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Annual Review of Pathology: Mechanisms of Disease

Volume 18, 2023

Common Variable Immunodeficiency: More Pathways than Roads to Rome

Abstract

Fifty years have elapsed since the term common variable immunodeficiency (CVID) was introduced to accommodate the many and varied antibody deficiencies being identified in patients with suspected inborn errors of immunity (IEIs). Since then, how the term is understood and applied for diagnosis and management has undergone many revisions, though controversy persists on how exactly to define and classify CVID. Many monogenic disorders have been added under its aegis, while investigations into polygenic, epigenetic, and somatic contributions to CVID susceptibility have gained momentum. Expansion of the overall IEI landscape has increasingly revealed genotypic and phenotypic overlap between CVID and various other immunological conditions, while increasingly routine genotyping of CVID patients continues to identify an incredible diversity of pathophysiological mechanisms affecting even single genes. Though many questions remain to be answered, the lessons we have already learned from CVID biology have greatly informed our understanding of adaptive, but also innate, immunity.

Keyword(s): B cell development, genetics, immunodeficiency, inborn errors of immunity, mutation, pathophysiology, primary antibody deficiency, variant
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/content/journals/10.1146/annurev-pathmechdis-031521-024229
2023-01-24
2024-04-23
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Literature Cited

  1. 1.
    Fudenberg H, Good RA, Goodman HC, Hitzig W, Kunkel HG et al. 1971. Primary immunodeficiencies. Report of a World Health Organization Committee. Pediatrics 47:5927–46
     [Google Scholar]
  2. 2.
    Janssen LMA, van der Flier M, de Vries E. 2021. Lessons learned from the clinical presentation of common variable immunodeficiency disorders: a systematic review and meta-analysis. Front. Immunol. 12:620709
     [Google Scholar]
  3. 3.
    Kienzler A-K, Hargreaves CE, Patel SY. 2017. The role of genomics in common variable immunodeficiency disorders. Clin. Exp. Immunol. 188:3326–32
     [Google Scholar]
  4. 4.
    Ho H-E, Cunningham-Rundles C. 2022. Seeking relevant biomarkers in common variable immunodeficiency. Front. Immunol. 13:857050
     [Google Scholar]
  5. 5.
    Farmer JR, Ong M-S, Barmettler S, Yonker LM, Fuleihan R et al. 2018. Common variable immunodeficiency non-infectious disease endotypes redefined using unbiased network clustering in large electronic datasets. Front. Immunol. 8:1740
     [Google Scholar]
  6. 6.
    Ameratunga R, Allan C, Lehnert K, Woon S-T. 2021. Perspective: application of the American College of Medical Genetics variant interpretation criteria to common variable immunodeficiency disorders. Clin. Rev. Allergy Immunol. 61:2226–35
     [Google Scholar]
  7. 7.
    Edwards ESJ, Bosco JJ, Ojaimi S, O'Hehir RE, van Zelm MC 2021. Beyond monogenetic rare variants: tackling the low rate of genetic diagnoses in predominantly antibody deficiency. Cell. Mol. Immunol. 18:3588–603
     [Google Scholar]
  8. 8.
    Ameratunga R, Lehnert K, Woon S-T, Gillis D, Bryant VL et al. 2018. Review: diagnosing common variable immunodeficiency disorder in the era of genome sequencing. Clin. Rev. Allergy Immunol. 54:2261–68
     [Google Scholar]
  9. 9.
    Bossen C, Schneider P. 2006. BAFF, APRIL and their receptors: structure, function and signaling. Semin. Immunol. 18:5263–75
     [Google Scholar]
  10. 10.
    Cascalho M, Platt JL. 2021. Diversification fueled by B cell responses to environmental challenges—a hypothesis. Front. Immunol. 12:634544
     [Google Scholar]
  11. 11.
    Salzer U, Grimbacher B. 2021. TACI deficiency—a complex system out of balance. Curr. Opin. Immunol. 71:81–88
     [Google Scholar]
  12. 12.
    Romberg N, Chamberlain N, Saadoun D, Gentile M, Kinnunen T et al. 2013. CVID-associated TACI mutations affect autoreactive B cell selection and activation. J. Clin. Investig. 123:104283–93
     [Google Scholar]
  13. 13.
    Garcia-Carmona Y, Ting AT, Radigan L, Athuluri Divakar SK, Chavez J et al. 2018. TACI isoforms regulate ligand binding and receptor function. Front. Immunol. 9:2125
     [Google Scholar]
  14. 14.
    Warnatz K, Salzer U, Rizzi M, Fischer B, Gutenberger S et al. 2009. B-cell activating factor receptor deficiency is associated with an adult-onset antibody deficiency syndrome in humans. PNAS 106:3313945–50
     [Google Scholar]
  15. 15.
    Yeh T-W, Okano T, Naruto T, Yamashita M, Okamura M et al. 2020. APRIL-dependent lifelong plasmacyte maintenance and immunoglobulin production in humans. J. Allergy Clin. Immunol. 146:51109–20.e4
     [Google Scholar]
  16. 16.
    Wang H-Y, Ma CA, Zhao Y, Fan X, Zhou Q et al. 2013. Antibody deficiency associated with an inherited autosomal dominant mutation in TWEAK. PNAS 110:135127–32
     [Google Scholar]
  17. 17.
    Lucas CL, Chandra A, Nejentsev S, Condliffe AM, Okkenhaug K. 2016. PI3Kδ and primary immunodeficiencies. Nat. Rev. Immunol. 16:11702–14
     [Google Scholar]
  18. 18.
    Patton DT, Garden OA, Pearce WP, Clough LE, Monk CR et al. 2006. Cutting edge: The phosphoinositide 3-kinase p110δ is critical for the function of CD4+CD25+Foxp3+ regulatory T cells. J. Immunol. 177:106598–602
     [Google Scholar]
  19. 19.
    Nademi Z, Slatter MA, Dvorak CC, Neven B, Fischer A et al. 2017. Hematopoietic stem cell transplant in patients with activated PI3K delta syndrome. J. Allergy Clin. Immunol. 139:31046–49
     [Google Scholar]
  20. 20.
    Elkaim E, Neven B, Bruneau J, Mitsui-Sekinaka K, Stanislas A et al. 2016. Clinical and immunologic phenotype associated with activated phosphoinositide 3-kinase δ syndrome 2: a cohort study. J. Allergy Clin. Immunol. 138:1210–18.e9
     [Google Scholar]
  21. 21.
