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Selective IgA deficiency (IgAD) (serum IgA concentration of

Selective deficiency of immunoglobulin A (IgA) is the most frequent primary hypogammaglobulinemia. As some IgA-deficient patients have IgA antibodies in their plasma which may cause anaphylactic reactions, blood centers usually maintain a list of IgA-deficient blood donors to prepare compatible blood components. In this study we determined the incidence of selective IgA deficiency (SIgAD) in normal adult Iranian population. 13022 normal Iranian blood donors were included in this study. The assay which we used was adapted to the manual pipetting system and ELISA reader was used for screening. Other classes of immunoglobulins (G, M), as well as secretory IgA and IgG subclasses were tested in IgA deficient cases by ELISA. SPSS was used for statistical analysis. Among 13022 studied cases, 11608 blood donors were males (89.14%) and 1414 were females (10.86%). Their mean (±SD) age and weight were 38.5±11 years and 82±12 Kg respectively. Twenty of the screened samples were found by means of ELISA to be IgA-deficient (less than 5mg/dl), (frequency; 1:651). The data could indicate a compensation for IgA deficiency by serum IgM in one of our IgA deficient cases (Patient 5). We observed a correlation between IgG3 and serum IgA in deficient cases (r=0.498, P=0.025). Our results indicate that in present study the prevalence of S IgA D is in agreement with data from other Caucasians populations (from 1:300 to 1:700). In conclusion, Selective IgA Deficiency could be almost asymptomatic in most cases in general population. Our study suggests that; due to high frequency of IgA deficiency in Iran, it seems necessary to measure IgA levels for every blood donor and blood recipient to find IgA deficient cases.

Hereditary Angioedema (HAE) is a rare autosomal dominant immunodeficiency disease with mutation in C1 inhibitor gene (SERPING1) which deficient and dysfunction of C1-INH protein result in HAE type I or type II, respectively. The present study aimed to define the genetic spectrum of HAE type I and type II among Iranian patients. Thirty-four patients with clinical phenotype of recurrent edematous attacks in face, upper and lower limbs, hands, and upper airway entered the study. Mutations in SERPING1 were analyzed using PCR and Sanger Sequencing. In addition, Multiplex Ligation-dependent Probe Amplification (MLPA) was performed to discover large deletions or duplications in negative screening samples by Sanger. Twenty-three patients were diagnosed with HAE type I and 11 with HAE type II. Fourteen distinctive pathogenic variations including five frameshift (p.G217Vfs*, p.V454Gfs*18, p.S422Lfs*9, p.S36Ffs*21, p.L243Cfs*9), seven missense (p.A2V, p.G493R, p.V147E, p.G143R, p.L481P, p.P399H, p.R466C), one nonsense (p.R494*), and one splicing defect (C.51 + 2 T˃C), which three of these mutations were identified novel. However, no mutation was found in seven patients by Sanger sequencing and MLPA. Final diagnosis with mutation analysis of HAE after clinical evaluation and assessment of C1INH level and function can prevent potential risks and life-threatening manifestations of the disorder. In addition, genetic diagnosis can play a significant role in facilitating early diagnosis, pre-symptomatic diagnosis, early diagnosis of children, asymptomatic cases, and those patients who have the borderline biochemical results of C1-INH deficiency and/or C4. [ABSTRACT FROM AUTHOR]

