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01-04-2022 | Primary Immunodeficiency | Original Article

Inherited IFNAR1 Deficiency in a Child with Both Critical COVID-19 Pneumonia and Multisystem Inflammatory Syndrome

Authors: Hassan Abolhassani, Nils Landegren, Paul Bastard, Marie Materna, Mohammadreza Modaresi, Likun Du, Maribel Aranda-Guillén, Fabian Sardh, Fanglei Zuo, Peng Zhang, Harold Marcotte, Nico Marr, Taushif Khan, Manar Ata, Fatima Al-Ali, Remi Pescarmona, Alexandre Belot, Vivien Béziat, Qian Zhang, Jean-Laurent Casanova, Olle Kämpe, Shen-Ying Zhang, Lennart Hammarström, Qiang Pan-Hammarström

Published in: Journal of Clinical Immunology | Issue 3/2022

Abstract

Background

Inborn errors of immunity (IEI) and autoantibodies to type I interferons (IFNs) underlie critical COVID-19 pneumonia in at least 15% of the patients, while the causes of multisystem inflammatory syndrome in children (MIS-C) remain elusive.

Objectives

To detect causal genetic variants in very rare cases with concomitant critical COVID-19 pneumonia and MIS-C.

Methods

Whole exome sequencing was performed, and the impact of candidate gene variants was investigated. Plasma levels of cytokines, specific antibodies against the virus, and autoantibodies against type I IFNs were also measured.

Results

We report a 3-year-old child who died on day 56 of SARS-CoV-2 infection with an unusual clinical presentation, combining both critical COVID-19 pneumonia and MIS-C. We identified a large, homozygous loss-of-function deletion in IFNAR1, underlying autosomal recessive IFNAR1 deficiency.

Conclusions

Our findings confirm that impaired type I IFN immunity can underlie critical COVID-19 pneumonia, while suggesting that it can also unexpectedly underlie concomitant MIS-C. Our report further raises the possibility that inherited or acquired dysregulation of type I IFN immunity might contribute to MIS-C in other patients.

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Johansson MA, Quandelacy TM, Kada S, Prasad PV, Steele M, Brooks JT, et al. SARS-CoV-2 transmission from people without COVID-19 symptoms. JAMA Netw Open. 2021;4(1): e2035057. https://doi.org/10.1001/jamanetworkopen.2020.35057.CrossRefPubMedPubMedCentral

Grant MC, Geoghegan L, Arbyn M, Mohammed Z, McGuinness L, Clarke EL, et al. The prevalence of symptoms in 24,410 adults infected by the novel coronavirus (SARS-CoV-2; COVID-19): a systematic review and meta-analysis of 148 studies from 9 countries. PLoS ONE. 2020;15(6): e0234765. https://doi.org/10.1371/journal.pone.0234765.CrossRefPubMedPubMedCentral

Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020;180(7):934–43. https://doi.org/10.1001/jamainternmed.2020.0994.CrossRefPubMed

Attaway AH, Scheraga RG, Bhimraj A, Biehl M, Hatipoglu U. Severe covid-19 pneumonia: pathogenesis and clinical management. BMJ. 2021;372: n436. https://doi.org/10.1136/bmj.n436.CrossRefPubMed

Zhang Q, Bastard P, Bolze A, Jouanguy E, Zhang SY, Effort CHG, et al. Life-threatening COVID-19: defective interferons unleash excessive inflammation. Med (N Y). 2020;1(1):14–20. https://doi.org/10.1016/j.medj.2020.12.001.CrossRef

Khanmohammadi S, Rezaei N, Khazaei M, Shirkani A. A case of autosomal recessive interferon alpha/beta receptor alpha chain (IFNAR1) deficiency with severe COVID-19. J Clin Immunol. 2021. https://doi.org/10.1007/s10875-021-01166-5.CrossRefPubMedPubMedCentral

Schmidt A, Peters S, Knaus A, Sabir H, Hamsen F, Maj C, et al. TBK1 and TNFRSF13B mutations and an autoinflammatory disease in a child with lethal COVID-19. NPJ Genom Med. 2021;6(1):55. https://doi.org/10.1038/s41525-021-00220-w.CrossRefPubMedPubMedCentral

Bastard P, Manry J, Chen J, Rosain J, Seeleuthner Y, AbuZaitun O, et al. Herpes simplex encephalitis in a patient with a distinctive form of inherited IFNAR1 deficiency. J Clin Invest. 2021;131(1). https://doi.org/10.1172/JCI139980.

