Combined immunodeficiency: The Middle East experience

doi:10.1016/j.jaci.2012.11.033

Journal of Allergy and Clinical Immunology

Volume 131, Issue 3, March 2013, Pages 658-660

https://doi.org/10.1016/j.jaci.2012.11.033 Get rights and content

Previous reports about primary immunodeficiency disorders have shown variations in the frequency and distribution among populations from different ethnic and geographic backgrounds. In this review we describe peculiarities about combined immunodeficiencies (CIDs) in the Middle East. The frequency and type of genetic defects causing CIDs in this region differ in comparison with those in other populations because of the common practice of consanguineous marriage in the Middle East, which results in the relative increase in autosomal recessive diseases. We highlight some of the challenges in the awareness, diagnosis, and therapy of CIDs in the region and the research opportunities, especially those directed toward the identification of novel disease-causing genes.

Section snippets

Lack of epidemiologic data

Few countries in the Middle East have established national registries to determine the prevalence of common primary immunodeficiency disorder (PID) phenotypes in their populations. Establishing such registries in the Middle East, as well as other countries, is essential not only for epidemiologic data but also for demonstrating to health authorities the magnitude of the health problem and the need for strategies to care for patients with these disorders.

Awareness and education about CIDs and consanguinity complications

Consanguineous marriage resulting from

Newborn screening

Because patients with CIDs are asymptomatic at birth and early diagnosis and initiation of therapy is essential for cure, CIDs have been recognized as candidates for population-based newborn screening. The T-cell receptor recombination excision circle assay is already implemented in a few countries.7, 8 Universal newborn screening is a cost-effective means to improve the quality and duration of life for children with CIDs, and disease incidence is a critical driving force affecting the

