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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. [ABSTRACT FROM AUTHOR]

The use of oral poliovirus vaccine in a worldwide scale has led to a 99.9% decrease in annual incidence of wild-type poliomyelitis and the eradication of serotype 2 poliovirus. However, the emergence of vaccine-derived polioviruses (VDPVs) is endangering the eradication program. Patients with combined immunodeficiencies are at increased risk of both vaccine-associated poliomyelitis and prolonged asymptomatic infection with immunodeficiency-associated VDPVs (iVDPVs). Herein, we present a severe combined immunodeficiency patient with prolonged and asymptomatic iVDPV infection. He continued to shed poliovirus during immunoglobulin replacement therapy and cleared the infection following successful hematopoietic stem cell transplantation (HSCT). To explain the efficiency of HSCT in clearing the infection, we reviewed the literature for all reports of HSCT in iVDPV-excreting patients and discussed novel ideas about the role of different immune mechanisms, including cell-mediated interactions, in mounting immune responses against poliovirus infections. This study could provide further insights into the immune mechanisms contributing to the clearance of enteroviral infections. [ABSTRACT FROM AUTHOR]

Key Clinical Message DOCK8 deficiency is a rare autosomal recessive combined immunodeficiency with high IgE level, eosinophilia, severe eczema, extensive cutaneous viral, and respiratory bacterial infections, mostly in populations with higher prevalence of consanguinity. Molecular diagnosis of this gene is a useful approach for early diagnosis and timely HSCT due to deleterious consequences. [ABSTRACT FROM AUTHOR]

Partial albinism with variable immunodeficiency are the two major characteristics of Griscelli syndrome type 2 ( GS-2). This syndrome is usually associated with a high mortality rate and commonly results in early childhood death. Patients suffer from different infections and experience crisis of HLH. HSCT remains the sole curative treatment for GS-2. We prospectively analyzed the outcomes of transplantation with RIC regimen in five patients. The median age at transplantation was 21.6 months (range: 12-30). All of the patients underwent HSCT from HLA-matched related donors. Currently, four patients are cured, and symptoms of recurrent infections and HLH crisis are not seen in them. The only patient who died had undergone HSCT in the accelerated phase of HLH. One patient who developed acute GvHD had a favorable response to therapy. No chronic GvHD occurred in patients. It seems that the use of RIC regimen as a method of transplant preparation is effective and tolerable in this group of patients with various comorbidities. It is recommended to carry out HSCT in these patients at lower ages, before presentations of different infections and HLH crisis. [ABSTRACT FROM AUTHOR]

Severe congenital neutropenia (SCN) is a rare primary immunodeficiency disease. Different genes are found to be associated with SCN, including ELA2, HAX1, WAS, GFI1, G-CSFR and G6PC3. The aim of this study was to find different gene mutations responsible for SCN in Iranian patients. Twenty-seven patients with SCN referred to Immunology, Asthma and Allergy Research Institute during a five year priod 5 years (May 2007 and May 2012), were included in this study. Neutropenia related exons and flanking regions of ELA2, HAX1, WAS, GFI1, G-CSFR and G6PC3 were amplified by PCR and the sequences were analyzed. The results showed different mutations including 4 ELANE mutations, 11 HAX1 mutations and 2 G6PC3 mutations. None of the patients had GFI1 mutation and also one mutation was found in G-CSFR in a patient with ELANE mutation. Ten patients had unknown genetic diagnosis which was compatible with other studies. According to these results, most of the patients showed HAX1 mutations and this finding which significantly differed from other reports, might be related to differences in Iranian ethnicity and also in high rate of consanguineous marriages in Iran. [ABSTRACT FROM AUTHOR]