Particulate matter (PM) as the carcinogenic air pollutants can lead to aggravated health outcomes. Epidemiological studies demonstrated that PM can be engaged in different diseases such as cardiovascular, respiratory and cancer. The in vitro secretion of proinflammatory cytokines by human peripheral blood mononuclear cells (PBMCs) has been used to assess the effects of PM with an aerodynamic diameter < 10 μm (PM10). This study compared the proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interleukin 1-beta (IL1-β) secretions of PBMCs exposed to PM10 of dust storm and inversion. We collected PM10 samples during the spring and autumn seasons in two locations. Isolated PBMCs were exposed separately to 50, 150, and 300 μg/ml of different type of PM10 for 4 and 24 h. The mean concentrations of TNF-α for the PM of dust storm and inversion were 6305.61 ± 2421 and 6651.74 ± 2820, respectively. Also the mean concentrations of IL1-β for the PM of dust storm and inversion were 556.86 ± 162 and 656.35 ± 196, respectively. Furthermore, these values for the production of IL-6 were 12,655 ± 5661 and 16,685 ± 8069, respectively. Although no significant difference was observed between the PM of dust storm and that of inversion with regard to PBMCs, the results showed a significant increase in the proinflammatory cytokine secretion of both PMs compared with the controls. Moreover, TNF-α, IL1-β, and IL-6 secreted in cells exposed to PM10 of dust storm were about 10 times more than the controls, these values for cells exposed to PM10 of inversion were around 10, 12, and 14 times more than the controls, respectively. It can be concluded that the PM10 of both dust storm and inversion can play a significant role in proinflammatory cytokine secretion due to its harmful effect on human health. [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]

Mannose-binding lectin (MBL) is a protein of innate immune system that is involved in opsonization and complement activation. MBL deficiency is associated with predisposition to infectious diseases; however subnormal levels are also seen in healthy subjects. The aim of this study was to investigate the prevalence and clinical manifestation of MBL deficiency in patients with increased susceptibility to infection. We studied the MBL serum concentration of 104 patients with a history of recurrent and/or severe infections referred to Immunology, Asthma and Allergy Research Institute (IAARI) in order to evaluate the primary immunodeficiency (PID). The distribution of MBL deficiency in these patients and 593 healthy subjects of previous study were analyzed. The frequency of individuals with MBL deficiency was significantly higher in patients with recurrent and/or severe infections (13.5% [14/104]) compared with healthy subjects (4.7% [28/593]; p=0.001; OR 3.1, 95% CI 1.5-6.1). However, in 10.9% (7/64) of patients with recurrent infections without any immunodeficiency background, the MBL deficiency was detected. On the whole, our findings indicate an association between MBL deficiency and increased susceptibility to infections. [ABSTRACT FROM AUTHOR]

Hyperimmunoglobulin E Syndrome (HIES) is a complex primary immunodeficiency characterized by both immunologic and non-immunologic manifestations. High serum IgE level, eosinophilia, eczema, recurrent skin and lung infections constitute the immunologic profile of HIES, whereas characteristic facial appearance, scoliosis, retained primary teeth, joint hyperextensibility, bone fractures following minimal trauma and craniosynostosis are the main non-immunologic manifestations. The diagnosis of HIES cannot be made by routine immunologic tests. As the main characteristic laboratory abnormalities of this syndrome are highly elevated serum IgE levels and eosinophilia; both features have a broad spectrum of differential diagnosis. The purpose of this essay was presenting the best way for diagnosis management of HIES. Based on the genetic reports of patients of the Center for Chronic Immunodeficiency (CCI) as a single center experience, and applying project management (PM) in health care research projects, we sought the best way for a rapid diagnosis of HIES. The combination of project management principles with immunologic and genetic knowledge to better define the laboratory and clinical diagnosis lead to an improvement of the management of patients with HIES. These results are shown in one "Decision Tree" which is based on 342 genetic reports of the CCI during the past ten years. It is necessary to facilitate the diagnostic analysis of suspected HIES patients; applying project management in health care research projects provides a better and more accurate diagnosis eventually leading to a better patients' care. This Abstract was presented at 16th Biennial Meeting of the European Society for Immunodeficiencies (ESID 2014), Prague, Czech Republic. [ABSTRACT FROM AUTHOR]

Cytokines have been introduced as critical inducers in the development of Th subpopulations.Cytokines like IL-10 are involved in inducing regulatory T cells such as Type 1 regulatory T (Tr1) cells cells. IL-22 is a member of IL-10 family of cytokines, and IL-28A is a member of IFN-γ family. In this study, cord blood mononuclear cells (CBMC) from normal healthy individuals were isolated by Ficoll and then naïve T cells were purified by CD4+CD25+ Regulatory T cell Isolation kit. The effect of these two cytokines on production of IL-5, TGF-β, IL-10, IL-4 and IFN-γ cytokines from cord blood T cells was investigated to identify Tr1 cells as well as Th1 and Th2 polarization. Flow cytometric analysis showed that IL-28A and IL-22 were not effective in expression of IL-5 and TGF-β either alone or in synergy, but in view of IL-10, IL-4 and IFN-γ, the results showed that IL-22 increased IL-10 and IL-4 but had a decreasing effect on IFN-γ. The results showed that IL-28A was not effective in increasing or decreasing the level of IL-10, IL-4 and IFN-γ. Therefore, according to these results, IL-22 and IL-28A were not effective in inducing Tr1 cells. [ABSTRACT FROM AUTHOR]

