The Middle East and North Africa Diagnosis and Management Guidelines for Inborn Errors of Immunity

Barış, Safa; Abolhassani, Hassan; Massaad, Michel J.; Al‐Nesf, Maryam; Chavoshzadeh, Zahra; Keleş, Sevgi; Reisli, İsmail; Tahiat, Azzeddine; Shendi, Hiba; Elaziz, Dalia Abd; Belaid, Brahim; Dhaheri, Fatima Al; Haskoloğlu, Şule; Doğu, Figen; Ben‐Mustapha, Imen; Sobh, Ali; Galal, Nermeen; Meshaal, Safa; Hawary, Rabab El; Elmarsafy, Aisha; Alroqi, Fayhan; Al‐Saud, Bandar; Al‐Ahmad, Mona; Farsi, Tariq Al; Sukaiti, Nashat Al; Al‐Tamemi, Salem; Mehawej, Cybel; Dbaibo, Ghassan; ElGhazali, Gehad; Kılıç, Sara Şebnem; Genel, Ferah; Kıykım, Ayça; Muşabak, Uğur; Artaç, Hasibe; Güner, Şükrü Nail; Boukari, Rachida; Djidjik, Réda; Kechout, Nadia; Çağdaş, Deniz; El-Sayed, Zeinab A.; Karakoç-Aydıner, Elif; Alzyoud, Raed; Barbouche, Mohamed Ridha; Adeli, Mehdi; Wakim, Rima Hanna; Reda, Shereen M.; İkincioğulları, Aydan; Özen, Ahmet; Bousfiha, Aziz; Al‐Mousa, Hamoud; Rezaei, Nima; Al‐Herz, Waleed; Geha, Raif S.

doi:10.1016/j.jaip.2022.10.003

Cited by 29 publications

(14 citation statements)

References 75 publications

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“…All available patients with known genetic defects in the B cell development and differentiation stages were included from the cases registered in the national IEI registry at Children’s Medical Center Hospital in Iran. The diagnosis of IEI was established based on the updated clinical diagnostic criteria recommended by the European Society for Immunodeficiencies (ESID) [ 17 ] and the Middle East and North Africa Diagnosis and Management Guidelines for IEI [ 18 ]. Genes involved in different stages of B lymphocyte differentiation, as well as intrinsic and mixed extrinsic and intrinsic genes, were categorized according to Amirifar et al [ 19 ].…”

Section: Methodsmentioning

confidence: 99%

The Autoimmune Manifestations in Patients with Genetic Defects in the B Cell Development and Differentiation Stages

et al. 2023

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Purpose Primary B cell defects manifesting as predominantly antibody deficiencies result from variable inborn errors of the B cell lineage and their development, including impairments in early bone marrow development, class switch recombination (CSR), or terminal B cell differentiation. In this study, we aimed to investigate autoimmunity in monogenic patients with B cell development and differentiation defects. Methods Patients with known genetic defects in the B cell development and differentiation were recruited from the Iranian inborn errors of immunity registry. Results A total of 393 patients with a known genetic defect in the B cell development and differentiation (257 males; 65.4%) with a median age of 12 (6–20) years were enrolled in this study. After categorizing patients, 109 patients had intrinsic B cell defects. More than half of the patients had defects in one of the ATM (85 patients), BTK (76 patients), LRBA (34 patients), and DOCK8 (33 patients) genes. Fifteen patients (3.8%) showed autoimmune complications as their first manifestation. During the course of the disease, autoimmunity was reported in 81 (20.6%) patients at a median age of 4 (2–7) years, among which 65 patients had mixed intrinsic and extrinsic and 16 had intrinsic B cell defects. The comparison between patients with the mentioned four main gene defects showed that the patient group with LRBA defect had a significantly higher frequency of autoimmunity compared to those with other gene defects. Based on the B cell defect stage, 13% of patients with early B cell defect, 17% of patients with CSR defect, and 40% of patients who had terminal B cell defect presented at least one type of autoimmunity. Conclusion Our results demonstrated that gene mutations involved in human B cell terminal stage development mainly LRBA gene defect have the highest association with autoimmunity.

