Allergol Immunopathol (Madr). 2021 Nov 01;49(6):1-7. doi: 10.15586/aei.v49i6.450. eCollection 2021.

Experience of Autoimmune and autoinflammatory diseases in a Turkish pediatric cohort with primary immunodeficiencies.

Allergologia et immunopathologia

Dilek Özcan, Mahir Serbes, Rabia Miray Kışla Ekinci, Sibel Balcı Çetinkaya, Ayşe Şenay Şaşihüseyinoğlu, Atıl Bişgin, Derya Ufuk Altıntaş

PMID: 34761650 DOI: 10.15586/aei.v49i6.450

Abstract

BACKGROUND: Primary immunodeficiency diseases (PID) are the diseases characterized by a dysfunction of the immune system. Affected patients share a different phenotype such as chronic infections, allergy, autoimmunity, and autoinflammation.

METHODS: In all, 433 children with PID were enrolled in this study. Clinical, laboratory, and demographic data of patients were reviewed retrospectively to investigate autoimmune and autoinflammatory complications. Autoinflammation in all patients with inflammation was confirmed by genetic analysis after excluding infectious etiology.

RESULTS: Clinical features of 433 PID patients were evaluated retrospectively with long-term follow-up. Autoimmune disorders were identified in 69 (15.9%) patients with PID; 31 (45%) patients had a history of autoimmune disease before diagnosis of PID. The frequency of autoimmunity in immune dysregulation subgroup (76.6%) was higher than other forms of PID. The most common autoimmune manifestations were reported to be Addison's disease, hypoparathyroidism, and autoimmune hemolytic anemia. Autoinflammation were identified in 22 of the 433 (5.1%) patients with PID, including hyper immunoglobulin D syndrome (n = 9), Aicardi-Goutieres syndrome 1 (n = 6), adenosine deaminase 2 deficiency (n = 3), Blau syndrome (n = 2), tumor necrosis factor (TNF) receptor-associated periodic syndrome (n = 1), and auto-inflammation and phospholipase Cγ2-associated antibody deficiency and immune dysregulation syndrome (n = 1).

CONCLUSIONS: It is important to recognize association between autoimmunity, autoinflammation, and PID, which in the future could be useful for increased awareness and early diagnosis for these diseases.

Keywords: autoimmunity; autoinflammation; immune dysregulation; immune system; primary immune diseases