A new competitive immunochromatography (ICG) strip test based on polyclonal antibody (pAb) conjugated with gold nanoparticles (NPs) was developed and its applications for primary screening of immunoglobulin (Ig) A in serum were evaluated. Nanocolloidal gold as the detection reagent, with an average particle diameter of 20 nm, was synthesized and labelled pAb. The antibody-nanocolloidal gold probe was applied on the conjugate pad, and human IgA was immobilized on a nitrocellulose membrane as the capture reagent to prepare the ICG strip test. It took only 10 minutes to accomplish a semi-quantitative detection of serum IgA in this assay. In the optimized investigational conditions, the ICG strip test could distinguish human serum IgA in the range from 1 to 270 ng/mL with a detection limit of 5 ng/mL. The reliability of testing procedures was examined by performing the ICG strip test with 11 serum samples and comparing the results with those obtained via enzyme-linked immunosorbent assay (ELISA). The ICG strip was sufficiently sensitive and accurate for a rapid screening of IgA in human serum. [ABSTRACT FROM AUTHOR]

Objective: Hyper-immunoglobulin E syndromes (HIES) are a group of rare primary immunodeficiencies characterized by a triad of recurrent bacterial or viral respiratory infection, skin abscesses with chronic eczema and elevated serum IgE levels. HIES have two common genes: STAT3 and DOCK8 with respectively autosomal dominant (AD) and autosomal recessive (AR) inheritance. We aimed to identify the molecular basis of these genes in HIES patients Material and Methods: Twenty-nine HIES suspected patients referred to the Immunology, Asthma and Allergy Research Institute (IAARI) between 2012 and 2015 were enrolled in this study due to their inclusion criteria. HIES scoring based on NIH questionnaire and subsequently immunological screening tests was done for each patient. Patients were divided by "Homozygosity Mapping" to two groups of heterozygous or homozygous and genetic study was done by PCR considering the priority of STAT3 or DOCK8 gene respectively. Results: Three out of 6 STAT3 mutations were seen in hot spots and the rest in other locations. Ten Dock8 mutations were detected, among them seven revealed large deletions. Totally, 16 out of 29 showed mutations in STAT3 or DOCK8. The mean age of HIES patients was 12.5 years (1.5-30) with a range of IgE level between 2500 to 42000 IU/mL and eosinophilia differs between 80 to 21200/μL. Recurrent pneumonia and skin abscesses with dental and skeletal abnormalities was the most prevalent problem of patients with STAT3 mutation. Severe and persistent viral infections, recurrent pneumonia, and CNS manifestations were seen in DOCK8 deficient patients. During the four years of study, unfortunately 7/10 of our DOCK8 patients died but all STAT3 patients are alive. Conclusion: The clinical phenotypes of the presented patients in both groups are consistent with that of other reports. Genetic study showed that half of the STAT3 mutations were in hot spots and half of them were seen in other locations. In DOCK8 group, the mutations were different from other reports and interestingly new mutations were found. DOCK8 deficiency was mostly due to large deletions. Molecular diagnosis of this gene is a useful approach for timely Hematopoietic Stem Cell Transplantation as a firm therapeutic plan due to deleterious consequences of this syndrome. In addition, the definitive prenatal diagnosis could prevent the birth of another patient child in these families. [ABSTRACT FROM AUTHOR]