Duncan CJA, Randall RE, Hambleton S. Genetic lesions of type I interferon signalling in human antiviral immunity. Trends Genet. 2021;37(1):46–58. https://doi.org/10.1016/j.tig.2020.08.017.CrossRefPubMed

10.

Zhang SY, Boisson-Dupuis S, Chapgier A, Yang K, Bustamante J, Puel A, et al. Inborn errors of interferon (IFN)-mediated immunity in humans: insights into the respective roles of IFN-alpha/beta, IFN-gamma, and IFN-lambda in host defense. Immunol Rev. 2008;226:29–40. https://doi.org/10.1111/j.1600-065X.2008.00698.x.CrossRefPubMed

11.

Bravo Garcia-Morato M, Calvo Apalategi A, Bravo-Gallego LY, Blazquez Moreno A, Simon-Fuentes M, Garmendia JV, et al. Impaired control of multiple viral infections in a family with complete IRF9 deficiency. J Allergy Clin Immunol. 2019;144(1):309-12 e10. https://doi.org/10.1016/j.jaci.2019.02.019.CrossRefPubMed

12.

Hambleton S, Goodbourn S, Young DF, Dickinson P, Mohamad SM, Valappil M, et al. STAT2 deficiency and susceptibility to viral illness in humans. Proc Natl Acad Sci U S A. 2013;110(8):3053–8. https://doi.org/10.1073/pnas.1220098110.CrossRefPubMedPubMedCentral

13.

Hernandez N, Melki I, Jing H, Habib T, Huang SSY, Danielson J, et al. Life-threatening influenza pneumonitis in a child with inherited IRF9 deficiency. J Exp Med. 2018;215(10):2567–85. https://doi.org/10.1084/jem.20180628.CrossRefPubMedPubMedCentral

14.

Hernandez N, Bucciol G, Moens L, Le Pen J, Shahrooei M, Goudouris E, et al. Inherited IFNAR1 deficiency in otherwise healthy patients with adverse reaction to measles and yellow fever live vaccines. J Exp Med. 2019;216(9):2057–70. https://doi.org/10.1084/jem.20182295.CrossRefPubMedPubMedCentral

15.

Kreins AY, Ciancanelli MJ, Okada S, Kong XF, Ramirez-Alejo N, Kilic SS, et al. Human TYK2 deficiency: mycobacterial and viral infections without hyper-IgE syndrome. J Exp Med. 2015;212(10):1641–62. https://doi.org/10.1084/jem.20140280.CrossRefPubMedPubMedCentral

16.

Bastard P, Rosen LB, Zhang Q, Michailidis E, Hoffmann HH, Zhang Y, et al. Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science. 2020;370(6515). https://doi.org/10.1126/science.abd4585.

17.

Sancho-Shimizu V, Brodin P, Cobat A, Biggs CM, Toubiana J, Lucas CL, et al. SARS-CoV-2-related MIS-C: a key to the viral and genetic causes of Kawasaki disease? J Exp Med. 2021;218(6). https://doi.org/10.1084/jem.20210446.

18.

Consiglio CR, Cotugno N, Sardh F, Pou C, Amodio D, Rodriguez L, et al. The immunology of multisystem inflammatory syndrome in children with COVID-19. Cell. 2020;183(4):968-81 e7. https://doi.org/10.1016/j.cell.2020.09.016.CrossRefPubMedPubMedCentral

19.

Belot A, Antona D, Renolleau S, Javouhey E, Hentgen V, Angoulvant F, et al. SARS-CoV-2-related paediatric inflammatory multisystem syndrome, an epidemiological study, France, 1 March to 17 May 2020. Euro Surveill. 2020;25(22). https://doi.org/10.2807/1560-7917.ES.2020.25.22.2001010.

20.

de Cevins C, Luka M, Smith N, Meynier S, Magerus A, Carbone F, et al. A monocyte/dendritic cell molecular signature of SARS-CoV-2-related multisystem inflammatory syndrome in children with severe myocarditis. Med (N Y). 2021;2(9):1072-92 e7. https://doi.org/10.1016/j.medj.2021.08.002.CrossRef

21.