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Section: Methodsmentioning

confidence: 99%

The Autoimmune Manifestations in Patients with Genetic Defects in the B Cell Development and Differentiation Stages

et al. 2023

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“…Emerging genomics platforms now offer the promise of identifying previously elusive IEI genetic lesions [144][145][146], but also demand the development of novel bioinformatics pipelines, data infrastructures, and analytical strategies. All of these considerations highlight the urgent need for flexible, evolving and realistic demographic-appropriate guidelines, as well as acknowledging and addressing the systemic biases currently found in our data [147]. Finally, regardless of the assays chosen, there is no replacement for the precise clinical and immune phenotyping needed to help navigate the complexities of the IEI landscape.…”

Section: Many Of Our Index Patients Did Not Present With the Most 'Ca...mentioning

confidence: 99%

A Next Generation Sequencing (NGS)-based approach to diagnosing Algerian patients with suspected Inborn Errors of Immunity (IEIs)

Peng

Al-Ddafari²,

Caballero-Oteyza³

et al. 2023

Preprint

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The advent of next-generation sequencing (NGS) technologies has greatly expanded our understanding of both the clinical spectra and genetic landscape of inborn errors of immunity (IEIs). As history has shown and recent large-scale studies of monogenic risk for severe COVID have confirmed, endogamous populations may be enriched for unique, ancestry-specific disease-causing variants as a consequence of geography and/or culture. From a diagnostic perspective, this consideration may significantly impact molecular testing and analysis strategies. Herein, we report on the diagnostic yield of a 2-step NGS-based testing approach beginning with targeted gene panels (TGPs) and reflexing to whole exome sequencing (WES) if negative for Northwest Algerian patients with suspected IEIs. A total of fourteen families were screened using TGPs tailored to their IEI subtypes of common variable immunodeficiency (CVID), inflammatory bowel disease (IBD) or chronic mucocutaneous candidiasis (CMC)-hyperIgE syndrome (HIES), resulting in a total of four definitive or highly likely molecular diagnoses (29% yield). Subsequent application of WES to eight of the ten remaining unsolved cases yielded an additional four diagnoses, giving a 57% overall yield. At least two additional individuals were found to harbor suggestive candidate variants on exome warranting further investigation, while others carried candidate variants or known risk alleles likely contributing to their clinical findings. Only in one patient’s case did we fail to identify any viable potential candidates. By achieving diagnostic yields comparable to those currently quoted for application of short-read NGS to IEI detection, our study demonstrates the viability of a 2-step NGS-based testing strategy in a selected endogamous population. Data from our localized cohort also showed some similarities and differences from NGS studies performed on larger regional IEI cohorts. Finally, our results also highlight many short-comings currently inherent to the application of genomics for clinical IEI diagnostics. Not only does the global community need to address ongoing inequities in representation, access, and infrastructure, but the ability to obtain precise and detailed clinical data remains paramount for achieving diagnostic certainty in the face of complex genotype-phenotype relationships.

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“…She did not have any liver test or imaging abnormality before HSCT. She was on antimicrobial prophylaxis (trimethoprim/sulfamethoxazole [TMP-SMZ], acyclovir, and fluconazole) for infection since first month as suggested by the guideline 3 . Family history was remarkable with a cousin with SCID and 2 siblings who died in the neonatal period.…”

Section: Casementioning

confidence: 99%

“…She was on antimicrobial prophylaxis (trimethoprim/sulfamethoxazole [TMP-SMZ], acyclovir, and fluconazole) for infection since first month as suggested by the guideline. 3 Family history was remarkable with a cousin with SCID and 2 siblings who died in the neonatal period. Her postnatal course was complicated with pneumonia at fifth day of life which was managed with gentamicin and ampicillin.…”

Section: Casementioning

confidence: 99%

Hepatocellular Carcinoma in ADA-SCID Patient After Hematopoietic Stem Cell Transplantation

Ucku¹,

Armutlu²,

Çipe

et al. 2023

Journal of Pediatric Hematology/Oncology

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Adenosine deaminase (ADA) deficiency is one of the most prevalent forms of severe combined immunodeficiency and results in the accumulation of toxic substrates which creates a systemic metabolic disease. It predisposes patients to the development of malignancies, most commonly lymphoma. We report an 8-month-old infant with ADA deficient severe combined immunodeficiency who developed progressive liver dysfunction and hepatocellular carcinoma after successful hematopoietic stem cell transplantation. This is the first case report of an ADA-deficient patient who presented with hepatocellular carcinoma and gives an insight into the complex etiology that can lie behind liver dysfunction in these patients.

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The Middle East and North Africa Diagnosis and Management Guidelines for Inborn Errors of Immunity

Cited by 29 publications

References 75 publications

The Autoimmune Manifestations in Patients with Genetic Defects in the B Cell Development and Differentiation Stages

The Autoimmune Manifestations in Patients with Genetic Defects in the B Cell Development and Differentiation Stages

A Next Generation Sequencing (NGS)-based approach to diagnosing Algerian patients with suspected Inborn Errors of Immunity (IEIs)

Hepatocellular Carcinoma in ADA-SCID Patient After Hematopoietic Stem Cell Transplantation

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