Objective: Hereditary Angioedema (HAE) is a rare autosomal dominant disorder that is caused by improper quantitative level or C1-inhibitor function and these lead to the HAE type I and type II, respectively. C1-inhibitor is a serine protease inhibitor, which controls the activation of complement system and regulation of the fibrinolytic, contact and coagulation systems. C1-inhibitor gene (SERPING1) is located in the q12-q13.1 sub-region of chromosome 11 and consists of eight exons. The aim of this study is genetic diagnosis of HAE type I patients. Material and Methods: The patients who referred to Immunology, Asthma & Allergy Research institute (IAARI) between Jan 2006 to Jan 2014 with clinical phenotype of HAE (subcutaneous angioedema, abdominal pain, laryngeal edema), were entered this study. Twenty HAE type I patients were evaluated for genetic analysis of SERPING1 gene based on low levels of C4 and C1-inhibitor. Blood samples were obtained from these patients and after the DNA extraction from EDTA treated blood samples, polymerase chain reaction (PCR) was accomplished for coding exons (exon 2 to 8) of SERPING1 gene and PCR products were sequenced and the results were analyzed by Finch TV program. Results: Among twenty patients from 15 families with HAE type I, 9 mutations in SERPING1 gene were identified in 12 patients. All mutations were in heterozygous state except one new homozygous missense mutation (c.440T>A) in a patient. The others including one splicing defect (c.51+2T>C) in intron 2, three frame shift mutations in exon four (c.650delG) and exon 8 (c.1356_1357delTG, c.1264delT), three missense mutations in exon 2 (c.5C>T), and exon 8 (c.1477G>A, c.1442T>C), and one nonsense (c.1480C>T) mutation in exon 8 which are previously reported. Conclusion: HAE is a life-threatening disease, and if laryngeal edema occurs possibly leads to death. Therefore, early genetic diagnosis in the families who carries the mutation with symptomatic or asymptomatic phenotype of disease could be helpful for prevention of acute edema and proper treatment in HAE patients and other family members. [ABSTRACT FROM AUTHOR]

Immunophenotyping of lymphocytes is very essential for evaluation of immune system. Due to the effect of environmental factors and ethnical diversity on immune system, establishment of an internal normal range of lymphocyte subsets is a necessity for each population. The aim of this study was to determine the normal range of T and B lymphocytes, and NK cells in normal Iranian adults. Two hundred and thirty three Iranian normal adult volunteers took part in this study. Complete Blood Count (CBC) was performed for them with Sysmex (KX21) and cells with CD3, CD4, CD8, CD19 and CD16/56 surface markers were simultaneously detected by flow cytometry method with FACstar system. Their percentile and absolute count were determined. The volunteers were 150 male and 83 female. Mean percentages of lymphocyte subpopulation were: CD3 (67.66 ±7.76), CD19 (14.41±5.09), CD4 (39.22±6.7), CD8 (25.42 ±5.4) and CD16/56 (10.14±6.42). Also, their mean absolute count of lymphocyte bearing CD3, CD19, CD4 and CD8 were 1,504±505/μl, 332±186/μl, 827±313/μl and 522±185/μl, respectively. Our results are comparable with similar Asian results from other Asian population, but are different from European population, we therefore conclude that it is necessary for each laboratory to establish an internal normal range for the lymphocytes bearing abovementioned markers. [ABSTRACT FROM AUTHOR]

Hematopoietic cord blood (CB) stem cell transplantation has more advantages to other cell sources because of lower Graft Versus Host Disease (GVHD). Interleukin-15(IL-15) is an immunoregulatory cytokine, known to enhance cytolytic function of cord Natural Killer (NK) cells. The aim of this study was to investigate the effect of IL-15 on NK cytotoxicity simultaneously in different cell death stages. We compared the ability of IL-15 to enhance the NK cytotoxicity of CB in comparison to adult blood Mononuclear Cells (MNCs) against K562 target cells by co-staining with AnnexinV-FITC and Propidium Iodide after 3.5 h incubation at 37C and 5% CO2 by using flow cytometric method. We also evaluated phenotypic changes after treatment by IL-15 in both cell sources. Our results indicated that CB samples had lower level of apoptosis, while necrosis was negligible; also by escalating Effector: Target (E: T), we got higher level of apoptosis and necrosis in peripheral blood (PB). NK activity of cord and adult MNCs was enhanced by incubation with IL-15 (10 ng/ml) for 72 h with significantly higher results of PB in comparison to CB (p<0.0001). Moreover, IL-15 increased the percentage of CD3-/CD56+ and CD25+ cells after 72 h incubation. Results showed incubation with human recombinant (hr) IL-15 for 3 days increased NK activity. Taken together, these results indicated that NK cytotoxicity of CB MNCs could be augmented by human recombinant (hr) IL-15, but this activity did not reach to same level of PB counterparts. We established that CD25 expression on CB MNCs could be increased with IL-15, in 72-hour cultures, but to a lesser degree compared to that on corresponding adult PB MNCs. [ABSTRACT FROM AUTHOR]

