Genetic Causes, Clinical Features, and Survival of Underlying Inborn Errors of Immunity in Omani Patients: a Single-Center Study.

PURPOSE: Early identification of inborn errors of immunity (IEIs) is crucial due to the significant risk of morbidity and mortality. This study aimed to describe the genetic causes, clinical features, and survival rate of IEIs in Omani patients. METHODS: A prospective study of all Omani patients evaluated for immunodeficiency was conducted over a 17-year period. Clinical features and diagnostic immunological findings were recorded. Targeted gene testing was performed in cases of obvious immunodeficiency. For cases with less conclusive phenotypes, a gene panel was performed, followed by whole-exome sequencing if necessary. RESULTS: A total of 185 patients were diagnosed with IEIs during the study period; of these, 60.5% were male. Mean ages at symptom onset and diagnosis were 30.0 and 50.5 months, respectively. Consanguinity and a family history of IEIs were present in 86.9% and 50.8%, respectively. Most patients presented with lower respiratory infections (65.9%), followed by growth and development manifestations (43.2%). Phagocytic defects were the most common cause of IEIs (31.9%), followed by combined immunodeficiency (21.1%). Overall, 109 of 132 patients (82.6%) who underwent genetic testing received a genetic diagnosis, while testing was inconclusive for the remaining 23 patients (17.4%). Among patients with established diagnoses, 37 genes and 44 variants were identified. Autosomal recessive inheritance was present in 81.7% of patients with gene defects. Several variants were novel. Intravenous immunoglobulin therapy was administered to 39.4% of patients and 21.6% received hematopoietic stem cell transplantation. The overall survival rate was 75.1%. CONCLUSION: This study highlights the genetic causes of IEIs in Omani patients. This information may help in the early identification and management of the disease, thereby improving survival and quality of life.

Combined immunodeficiency due to a homozygous mutation in ORAI1 that deletes the C-terminus that interacts with STIM 1.

ORAI1 is the pore-forming subunit of the calcium release-activated calcium channel responsible for calcium influx into cells triggered by endoplasmic reticulum store depletion. We report here a patient with severe combined immunodeficiency and absent store-operated calcium entry due to a novel mutation in ORAI1 that results in the expression of a C-terminally truncated protein that abolishes ORAI1 binding to STIM1.

Primary Immunodeficiency Diseases in Oman: 10-Year Experience in a Tertiary Care Hospital.

PURPOSE: Primary immunodeficiency (PID) diseases are rare, complex medical disorders that often are overlooked in clinical settings. There are emerging reports of PID from Middle Eastern populations. This study describes the features of PID patients in a tertiary care setting in Oman and compares them with regional and worldwide reports. METHOD: Sultan Qaboos University Hospital (SQUH) is an academic tertiary care-level hospital for specialized healthcare, including PID patients. At the time of diagnosis, patients' sociodemographics, clinical features, laboratory investigations, and management were entered in electronic form. This study included patients seen between August 2005 and July 2015. RESULTS: One hundred forty patients were registered with a minimum estimated population prevalence of 7.0/100,000. The male/female ratio was 1.6:1, the median age of onset of symptoms was 8 months, and diagnosis was 21 months with a delay of 13 months. Family history was positive in 44 %, consanguinity was present in 76 %, death of a previous sibling was present in 36 %, and there was an overall mortality in 18 %, with an 85 % probability of survival 10 years following diagnosis. The most common type of immunodeficiency was phagocytic disorders (35.0 %), followed by predominantly antibody disorders (20.7 %), combined immunodeficiency (17.8 %), other well-defined PID syndromes (15.0 %), immune dysregulation syndromes (3.5 %), complement deficiencies (3.5 %), and unclassified immunodeficiency (4.2 %). The commonest presenting infection was pneumonia (47.1 %). CONCLUSION: PID is not a rare condition in Oman. The prevalence is in concordance with reports from the region but higher than in Western populations. The findings of the current study would help to improve the awareness and management of, and policy making for PID.

Anaphylaxis in Omani Patients: A Study from a Tertiary Care Center.