    Coulter TI, Chandra A, Bacon CM, Babar J, Curtis J et al. 2017. Clinical spectrum and features of activated phosphoinositide 3-kinase δ syndrome: a large patient cohort study. J. Allergy Clin. Immunol. 139:2597–606.e4
     [Google Scholar]
  22. 22.
    Mandola AB, Dadi H, Reid B, Roifman CM 2020. Novel heterozygous PIK3CD mutation presenting with only laboratory markers of combined immunodeficiency. LymphoSign J 7:249–55
     [Google Scholar]
  23. 23.
    Conley ME, Dobbs AK, Quintana AM, Bosompem A, Wang Y-D et al. 2012. Agammaglobulinemia and absent B lineage cells in a patient lacking the p85α subunit of PI3K. J. Exp. Med. 209:3463–70
     [Google Scholar]
  24. 24.
    Crank MC, Grossman JK, Moir S, Pittaluga S, Buckner CM et al. 2014. Mutations in PIK3CD can cause hyper IgM syndrome (HIGM) associated with increased cancer susceptibility. J. Clin. Immunol. 34:3272–76
     [Google Scholar]
  25. 25.
    Lougaris V, Faletra F, Lanzi G, Vozzi D, Marcuzzi A et al. 2015. Altered germinal center reaction and abnormal B cell peripheral maturation in PI3KR1-mutated patients presenting with HIGM-like phenotype. Clin. Immunol. 159:133–36
     [Google Scholar]
  26. 26.
    Thaventhiran JED, Lango Allen H, Burren OS, Rae W, Greene D et al. 2020. Whole-genome sequencing of a sporadic primary immunodeficiency cohort. Nature 583:781490–95
     [Google Scholar]
  27. 27.
    Alkhairy OK, Rezaei N, Graham RR, Abolhassani H, Borte S et al. 2015. RAC2 loss-of-function mutation in 2 siblings with characteristics of common variable immunodeficiency. J. Allergy Clin. Immunol. 135:51380–84.e
     [Google Scholar]
  28. 28.
    Lougaris V, Chou J, Beano A, Wallace JG, Baronio M et al. 2019. A monoallelic activating mutation in RAC2 resulting in a combined immunodeficiency. J. Allergy Clin. Immunol. 143:41649–53.e3
     [Google Scholar]
  29. 29.
    Hsu AP, Donkó A, Arrington ME, Swamydas M, Fink D et al. 2019. Dominant activating RAC2 mutation with lymphopenia, immunodeficiency, and cytoskeletal defects. Blood 133:181977–88
     [Google Scholar]
  30. 30.
    Ambruso DR, Knall C, Abell AN, Panepinto J, Kurkchubasche A et al. 2000. Human neutrophil immunodeficiency syndrome is associated with an inhibitory Rac2 mutation. PNAS 97:94654–59
     [Google Scholar]
  31. 31.
    Williams DA, Tao W, Yang F, Kim C, Gu Y et al. 2000. Dominant negative mutation of the hematopoietic-specific Rho GTPase, Rac2, is associated with a human phagocyte immunodeficiency. Blood 96:51646–54
     [Google Scholar]
  32. 32.
    Kuehn HS, Nunes-Santos CJ, Rosenzweig SD. 2021. Germline mutations and their impact on immunity: IKAROS-associated diseases and pathophysiology. Expert Rev. Clin. Immunol. 17:4407–16
     [Google Scholar]
  33. 33.
    Kuehn HS, Gloude NJ, Dimmock D, Tokita M, Wright M et al. 2021. Abnormal SCID newborn screening and spontaneous recovery associated with a novel haploinsufficiency IKZF1 mutation. J. Clin. Immunol. 41:61241–49
     [Google Scholar]
  34. 34.
    Brodie SA, Khincha PP, Giri N, Bouk AJ, Steinberg M et al. 2021. Pathogenic germline variant alters hematopoietic gene expression profiles. Cold Spring Harb. Mol. Case Stud. 7:4a006015
     [Google Scholar]
  35. 35.
    Eskandarian Z, Fliegauf M, Bulashevska A, Proietti M, Hague R et al. 2019. Assessing the functional relevance of variants in the IKAROS Family Zinc Finger Protein 1 (IKZF1) in a cohort of patients with primary immunodeficiency. Front. Immunol. 10:568
     [Google Scholar]
  36. 36.
    Yilmaz E, Kuehn HS, Odakir E, Niemela JE, Ozcan A et al. 2021. Common variable immunodeficiency, autoimmune hemolytic anemia, and pancytopenia associated with a defect in IKAROS. J. Pediatr. Hematol. Oncol. 43:3e351–57
     [Google Scholar]
  37. 37.
    Liou HC, Nolan GP, Ghosh S, Fujita T, Baltimore D. 1992. The NF-κB p50 precursor, p105, contains an internal IκB-like inhibitor that preferentially inhibits p50. EMBO J 11:83003–9
     [Google Scholar]
  38. 38.
    Fliegauf M, Bryant VL, Frede N, Slade C, Woon S-T et al. 2015. Haploinsufficiency of the NF-κB1 subunit p50 in common variable immunodeficiency. Am. J. Hum. Genet. 97:3389–403
     [Google Scholar]
  39. 39.
    Kaustio M, Haapaniemi E, Göös H, Hautala T, Park G et al. 2017. Damaging heterozygous mutations in NFKB1 lead to diverse immunologic phenotypes. J. Allergy Clin. Immunol. 140:3782–96
     [Google Scholar]
  40. 40.
    Tuijnenburg P, Lango Allen H, Burns SO, Greene D, Jansen MH et al. 2018. 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. 142:41285–96
     [Google Scholar]
  41. 41.
    Lorenzini T, Fliegauf M, Klammer N, Frede N, Proietti M et al. 2020. Characterization of the clinical and immunologic phenotype and management of 157 individuals with 56 distinct heterozygous NFKB1 mutations. J. Allergy Clin. Immunol. 146:4901–11
     [Google Scholar]
  42. 42.
    Lin L, DeMartino GN, Greene WC. 2000. Cotranslational dimerization of the Rel homology domain of NF-κB1 generates p50–p105 heterodimers and is required for effective p50 production. EMBO J 19:174712–22
     [Google Scholar]
  43. 43.
