Comparison of the Familial and Sporadic Forms of Hyper IgM Syndrome in the Iranian Patients
Abstract
Background: Hyper IgM (HIGM) syndrome or immunoglobulin class-switch recombination deficiency (Ig-CSR) is a group of primary immunodeficiencies (PIDs) where B cells are unable to undergo the process of immunoglobulin class -switching recombination (CSR), a process in which B-cells modify their DNA to switch from production of IgM to other immunoglobulins. Hence, the affected patients exhibit normal to high levels of serum IgM and low or absence of other immunoglobulin isotypes relative to mean values of age. Therefore, the present study was conducted to assess the demographic data, clinical manifestation, and immunological findings in the sporadic and familial types of HIGM.
Method: Demographic data, laboratory findings, and clinical presentations of 79 Iranian patients diagnosed with HIgM syndrome were collected. All the patients were classified into two different groups: sporadic and familial types of HIGM.
Results: Male to female ratio was significantly higher in the familial group compared to the sporadic group so that, 94.7% of the patients were male in the familial group, while only 70% of the sporadic patients were male (P=0.032). It was also found that the familial group had a significantly higher consanguinity rate (P=0.047) and a significantly lower delay of diagnosis compared to the sporadic group (P=0.006). The lower respiratory infection (42%) followed by upper respiratory infection (26%) and diarrhea (15%) were the most frequent initial presentations. It was shown that diarrhea, as an initial presentation was about three times more common among the familial group (31.6%) compared to the sporadic group (10%, P=0.028). Otitis was also found to be more prevalent in the sporadic group (P=0.042).
Conclusion: Our findings could be explained by more careful screenings and more vigilant and informative parents in the families with another affected member.
2. Tsai HY, Yu HH, Chien YH, Chu KH, Lau YL, Lee JH, et al. X-linked hyper-IgM syndrome with CD40LG mutation: two case reports and literature review in Taiwanese patients. J Microbiol Immunol Infect. 2015;48(1):113-8.
3. Korthauer U, Graf D, Mages HW, Briere F, Padayachee M, Malcolm S, et al. Defective expression of T-cell CD40 ligand causes X-linked immunodeficiency with hyper-IgM. Nature. 1993;361(6412):539-41.
4. Yazdani R, Abolhassani H, Kiaee F, Habibi S, Azizi G, Tavakol M, et al. Comparison of Common Monogenic Defects in a Large Predominantly Antibody Deficiency Cohort. J Allergy Clin Immunol Pract. 2019;7(3):864-78.e9.
5. Etzioni A, Ochs HD. The hyper IgM syndrome--an evolving story. Pediatr Res. 2004;56(4):519-25.
6. Leven EA, Maffucci P, Ochs HD, Scholl PR, Buckley RH, Fuleihan RL, et al. Hyper IgM Syndrome: a Report from the USIDNET Registry. J Clin Immunol. 2016;36(5):490-501.
7. Lee WI, Torgerson TR, Schumacher MJ, Yel L, Zhu Q, Ochs HD. Molecular analysis of a large cohort of patients with the hyper immunoglobulin M (IgM) syndrome. Blood. 2005;105(5):1881-90.
8. Cabral-Marques O, Klaver S, Schimke LF, Ascendino EH, Khan TA, Pereira PV, et al. First report of the Hyper-IgM syndrome Registry of the Latin American Society for Immunodeficiencies: novel mutations, unique infections, and outcomes. J Clin Immunol. 2014;34(2):146-56.
9. Rawat A, Mathew B, Pandiarajan V, Jindal A, Sharma M, Suri D, et al. Clinical and molecular features of X-linked hyper IgM syndrome - An experience from North India. Clin Immunol. 2018;195:59-66.
10. Azizi G, Abolhassani H, Asgardoon MH, Rahnavard J, Dizaji MZ, Yazdani R, et al. The use of Immunoglobulin Therapy in Primary Immunodeficiency Diseases. Endocr Metab Im‐ mune Disord Drug Targets. 2016;16(2):80-8.