McArdle AJ, Vito O, Patel H, Seaby EG, Shah P, Wilson C, et al. Treatment of multisystem inflammatory syndrome in children. N Engl J Med. 2021;385(1):11–22. https://doi.org/10.1056/NEJMoa2102968.CrossRefPubMed

22.

Hoste L, Van Paemel R, Haerynck F. Multisystem inflammatory syndrome in children related to COVID-19: a systematic review. Eur J Pediatr. 2021. https://doi.org/10.1007/s00431-021-03993-5.CrossRefPubMedPubMedCentral

23.

Godfred-Cato S, Bryant B, Leung J, Oster ME, Conklin L, Abrams J, et al. COVID-19-Associated multisystem inflammatory syndrome in children—United States, March-July 2020. MMWR Morb Mortal Wkly Rep. 2020;69(32):1074–80. https://doi.org/10.15585/mmwr.mm6932e2.CrossRefPubMedPubMedCentral

24.

Abolhassani H, Kiaee F, Tavakol M, Chavoshzadeh Z, Mahdaviani SA, Momen T, et al. Fourth update on the Iranian National Registry of Primary Immunodeficiencies: integration of molecular diagnosis. J Clin Immunol. 2018;38(7):816–32. https://doi.org/10.1007/s10875-018-0556-1.CrossRefPubMed

25.

Delavari S, Abolhassani H, Abolnezhadian F, Babaha F, Iranparast S, Ahanchian H, et al. Impact of SARS-CoV-2 pandemic on patients with primary immunodeficiency. J Clin Immunol. 2021;41(2):345–55. https://doi.org/10.1007/s10875-020-00928-x.CrossRefPubMed

26.

Seidel MG, Kindle G, Gathmann B, Quinti I, Buckland M, van Montfrans J, et al. The European Society for Immunodeficiencies (ESID) registry working definitions for the clinical diagnosis of inborn errors of immunity. J Allergy Clin Immunol Pract. 2019;7(6):1763–70. https://doi.org/10.1016/j.jaip.2019.02.004.CrossRefPubMed

27.

Team CC-R. Severe outcomes among patients with coronavirus disease 2019 (COVID-19)—United States, February 12-March 16, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(12):343–6. https://doi.org/10.15585/mmwr.mm6912e2.

28.

Abolhassani H, Aghamohammadi A, Fang M, Rezaei N, Jiang C, Liu X, et al. Clinical implications of systematic phenotyping and exome sequencing in patients with primary antibody deficiency. Genet Med. 2019;21(1):243–51. https://doi.org/10.1038/s41436-018-0012-x.CrossRefPubMed

29.

Abolhassani H, Hammarstrom L, Cunningham-Rundles C. Current genetic landscape in common variable immune deficiency. Blood. 2020;135(9):656–67. https://doi.org/10.1182/blood.2019000929.CrossRefPubMedPubMedCentral

30.

Itan Y, Shang L, Boisson B, Ciancanelli MJ, Markle JG, Martinez-Barricarte R, et al. The mutation significance cutoff: gene-level thresholds for variant predictions. Nat Methods. 2016;13(2):109–10. https://doi.org/10.1038/nmeth.3739.CrossRefPubMedPubMedCentral

31.

Li Q, Wang K. InterVar: Clinical interpretation of genetic variants by the 2015 ACMG-AMP guidelines. Am J Hum Genet. 2017;100(2):267–80. https://doi.org/10.1016/j.ajhg.2017.01.004.CrossRefPubMedPubMedCentral

32.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405–24. https://doi.org/10.1038/gim.2015.30.CrossRefPubMedPubMedCentral

33.

Sherina N, Piralla A, Du L, Wan H, Kumagai-Braesch M, Andrell J, et al. Persistence of SARS-CoV-2-specific B and T cell responses in convalescent COVID-19 patients 6–8 months after the infection. Med (N Y). 2021;2(3):281-95 e4. https://doi.org/10.1016/j.medj.2021.02.001.CrossRef

34.

Mohan D, Wansley DL, Sie BM, Noon MS, Baer AN, Laserson U, et al. Publisher correction: PhIP-Seq characterization of serum antibodies using oligonucleotide-encoded peptidomes. Nat Protoc. 2019;14(8):2596. https://doi.org/10.1038/s41596-018-0088-4.CrossRefPubMed

35.