    Fliegauf M, Krüger R, Steiner S, Hanitsch LG, Büchel S et al. 2021. A pathogenic missense variant in NFKB1 causes common variable immunodeficiency due to detrimental protein damage. Front. Immunol. 12:621503
     [Google Scholar]
  44. 44.
    Grundström S, Anderson P, Scheipers P, Sundstedt A. 2004. Bcl-3 and NFκB p50-p50 homodimers act as transcriptional repressors in tolerant CD4+ T cells. J. Biol. Chem. 279:98460–68
     [Google Scholar]
  45. 45.
    Cao S, Zhang X, Edwards JP, Mosser DM. 2006. NF-κB1 (p50) homodimers differentially regulate pro- and anti-inflammatory cytokines in macrophages. J. Biol. Chem. 281:3626041–50
     [Google Scholar]
  46. 46.
    Li J, Lei W-T, Zhang P, Rapaport F, Seeleuthner Y et al. 2021. Biochemically deleterious human NFKB1 variants underlie an autosomal dominant form of common variable immunodeficiency. J. Exp. Med. 218:11e20210566
     [Google Scholar]
  47. 47.
    Brue T, Quentien M-H, Khetchoumian K, Bensa M, Capo-Chichi J-M et al. 2014. Mutations in NFKB2 and potential genetic heterogeneity in patients with DAVID syndrome, having variable endocrine and immune deficiencies. BMC Med. Genet. 15:139
     [Google Scholar]
  48. 48.
    Aird A, Lagos M, Vargas-Hernández A, Posey JE, Coban-Akdemir Z et al. 2019. Novel heterozygous mutation in NFKB2 is associated with early onset CVID and a functional defect in NK cells complicated by disseminated CMV infection and severe nephrotic syndrome. Front. Pediatr. 7:303
     [Google Scholar]
  49. 49.
    Lindsley AW, Qian Y, Valencia CA, Shah K, Zhang K, Assa'ad A 2014. Combined immune deficiency in a patient with a novel NFKB2 mutation. J. Clin. Immunol. 34:8910–15
     [Google Scholar]
  50. 50.
    Lougaris V, Tabellini G, Vitali M, Baronio M, Patrizi O et al. 2015. Defective natural killer-cell cytotoxic activity in NFKB2-mutated CVID-like disease. J. Allergy Clin. Immunol. 135:61641–43
     [Google Scholar]
  51. 51.
    Blommaert E, Péanne R, Cherepanova NA, Rymen D, Staels F et al. 2019. Mutations in MAGT1 lead to a glycosylation disorder with a variable phenotype. PNAS 116:209865–70
     [Google Scholar]
  52. 52.
    Li F-Y, Chaigne-Delalande B, Kanellopoulou C, Davis JC, Matthews HF et al. 2011. Second messenger role for Mg2+ revealed by human T-cell immunodeficiency. Nature 475:7357471–76
     [Google Scholar]
  53. 53.
    Sassi A, Lazaroski S, Wu G, Haslam SM, Fliegauf M et al. 2014. Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) impair immunity and increase serum IgE levels. J. Allergy Clin. Immunol. 133:51410–19.e13
     [Google Scholar]
  54. 54.
    Zhang Y, Yu X, Ichikawa M, Lyons JJ, Datta S et al. 2014. Autosomal recessive phosphoglucomutase 3 (PGM3) mutations link glycosylation defects to atopy, immune deficiency, autoimmunity, and neurocognitive impairment. J. Allergy Clin. Immunol. 133:51400–9.e5
     [Google Scholar]
  55. 55.
    De Praeter CM, Gerwig GJ, Bause E, Nuytinck LK, Vliegenthart JF et al. 2000. A novel disorder caused by defective biosynthesis of N-linked oligosaccharides due to glucosidase I deficiency. Am. J. Hum. Genet. 66:61744–56
     [Google Scholar]
  56. 56.
    Aghamohammadi A, Mohammadi J, Parvaneh N, Rezaei N, Moin M et al. 2008. Progression of selective IgA deficiency to common variable immunodeficiency. Int. Arch. Allergy Immunol. 147:287–92
     [Google Scholar]
  57. 57.
    Lougaris V, Chou J, Baronio M, Gazzurelli L, Lorenzini T et al. 2018. Novel biallelic TRNT1 mutations resulting in sideroblastic anemia, combined B and T cell defects, hypogammaglobulinemia, recurrent infections, hypertrophic cardiomyopathy and developmental delay. Clin. Immunol. 188:20–22
     [Google Scholar]
  58. 58.
    Yang L, Xue X, Zeng T, Chen X, Zhao Q et al. 2020. Novel biallelic mutations lead to atypical SIFD and multiple immune defects. Genes Dis 7:1128–37
     [Google Scholar]
  59. 59.
    Frans G, Moens L, Schaballie H, Wuyts G, Liston A et al. 2017. Homozygous N-terminal missense mutation in TRNT1 leads to progressive B-cell immunodeficiency in adulthood. J. Allergy Clin. Immunol. 139:1360–63.e6
     [Google Scholar]
  60. 60.
    Wiseman DH, May A, Jolles S, Connor P, Powell C et al. 2013. A novel syndrome of congenital sideroblastic anemia, B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD). Blood 122:1112–23
     [Google Scholar]
  61. 61.
    Kumaki E, Tanaka K, Imai K, Aoki-Nogami Y, Ishiguro A et al. 2019. Atypical SIFD with novel TRNT1 mutations: a case study on the pathogenesis of B-cell deficiency. Int. J. Hematol. 109:4382–89
     [Google Scholar]
  62. 62.
    Khan S, Hinks J, Shorto J, Schwarz MJ, Sewell WAC. 2008. Some cases of common variable immunodeficiency may be due to a mutation in the SBDS gene of Shwachman-Diamond syndrome. Clin. Exp. Immunol. 151:3448–54
     [Google Scholar]
  63. 63.
    Hou J-W. 2021. Shwachman–Diamond syndrome with initial features mimicking common variable immunodeficiency. Pediatr. Neonatol. 62:6668–69
     [Google Scholar]
  64. 64.
    Kudlaty E, Agnihotri N, Khojah A. 2022. Hypogammaglobulinaemia and B cell lymphopaenia in Barth syndrome. BMJ Case Rep 15:6e249254
     [Google Scholar]
  65. 65.