Bronchiectasis is a chronic debilitating condition characterized by abnormal dilated thickwalled bronchi. To investigate humoral immune function in bronchiectatic patients, this study was performed. Forty patients with established diagnosis of bronchiectasis, who were referred from two tertiary care pulmonology centers in Tehran, were investigated in this study. Immunoglobulin isotypes concentrations and IgG-subclasses were measured by nephelometry and enzymelinked immunosorbent assay (ELISA) methods, respectively. All patients received unconjugated pneumococcal vaccine, and blood samples were taken before and 21 days after vaccination. Specific antibodies against whole pneumococcal antigens were measured using the ELISA method. Fifteen (37.5%) out of 40 patients were diagnosed to have defects in antibody mediated immunity including 5 (12.5%) patients with immunoglobulin class deficiency (2 with common variable immunodeficiency and 3 with IgA deficiency), 3 (7.5%) with IgG subclass deficiency and 7 (17.5%) patients had Specific antibody deficiency (SAD) against polysaccharide antigen despite normal levels of serum immunoglobulins and IgG subclasses. Our study along with several other studies confirmed that all patients with bronchiectasis should undergo thorough immunological evaluation in order to identify the presence of the underlying immunologic defect. This evaluation should include serum immunoglobulins, IgG subclasses concentrations and also determination of serum antibodies against pneumococcal antigens. Early diagnosis and appropriate treatment will prevent the subsequent complications and improve quality of life of affected individuals. [ABSTRACT FROM AUTHOR]

Objective: Hereditary Angioedema (HAE) is a rare autosomal dominant disorder caused by low serum levels (type I) or dysfunction (type II) of C1 Inhibitor (C1INH), which is characterized by subcutaneous and/ or submucosal edema attacks involving face, limbs, genitalia, gastrointestinal and respiratory system. HAE could give rise to fatal laryngeal edema, acute abdominal pain leading to unnecessary emergency surgeries, and reduced quality of life. Therefore, the aim of this study was to investigate and report the demographic, clinical and laboratory findings of patients registered in Iranian HAE registry (IHAER). Material and Methods: The patients referred (2006-2016) to Immunology, Asthma and Allergy Research Institute (IAARI) with symptoms suggestive of HAE were investigated (after signing informed consent form) using a questionnaire and laboratory tests. The patients with a definite diagnosis of HAE (type I, II) based on low serum levels of C4 and C1INH quantity/quality accompanying with suggestive clinical findings (after ruling out other possible etiologies) were enrolled into this study. Moreover, in some cases genetic analysis reconfirmed laboratory results. Results: Among 80 patients registered in IHAER with definite diagnosis of HAE (Type I, II; 48.8%, 51.3%) 30 patients belonged to children and adolescents group (aged ≤ 21). The median symptoms age-onset and median diagnostic delay were 11 (min, max; 1, 72) and seven (min, max; 0, 39) years, respectively. Physical trauma (69.7%) and emotional stress (57.6%) were found to be the most common triggers of attacks; however, 82% of patients reported spontaneous attacks as well. The most commonly involved sites were face and limbs. Moreover, laryngeal edema was reported in 56.1% of patients leading to death in three patients during this study. Conclusion: HAE is a life-threatening disease diagnosed with significant delay possibly due to mistaking it for other disorders causing similar symptoms such as acute face and limbs edema. On the other hand, complete avoidance of emotional and physical stress as common HAE triggers could not be easily achieved. Thus, the outcomes of IHEAR in the form of scientific papers/reports is meant to inform health care providers, and policy makers about this rare disease, which would in turns, help with an earlier diagnosis, and improvement in patient care and quality of life. [ABSTRACT FROM AUTHOR]