Kerner G, Rosain J, Guerin A, Al-Khabaz A, Oleaga-Quintas C, Rapaport F, et al. Inherited human IFN-gamma deficiency underlies mycobacterial disease. J Clin Invest. 2020;130(6):3158–71. https://doi.org/10.1172/JCI135460.CrossRefPubMedPubMedCentral

36.

Hasan MR, Rahman M, Khan T, Saeed A, Sundararaju S, Flores A, et al. Virome-wide serological profiling reveals association of herpesviruses with obesity. Sci Rep. 2021;11(1):2562. https://doi.org/10.1038/s41598-021-82213-4.CrossRefPubMedPubMedCentral

37.

Khan T, Rahman M, Ali FA, Huang SSY, Ata M, Zhang Q, et al. Distinct antibody repertoires against endemic human coronaviruses in children and adults. JCI Insight. 2021;6(4). https://doi.org/10.1172/jci.insight.144499.

38.

Moreews M, Le Gouge K, Khaldi-Plassart S, Pescarmona R, Mathieu AL, Malcus C, et al. Polyclonal expansion of TCR Vbeta 21.3(+) CD4(+) and CD8(+) T cells is a hallmark of multisystem inflammatory syndrome in children. Sci Immunol. 2021;6(59). https://doi.org/10.1126/sciimmunol.abh1516.

39.

Abolhassani H, Vosughimotlagh A, Asano T, Landegren N, Boisson B, Delavari S, et al. X-linked TLR7 deficiency underlies critical COVID-19 pneumonia in a male patient with ataxia-telangiectasia. J Clin Immunol. 2021. https://doi.org/10.1007/s10875-021-01151-y.CrossRefPubMedPubMedCentral

40.

Landegren N, Sharon D, Freyhult E, Hallgren A, Eriksson D, Edqvist PH, et al. Proteome-wide survey of the autoimmune target repertoire in autoimmune polyendocrine syndrome type 1. Sci Rep. 2016;6:20104. https://doi.org/10.1038/srep20104.CrossRefPubMedPubMedCentral

41.

Landegren N, Rosen LB, Freyhult E, Eriksson D, Fall T, Smith G, et al. Comment on ‘AIRE-deficient patients harbor unique high-affinity disease-ameliorating autoantibodies’. Elife. 2019;8. https://doi.org/10.7554/eLife.43578.

42.

McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, et al. Diagnosis, treatment, and long-term management of Kawasaki Disease: a scientific statement for health professionals from the American Heart Association. Circulation. 2017;135(17):e927–99. https://doi.org/10.1161/CIR.0000000000000484.CrossRefPubMed

43.

Gothe F, Hatton CF, Truong L, Klimova Z, Kanderova V, Fejtkova M, et al. A novel case of homozygous IFNAR1 deficiency with haemophagocytic lymphohistiocytosis. Clin Infect Dis. 2020. https://doi.org/10.1093/cid/ciaa1790.CrossRefPubMedCentral

44.

Hoyos-Bachiloglu R, Chou J, Sodroski CN, Beano A, Bainter W, Angelova M, et al. A digenic human immunodeficiency characterized by IFNAR1 and IFNGR2 mutations. J Clin Invest. 2017;127(12):4415–20. https://doi.org/10.1172/JCI93486.CrossRefPubMedPubMedCentral

45.

Duncan CJ, Mohamad SM, Young DF, Skelton AJ, Leahy TR, Munday DC, et al. Human IFNAR2 deficiency: lessons for antiviral immunity. Sci Transl Med. 2015;7(307):307ra154. https://doi.org/10.1126/scitranslmed.aac4227.CrossRefPubMedPubMedCentral

46.

Meyts I, Casanova JL. Viral infections in humans and mice with genetic deficiencies of the type I IFN response pathway. Eur J Immunol. 2021;51(5):1039–61. https://doi.org/10.1002/eji.202048793.CrossRefPubMedPubMedCentral

47.

Garg D, Muthu V, Sehgal IS, Ramachandran R, Kaur H, Bhalla A, et al. Coronavirus disease (Covid-19) associated mucormycosis (CAM): case report and systematic review of literature. Mycopathologia. 2021;186(2):289–98. https://doi.org/10.1007/s11046-021-00528-2.CrossRefPubMedPubMedCentral

48.

