Clinical Heterogeneity in Families With Multiple Cases of Inborn Errors of Immunity

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):

Share this content! On (X network) By

Clinical Heterogeneity in Families With Multiple Cases of Inborn Errors of Immunity Publisher Pubmed

Delavari S^{1, 2} ; Rasouli SE^{1, 2} ; Fekrvand S^{1, 2} ; Chavoshzade Z³ ; Mahdaviani SA⁴ ; Shirmast P^{1, 2, 25} ; Sharafian S³ ; Sherkat R⁵ ; Momen T⁶ ; Aleyasin S⁷ ; Ahanchian H⁸ ; Sadeghishabestari M⁹ ; Esmaeilzadeh H⁷ ; Barzamini S¹⁰ Show All Authors

Delavari S^{1, 2}
Rasouli SE^{1, 2}
Fekrvand S^{1, 2}
Chavoshzade Z³
Mahdaviani SA⁴
Shirmast P^{1, 2, 25}
Sharafian S³
Sherkat R⁵
Momen T⁶
Aleyasin S⁷
Ahanchian H⁸
Sadeghishabestari M⁹
Esmaeilzadeh H⁷
Barzamini S¹⁰
Tarighatmonfared F¹¹
Salehi H¹
Esmaeili M^{1, 2}
Marzani Z¹
Fathi N^{1, 2}
Abolnezhadian F¹²
Rad MK¹
Saeediboroujeni A¹³
Shirkani A¹⁴
Bagheri Z¹
Salami F^{1, 2}
Shad TM^{1, 2}
Marzbali MY¹
Mojtahedi H¹⁵
Razavi A¹
Tavakolinia N^{16, 17}
Cheraghi T¹⁸
Tavakol M¹⁹
Shafiei A²⁰
Behniafard N²¹
Ebrahimi SS²²
Sepahi N⁷
Ghaneimoghadam A²¹
Rezaei A^{1, 2}
Kalantari A²³
Abolhassani H^{1, 2, 24}
Rezaei N^{1, 2}

Show Affiliations

1. Research Center for Primary Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
2. Primary Immunodeficiency Diseases Network (PIDNet), Universal Scientific Education and Research Network (USERN), Tehran, Iran
3. Department of Allergy and Clinical Immunology, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4. Pediatric Respiratory Disease Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
5. Immunodeficiency Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
6. Department of Asthma, Allergy and Clinical Immunology, Child Growth and Development Research Center, Research Institute of Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
7. Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
8. Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
9. Department of Immunology and Allergy, Tabriz University of Medical Sciences, Tabriz, Iran
10. Department of Rheumatology, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
11. Pediatric Respiratory and Sleep Medicine Research Center, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
12. Department of Pediatrics, Abuzar Children's Hospital, Ahvaz University of Medical Sciences, Ahvaz, Iran
13. Department of Basic Medical Sciences, Faculty of Medicine, Abadan University of Medical Sciences, Abadan, Iran
14. Allergy and Clinical Immunology Department, Bushehr University of Medical Sciences, School of Medicine, Bushehr, Iran
15. Molecular Immunology Research Center Tehran University of Medical Sciences, Tehran, Iran
16. Murdoch Children's Research Institute, Melbourne, Australia
17. Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia
18. Department of Pediatrics, Guilan University of Medical Sciences, 17 Shahrivar Children's Hospital, Rasht, Iran
19. Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
20. Department of Immunology, Bahrami Hospital, Tehran University of Medical Sciences, Tehran, Iran
21. Children Growth Disorder Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
22. Department of Immunology and Allergy, Kerman University of Medical Sciences, Kerman, Iran
23. Department of Immunology and Allergy, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
24. Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
25. Menzies Health Institute Queensland and School of Medical Sciences, Griffith University, Gold Coast, QLD, Australia

