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Background: According to the WHO's recommendation for developing countries, Bacillus Calmette-Guerin (BCG) vaccination has been implemented in some countries as part of national vaccination programs at birth. Although it is generally considered safe, some complications may occur; including BCGitis (local) or BCGosis (systemic), ranging from mild like local abscesses to fatal impediments like osteomyelitis and disseminated BCG infection. This study aimed to determine the spectrum of inborn errors of immunity (IEI) in BCG-vaccinated neonates experiencing local or systemic complications. Methods: In this cross-sectional study, we investigated Iranian children referred to the Immunology, Asthma, and Allergy Research Institute (IAARI) between 2007-2023 for suspected immunodeficiency. Medical history was recorded, and primary screening tests for immunodeficiency were conducted for all cases. For suspected cases, more advanced immunologic investigations were performed to reach a definitive diagnosis. Furthermore, the study incorporated the documented genetic findings of the patients under investigation. All patients with inborn error of immunity who had a history of BCG vaccine complications within the first year of vaccination were enrolled in the study. Results: We investigated 3,275 cases suspected of IEI, identifying197 patients with both IEI and BCG vaccine complications. Among these, 127 (64.5%) were male. Symptoms began at or before 3 months of age in 64.8% of the cases, and parental consanguinity was reported in 79.2%. Genetic diagnoses were confirmed in 108 patients. Of the 197 patients, 108 (54.8%) had BCGitis, while 89 (45.2%) experienced systemic complications (BCGosis). A family history of IEI, BCG-related complications, and unexplained deaths were observed in 20.3%, 12.2%, and 29.9% of cases, respectively. Furthermore, 46.2% had at least one of these three risk factors in their history. Conclusions: Early BCG vaccine complications may indicate an underlying immunodeficiency, particularly when there is a positive family history of BCG complications, immunodeficiency, or unexplained deaths. Nation-wide vaccination protocols should address this issue by delaying inoculation to allow for immunological screening of suspected immunodeficient patients, thereby preventing BCG vaccine-related morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background: Primary immunodeficiency diseases (inborn errors of immunity) with partial albinism are a group of autosomal recessive syndromes including Chediak Higashi Syndrome (CHS), Griscelli Syndrome type 2 (GS2), Hermansky‐Pudlak Syndromes type 2 and 10 (HPS2, HPS10), Vici syndrome and P14/LAMTOR2 deficiency. Methods: Twenty‐five patients including 10 CHS, 10 GS2, and 5 HPS2 were evaluated in this study within the last 10 years. Five cases with oculocutaneous albinism (OCA) and 5 healthy subjects without albinism were used as two control groups. Genetic analyses were performed by whole exome or panel sequencing or targeted Sanger sequencing. Subsequently, leukocyte granules in peripheral blood smear and hair shaft were examined as screening tests. Results: Giant granules were only presented in the leukocytes cytoplasm of 10/10 CHS patients. The uneven cluster of pigments and giant melanin granules in hair samples were observed in 10/10 GS2 and 10/10 CHS patients, respectively. In both 5/5 OCA and 5/5 HPS2 patients, there were regular pigments in the middle of hair shafts. Genetic analyses were performed for all patients, revealing 7 novel variants in LYST gene for CHS patients and 4 novel variants in AP3B1 for HPS2 patients. Conclusion: Receiving hematopoietic stem cell transplantation (HSCT) in a timely manner is crucial in CHS and GS2 patients; therefore, screening tests may provide a vital clue for early diagnosis in these patients. However, the final confirmation of CHS, GS2, and HPS2 disorders is done by genetic assay. [ABSTRACT FROM AUTHOR]

