Comparison of Common Monogenic Defects in a Large Predominantly Antibody Deficiency Cohort.

BACKGROUND: Predominantly antibody deficiencies (PADs) are the most common primary immunodeficiencies, characterized by hypogammaglobulinemia and inability to generate effective antibody responses. OBJECTIVE: We intended to report most common monogenic PADs and to investigate how patients with PAD who were primarily diagnosed as suffering from agammaglobulinemia, hyper-IgM (HIgM) syndrome, and common variable immunodeficiency (CVID) have different clinical and immunological findings. METHODS: Stepwise next-generation sequencing and Sanger sequencing were performed for confirmation of the mutations in the patients clinically diagnosed as suffering from agammaglobulinemia, HIgM syndrome, and CVID. RESULTS: Among 550 registered patients, the predominant genetic defects associated with agammaglobulinemia (48 Bruton's tyrosine kinase [BTK] and 6 µ heavy chain deficiencies), HIgM syndrome (21 CD40 ligand and 7 activation-induced cytidine deaminase deficiencies), and CVID (17 lipopolysaccharides-responsive beige-like anchor deficiency and 12 atypical Immunodeficiency, Centromeric instability, and Facial dysmorphism syndromes) were identified. Clinical disease severity was significantly higher in patients with µ heavy chain and CD40 ligand mutations compared with patients with BTK (P = .003) and activation-induced cytidine deaminase (P = .009) mutations. Paralysis following live polio vaccination was considerably higher in patients with µ heavy chain deficiency compared with BTK deficiency (P < .001). We found a genotype-phenotype correlation among patients with BTK mutations regarding clinical manifestation of meningitis and chronic diarrhea. Surprisingly, we noticed that first presentations in most patients with Immunodeficiency, Centromeric instability, and Facial dysmorphism were respiratory complications (P = .008), whereas first presentations in patients with lipopolysaccharides-responsive beige-like anchor deficiency were nonrespiratory complications (P = .008). CONCLUSIONS: This study highlights similarities and differences in the clinical and genetic spectrum of the most common PAD-associated gene defects. This comprehensive comparison will facilitate clinical decision making, and improve prognosis and targeted treatment.

Fourth Update on the Iranian National Registry of Primary Immunodeficiencies: Integration of Molecular Diagnosis.

BACKGROUND: The number of inherited diseases and the spectrum of clinical manifestations of primary immunodeficiency disorders (PIDs) are ever-expanding. Molecular diagnosis using genomic approaches should be performed for all PID patients since it provides a resource to improve the management and to estimate the prognosis of patients with these rare immune disorders. METHOD: The current update of Iranian PID registry (IPIDR) contains the clinical phenotype of newly registered patients during last 5 years (2013-2018) and the result of molecular diagnosis in patients enrolled for targeted and next-generation sequencing. RESULTS: Considering the newly diagnosed patients (n = 1395), the total number of registered PID patients reached 3056 (1852 male and 1204 female) from 31 medical centers. The predominantly antibody deficiency was the most common subcategory of PID (29.5%). The putative causative genetic defect was identified in 1014 patients (33.1%) and an autosomal recessive pattern was found in 79.3% of these patients. Among the genetically different categories of PID patients, the diagnostic rate was highest in defects in immune dysregulation and lowest in predominantly antibody deficiencies and mutations in the MEFV gene were the most frequent genetic disorder in our cohort. CONCLUSIONS: During a 20-year registration of Iranian PID patients, significant changes have been observed by increasing the awareness of the medical community, national PID network establishment, improving therapeutic facilities, and recently by inclusion of the molecular diagnosis. The current collective study of PID phenotypes and genotypes provides a major source for ethnic surveillance, newborn screening, and genetic consultation for prenatal and preimplantation genetic diagnosis.

The mediating effects of cognitive emotion regulation strategies on the relationship between alexithymia and physical symptoms: Evidence from Iranian asthmatic patients.

Asthma is a chronic and episodic psychosomatic disease whose symptoms include coughing, wheezing, chest tightness, and shortness of breath. The present study aimed to investigate the effects of cognitive emotion regulation strategies (CERS) as mediators on the relationships between alexithymia subscales and physical symptoms (PS). 300 asthmatic patients (males=42.7%, females=57.3%, age range=16-65, mean age=29.40) and 100 normal controls participated in the study and completed the demographic questionnaire, the Cognitive Emotion Regulation Questionnaire (CERQ), the Persian version of the Toronto Alexithymia Scale (FTAS-20), and the Powell & Enright Physical Symptoms Inventory (PSI). Asthmatic patients showed higher scores on all three alexithymia subscales including difficulty in identifying feelings (DIF), difficulty in describing feelings (DDF), and externally oriented thinking (EOT) as well as non-adaptive CERS than normal controls. On the other hand, normal controls earned higher means in adaptive CERS. Results revealed that each of the three alexithymia subscales had indirect effects on PS through the non-adaptive cognitive emotion regulation strategy of catastrophizing. It is concluded that alexithymia can intensify PS through catastrophizing in asthmatic patients.

Frequency and clinical manifestations of patients with primary immunodeficiency disorders in Iran: update from the Iranian Primary Immunodeficiency Registry.

Primary immunodeficiency disorders (PID) are a heterogeneous group of diseases, characterized by an increased susceptibility to infections. A total of 930 patients (573 males and 357 females) are registered in Iranian PID Registry (IPIDR) during three decades. Predominantly antibody deficiencies were the most common (38.4%), followed by congenital defects of phagocyte number and/or function (28.3%), other well-defined immunodeficiency syndromes (17.7%), combined T- and B-cell immunodeficiencies (11.0%), complement deficiencies (2.4%), and diseases of immune dysregulation (2.3%). Common variable immunodeficiency was the most frequent disorder (20.8%), followed by chronic granulomatous disease, ataxia-telangiectasia, btk deficiency, selective IgA deficiency, and T-B-severe combined immunodeficiency. The frequency of other PID disorders was less than 50 in number (<5%). There is an increasing trend in recognition of more PID in the recent years. Construction of such registry is not only important for its epidemiological aspect but also for its role in increasing the physician's knowledge about such disorders.

Prevalence of allergic rhinitis and nasal smear eosinophilia in 11- to 15 yr-old children in Shiraz.

Allergic rhinitis (AR) is a common condition among schoolchildren. The prevalence rate of AR differs among countries and even among regions within the same country. The objective of this study was to determine the prevalence of nasal symptoms and signs of AR and nasal smear eosinophilia in 11- to 15-yr-old children in Shiraz. A total of 4584 children aged 11-15 yr of both sexes were surveyed from May 1995 to April 1996, and nasal symptoms and signs of AR (sneezing, rhinorrhea, nasal blockage, itching, color change, mucosal swelling, nasal wetness, and nasal crease), based on questionnaire and ear, nose and throat (ENT) examination were recorded. In addition, smears were taken from nasal secretions and stained. The results compared with nasal smears related to 340 healthy children. 1008 (22%) schoolchildren had nasal symptoms of AR (based on the questionnaire), 445 (9.7%) were identified as having nasal symptoms and signs of AR (based on the questionnaire and ENT specialist examination), and 226 (5.8%) had nasal symptoms and signs of AR associated with nasal eosinophilia (based on the questionnaire, ENT specialist examination and positive nasal smear for eosinophilia). Nasal eosinophilia was present in 274 (62%) children with nasal symptoms and signs of AR. This survey showed that prevalence of nasal symptoms and signs of AR was high in schoolchildren in Shiraz. Nasal smear eosinophilia had a diagnostic specificity of 96% and sensitivity of 62% and seems to be a potentially valuable test for AR.