    Yong PFK, Thaventhiran JED, Grimbacher B. 2011.. “ A rose is a rose is a rose,” but CVID is not CVID: common variable immune deficiency (CVID), what do we know in 2011?. Adv. Immunol. 111:47–107
     [Google Scholar]
  66. 66.
    Warnatz K, Bossaller L, Salzer U, Skrabl-Baumgartner A, Schwinger W et al. 2006. Human ICOS deficiency abrogates the germinal center reaction and provides a monogenic model for common variable immunodeficiency. Blood 107:83045–52
     [Google Scholar]
  67. 67.
    Kuhny M, Forbes LR, Çakan E, Vega-Loza A, Kostiuk V et al. 2020. Disease-associated CTNNBL1 mutation impairs somatic hypermutation by decreasing nuclear AID. J. Clin. Investig. 130:84411–22
     [Google Scholar]
  68. 68.
    Thurlapati A, Boudreaux K, Guntupalli S, Mansour RP, Bhayani S. 2022. A case of aplastic anemia and colon cancer with underlying spliceosome mutation: Is it an incidental finding or a novel association?. Cureus 14:2e22632
     [Google Scholar]
  69. 69.
    Dieli-Crimi R, Martínez-Gallo M, Franco-Jarava C, Antolin M, Blasco L et al. 2018. Th1-skewed profile and excessive production of proinflammatory cytokines in a NFKB1-deficient patient with CVID and severe gastrointestinal manifestations. Clin. Immunol. 195:49–58
     [Google Scholar]
  70. 70.
    Preite S, Gomez-Rodriguez J, Cannons JL, Schwartzberg PL. 2019. T and B-cell signaling in activated PI3K delta syndrome: from immunodeficiency to autoimmunity. Immunol. Rev. 291:1154–73
     [Google Scholar]
  71. 71.
    Hao H, Nakayamada S, Tanaka Y. 2021. Differentiation, functions, and roles of T follicular regulatory cells in autoimmune diseases. Inflamm. Regen. 41:114
     [Google Scholar]
  72. 72.
    Fabre A, Marchal S, Barlogis V, Mari B, Barbry P et al. 2019. Clinical aspects of STAT3 gain-of-function germline mutations: a systematic review. J. Allergy Clin. Immunol. Pract. 7:61958–69.e9
     [Google Scholar]
  73. 73.
    Russell MA, Pigors M, Houssen ME, Manson A, Kelsell D et al. 2018. A novel de novo activating mutation in STAT3 identified in a patient with common variable immunodeficiency (CVID). Clin. Immunol. 187:132–36
     [Google Scholar]
  74. 74.
    Saarimäki-Vire J, Balboa D, Russell MA, Saarikettu J, Kinnunen M et al. 2017. An activating STAT3 mutation causes neonatal diabetes through premature induction of pancreatic differentiation. Cell Rep 19:2281–94
     [Google Scholar]
  75. 75.
    Yoshimura A, Suzuki M, Sakaguchi R, Hanada T, Yasukawa H. 2012. SOCS, inflammation, and autoimmunity. Front. Immunol. 3:20
     [Google Scholar]
  76. 76.
    Körholz J, Gabrielyan A, Sowerby JM, Boschann F, Chen L-S et al. 2021. One gene, many facets: multiple immune pathway dysregulation in SOCS1 haploinsufficiency. Front. Immunol. 12:680334
     [Google Scholar]
  77. 77.
    Afzali B, Grönholm J, Vandrovcova J, O'Brien C, Sun H-W et al. 2017. BACH2 immunodeficiency illustrates an association between super-enhancers and haploinsufficiency. Nat. Immunol. 18:7813–23
     [Google Scholar]
  78. 78.
    Richer MJ, Lang ML, Butler NS. 2016. T cell fates zipped up: how the Bach2 basic leucine zipper transcriptional repressor directs T cell differentiation and function. J. Immunol. 197:41009–15
     [Google Scholar]
  79. 79.
    Ochiai K, Katoh Y, Ikura T, Hoshikawa Y, Noda T et al. 2006. Plasmacytic transcription factor Blimp-1 is repressed by Bach2 in B cells. J. Biol. Chem. 281:5038226–34
     [Google Scholar]
  80. 80.
    Walker LSK, Sansom DM. 2011. The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses. Nat. Rev. Immunol. 11:12852–63
     [Google Scholar]
  81. 81.
    Qureshi OS, Zheng Y, Nakamura K, Attridge K, Manzotti C et al. 2011. Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science 332:6029600–3
     [Google Scholar]
  82. 82.
    Jamee M, Hosseinzadeh S, Sharifinejad N, Zaki-Dizaji M, Matloubi M et al. 2021. Comprehensive comparison between 222 CTLA-4 haploinsufficiency and 212 LRBA deficiency patients: a systematic review. Clin. Exp. Immunol. 205:128–43
     [Google Scholar]
  83. 83.
    Ren Y, Xiao F, Cheng F, Huang X, Li J et al. 2021. Whole exome sequencing reveals a novel LRBA mutation and clonal hematopoiesis in a common variable immunodeficiency patient presented with hemophagocytic lymphohistiocytosis. Exp. Hematol. Oncol. 10:138
     [Google Scholar]
  84. 84.
    Lopez-Herrera G, Tampella G, Pan-Hammarström Q, Herholz P, Trujillo-Vargas CM et al. 2012. Deleterious mutations in LRBA are associated with a syndrome of immune deficiency and autoimmunity. Am. J. Hum. Genet. 90:6986–1001
     [Google Scholar]
  85. 85.
    Alangari A, Alsultan A, Adly N, Massaad MJ, Kiani IS et al. 2012. LPS-responsive beige-like anchor (LRBA) gene mutation in a family with inflammatory bowel disease and combined immunodeficiency. J. Allergy Clin. Immunol. 130:2481–88.e2
     [Google Scholar]
  86. 86.
    Wang JW, Howson J, Haller E, Kerr WG. 2001. Identification of a novel lipopolysaccharide-inducible gene with key features of both A kinase anchor proteins and chs1/beige proteins. J. Immunol. 166:74586–95
     [Google Scholar]
  87. 87.