Sharma S, Grover M, Bhargava S, Samdani S, Kataria T. Post coronavirus disease mucormycosis: a deadly addition to the pandemic spectrum. J Laryngol Otol. 2021:1–6. https://doi.org/10.1017/S0022215121000992.

49.

Boehmer DFR, Koehler LM, Magg T, Metzger P, Rohlfs M, Ahlfeld J, et al. A novel complete autosomal-recessive STAT1 LOF variant causes immunodeficiency with hemophagocytic lymphohistiocytosis-like hyperinflammation. J Allergy Clin Immunol Pract. 2020;8(9):3102–11. https://doi.org/10.1016/j.jaip.2020.06.034.CrossRefPubMed

50.

Freij BJ, Hanrath AT, Chen R, Hambleton S, Duncan CJA. Life-threatening influenza, hemophagocytic lymphohistiocytosis and probable vaccine-strain varicella in a novel case of homozygous STAT2 deficiency. Front Immunol. 2020;11: 624415. https://doi.org/10.3389/fimmu.2020.624415.CrossRefPubMed

51.

Alosaimi MF, Maciag MC, Platt CD, Geha RS, Chou J, Bartnikas LM. A novel variant in STAT2 presenting with hemophagocytic lymphohistiocytosis. J Allergy Clin Immunol. 2019;144(2):611-3 e3. https://doi.org/10.1016/j.jaci.2019.05.008.CrossRefPubMedPubMedCentral

52.

Passarelli C, Civino A, Rossi MN, Cifaldi L, Lanari V, Moneta GM, et al. IFNAR2 deficiency causing dysregulation of NK cell functions and presenting with hemophagocytic lymphohistiocytosis. Front Genet. 2020;11:937. https://doi.org/10.3389/fgene.2020.00937.CrossRefPubMedPubMedCentral

53.

Fardet L, Galicier L, Lambotte O, Marzac C, Aumont C, Chahwan D, et al. Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome. Arthritis Rheumatol. 2014;66(9):2613–20. https://doi.org/10.1002/art.38690.CrossRefPubMed

54.

Diorio C, Henrickson SE, Vella LA, McNerney KO, Chase J, Burudpakdee C, et al. Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS-CoV-2. J Clin Invest. 2020;130(11):5967–75. https://doi.org/10.1172/JCI140970.CrossRefPubMedPubMedCentral

55.

Duarte-Neto AN, Caldini EG, Gomes-Gouvea MS, Kanamura CT, de Almeida Monteiro RA, Ferranti JF, et al. An autopsy study of the spectrum of severe COVID-19 in children: from SARS to different phenotypes of MIS-C. EClinicalMedicine. 2021;35: 100850. https://doi.org/10.1016/j.eclinm.2021.100850.CrossRefPubMedPubMedCentral

56.

Gruber CN, Patel RS, Trachtman R, Lepow L, Amanat F, Krammer F, et al. Mapping systemic inflammation and antibody responses in multisystem inflammatory syndrome in children (MIS-C). Cell. 2020;183(4):982-95 e14. https://doi.org/10.1016/j.cell.2020.09.034.CrossRefPubMedPubMedCentral

57.

Rowley AH. Understanding SARS-CoV-2-related multisystem inflammatory syndrome in children. Nat Rev Immunol. 2020;20(8):453–4. https://doi.org/10.1038/s41577-020-0367-5.CrossRefPubMed

Title: Inherited IFNAR1 Deficiency in a Child with Both Critical COVID-19 Pneumonia and Multisystem Inflammatory Syndrome
Authors: Hassan Abolhassani
Nils Landegren
Paul Bastard
Marie Materna
Mohammadreza Modaresi
Likun Du
Maribel Aranda-Guillén
Fabian Sardh
Fanglei Zuo
Peng Zhang
Harold Marcotte
Nico Marr
Taushif Khan
Manar Ata
Fatima Al-Ali
Remi Pescarmona
Alexandre Belot
Vivien Béziat
Qian Zhang
Jean-Laurent Casanova
Olle Kämpe
Shen-Ying Zhang
Lennart Hammarström
Qiang Pan-Hammarström
Publication date: 01-04-2022
Publisher: Springer US
Keywords: Primary Immunodeficiency
SARS-CoV-2
Pneumonia
COVID-19
Interferon
Published in: Journal of Clinical Immunology / Issue 3/2022
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-022-01215-7

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