Source: Clinical Immunology Published:2024

Abstract

Background: Inborn errors of immunity (IEI) are a diverse range of genetic immune system illnesses affecting the innate and/or adaptive immune systems. Variable expressivity and incomplete penetrance have been reported in IEI patients with similar clinical diagnoses or even the same genetic mutation. Methods: Among all recorded patients in the national IEI registry, 193 families with multiple cases have been recognized. Clinical, laboratory and genetic variability were compared between 451 patients with different IEI entities. Results: The diagnosis of the first children led to the earlier diagnosis, lower diagnostic delay, timely treatment and improved survival in the second children in the majority of IEI. The highest discordance in familial lymphoproliferation, autoimmunity and malignancy were respectively observed in STK4 deficiency, DNMT3B deficiency and ATM deficiency. Regarding immunological heterogeneity within a unique family with multiple cases of IEI, the highest discordance in CD3+, CD4+, CD19+, IgM and IgA levels was observed in syndromic combined immunodeficiencies (CID), while non-syndromic CID particularly severe combined immunodeficiency (SCID) manifested the highest discordance in IgG levels. Identification of the first ATM-deficient patient can lead to improved care and better survival in the next IEI children from the same family. Conclusion: Intrafamilial heterogeneity in immunological and/or clinical features could be observed in families with multiple cases of IEI indicating the indisputable role of appropriate treatment and preventive environmental factors besides specific gene mutations in the variable observed penetrance or expressivity of the disease. This also emphasizes the importance of implementing genetic evaluation in all members of a family with a history of IEI even if there is no suspicion of an underlying IEI as other factors besides the underlying genetic defects might cause a milder phenotype or delay in presentation of clinical features. Thus, affected patients could be timely diagnosed and treated, and their quality of life and survival would improve. © 2024 Elsevier Inc.

Related Docs

View other Related Docs

1. Global Systematic Review of Primary Immunodeficiency Registries, Expert Review of Clinical Immunology (2020)

2. Autoimmune Versus Non-Autoimmune Cutaneous Features in Monogenic Patients With Inborn Errors of Immunity, Biology (2023)

3. Autoimmune Manifestations Among 461 Patients With Monogenic Inborn Errors of Immunity, Pediatric Allergy and Immunology (2021)

4. Diversity of Malignancies in Patients With Different Types of Inborn Errors of Immunity, Allergy, Asthma and Clinical Immunology (2022)

5. Copy Number Analysis in a Large Cohort Suggestive of Inborn Errors of Immunity Indicates a Wide Spectrum of Relevant Chromosomal Losses and Gains, Journal of Clinical Immunology (2022)

6. Noninfectious Complications in B-Lymphopenic Common Variable Immunodeficiency, Journal of Investigational Allergology and Clinical Immunology (2024)

7. Fourth Update on the Iranian National Registry of Primary Immunodeficiencies: Integration of Molecular Diagnosis, Journal of Clinical Immunology (2018)

8. Clinical, Immunologic, and Genetic Spectrum of 696 Patients With Combined Immunodeficiency, Journal of Allergy and Clinical Immunology (2018)

Experts (# of related papers)

View all Related Experts

Tooba Momen (16)

Mohammad Amin Tabatabaiefar (2)

Other Related Docs

9. Comparison of Common Monogenic Defects in a Large Predominantly Antibody Deficiency Cohort, Journal of Allergy and Clinical Immunology: In Practice (2019)

10. The First Cohort of Iranian Patients With Hyper Immunoglobulin E Syndrome: A Long-Term Follow-Up and Genetic Analysis, Pediatric Allergy and Immunology (2019)

11. Expanding the Clinical and Immunological Phenotypes and Natural History of Malt1 Deficiency, Journal of Clinical Immunology (2022)

12. The First Iranian Cohort of Pediatric Patients With Activated Phosphoinositide 3-Kinase-Δ (Pi3kδ) Syndrome (Apds), Immunological Investigations (2022)

13. Monogenic Primary Immunodeficiency Disorder Associated With Common Variable Immunodeficiency and Autoimmunity, International Archives of Allergy and Immunology (2020)

14. Impact of Sars-Cov-2 Pandemic on Patients With Primary Immunodeficiency, Journal of Clinical Immunology (2021)

15. Genetic Mutations and Immunological Features of Severe Combined Immunodeficiency Patients in Iran, Immunology Letters (2019)

16. Role of Rare Immune Cells in Common Variable Immunodeficiency, Pediatric Allergy and Immunology (2022)

17. Decreased Expression of Hsa-Mir-142-3P and Hsa-Mir-155-5P in Common Variable Immunodeficiency and Involvement of Their Target Genes and Biological Pathways, Allergologia et Immunopathologia (2025)

18. The Sufficiency of Genetic Diagnosis in Managing Patients With Inborn Errors of Immunity During Prenatal Care and Childbearing, Immunogenetics (2024)

19. Genomic Testing Identifies Monogenic Causes in Patients With Very Early-Onset Inflammatory Bowel Disease: A Multicenter Survey in an Iranian Cohort, Clinical and Experimental Immunology (2024)

20. Primary Immunodeficiency Disorders in Iran: Update and New Insights From the Third Report of the National Registry, Journal of Clinical Immunology (2014)