OBJECTIVES: Anaphylaxis is an acute and potentially fatal allergic reaction. No studies have yet been conducted to evaluate the spectrum of anaphylactic reactions among Omani patients. As such, this study aimed to describe the clinical features, causes, investigation, and management of anaphylaxis among patients presenting to a tertiary care center in Oman. METHODS: This retrospective study took place between August 2005 and June 2020 at the allergy and immunology clinic of Sultan Qaboos University Hospital, Muscat, Oman. All patients diagnosed with anaphylaxis during the study period were included. Data were collected from electronic medical records. RESULTS: One hundred patients were diagnosed with anaphylaxis during the study period. Of these, 52.0% were male. The mean age was 15.9±16.2 years, with 70.0% aged < 18 years old. The eosinophil count ranged from 0.0-16.9 × 109/L, with a mean of 0.8±2.2 × 109/L and a median of 0.3 (0.1-0.6) × 109/L. Total immunoglobulin (Ig) E levels ranged from 25-8706 kIU/L, with a mean of 935.1±1369.5 kIU/L and a median of 500.4 (186.0-972.5) kIU/L. The majority of patients had a family history of allergies (72.0%), and other had concomitant allergic conditions (66.0%). All were prescribed epinephrine (100%). The most common cause of anaphylaxis was food (65.0%). The second most frequent trigger was insect venom (32.0%). Most patients had one category cause (81.0%); two or more causes were present in 12.0% of patients. Clinical symptoms manifested most frequently as cutaneous (92.0%) and respiratory (85.0%). The majority of patients (87.0%) demonstrated the involvement of more than one bodily system. Mean total IgE levels were significantly higher in patients with concomitant presence of other allergic conditions (1193.8 kIU/L) than patients without another concomitant allergic disease (503.6 kIU/L; p =0.030). In addition, concomitant allergic disease is significantly higher in patients < 18 years of age (75.4%) compared to patients > 18 years of age (45.2%; p =0.010). CONCLUSIONS: Due to its life-threatening nature, knowledge of the epidemiology and clinical features of anaphylaxis in different populations is necessary to deliver rapid treatment. This study found that the clinical features of anaphylactic patients in Oman were similar to those reported elsewhere. Further research is needed to determine the true incidence of anaphylaxis in Oman to minimize associated morbidity and mortality.

Combined immunodeficiency due to a mutation in the γ1 subunit of the coat protein I complex.

The coat protein I (COPI) complex mediates retrograde trafficking from the Golgi to the endoplasmic reticulum (ER). Five siblings with persistent bacterial and viral infections and defective humoral and cellular immunity had a homozygous p.K652E mutation in the γ1 subunit of COPI (γ1-COP). The mutation disrupts COPI binding to the KDEL receptor and impairs the retrieval of KDEL-bearing chaperones from the Golgi to the ER. Homozygous Copg1K652E mice had increased ER stress in activated T and B cells, poor antibody responses, and normal numbers of T cells that proliferated normally, but underwent increased apoptosis upon activation. Exposure of the mutants to pet store mice caused weight loss, lymphopenia, and defective T cell proliferation that recapitulated the findings in the patients. The ER stress-relieving agent tauroursodeoxycholic acid corrected the immune defects of the mutants and reversed the phenotype they acquired following exposure to pet store mice. This study establishes the role of γ1-COP in the ER retrieval of KDEL-bearing chaperones and thereby the importance of ER homeostasis in adaptive immunity.

Food Allergen Sensitisation Patterns in Omani Patients with Allergic Manifestations.

OBJECTIVES: This study aimed to evaluate the relationship between food allergen sensitisation patterns and allergic manifestations in Omani patients and highlight the importance of specific immunoglobulin E (IgE) testing. METHODS: This retrospective study included all patients referred due to allergic manifestations to the Sultan Qaboos University Hospital (SQUH), Muscat, Oman, from November 2012 to November 2016. Specific IgE blood testing was performed to determine sensitisation to common foods known to cause allergic reactions. RESULTS: A total of 164 patients were referred to SQUH over the study period, with 35.4% presenting with one allergic manifestation, 48.8% with 2-3 and 15.9% presenting with more than three manifestations. There was a family history of allergies in 70.7% of patients. Eosinophil counts and total and specific IgE levels were elevated in 18.9%, 54.9% and 73.2% of patients, respectively. Patients demonstrated sensitisation to cow milk (47.6%), wheat (41.5%), chicken eggs (34.8%), mixed tree nuts (34.1%), lentils (33.5%), peanuts (32.9%), soy (32.3%), shrimp (23.2%) and fish (15.2%). Overall, 19.5% were sensitised to a single allergen, 14% were sensitised to 2-3 and 39.6% were sensitised to more than three allergens. Almost one-third (29.3%) of patients suffered from food-induced anaphylaxis, of which 85.4% were prescribed self-injectable adrenaline. CONCLUSION: To the best of the authors' knowledge, this study is the first to describe food allergen sensitisation patterns among Omani patients with allergic manifestations. In conjunction with clinical symptoms, the correct interpretation of specific IgE levels is important to diagnose food allergies and make safe decisions about reintroducing foods.