary immune deficiency using an extended gene panel and structural variation calling. Front Immunol. 2022;13:906328. https:\/\/doi.org\/10.3389\/fimmu.2022.906328","DOI":"10.3389\/fimmu.2022.906328"},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"Drabe CH, Laustsen MM, Marquart HV et al. Genetics in a Danish common variable immunodeficiency cohort. J Clin Immunol. 2025;45(1):102. https:\/\/doi.org\/10.1007\/s10875-025-01896-w","DOI":"10.1007\/s10875-025-01896-w"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"Stewart O, Gruber C, Randolph HE et al. Monoallelic expression can govern penetrance of inborn errors of immunity. Nature. 2025;637(8048):1186-1197. https:\/\/doi.org\/10.1038\/s41586-024-08346-4","DOI":"10.1038\/s41586-024-08346-4"},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"Richardson AM, Moyer AM, Hasadsri L, Abraham RS. Diagnostic tools for inborn errors of human immunity (primary immunodeficiencies and immune dysregulatory diseases). Curr Allergy Asthma Rep. 2018;18(3):19. https:\/\/doi.org\/10.1007\/s11882-018-0770-1","DOI":"10.1007\/s11882-018-0770-1"},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"Bucciol G, Meyts I. Recent advances in primary immunodeficiency: from molecular diagnosis to treatment. 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