    Lo B, Zhang K, Lu W, Zheng L, Zhang Q et al. 2015. Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy. Science 349:6246436–40
     [Google Scholar]
  88. 88.
    Hou TZ, Verma N, Wanders J, Kennedy A, Soskic B et al. 2017. Identifying functional defects in patients with immune dysregulation due to LRBA and CTLA-4 mutations. Blood 129:111458–68
     [Google Scholar]
  89. 89.
    Rensing-Ehl A, Warnatz K, Fuchs S, Schlesier M, Salzer U et al. 2010. Clinical and immunological overlap between autoimmune lymphoproliferative syndrome and common variable immunodeficiency. Clin. Immunol. 137:3357–65
     [Google Scholar]
  90. 90.
    Meeths M, Entesarian M, Al-Herz W, Chiang SCC, Wood SM et al. 2010. Spectrum of clinical presentations in familial hemophagocytic lymphohistiocytosis type 5 patients with mutations in STXBP2. Blood 116:152635–43
     [Google Scholar]
  91. 91.
    Rohr J, Beutel K, Maul-Pavicic A, Vraetz T, Thiel J et al. 2010. Atypical familial hemophagocytic lymphohistiocytosis due to mutations in UNC13D and STXBP2 overlaps with primary immunodeficiency diseases. Haematologica 95:122080–87
     [Google Scholar]
  92. 92.
    Malphettes M, Gérard L, Carmagnat M, Mouillot G, Vince N et al. 2009. Late-onset combined immune deficiency: a subset of common variable immunodeficiency with severe T cell defect. Clin. Infect. Dis. 49:91329–38
     [Google Scholar]
  93. 93.
    Delmonte OM, Schuetz C, Notarangelo LD. 2018. RAG deficiency: two genes, many diseases. J. Clin. Immunol. 38:6646–55
     [Google Scholar]
  94. 94.
    Gennery A. 2019. Recent advances in understanding RAG deficiencies. F1000Res 8:148
     [Google Scholar]
  95. 95.
    Crow YJ, Stetson DB. 2021. The type I interferonopathies: 10 years on. Nat. Rev. Immunol. 22:8471–83
     [Google Scholar]
  96. 96.
    Arredondo-Vega FX, Santisteban I, Richard E, Bali P, Koleilat M et al. 2002. Adenosine deaminase deficiency with mosaicism for a “second-site suppressor” of a splicing mutation: decline in revertant T lymphocytes during enzyme replacement therapy. Blood 99:31005–13
     [Google Scholar]
  97. 97.
    Speckmann C, Pannicke U, Wiech E, Schwarz K, Fisch P et al. 2008. Clinical and immunologic consequences of a somatic reversion in a patient with X-linked severe combined immunodeficiency. Blood 112:104090–97
     [Google Scholar]
  98. 98.
    Pietzsch L, Körholz J, Boschann F, Sergon M, Dorjbal B et al. 2022. Hyper-IgE and carcinoma in CADINS disease. Front. Immunol. 13:878989
     [Google Scholar]
  99. 99.
    Labrador-Horrillo M, Franco-Jarava C, Garcia-Prat M, Parra-Martínez A, Antolín M et al. 2022. Case report: X-linked SASH3 deficiency presenting as a common variable immunodeficiency. Front. Immunol. 13:881206
     [Google Scholar]
  100. 100.
    Grimbacher B, Hutloff A, Schlesier M, Glocker E, Warnatz K et al. 2003. Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency. Nat. Immunol. 4:3261–68
     [Google Scholar]
  101. 101.
    Salzer U, Maul-Pavicic A, Cunningham-Rundles C, Urschel S, Belohradsky BH et al. 2004. ICOS deficiency in patients with common variable immunodeficiency. Clin. Immunol. 113:3234–40
     [Google Scholar]
  102. 102.
    Carreno BM, Collins M. 2002. The B7 family of ligands and its receptors: new pathways for costimulation and inhibition of immune responses. Annu. Rev. Immunol. 20:29–53
     [Google Scholar]
  103. 103.
    Hutloff A, Dittrich AM, Beier KC, Eljaschewitsch B, Kraft R et al. 1999. ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28. Nature 397:6716263–66
     [Google Scholar]
  104. 104.
    Akiba H, Takeda K, Kojima Y, Usui Y, Harada N et al. 2005. The role of ICOS in the CXCR5+ follicular B helper T cell maintenance in vivo. J. Immunol. 175:42340–48
     [Google Scholar]
  105. 105.
    Choi YS, Kageyama R, Eto D, Escobar TC, Johnston RJ et al. 2011. ICOS receptor instructs T follicular helper cell versus effector cell differentiation via induction of the transcriptional repressor Bcl6. Immunity 34:6932–46
     [Google Scholar]
  106. 106.
    Rousset F, Garcia E, Defrance T, Péronne C, Vezzio N et al. 1992. Interleukin 10 is a potent growth and differentiation factor for activated human B lymphocytes. PNAS 89:51890–93
     [Google Scholar]
  107. 107.
    Takahashi N, Matsumoto K, Saito H, Nanki T, Miyasaka N et al. 2009. Impaired CD4 and CD8 effector function and decreased memory T cell populations in ICOS-deficient patients. J. Immunol. 182:95515–27
     [Google Scholar]
  108. 108.
    Goldman FD, Ballas ZK, Schutte BC, Kemp J, Hollenback C et al. 1998. Defective expression of p56lck in an infant with severe combined immunodeficiency. J. Clin. Investig. 102:2421–29
     [Google Scholar]
  109. 109.
    Sawabe T, Horiuchi T, Nakamura M, Tsukamoto H, Nakahara K et al. 2001. Defect of lck in a patient with common variable immunodeficiency. Int. J. Mol. Med. 7:6609–14
     [Google Scholar]
  110. 110.
    Hauck F, Randriamampita C, Martin E, Gerart S, Lambert N et al. 2012. Primary T-cell immunodeficiency with immunodysregulation caused by autosomal recessive LCK deficiency. J. Allergy Clin. Immunol. 130:51144–52.e11
     [Google Scholar]
  111. 111.
    Li G, Zan H, Xu Z, Casali P. 2013. Epigenetics of the antibody response. Trends Immunol 34:9460–70
     [Google Scholar]
  112. 112.