Conflict of interest statement

References

1. 1. Schmidt RE, Grimbacher B, Witte T. Autoimmunity and primary immunodeficiency: Two sides of the same coin? Nat Rev Rheumatol. 2017 Dec 19;14(1):7–18. 10.1038/nrrheum.2017.198 - PubMed
2. 2. Fischer A, Provot J, Jais JP, Alcais A, Mahlaoui N, Members of the CEREDIH French PID Study Group. Autoimmune and inflammatory manifestations occur frequently in patients with primary immunodeficiencies. J Allergy Clin Immunol. 2017 Nov;140(5):1388–93. - PubMed
3. 3. Agarwal S, Cunningham-Rundles C. Autoimmunity in common variable immunodeficiency. Ann Allergy Asthma Immunol. 2019 Nov;123(5):454–60. 10.1016/j.anai.2019.07.014 - PubMed
4. 4. Amaya-Uribe L, Rojas M, Azizi G, Anaya JM, Gershwin ME. Primary immunodeficiency and autoimmunity: A comprehensive review. J Autoimmun. 2019 May;99:52–72. 10.1016/j.jaut.2019.01.011 - PubMed
5. 5. Bousfih A, Jeddane L, Picard C, Ailal F, Gaspar HB, Al-Herz W, et al. The 2017 IUIS phenotypic classification for primary immunodeficiencies. J Clin Immunol. 2018 Jan 38(1):129–43. 10.1007/s10875-017-0465-8 - PubMed
6. 6. Műzes G, Sipos F. Primary immunodeficiency and autoimmune diseases. Orv Hetil. 2018 Jun;159(23):908–18. 10.1556/650.2018.31064 - PubMed
7. 7. Patıroğlu T, Gungor HE, Unal E. Autoimmune diseases detected in children with primary immunodeficiency diseases: Resultsfrom a reference centre at middle Anatolia. Acta Microbiol Immunol Hung. 2012;59:343–53. 10.1556/amicr.59.2012.3.5 - PubMed
8. 8. Kaplan MY, Ozen S, Akcal O, Gulez N, Genel F. Autoimmune and inflammatory manifestations in pediatric patients with primary immunodeficiencies and their importance as a warning sign. Allergol Immunopathol. 2020;48(6):701–10. 10.1016/j.aller.2020.02.009 - PubMed
9. 9. Blazina S, Markelj G, Jeverica AK, Toplak N, Bratanič N, Jazbec J, et al. Autoimmune and inflammatory manifestations in 247 patients with primary immunodeficiency—A report from the Slovenian national registry. J ClinImmunol. 2016;36:764–73. 10.1007/s10875-016-0330-1 - PubMed
10. 10. Azizi G, Tavakolinia M, Rafiemanesh H, Kiaee F, Yazdani R, Heydari A, et al. Autoimmunity in a cohort of 471 patients with primary antibody deficiencies. Expert Rev Clin Immunol. 2017;13:1099–1106. 10.1080/1744666X.2017.1384312 - PubMed
11. 11. Pellegrino M, Bellacchio E, Dhamo R, Frasca F, Betterle C, Fierabracci A. A novel homozygous mutation of the - PubMed
12. 12. Humbert L, Cornu M, Proust-Lemoine E, Bayry J, Wemeau JL, Vantyghem MC, et al. Chronic mucocutaneous candidiasis in autoimmune Polyendocrine Syndrome Type 1. Front Immunol. 2018 Nov 19;9:2570-8. 10.3389/fimmu.2018.02570 - PubMed
13. 13. Man SM, Karki R, Kanneganti TD. AIM2 inflammasome in infection, cancer, and autoimmunity: Role in DNA sensing, inflammation, and innate immunity. Eur J Immunol. 2016 Feb;46(2):269–80. 10.1002/eji.201545839 - PubMed
14. 14. Croker BA, Silke J, Gerlic M. Fight or flight—Regulation of emergency hematopoiesis by pyroptosis and necroptosis. Curr Opin Hematol. 2015 Jul;22(4):293–301. 10.1097/MOH.0000000000000148 - PubMed
15. 15. Azizi G, Abolhassani H, Kiaee F, Tavakolinia M, Rafiemanesh H, Yazdani R, et al. Autoimmunity and its association with regulatory T cells and B cell subsets in patients with common variable immunodeficiency. Allergol Immunopathol. 2018;46(2):127–35. 10.1016/j.aller.2017.04.004 - PubMed
16. 16. Singh K, Chang C, Gershwin ME. IgA deficiency and autoimmunity. Autoimmun Rev. 2014 Feb;13(2):163–77. 10.1016/j.autrev.2013.10.005 - PubMed
17. 17. Conigliaro P, Triggianese P, Ballanti E, Perricone C, Perricone R, Chimenti MS. Complement, infection, and autoimmunity. Curr Opin Rheumatol. 2019 Sep;31(5):532–41. 10.1097/BOR.0000000000000633 - PubMed
18. 18. Michel M, Chanet V, Galicier L, Ruivard M, Levy Y, Hermine O, et al. Autoimmune thrombocytopenic purpura and common variable immunodeficiency: Analysis of 21 cases and review of the literature. Medicine. 2004;83:254–63. 10.1097/01.md.0000133624.65946.40 - PubMed
19. 19. Wang J, Cunningham-Rundles C. Treatment and outcome of autoimmune hematologic disease in common variable immunodeficiency (CVID). J Autoimmun. 2005;25:57–62. 10.1016/j.jaut.2005.04.006 - PubMed
20. 20. Georgin-Lavialle S, Fayand A, Rodrigues F, Bachmeyer C, Savey L, Grateau G. Autoinflammatory diseases: State of the art. Presse Med. 2019;48:25–48. 10.1016/j.lpm.2018.12.003 - PubMed
21. 21. Rice G, Newman WG, Dean J, Patrick T, Parmar R, Flintoff K, et al. Heterozygous mutations in TREX1 cause familial chilblain lupus and dominant Aicardi–Goutieres syndrome. Am J Hum Genet. 2007;80:811–15. 10.1086/513443 - PubMed

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