Severe Congenital Neutropenia is one of primary immunodeficiency disorders that characterized by severe neutropenia and is associated with severe systemic bacterial infections from early infancy. Granulocyte Colony Stimulating Factor (GCSF) is clinically used as a treatment for congenital and acquired neutropenia. The aim of this study was evaluation of GCSF (PD- Grastim) in treatment of these patients. Patients with severe congenital neutropenia referred to Immunology, Asthma and Allergy Research Institute between Jan 2007 and Dec 2010 enrolled the study. Other causes of neutropenia were excluded by serial CBC and bone marrow studies, medical and drug histories and immunological tests. Patients were visited and examined monthly to evaluate their CBC and ANC (Absolute Neutrophil Count), GCSF side effects and dosage adjustment. Cytogenetic studies were being done for all the patients for early detection of progression to AML/MDS. From twenty two patients who enrolled this study, 16 patients regularly evaluated. They were ten males and six females, range in age from 2 to 18 years old. Two patients failed to continue our follow up unfortunately and four patients died due to disease complications. Patients were followed for 24 to 48 months. In a period of 12-24 months before treatment, the mean of hospitalization frequency was 3.1 times and duration was 10 days; while during receiving treatment, they decreased to 0.2 times and 3 days, respectively (p<0.01). Also significant increase in mean ANC was observed during follow up (315/μl before treatment versus 1749/μl after 12 month regular treatment). Bone pain was the most common side effect. There have been no evidences of developing AML/MDS up to present time. Treatment with GCSF significantly reduced the duration and the frequency of hospitalization. Because of plausible progression to AML/MDS, regular follow-up of patients should be continued. [ABSTRACT FROM AUTHOR]

Severe congenital neutropenia (SCN) is a rare primary immunodeficiency. Different genes are found to be associated with SCN, including ELA2, HAX1, WAS, GFI1, G-CSFR. Also, recently G6PC3 as a rare gene in SCN has been reported. Patients with G6PC3 often have cardiac and/or urogenital malformations. Two patients with persistent severe neutropenia, recurrent infections and maturation arrest at promyelocyte-myelocyte stage in their bone marrow were assessed in this study. Both patients showed structural heart disease and one of them also showed urogenital anomaly. Sequence analyses of G6PC3 in 2 patients revealed two different homozygous mutations, one in exon 6 (Asn 313 fs), and the other in exon 3 (Ser 139 Met), the latter is a new mutation which has not been reported in previous studies. It can be concluded that G6PC3 is one of the responsible gene for SCN in Iranian patients. Based on the results, a new mutation in G6PC3 observed in one patient. [ABSTRACT FROM AUTHOR]

Hamidieh AA, Pourpak Z, Alimoghaddam K, Movahedi M, Bahoush G, Behmanesh F, Moin M, Ghavamzadeh A. Successful allogeneic stem cell transplantation with a reduced-intensity conditioning in a leukocyte adhesion deficiency type I patient. Pediatr Transplantation 2011: 15:E30-E33. © 2009 John Wiley & Sons A/S. LAD-I is a rare, autosomal recessive, primary immunodeficiency in which phagocyte adhesion and chemotaxis are impaired. Multiple infections in the absence of pus accumulation and persistent elevated peripheral blood neutrophil counts are the hallmark of LAD-I. Allogeneic HSCT is the only treatment proved to be potentially curative for phagocyte adhesion impairment in LAD-I. Here, we report on a case of a 30-month-old girl with LAD-I, in whom peripheral blood stem cell from a genotypically identical sibling resulted in mixed chimerism. [ABSTRACT FROM AUTHOR]

Background: Leukocyte adhesion deficiency type I (LAD-I) is a rare, autosomal recessive inherited immunodeficiency disease. LAD-I is caused by mutations in the ITGB2 gene and characterized by recurrent severe bacterial infections, as well as impaired wound healing with lack of pus formation. Methods: In this study, we investigated /TG62 gene mutations in 12 patients and their parents. Genomic DNA was extracted from whole blood samples. All coding regions of the ITGB2 gene were amplified using PCR and followed by direct sequencing. Results: Genetic analysis revealed 12 different homozygous mutations, including six missense (c.382G>A, c.2146G>C, c.715G>A, C.691OC, C.1777C and new C.1686OA), two new nonsense (c.1336G>T and C.1821OA), three-frame shift (c.1143delc, c.1907delA and new c.474dupC) and a splice site (c.1877+2T>C). Flow cytometry analysis of CD11/CD18 expression on neutrophils revealed defect in CD18 in all twelve cases (1.4% to 42%), CD11a in ten cases (0.1% to 26.7%), CD11b in nine cases (1.2% to 58.8%), and CD11c in all cases (0% to 18.1 %). The patients' parents were both heterozygous carriers. Conclusion: Our findings showed four new mutations in the ITGB2 gene. These results can be used for decisive genetic diagnosis, genetic counseling, as well as prenatal diagnosis for all patients who are suspended to LADI. [ABSTRACT FROM AUTHOR]