    Hoffman JD, Ciprero KL, Sullivan KE, Kaplan PB, McDonald-McGinn DM et al. 2005. Immune abnormalities are a frequent manifestation of Kabuki syndrome. Am. J. Med. Genet. A 135:3278–81
     [Google Scholar]
  113. 113.
    Giordano P, Lassandro G, Sangerardi M, Faienza MF, Valente F, Martire B. 2014. Autoimmune haematological disorders in two Italian children with Kabuki syndrome. Ital. J. Pediatr. 40:10
     [Google Scholar]
  114. 114.
    Roskin KM, Simchoni N, Liu Y, Lee J-Y, Seo K et al. 2015. IgH sequences in common variable immune deficiency reveal altered B cell development and selection. Sci. Transl. Med. 7:302302ra135
     [Google Scholar]
  115. 115.
    Frans G, Meyts I, Devriendt K, Liston A, Vermeulen F, Bossuyt X. 2016. Mild humoral immunodeficiency in a patient with X-linked Kabuki syndrome. Am. J. Med. Genet. A 170:3801–3
     [Google Scholar]
  116. 116.
    Hulten M. 2008. Selective somatic pairing and fragility at 1q12 in a boy with common variable immuno deficiency. Clin. Genet. 14:5294–94
     [Google Scholar]
  117. 117.
    de Greef JC, Wang J, Balog J, den Dunnen JT, Frants RR et al. 2011. Mutations in ZBTB24 are associated with immunodeficiency, centromeric instability, and facial anomalies syndrome type 2. Am. J. Hum. Genet. 88:6796–804
     [Google Scholar]
  118. 118.
    Weemaes CMR, van Tol MJD, Wang J, van Ostaijen-ten Dam MM, van Eggermond MCJA et al. 2013. Heterogeneous clinical presentation in ICF syndrome: correlation with underlying gene defects. Eur. J. Hum. Genet. 21:111219–25
     [Google Scholar]
  119. 119.
    Alghamdi HA, Tashkandi SA, Alidrissi EM, Aledielah RD, AlSaidi KA et al. 2018. Three types of immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome identified by whole-exome sequencing in Saudi hypogammaglobulinemia patients: clinical, molecular, and cytogenetic features. J. Clin. Immunol. 38:8847–53
     [Google Scholar]
  120. 120.
    Mehawej C, Khalife H, Hanna-Wakim R, Dbaibo G, Farra C 2020. DNMT3B deficiency presenting as severe combined immune deficiency: a case report. Clin. Immunol. 215:108453
     [Google Scholar]
  121. 121.
    Pezzolo A, Prigione I, Facchetti P, Castellano E, Viale M et al. 2001. T-cell apoptosis in ICF syndrome. J. Allergy Clin. Immunol. 108:2310–12
     [Google Scholar]
  122. 122.
    Blanco-Betancourt CE, Moncla A, Milili M, Jiang YL, Viegas-Péquignot EM et al. 2004. Defective B-cell-negative selection and terminal differentiation in the ICF syndrome. Blood 103:72683–90
     [Google Scholar]
  123. 123.
    von Bernuth H, Ravindran E, Du H, Fröhler S, Strehl K et al. 2014. Combined immunodeficiency develops with age in immunodeficiency-centromeric instability-facial anomalies syndrome 2 (ICF2). Orphanet J. Rare Dis. 9:116
     [Google Scholar]
  124. 124.
    Jin B, Tao Q, Peng J, Soo HM, Wu W et al. 2008. DNA methyltransferase 3B (DNMT3B) mutations in ICF syndrome lead to altered epigenetic modifications and aberrant expression of genes regulating development, neurogenesis and immune function. Hum. Mol. Genet. 17:5690–709
     [Google Scholar]
  125. 125.
    Deaton AM, Bird A. 2011. CpG islands and the regulation of transcription. Genes Dev 25:101010–22
     [Google Scholar]
  126. 126.
    Zheng Y, Josefowicz S, Chaudhry A, Peng XP, Forbush K, Rudensky AY. 2010. Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate. Nature 463:7282808–12
     [Google Scholar]
  127. 127.
    Jiang YL, Rigolet M, Bourc'his D, Nigon F, Bokesoy I et al. 2005. DNMT3B mutations and DNA methylation defect define two types of ICF syndrome. Hum. Mutat. 25:156–63
     [Google Scholar]
  128. 128.
    Herriot R, Miedzybrodzka Z. 2016. Antibody deficiency in Rubinstein-Taybi syndrome. Clin. Genet. 89:3355–58
     [Google Scholar]
  129. 129.
    Saettini F, Herriot R, Prada E, Nizon M, Zama D et al. 2020. Prevalence of immunological defects in a cohort of 97 Rubinstein-Taybi syndrome patients. J. Clin. Immunol. 40:6851–60
     [Google Scholar]
  130. 130.
    Musabak U, Ceylaner S, Erdogan T, Ayva ES. 2022. A case of common variable immunodeficiency with CREBP gene mutation without Rubinstein Taybi syndrome features. Case Rep. Immunol. 2022:4970973
     [Google Scholar]
  131. 131.
    Forster N, Gallinat S, Jablonska J, Weiss S, Elsässer H-P, Lutz W. 2007. p300 protein acetyltransferase activity suppresses systemic lupus erythematosus-like autoimmune disease in mice. J. Immunol. 178:116941–48
     [Google Scholar]
  132. 132.
    Park J, Munagala I, Xu H, Blankenship D, Maffucci P et al. 2013. Interferon signature in the blood in inflammatory common variable immune deficiency. PLOS ONE 8:9e74893
     [Google Scholar]
  133. 133.
    Schepp J, Proietti M, Frede N, Buchta M, Hübscher K et al. 2017. Screening of 181 patients with antibody deficiency for deficiency of adenosine deaminase 2 sheds new light on the disease in adulthood. Arthritis Rheumatol 69:81689–700
     [Google Scholar]
  134. 134.
    Schepp J, Bulashevska A, Mannhardt-Laakmann W, Cao H, Yang F et al. 2016. Deficiency of adenosine deaminase 2 causes antibody deficiency. J. Clin. Immunol. 36:3179–86
     [Google Scholar]
  135. 135.
    Trotta L, Martelius T, Siitonen T, Hautala T, Hämäläinen S et al. 2018. ADA2 deficiency: clonal lymphoproliferation in a subset of patients. J. Allergy Clin. Immunol. 141:41534–37.e8
     [Google Scholar]
  136. 136.