21. Clinical, Immunological, Molecular and Therapeutic Findings in Monogenic Immune Dysregulation Diseases: Middle East and North Africa Registry, Clinical Immunology (2022)

22. A Comparison of Clinical and Immunologic Phenotypes in Familial and Sporadic Forms of Common Variable Immunodeficiency, Scandinavian Journal of Immunology (2017)

23. Gene Mutations Responsible for Primary Immunodeficiency Disorders: A Report From the First Primary Immunodeficiency Biobank in Iran, Allergy, Asthma and Clinical Immunology (2016)

24. Genotypes of European and Iranian Patients With Type 3 Von Willebrand Disease Enrolled in 3Winters-Ips, Blood Advances (2021)

25. Long-Term Evaluation of a Historical Cohort of Iranian Common Variable Immunodeficiency Patients, Expert Review of Clinical Immunology (2014)

26. Extended Clinical and Immunological Phenotype and Transplant Outcome in Cd27 and Cd70 Deficiency, Blood (2020)

27. Autoimmunity in Primary Antibody Deficiencies, International Archives of Allergy and Immunology (2017)

28. Clinical, Immunological, and Genetic Findings in Iranian Patients With Mhc-Ii Deficiency: Confirmation of C.162Delg Rfxank Founder Mutation in the Iranian Population, Journal of Clinical Immunology (2023)

29. Impaired Il-23–Dependent Induction of Ifn-Γ Underlies Mycobacterial Disease in Patients With Inherited Tyk2 Deficiency, Journal of Experimental Medicine (2022)

30. B-Cells Absence in Patients Diagnosed As Inborn Errors of Immunity: A Registry-Based Study, Immunogenetics (2024)

31. Exome-First Approach Identified Novel Homozygous Dedicator of Cytokinesis 8 (Dock8) Mutations in Three Unrelated Iranian Pedigrees Suspected With Hyper-Ige Syndrome, Iranian Journal of Allergy, Asthma and Immunology (2020)

32. Important Factors Influencing Severity of Common Variable Immunodeficiency, Archives of Iranian Medicine (2016)

33. Primary Immunodeficiency in Iran: First Report of the National Registry of Pid in Children and Adults, Journal of Clinical Immunology (2002)

34. Whole-Transcriptome Sequencing–Based Concomitant Detection of Viral and Human Genetic Determinants of Cutaneous Lesions, JCI Insight (2022)

35. Evaluation of Mutation in B Cell Maturation Antigen (Bcma) Gene in Patients With Common Variable Immunodeficiency (Cvid), Journal of Isfahan Medical School (2016)

36. Molecular Diagnosis of Slc26a4-Related Hereditary Hearing Loss in a Group of Patients From Two Provinces of Iran, Intractable and Rare Diseases Research (2021)

37. Clinical Phenotype Classification for Selective Immunoglobulin a Deficiency, Expert Review of Clinical Immunology (2015)

38. Primary Antibody Deficiency in a Tertiary Referral Hospital: A 30-Year Experiment, Journal of Investigational Allergology and Clinical Immunology (2015)

39. Monogenic Etiologies of Persistent Human Papillomavirus Infections: A Comprehensive Systematic Review, Genetics in Medicine (2024)

40. Clinical, Immunologic, Molecular Analyses and Outcomes of Iranian Patients With Lrba Deficiency: A Longitudinal Study, Pediatric Allergy and Immunology (2017)

41. Selective Iga Deficiency: Epidemiology, Pathogenesis, Clinical Phenotype, Diagnosis, Prognosis and Management, Scandinavian Journal of Immunology (2017)

42. The Identification of Two Pathogenic Variants in a Family With Mild and Severe Forms of Developmental Delay, Journal of Human Genetics (2021)

43. Frequency and Clinical Manifestations of Patients With Primary Immunodeficiency Disorders in Iran: Update From the Iranian Primary Immunodeficiency Registry, Journal of Clinical Immunology (2006)

44. Spontaneous Regression of Diffuse Large B-Cell Lymphoma in a Patient With Ataxia-Telangiectasia, Advanced Biomedical Research (2022)

45. Tnfaip3 Mutation Causing Haploinsufficiency of A20 With a Hemophagocytic Lymphohistiocytosis Phenotype: A Report of Two Cases, Pediatric Rheumatology (2022)

46. Genetic Analysis of a Cohort of 275 Patients With Hyper-Ige Syndromes And/Or Chronic Mucocutaneous Candidiasis, Journal of Clinical Immunology (2021)

