Respiratory Complications in Patients with Hyper IgM Syndrome
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Hyper Immunoglobulin M (HIgM) syndrome is a heterogeneous group of primary immunodeficiency disorders, characterized by recurrent infections and associated with decreased serum IgG and IgA, but normal or increased IgM. The aim of the present study was to evaluate respiratory manifestations in patients with HIgM syndrome.
A total number of 62 patients, including 46 males and 16 females were included in the present study. To investigate the respiratory complications among HIgM patients, we evaluated the clinical hospital records, immunologic and molecular diagnostic assays, pulmonary function tests (PFT), and high-resolution computed tomography (HRCT) scans.
Pneumonia was the most common respiratory manifestation (n = 35, 56.4%), followed by otitis media (45.1%), sinusitis (33.8%), and bronchiectasis (14.5%). 52.1% of the patients had abnormal PFT results, with a predominant restrictive pattern of changes. HRCT scans demonstrated abnormal findings in 85.7% of patients with found mutations. Ten cases had hilar lymphadenopathy and para-hilar infiltrates in their HRCT findings. Genetic diagnosis was confirmed in 29 HIgM patients (72.4% CD40 ligand (CD40L) and 24.1% activation-induced cytidine deaminase (AICDA/AID) deficiencies). Majority of patients with CD40L (71.4%) and AID (57.1%) deficiencies had missense mutations. Pneumonia and abnormal high-resolution computed tomography (HRCT) findings were more frequent among patients with CD40L mutation. Respiratory failure constituted the major cause of mortality (37.5%) with majority of cases occurring in CD40L-deficient patients (50%).
Respiratory complications are common in patients with HIgM syndrome. A proper awareness of respiratory manifestations in patients with HIgM may result in improved management, reduced morbidity and mortality, and an improvement in the quality of life of the patients.
KeywordsHyper immunoglobulin M primary immunodeficiency respiratory complications pneumonia otitis media sinusitis bronchiectasis
We would like to thank Dr. Zamani for her contribution in the radiologic assessment of our patients.
Compliance with Ethical Standards
This study was approved by the Ethics Committee of the Tehran University of the Medical Sciences and informed consents were obtained from all patients and/or their parents.
Conflict of Interest
The authors declare that they have no conflict of interest.
- 2.Notarangelo LD, Duse M, Ugazio AG. Immunodeficiency with hyper-IgM (HIM). Immunodefic Rev. 1992;3(2):101–21.Google Scholar
- 8.Abolhassani H, Parvaneh N, Rezaei N, Hammarstrom L, Aghamohammadi A. Genetic defects in B-cell development and their clinical consequences. J Investig Allergol Clin Immunol. 2014;24(1):6–22 quiz 2 p following.Google Scholar
- 12.Picard C, Bobby Gaspar H, Al-Herz W, Bousfiha A, Casanova JL, Chatila T, et al. International union of immunological societies: 2017 primary mmunodeficiency diseases committee report on inborn errors of immunity. J Clin Immunol. 2018;38(1):96–128. https://doi.org/10.1007/s10875-017-0464-9.CrossRefGoogle Scholar
- 16.Azizi G, Abolhassani H, Rezaei N, Aghamohammadi A, Asgardoon MH, Rahnavard J, et al. The use of immunoglobulin therapy in primary immunodeficiency diseases. Endocr Metab Immune Disord Drug Targets. 2016;24(77293):EPUB-77293.Google Scholar
- 19.Abolhassani H, Akbari F, Mirminachi B, Bazregari S, Hedayat E, Rezaei N, et al. Morbidity and mortality of Iranian patients with hyper IgM syndrome: a clinical analysis. Iran J Immunol. 2014;11(2):123–33.Google Scholar
- 21.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. 2018. https://doi.org/10.1038/s41436-018-0012-x.
- 23.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. https://doi.org/10.1007/s10875-014-0001-z.CrossRefGoogle Scholar
- 29.Gharagozlou M, Ebrahimi FA, Farhoudi A, Aghamohammadi A, Bemanian MH, Chavoshzadeh Z, et al. Pulmonary complications in primary hypogammaglobulinemia: a survey by high resolution CT scan. Monaldi Arch Chest Dis. 2006;65(2):69–74.Google Scholar
- 31.van Zeggeren L, van de Ven AA, Terheggen-Lagro SW, Mets OM, Beek FJ, van Montfrans JM, et al. High-resolution computed tomography and pulmonary function in children with common variable immunodeficiency. Eur Respir J. 2011;38(6):1437–43. https://doi.org/10.1183/09031936.00173410.CrossRefGoogle Scholar
- 33.van de Ven AA, van Montfrans JM, Terheggen-Lagro SW, Beek FJ, Hoytema van Konijnenburg DP, Kessels OA, et al. A CT scan score for the assessment of lung disease in children with common variable immunodeficiency disorders. Chest. 2010;138(2):371–9. https://doi.org/10.1378/chest.09-2398.CrossRefGoogle Scholar
- 35.Standardization of spirometry--1987 update. Statement of the American Thoracic Society. Am Rev Respir Dis. 1987;136(5):1285–98. https://doi.org/10.1164/ajrccm/136.5.1285.
- 36.Polgar G, Promadhat V. Pulmonary function testing in children : techniques and standards. Philadelphia: Saunders; 1971.Google Scholar
- 37.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. https://doi.org/10.1007/s10875-013-9980-4.CrossRefGoogle Scholar
- 52.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. 2018. https://doi.org/10.1016/j.jaip.2018.09.004.