    Zhou Q, Yang D, Ombrello AK, Zavialov AV, Toro C et al. 2014. Early-onset stroke and vasculopathy associated with mutations in ADA2. N. Engl. J. Med. 370:10911–20
     [Google Scholar]
  137. 137.
    Schena F, Penco F, Volpi S, Pastorino C, Caorsi R et al. 2021. Dysregulation in B-cell responses and T follicular helper cell function in ADA2 deficiency patients. Eur. J. Immunol. 51:1206–19
     [Google Scholar]
  138. 138.
    Yap JY, Moens L, Lin M-W, Kane A, Kelleher A et al. 2021. Intrinsic defects in B cell development and differentiation, T cell exhaustion and altered unconventional T cell generation characterize human adenosine deaminase type 2 deficiency. J. Clin. Immunol. 41:81915–35
     [Google Scholar]
  139. 139.
    Aksentijevich I, Zhou Q. 2017. NF-κB pathway in autoinflammatory diseases: dysregulation of protein modifications by ubiquitin defines a new category of autoinflammatory diseases. Front. Immunol. 8:399
     [Google Scholar]
  140. 140.
    Hostager BS, Kashiwada M, Colgan JD, Rothman PB. 2011. HOIL-1L interacting protein (HOIP) is essential for CD40 signaling. PLOS ONE 6:8e23061
     [Google Scholar]
  141. 141.
    Oda H, Beck DB, Kuehn HS, Sampaio Moura N, Hoffmann P et al. 2019. Second case of HOIP deficiency expands clinical features and defines inflammatory transcriptome regulated by LUBAC. Front. Immunol. 10:479
     [Google Scholar]
  142. 142.
    Zhou Q, Lee G-S, Brady J, Datta S, Katan M et al. 2012. A hypermorphic missense mutation in PLCG2, encoding phospholipase Cγ2, causes a dominantly inherited autoinflammatory disease with immunodeficiency. Am. J. Hum. Genet. 91:4713–20
     [Google Scholar]
  143. 143.
    Chae JJ, Park YH, Park C, Hwang I-Y, Hoffmann P et al. 2015. Connecting two pathways through Ca2+ signaling: NLRP3 inflammasome activation induced by a hypermorphic PLCG2 mutation. Arthritis Rheumatol 67:2563–67
     [Google Scholar]
  144. 144.
    Ameratunga R, Woon S-T, Bryant VL, Steele R, Slade C et al. 2017. Clinical implications of digenic inheritance and epistasis in primary immunodeficiency disorders. Front. Immunol. 8:1965
     [Google Scholar]
  145. 145.
    Kerner G, Bouaziz M, Cobat A, Bigio B, Timberlake AT et al. 2020. A genome-wide case-only test for the detection of digenic inheritance in human exomes. PNAS 117:3219367–75
     [Google Scholar]
  146. 146.
    Zhang K, Chandrakasan S, Chapman H, Valencia CA, Husami A et al. 2014. Synergistic defects of different molecules in the cytotoxic pathway lead to clinical familial hemophagocytic lymphohistiocytosis. Blood 124:81331–34
     [Google Scholar]
  147. 147.
    Cerutti E, Campagnoli MF, Ferretti M, Garelli E, Crescenzio N et al. 2007. Co-inherited mutations of Fas and caspase-10 in development of the autoimmune lymphoproliferative syndrome. BMC Immunol 8:28
     [Google Scholar]
  148. 148.
    Conley ME, Notarangelo LD, Etzioni A. 1999. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clin. Immunol. 93:3190–97
     [Google Scholar]
  149. 149.
    Hogendorf A, Zieliński M, Constantinou M, Śmigiel R, Wierzba J et al. 2021. Immune dysregulation in patients with chromosome 18q deletions—searching for putative loci for autoimmunity and immunodeficiency. Front. Immunol. 12:742834
     [Google Scholar]
  150. 150.
    Chinn IK, Chan AY, Chen K, Chou J, Dorsey MJ et al. 2020. Diagnostic interpretation of genetic studies in patients with primary immunodeficiency diseases: a working group report of the Primary Immunodeficiency Diseases Committee of the American Academy of Allergy, Asthma & Immunology. J. Allergy Clin. Immunol. 145:146–69
     [Google Scholar]
  151. 151.
    Frans G, Meert W, Van der Werff Ten Bosch J, Meyts I, Bossuyt X et al. 2018. Conventional and single-molecule targeted sequencing method for specific variant detection in IKBKG while bypassing the IKBKGP1 pseudogene. J. Mol. Diagn. 20:2195–202
     [Google Scholar]
  152. 152.
    Woon S-T, Mayes J, Quach A, Longhurst H, Ferrante A, Ameratunga R. 2021. Droplet digital PCR for identifying copy number variations in patients with primary immunodeficiency disorders. Clin. Exp. Immunol. 207:3329–35
     [Google Scholar]
  153. 153.
    Stray-Pedersen A, Sorte HS, Samarakoon P, Gambin T, Chinn IK et al. 2017. Primary immunodeficiency diseases: Genomic approaches delineate heterogeneous Mendelian disorders. J. Allergy Clin. Immunol. 139:1232–45
     [Google Scholar]
  154. 154.
    Sherman RM, Forman J, Antonescu V, Puiu D, Daya M et al. 2019. Assembly of a pan-genome from deep sequencing of 910 humans of African descent. Nat. Genet. 51:130–35
     [Google Scholar]
  155. 155.
    Ebert P, Audano PA, Zhu Q, Rodriguez-Martin B, Porubsky D et al. 2021. Haplotype-resolved diverse human genomes and integrated analysis of structural variation. Science 372:6537eabf7117
     [Google Scholar]
  156. 156.
    Savola P, Martelius T, Kankainen M, Huuhtanen J, Lundgren S et al. 2020. Somatic mutations and T-cell clonality in patients with immunodeficiency. Haematologica 105:122757–68
     [Google Scholar]
  157. 157.
    Hsu AP, Pittaluga S, Martinez B, Rump AP, Raffeld M et al. 2015. IL2RG reversion event in a common lymphoid progenitor leads to delayed diagnosis and milder phenotype. J. Clin. Immunol. 35:5449–53
     [Google Scholar]
  158. 158.