11. Brandt D, Gershwin ME. Common variable immune deficiency and autoimmunity. Autoimmun Rev. 2006;5(7):465-70.
12. Alkhairy OK, Perez-Becker R, Driessen GJ, Abolhassani H, van Montfrans J, Borte S, et al. Novel mutations in TNFRSF7/CD27: Clinical, immunologic, and genetic characterization of human CD27 deficiency. J Allergy Clin Immunol. 2015;136(3):703-12.e10.
13. Notarangelo LD, Duse M, Ugazio AG. Immunodeficiency with hyper-IgM (HIM). Immunodefic rev. 1992;3(2):101-21.
14. Qamar N, Fuleihan RL. The hyper IgM syndromes. Clin Rev Allergy Immunol. 2014;46(2):120-30.
15. Günaydin NC, Chou J, Karaca NE, Aksu G, Massaad MJ, Azarsiz E, et al. A novel disease-causing CD40L mutation reduces expression of CD40 ligand, but preserves CD40 bind-ing capacity. Clin Immunol. 2014;153(2):288-91.
16. Rosen FS, Kevy SV, Merler E, Janeway CA, Gitlin D. Recurrent bacterial infections and dysgamma-globulinemia: deficiency of 7S gamma-globulins in the presence of elevated 19S gamma-globulins. Report of two cases. Pediatrics. 1961;28:182-95.
17. Yazdani R, Fekrvand S, Shahkarami S, Azizi G, Moazzami B, Abolhassani H, et al. The hyper IgM syndromes: Epidemiology, pathogenesis, clinical manifestations, diagnosis and management. Clin Immunol. 2019;198:19-30.
18. Aghamohammadi A, Mohammadinejad P, Abolhassani H, Mirminachi B, Movahedi M, Gharagozlou M, et al. Primary immunodeficiency disorders in Iran: update and new insights from the third report of the national registry. J Clin Immunol. 2014;34(4):478-90.
19. Jain A, Ma CA, Liu S, Brown M, Cohen J, Strober W. Specific missense mutations in NEMO result in hyper-IgM syndrome with hypohydrotic ectodermal dysplasia. Nat Immunol. 2001;2(3):223-8.
20. Abinun M. Ectodermal dysplasia and immunodeficiency. Arch Dis Child. 1995;73(2):185.
21. Zonana J, Elder ME, Schneider LC, Orlow SJ, Moss C, Golabi M, et al. A novel X-linked disorder of immune deficiency and hypohidrotic ectodermal dysplasia is allelic to incontinentia pigmenti and due to mutations in IKK-gamma (NEMO). Am J Hum Genet. 2000;67(6):1555-62.
22. Rezaei N, Aghamohammadi A, Moin M, Pourpak Z, Movahedi M, Gharagozlou M, et al. Frequency and clinical manifestations of patients with primary immunodeficiency disorders in Iran: update from the Iranian Primary Immunodeficiency Registry. J Clin Immunol. 2006;26(6):519-32.
23. Rezaei N, Pourpak Z, Aghamohammadi A, Farhoudi A, Movahedi M, Gharagozlou M, et al. Consanguinity in primary immunodeficiency disorders; the report from Iranian Primary Immunodeficiency Registry. Am J Reprod Immunol (New York, NY : 1989). 2006;56(2):145-51.
24. Al-Herz W, Aldhekri H, Barbouche MR, Rezaei N. Consanguinity and primary immunodeficiencies. Hum Hered. 2014;77(1-4):138-43.
25. Rivoisy C, Gérard L, Boutboul D, Malphettes M, Fieschi C, Durieu I, et al. Parental consanguinity is associated with a severe phenotype in common variable immunodeficiency. J Clin Immunol. 2012;32(1):98-105.
26. Schonell ME. Immunoglobulin levels in pneumonia. Clin Exp Immuno. 1971;8(1):63-8.
27. Valizadeh A, Yazdani R, Azizi G, Abolhassani H, Aghamohammadi A. A Comparison of Clinical and Immunologic Phenotypes in Familial and Sporadic Forms of Common Variable Immunodeficiency. Scand J Immunol. 2017;86(4):239-47.
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| Issue | Vol 3, No 3 (2020) | |
| Section | Original Article | |
| DOI | https://doi.org/10.22034/igj.2020.247400.1048 | |
| Keywords | ||
| Hyper IgM Primary immunodeficiency Sporadic HIGM Familial HIGM | ||
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