Background: Hereditary angioedema (HAE) is a rare autosomal dominant disorder characterized by Cl-INH (Cl esterase inhibitor), low serum levels (type I), dysfunction (type II) or normal serum levels and function (type III), which lead to subcutaneous and submucosal edema attacks. The aim of this study was to investigate the demographic, clinical and laboratory findings of Iranian patients with HAE. Methods: The patients with a history or symptoms of angioedema who were referred to Immunology, Asthma and Allergy Research Institute (IAARI) between Jan 2006 and Jan 2014, were assessed based on a specific questionnaire and laboratory evaluation. The patients with a definite diagnosis of HAE type I and type II were entered into this study. Results: Among 51 patients, 63.3% were diagnosed with HAE type I and 36.7% with HAE type II. Fifteen patients were under 18 years and 36 were adults. The mean age of symptoms onset and diagnosis were 12.33 ± 10.20 years and 24.48 ± 14.64 years, respectively. The mean delay of diagnosis was 11.02 ± 11.60 years. The most commonly involved locations of edema were hands, face and genitalia. Moreover, laryngeal edema was observed in 61.2% of patients, which led to death in two patients during this study. Conclusion: Hereditary angioedema is a life threatening disease with considerable morbidity and mortality. The outcomes of this study can be used to inform clinicians and health care providers about HAE, which can help earlier diagnosis and better management of the patients, specifically in life threatening attacks. [ABSTRACT FROM AUTHOR]

Immunophenotyping of lymphocytes is very essential for evaluation of immune system. Due to the effect of environmental factors and ethical diversity on immune system, establishment of an internal normal range of lymphocyte subsets is a necessity for each population. The aim of this study was to determine the normal range of T and B lymphocytes, and NK cells in normal Iranian adults. Two hundred and thirty three Iranian normal adult volunteers took part in this study. Complete Blood Count (CBC) was performed for them with Sysmex (KX21) and cells with CD3, CD4, CD8, CD19 and CD16/56 surface markers were simultaneously detected by flow cytometry method with FACstar system. Their percentile and absolute count were determined.The volunteers were 150 male and 83 female. Mean percentages of lymphocyte subpopulation were: CD3 (67.66 ±7.76), CD19 (14.41±5.09), CD4 (39.22±6.7), CD8 (25.42 ±5.4) and CD16/56 (10.14±6.42). Also, their mean absolute count of lymphocyte bearing CD3, CD19, CD4 and CD8 were 1,504±505/µl, 332±186/µl, 827±313/µl and 522±185/µl, respectively.Our results are comparable with similar Asian results from other Asian population, but are different from European population, we therefore conclude that it is necessary for each laboratory to establish an internal normal range for the lymphocytes bearing above- mentioned markers.

Epilepsy is one of the most frequent neurological disorders. Despite the advances and improvements in treatment of seizure disorders, immunologic alterations related to anticonvulsant drugs have been described. The aim of this paper is to assess the effect of some antiepileptic drugs on serum immunoglobulin levels in epileptic patients. Seventy-one patients with epilepsy were included in the study. Participants were divided into three groups based on their treatment with carbamazepine (n=33), sodium valproate (n=22) or phenobarbital (n=16) as monotherapy. Three samples were taken from each patient and serum immunoglobulin levels were measured before treatment, 3 months and 6 months after therapy. Overall, eleven patients out of 71 (15.5%) had a decrease in at least one serum immunoglobulin level (more than 2SD below age-matched control). In the patients receiving carbamazepine, 8 patients (24.2%) showed significant decline in at least one immunoglobulin (3 cases in IgA and 5 cases in IgG). In the group of treated with sodium valproate, 2 patients showed significant decrease in serum IgA level. Results of the last group indicated a significant reduction in serum IgG concentration only in one patient. No patient at all showed significant decrease in serum IgM level. This study suggests that anti-epileptic drugs could reduce serum immunoglobulins, especially IgA and IgG; among them carbamazepine effect is of more concern.