Griscelli syndrome type 2 (GS2) is an autosomal recessive immunodeficiency characterized by hair hypopigmentation, recurrent fever, hepatosplenomegaly and pancytopenia. This study aims to find new genetic changes and clinical features in 18 children with GS2 caused by the RAB27A gene defect. In all, 18 Iranian children with GS2 who presented with silver grey hair and frequent pyogenic infection were included in this study. After recording demographic and clinical data, PCR sequencing of the RAB27A gene was performed for all exons and exon–intron boundaries. Two patients in this study were subjected to whole‐exome sequencing followed by Sanger sequencing. Light microscopy study of hair showed large irregular clumps of pigment with the absence of giant granules on the blood smear. Mutation analysis of the RAB27A gene identified two novel missense mutations as homozygous in a patient, one in exon 2, c.140G>C and another in exon 4, c.328G>T. In addition, for 17 other patients, 6 reported mutations were obtained including c.514_518delCAAGC, c.150_151delAGinsC, c.400_401delAA, c.340delA, c.428T>C and c.221A>G. The mutation c.514_518delCAAGC was the most frequent and found in 10 patients; this mutation may be considered a hotspot in Iran. Early diagnosis and treatment of RAB27A deficiency can contribute to better disease outcomes. In affected families, genetic results could be urgently needed to make a timely decision about haematopoietic stem cell transplantation and prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder due to a genetic defect in one of the components of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. This complex is composed of membrane-bound gp91-phox and p22-phox subunits, and cytosolic subunits consisting of p47-phox, p67-phox, and p40-phox. A mutation in CYBB gene encoding gp91-phox located on chromosome Xp21.1, leads to X-linked CGD. Herein, we report a 4-year-old Iranian boy presented with episodes of recurrent fever, cervical lymphadenopathy, and abdominal abscesses. Mutation analysis of the CYBB gene in the patient indicated a one-nucleotide deletion, c.316delT, resulting in p.W106GfsX. [ABSTRACT FROM AUTHOR]

Chronic granulomatous disease (CGD), a rare inherited primary immunodeficiency disorder, is caused by mutation in any one of the genes encoding components of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase enzyme. NCF2 gene (encoding P67-phox component) is one of them and its mutation is less common to cause CGD (around 5-6%). Here, we assessed mutation analysis of NCF2 in 4 CGD patients with p67-phox defect in Iran. These patients showed classical CGD symptoms. NCF2 sequence analyses revealed two different homozygous mutations including a nonsense mutation in exon 4, c.304C>T (Arg 102X) in one case and a CA deletion in exon 13 (Leu346fsX380) in one brother and sister; the latter is a new mutation which has not been reported in previous studies. In another patient in whom the attempts to amplify exon 2 individually from genomic DNA were unsuccessful, PCR amplification of exon 2 revealed no band of this exon on agarose gel. A PCR amplification mix of exon 2 and exon 7, with an internal control, confirmed the lack of exon 2 in this patient. Although a gross deletion in other exons of NCF2 has been previously reported, a large deletion encompassing exon 2 has been not reported yet. This abstract was also presented in ESID 2012, Florence, Italy. [ABSTRACT FROM AUTHOR]

Objective: Pomalidomide is one of the newest anticancer drugs that notable research has yet to be conducted on its anticancer effect. In this study, the anti- apoptotic and immune potentiating effects of pomalidomide were examined on bone marrow mononuclear cells in 10 multiple myeloma patients and 10 control subjects simultaneously. Material and Methods: The bone marrow mononuclear cells of both groups were cultured with pomalidomide for 48-hour. Apoptosis induction rate, viability, cytotoxicity, and immunomodulatory effect were evaluated. Results: The results showed that apoptosis and cytotoxicity increased significantly in bone marrow mononuclear cells of multiple myeloma patients cultured in the presence of pomalidomide (p <0.05). However, in the control group, pomalidomide lead to an increase in vital activity of bone marrow mononuclear cells. Moreover, the concentration of IL2 in the presence of pomalidomide was increased significantly in the multiple myeloma group (p <0.05). Conclusion: It seems that pomalidomide could amplify the immune system and eliminate tumor cells in multiple myeloma patients; however, it has no toxic effect on bone marrow mononuclear cells in controls. Pomalidomide could be introduced as first-line treatment in multiple myeloma as well as relapsed or refractory one. Therefore, it could be preferred in order to avoid the side effects in normal cells. [ABSTRACT FROM AUTHOR]

Objective: Biobank is a collection of resources containing biological and genetic materials that help store valuable samples. Establishing a biobank makes easy to access samples for assessing their characteristics. Our biobank consists of four separate biobanks including DNA, HLA, serum, and cell banks. Our aim is to standardize banking the samples of patients and their families who referred to Immunology, Asthma and Allergy Research Institute (IAARI) and suffered from primary immunodeficiency (PID), asthma and allergy. Materials and Methods: IAARI's biobank was established in 2006 with DNA and serum banks, then cell and HLA banks were added in 2012. All of the cases with diagnosis of PID, asthma and allergy entered in this registry and after taking informed consent, their samples were stored in the biobank. Results: Up to now, we stored a total of 3288 DNA samples from PID patients and their relatives, 450 serums from allergic patients, 186 samples of asthmatic patients, more than 700 HLA samples of healthy donors' volunteers, and 43 cell samples from PID patients. Conclusion: This biobank can be used to early diagnosis of PID genetics, and finding matched hematopoietic stem cell transplantation (HSCT) candidates for them. In addition, it can be helpful for investigating prospective genetic and familial surveys. This also decreases need for cost and resampling from patients. [ABSTRACT FROM AUTHOR]