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Cystinosis is a rare autosomal recessive lysosomal storage disorder characterized by cystine buildup in various tissues, including the kidneys. Renal involvement is the primary manifestation, leading to end-stage renal disease (ESRD) if left untreated. Kidney transplantation (KT) in patients with cystinosis has significantly improved their prognosis for the disease outcome. Detailed reports on preoperative and Long-term postoperative management in these patients remain sparse. This report discusses the outcomes of two young adult patients of Middle Eastern descent with cystinosis who underwent KT. The first patient, diagnosed with infantile nephropathic cystinosis treated by cystine-depleting therapy, was operated by KT at the age of 18. The second patient, diagnosed with juvenile cystinosis, underwent transplantation at the age of 35 after being treated with hemodialysis. Our report describes detailed pre- and postoperative managements, including laboratory results, and pharmacological interventions. Both cases highlighted the varying clinical manifestations and disease severity between infantile and juvenile cystinosis. Pre-transplant conditions included renal dysfunction, growth retardation, secondary hyperparathyroidism, anemia, and extrarenal manifestations. Following KT, both patients experienced regained renal function, resolution of extrarenal complications, and normalization of laboratory parameters. Furthermore, both patients showed excellent postoperative outcomes with no acute rejection or allograft-related complications. KT is the treatment of choice for cystinosis patients with ESRD. Long-term follow-up post-transplantation is crucial to maintain good graft function. Further studies may elucidate optimal pre- and postoperative management protocols for this rare condition.
Effect of the Israel-Hamas war on allergy and immunology care and research
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Epidemiology of combined immunodeficiencies affecting cellular and humoral immunity– a multicentric retrospective cohort study from the Arabian Peninsula
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To understand the characteristics of combined immunodeficiency disorders that affect cellular and humoral immunity (CID) in the Arabian Peninsula.
Retrospective study of 236 patients with CID from the region were enrolled from 2004 to 2022.
236 patients were included with a majority being profound CID. Among patients with a family history of CID, the ages at onset and diagnosis, and the delay in diagnosis were lower compared to those with no family history of CID, but this did not affect time to transplant. HSCT was performed for 51.27% of the patients with median time from diagnosis to HSCT of 6.36 months. On multivariate analysis, patients who underwent early transplant had increased odds of having CD3 count ≤1000 cell/μl, diagnosed by screening or erythroderma.
There is a delay in diagnosis and treatment of CID in our region. Establishing newborn screening programs and HSCT units in our region are the urgent need.
The Middle East and North Africa Diagnosis and Management Guidelines for Inborn Errors of Immunity
2023, Journal of Allergy and Clinical Immunology: In Practice
Citation Excerpt :
In the first- and second-line referrals by general practitioners, pediatricians, and infectious disease specialists, the assessment of complete blood counts, quantitative serum immunoglobulin levels, and lymphocyte subpopulations, and the evaluation of the natural or postvaccine immune responses are crucial for early diagnosis (Figure 2). On the other hand, awareness of the common IEI (especially the AR forms) in the MENA region could enhance the likelihood of a genetic diagnosis using a targeted single-gene sequencing approach, particularly in areas with low resources, such as in the case of leukocyte adhesion defect type 1 and major histocompatibility complex class II deficiency, which are commonly observed in North African patients,16,20,40 Janus kinase 3 deficiency with T−B+ phenotype in Egypt,41 and recombination activating gene (RAG1) and RAG2 deficiencies as the most common cause of CID in many MENA countries.3,29,42,43 For other cases, next-generation sequencing approaches including sequencing a targeted gene panel or whole exome/genomes can be used to establish the molecular diagnoses in many patients with IEI.
Human inborn errors of immunity (IEI) are a group of 485 distinct genetic disorders affecting children and adults. Signs and symptoms of IEI are heterogeneous, and accurate diagnosis can be challenging and depends on the available human expertise and laboratory resources. The Middle East and North Africa (MENA) region has an increased prevalence of IEI because of the high rate of consanguinity with a predominance of autosomal recessive disorders. This area also exhibits more severe disease phenotypes compared with other regions, probably due to the delay in diagnosis. The MENA-IEI registry network has designed protocols and guidelines for the diagnosis and treatment of IEI, taking into consideration the variable regional expertise and resources. These guidelines are primarily meant to improve the care of patients within the region, but can also be followed in other regions with similar patient populations.
Morbidity, Mortality, and Therapeutics in Combined Immunodeficiency: Data From the USIDNET Registry
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Optimal management of patients with combined immunodeficiency, especially pertaining to hematopoietic stem cell transplantation (HSCT), remains unclear.
To identify factors influencing HSCT and mortality in the population with combined immunodeficiency in North America.
We identified 337 participants in the United States Immunodeficiency Network database with diverse forms of combined immunodeficiency and their characteristics, including demographic characteristics, laboratory values, infectious history, comorbidities, and treatment strategies. Univariate analysis was performed using logistic regression, whereas multivariate analysis was performed using multiple Cox proportional hazards.
On univariate analysis, disseminated invasive viral infections and variants in STAT3, GATA2, and, DOCK8 were associated with increased odds of HSCT. Mucocutaneous fungal infections and variants in STAT3 were associated with increased odds of survival, whereas disseminated/invasive fungal infections, disseminated/invasive viral infections, and parasitic infections were associated with decreased odds of survival. On multiple variable Cox proportional hazards analysis, variants in ZAP70, nonspecific bacterial, and disseminated/invasive viral infections were associated with increased hazards of transplantation, whereas variants in multiple genes (RMRP, NEMO, DOCK8, CD40L, and CARD9), disseminated/invasive viral infections, autoimmune disease, and higher absolute lymphocyte count were associated with increased hazards of death. Importantly, demographic characteristics, basic lymphocyte subset counts, and absence of genetic diagnosis were not associated with HSCT or mortality.
We determined that specific genetic diagnoses and infection burden impacts the decision to undergo HSCT in this cohort. In addition, certain genetic diagnoses and invasive viral infections carry an increased risk of mortality.
Social determinants of health and primary immunodeficiency
2022, Annals of Allergy, Asthma and Immunology
Inborn errors of immunity (IEI) are rare genetic conditions affecting the immune system. The rate of IEI and their presentation, course, and treatment are all affected by a multitude of social determinants, eventually affecting prognosis. This review summarizes the current knowledge of the social determinants affecting infectious susceptibility, genetic predisposition, diagnosis, and treatment of IEI.
PubMed.
Search terms included “consanguinity,” “social determinants,” and “founder effect.” Further studies were selected based on relevant citations.
Changes in climate and human behavior have modulated the spread of disease vectors and infectious organisms. Consanguinity increases the rate of autosomal recessive conditions, changes the distribution, and affects the severity of IEI. Access to sophisticated genetic and immunologic diagnostic modalities affects genetic counseling and timely diagnosis. Effective genetic counseling should address to the patient's genetic background and ethical code. Access to appropriate and timely treatment of immunodeficiencies is scarce in some regions of the world.
High consanguinity rate and reduced access to prophylactic measures increase the burden of immunodeficiencies in many low- and medium-income countries. Furthermore, poor access to diagnostic and treatment modalities in these regions adversely affects patients’ prognosis. Increased awareness among health care professionals and the public and increased collaboration with Western countries aid in diagnosis of these conditions. Further advancements require improved public funding to the prevention, diagnosis, and treatment of IEI.

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: Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.

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Reviews and feature articleCombined immunodeficiency: The Middle East experience

Section snippets

Lack of epidemiologic data

Awareness and education about CIDs and consanguinity complications

Newborn screening

J Allergy Clin Immunol

J Pediatr

Mol Genet Metab

Cell

Am J Hum Genet

Curr Opin Immunol

Primary immunodeficiency diseases: an update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency

Front Immunol

Systematic evidence review of newborn screening and treatment of severe combined immunodeficiency

Pediatrics

Molecular diagnosis of severe combined immunodeficiency—identification of IL2RG, JAK3, IL7R, DCLRE1C, RAG1, and RAG2 mutations in a cohort of Chinese and Southeast Asian children

J Clin Immunol

Reviews and feature article
Combined immunodeficiency: The Middle East experience