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. 2021 Aug;41(6):1339-1351.
doi: 10.1007/s10875-021-01053-z. Epub 2021 May 29.

Consensus Middle East and North Africa Registry on Inborn Errors of Immunity

Asghar Aghamohammadi  1 , Nima Rezaei  1 , Reza Yazdani  1 , Samaneh Delavari  1 , Necil Kutukculer  2 , Ezgi Topyildiz  2 , Ahmet Ozen  3   4 , Safa Baris  3   4 , Elif Karakoc-Aydiner  3   4 , Sara Sebnem Kilic  5 , Hulya Kose  5 , Nesrin Gulez  6 , Ferah Genel  6 , Ismail Reisli  7 , Kamel Djenouhat  8 , Azzeddine Tahiat  8 , Rachida Boukari  9 , Samir Ladj  9 , Reda Belbouab  9 , Yacine Ferhani  9 , Brahim Belaid  10 , Reda Djidjik  10 , Nadia Kechout  11 , Nabila Attal  11 , Khalissa Saidani  11 , Ridha Barbouche  12 , Aziz Bousfiha  13 , Ali Sobh  14 , Ragheed Rizk  14 , Marwa H Elnagdy  15 , Mona Al-Ahmed  16   17 , Salem Al-Tamemi  18 , Gulnara Nasrullayeva  19 , Mehdi Adeli  20 , Maryam Al-Nesf  21 , Amel Hassen  20 , Cybel Mehawej  22 , Carla Irani  23 , Andre Megarbane  22 , Jessica Quinn  24 ; MENA-I. E. I. Study Group; László Maródi  25   26 , Vicki Modell  24 , Fred Modell  24 , Waleed Al-Herz  27   28 , Raif S Geha  29 , Hassan Abolhassani  30   31
Collaborators, Affiliations

Consensus Middle East and North Africa Registry on Inborn Errors of Immunity

Asghar Aghamohammadi et al. J Clin Immunol. 2021 Aug.

Abstract

Background: Inborn errors of immunity (IEIs) are a heterogeneous group of genetic defects of immunity, which cause high rates of morbidity and mortality mainly among children due to infectious and non-infectious complications. The IEI burden has been critically underestimated in countries from middle- and low-income regions and the majority of patients with IEI in these regions lack a molecular diagnosis.

Methods: We analyzed the clinical, immunologic, and genetic data of IEI patients from 22 countries in the Middle East and North Africa (MENA) region. The data was collected from national registries and diverse databases such as the Asian Pacific Society for Immunodeficiencies (APSID) registry, African Society for Immunodeficiencies (ASID) registry, Jeffrey Modell Foundation (JMF) registry, J Project centers, and International Consortium on Immune Deficiency (ICID) centers.

Results: We identified 17,120 patients with IEI, among which females represented 39.4%. Parental consanguinity was present in 60.5% of cases and 27.3% of the patients were from families with a confirmed previous family history of IEI. The median age of patients at the onset of disease was 36 months and the median delay in diagnosis was 41 months. The rate of registered IEI patients ranges between 0.02 and 7.58 per 100,000 population, and the lowest rates were in countries with the highest rates of disability-adjusted life years (DALY) and death rates for children. Predominantly antibody deficiencies were the most frequent IEI entities diagnosed in 41.2% of the cohort. Among 5871 patients genetically evaluated, the diagnostic yield was 83% with the majority (65.2%) having autosomal recessive defects. The mortality rate was the highest in patients with non-syndromic combined immunodeficiency (51.7%, median age: 3.5 years) and particularly in patients with mutations in specific genes associated with this phenotype (RFXANK, RAG1, and IL2RG).

Conclusions: This comprehensive registry highlights the importance of a detailed investigation of IEI patients in the MENA region. The high yield of genetic diagnosis of IEI in this region has important implications for prevention, prognosis, treatment, and resource allocation.

Keywords: Burden of disease; Epidemiology; Inborn errors of immunity; Molecular diagnosis; Primary immunodeficiency.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
The association of rate of inborn errors of immunity (IEI) diagnosis and rate of disability-adjusted life year (DALY) [10] in children within countries from the Middle East and North Africa region
Fig. 2
Fig. 2
Distribution of different inborn errors of immunity (IEI) entities among different countries in the Middle East and North Africa (MENA) region. PAD, primary antibody deficiency; CID, combined immunodeficiency. Global data has been retrieved from references (for more details, please see Table 2) [2, 9]
Fig. 3
Fig. 3
Number of patients with frequent genetic defects in the Middle East and North Africa cohort classified based on International Union of Immunological Societies (IUIS) categories of inborn errors of immunity (only genetic defects with > 40 patients are shown)
See this image and copyright information in PMC

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