Objective: Nowadays genetic information is need to diagnose, treat, and generally manage different diseases. So genetic testing of immunodeficiency (PID) disorders is also of importance, especially for decisive diagnosis as well as bone marrow transplantation. Registration of information based on genetics has potential benefits for families possessing individuals with that disease for both present and future. This registry aims to collect genetics information about PID patients and their families' members. Materials and Methods: All of the Iranian patients suspected to PID who referred to immunology, asthma and allergy research institute (IAARI) between 2007 and 2016have been investigated regarding to PID. After taking informed consent, screening tests for PID were performed completely. Genetics data of individuals after definite diagnosis were enrolled in the genetic registry. Results: Genetic testing of 15 different PID diseases has been performed for more than 450 cases and collected in this registry. Of these 258 cases and their families had decisive mutation and genetic diagnosis. The rate of diseases was: Chronic Granulomatous Disease 22.17%, Severe Combined Immunodeficiency 21.33%, Wiskott-Aldrich Syndrome 10.46%, Congenital Neutropenia 8.36%, Leukocyte Adhesion Deficiency 7.53%, Griscelli 5.85%, Hemophagocytic Lymphohistiocytosis 5.23%, Angioedema 5.23%, Cystic Fibrosis 3.76%, Hyper IgE 2.92%, Hyper IgM 2.92%, X-linked Agammaglobulinemia 2.72%, Hermansky-Pudlak Syndrome 0.83%, Ataxia-Telangiectasia 0.41% and WHIM Syndrome 0.20%. Conclusions: This registry can be valuable for making aware of patients including decisive diagnosis, genetic counseling, carrier detection and prenatal diagnosis. In addition, this is a bank of data for future research. [ABSTRACT FROM AUTHOR]

Background: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency (approximately 1 case in 200.000-250.000 newborns) caused by defect in one of the components of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase enzyme (membrane-bound glycoproteins gp91, and cytosolic subunits p47-phox, p67-phox, p40-phox and p22-phox). This leads to defective intracellular killing by phagocyte cells. One of the components of NADPH-oxidase is p22-phox which is encoded by CYBA gene. In this study were identified new genetic changes of CYBA in 22 Iranian patients with autosomal recessive-CGD (AR-CGD). Methods: Twenty two CGD patients based on defect in NADPH oxidase activity (by NBT slide test and DHR-123 assay) and their demographic data and clinical histories were entered this study. They were referred to Immunology, Asthma and Allergy Research Institute (IAARI) for diagnosis and treatment. All patients had p22-phox deficiency based on western blotting. Genomic DNA was extracted from peripheral blood mononuclear cells (PBMCs) and PCR followed by direct sequencing to find p22-phox mutations. Results: Mutation analysis of CYBA revealed 12 different mutations, including three novel mutations: one deletion in exon 1, and two transitions in exon 3 [c.136G>A (p.Gly46Ser)], and exon 6 [c.388C>T (p.Gln130X)]. Conclusions: Three new mutations of CYBA gene in 4 of 22 Iranian patients with AR-CGD were found. These 3 novel mutations can partly complete the data base of Human Gene Mutation Database (HGMD). It can also be helpful for further prenatal diagnosis of next children in the affected families. Also it will be useful for timely decision making in bone marrow transplantation as treatment for CGD patients. [ABSTRACT FROM AUTHOR]

Chronic granulomatous disease is a rare primary immunodeficiency disorder, which leads to increased susceptibility to recurrent infections and severe inflammatory manifestations.  There have been reports regarding different aspects of genitourinary involvement in chronic granulomatous disease, some of which are hydronephrosis, granulomatous cystitis, and glomerulonephritis, but among these complications, amyloidosis is rather rare. We report a patient with chronic granulomatous disease that developed amyloidosis later in the course of the disease. [ABSTRACT FROM AUTHOR]