    Papa R, Rusmini M, Schena F, Traggiai E, Coccia MC et al. 2021. Type I interferon activation in RAS-associated autoimmune leukoproliferative disease (RALD). Clin. Immunol. 231:108837
     [Google Scholar]
  159. 159.
    Tangye SG, Al-Herz W, Bousfiha A, Cunningham-Rundles C, Franco JL et al. 2022. Human inborn errors of immunity: 2022 update on the classification from the International Union of Immunological Societies Expert Committee. J. Clin. Immunol. 42:1473–507
     [Google Scholar]
  160. 160.
    Bryant A, Calver NC, Toubi E, Webster AD, Farrant J. 1990. Classification of patients with common variable immunodeficiency by B cell secretion of IgM and IgG in response to anti-IgM and interleukin-2. Clin. Immunol. Immunopathol. 56:2239–48
     [Google Scholar]
  161. 161.
    Warnatz K, Denz A, Dräger R, Braun M, Groth C et al. 2002. 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 99:51544–51
     [Google Scholar]
  162. 162.
    Piqueras B, Lavenu-Bombled C, Galicier L, Bergeron-van der Cruyssen F, Mouthon L et al. 2003. Common variable immunodeficiency patient classification based on impaired B cell memory differentiation correlates with clinical aspects. J. Clin. Immunol. 23:5385–400
     [Google Scholar]
  163. 163.
    Wehr C, Kivioja T, Schmitt C, Ferry B, Witte T et al. 2008. The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood 111:177–85
     [Google Scholar]
  164. 164.
    Chapel H, Lucas M, Lee M, Bjorkander J, Webster D et al. 2008. Common variable immunodeficiency disorders: division into distinct clinical phenotypes. Blood 112:2277–86
     [Google Scholar]
  165. 165.
    Driessen GJ, van Zelm MC, van Hagen PM, Hartwig NG, Trip M et al. 2011. B-cell replication history and somatic hypermutation status identify distinct pathophysiologic backgrounds in common variable immunodeficiency. Blood 118:266814–23
     [Google Scholar]
  166. 166.
    Chapel H, Lucas M, Patel S, Lee M, Cunningham-Rundles C et al. 2012. Confirmation and improvement of criteria for clinical phenotyping in common variable immunodeficiency disorders in replicate cohorts. J. Allergy Clin. Immunol. 130:51197–98.e9
     [Google Scholar]
  167. 167.
    Kamae C, Nakagawa N, Sato H, Honma K, Mitsuiki N et al. 2013. Common variable immunodeficiency classification by quantifying T-cell receptor and immunoglobulin κ-deleting recombination excision circles. J. Allergy Clin. Immunol. 131:51437–40.e5
     [Google Scholar]
  168. 168.
    Ameratunga R, Woon ST, Gillis D, Koopmans W, Steele R. 2013. New diagnostic criteria for common variable immune deficiency (CVID), which may assist with decisions to treat with intravenous or subcutaneous immunoglobulin. Clin. Exp. Immunol. 174:2203–11
     [Google Scholar]
  169. 169.
    Seidel MG, Kindle G, Gathmann B, Quinti I, Buckland M et al. 2019. The European Society for Immunodeficiencies (ESID) registry working definitions for the clinical diagnosis of inborn errors of immunity. J. Allergy Clin. Immunol. 7:61763–70
     [Google Scholar]
  170. 170.
    Bonilla FA, Barlan I, Chapel H, Costa-Carvalho BT, Cunningham-Rundles C et al. 2016. International Consensus Document (ICON): common variable immunodeficiency disorders. J. Allergy Clin. Immunol. 4:138–59
     [Google Scholar]
  171. 171.
    Ameratunga R. 2018. Assessing disease severity in common variable immunodeficiency disorders (CVID) and CVID-like disorders. Front. Immunol. 9:2130
     [Google Scholar]
  172. 172.
    Berbers RM, Drylewicz J, Ellerbroek PM, van Montfrans JM, Dalm V et al. 2021. Targeted proteomics reveals inflammatory pathways that classify immune dysregulation in common variable immunodeficiency. J. Clin. Immunol. 41:2362–73
     [Google Scholar]
  173. 173.
    Abyazi ML, Bell KA, Gyimesi G, Baker TS, Byun M et al. 2022. Convergence of cytokine dysregulation and antibody deficiency in common variable immunodeficiency with inflammatory complications. J. Allergy Clin. Immunol. 149:1315–26.e9
     [Google Scholar]
  174. 174.
    Guevara-Hoyer K, Jiménez-Huete A, Vasconcelos J, Neves E, Sánchez-Ramón S. 2021. Variable immunodeficiency score upfront analytical link (VISUAL), a proposal for combined prognostic score at diagnosis of common variable immunodeficiency. Sci. Rep. 11:112211
     [Google Scholar]
  175. 175.
    Seidel MG, Tesch VK, Yang L, Hauck F, Horn AL et al. 2022. The immune deficiency and dysregulation activity (IDDA2.1 ‘kaleidoscope’) score and other clinical measures in inborn errors of immunity. J. Clin. Immunol. 42:3484–98
     [Google Scholar]
  176. 176.
    Tofighi Zavareh F, Mirshafiey A, Yazdani R, Keshtkar AA, Abolhassani H et al. 2022. Immunophenotypic and functional analysis of lymphocyte subsets in common variable immunodeficiency patients without monogenic defects. Scandinavian J. Immunol. 96:1e13164
     [Google Scholar]
  177. 177.
    Fekrvand S, Khanmohammadi S, Abolhassani H, Yazdani R. 2022. B- and T-cell subset abnormalities in monogenic common variable immunodeficiency. Front. Immunol. 13:912826
     [Google Scholar]
  178. 178.
    Bogaert DJ, Dullaers M, Kuehn HS, Leroy BP, Niemela JEet al 2017. Early-onset primary antibody deficiency resembling common variable immunodeficiency challenges the diagnosis of Wiedeman-Steiner and Roifman syndromes. Sci. Rep 7:13702
     [Google Scholar]
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Common Variable Immunodeficiency: More Pathways than Roads to Rome
Annual Review of Pathology: Mechanisms of Disease 18, 283 (2023); https://doi.org/10.1146/annurev-pathmechdis-031521-024229
/content/journals/10.1146/annurev-pathmechdis-031521-024229
/content/journals/10.1146/annurev-pathmechdis-031521-024229
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