47. Immunocompromised Patients: Review of the Most Common Infections Happened in 446 Hospitalized Patients, Journal of Research in Medical Sciences (2014)

48. Genetic Variant Profiling of Neonatal Diabetes Mellitus in Iranian Patients: Unveiling 58 Distinct Variants in 14 Genes, Journal of Diabetes Investigation (2024)

49. Consanguinity in Primary Immunodeficiency Disorders; the Report From Iranian Primary Immunodeficiency Registry, American Journal of Reproductive Immunology (2006)

50. Autoimmunity in Primary T-Cell Immunodeficiencies, Expert Review of Clinical Immunology (2016)

Style	Citing Format
MLA	Delavari S, et al.. "Clinical Heterogeneity in Families With Multiple Cases of Inborn Errors of Immunity." Clinical Immunology, vol. 259, no. , 2024, pp. -.
APA	Delavari S, Rasouli SE, Fekrvand S, Chavoshzade Z, Mahdaviani SA, Shirmast P, Sharafian S, Sherkat R, Momen T, Aleyasin S, Ahanchian H, Sadeghishabestari M, Esmaeilzadeh H, Barzamini S, Tarighatmonfared F, Salehi H, Esmaeili M, Marzani Z, Fathi N, ... Rezaei N (2024). Clinical Heterogeneity in Families With Multiple Cases of Inborn Errors of Immunity. Clinical Immunology, 259(), -.
Chicago	Delavari S, Rasouli SE, Fekrvand S, Chavoshzade Z, Mahdaviani SA, Shirmast P, Sharafian S, et al.. "Clinical Heterogeneity in Families With Multiple Cases of Inborn Errors of Immunity." Clinical Immunology 259, no. (2024): -.
Harvard	Delavari S et al. (2024) 'Clinical Heterogeneity in Families With Multiple Cases of Inborn Errors of Immunity', Clinical Immunology, 259(), pp. -.
Vancouver	Delavari S, Rasouli SE, Fekrvand S, Chavoshzade Z, Mahdaviani SA, Shirmast P, et al.. Clinical Heterogeneity in Families With Multiple Cases of Inborn Errors of Immunity. Clinical Immunology. 2024;259():-.
BibTex	@article{ author = {Delavari S and Rasouli SE and Fekrvand S and Chavoshzade Z and Mahdaviani SA and Shirmast P and Sharafian S and Sherkat R and Momen T and Aleyasin S and Ahanchian H and Sadeghishabestari M and Esmaeilzadeh H and Barzamini S and Tarighatmonfared F and Salehi H and Esmaeili M and Marzani Z and Fathi N and Abolnezhadian F and Rad MK and Saeediboroujeni A and Shirkani A and Bagheri Z and Salami F and Shad TM and Marzbali MY and Mojtahedi H and Razavi A and Tavakolinia N and Cheraghi T and Tavakol M and Shafiei A and Behniafard N and Ebrahimi SS and Sepahi N and Ghaneimoghadam A and Rezaei A and Kalantari A and Abolhassani H and Rezaei N}, title = {Clinical Heterogeneity in Families With Multiple Cases of Inborn Errors of Immunity}, journal = {Clinical Immunology}, volume = {259}, number = {}, pages = {-}, year = {2024} }
RIS	TY - JOUR AU - Delavari S AU - Rasouli SE AU - Fekrvand S AU - Chavoshzade Z AU - Mahdaviani SA AU - Shirmast P AU - Sharafian S AU - Sherkat R AU - Momen T AU - Aleyasin S AU - Ahanchian H AU - Sadeghishabestari M AU - Esmaeilzadeh H AU - Barzamini S AU - Tarighatmonfared F AU - Salehi H AU - Esmaeili M AU - Marzani Z AU - Fathi N AU - Abolnezhadian F AU - Rad MK AU - Saeediboroujeni A AU - Shirkani A AU - Bagheri Z AU - Salami F AU - Shad TM AU - Marzbali MY AU - Mojtahedi H AU - Razavi A AU - Tavakolinia N AU - Cheraghi T AU - Tavakol M AU - Shafiei A AU - Behniafard N AU - Ebrahimi SS AU - Sepahi N AU - Ghaneimoghadam A AU - Rezaei A AU - Kalantari A AU - Abolhassani H AU - Rezaei N TI - Clinical Heterogeneity in Families With Multiple Cases of Inborn Errors of Immunity JO - Clinical Immunology VL - 259 IS - SP - EP - PY - 2024 ER -

Science Communicator Platform

Authors

Authors Affiliations

Abstract