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X-linked Agammaglobulinemia (XLA) is a hereditary immunodeficiency, characterized by an early onset of recurrent bacterial infections, hypogammaglobulinemia and markedly reduced B lymphocytes number. In order to determine the association of neutropenia among Iranian patients with XLA, hospital records of 30 patients with confirmed XLA in Children Medical Center Hospital, were reviewed. Eight out of 30 XLA patients (26.7%) developed neutropenia during the course of the disease. In two patients, episodes of neutropenia were identified before or at the time of diagnosis of XLA. Other six patients whom were not visited regularly and did not receive periodical immunoglobulin replacement therapy experienced neutropenia after diagnosis of XLA. Neutropenia in XLA is mainly associated with infection and is resolved with intravenous immunoglobulin replacement and antibiotics therapy.

Bovine β-casein (β-CN) is a highly amphiphilic micellising phospho-protein showing chaperone-like activity 24 in vitro. Recently, existence of multiple sequential epitopes on β-CN polypeptide chain in both hydrophilic– 25 polar (ψ) and hydrophobic–apolar domains (φ) has been evidenced. In order to clarify specific contribution 26 of polar and apolar domains in micellisation process and in shaping immunoreactivity of β-CN, its dimeric/ 27 bi-amphiphilic “quasi palindromic” forms covalently connected by a disulfide bond linking either N-terminal 28 (C4 β-CND) or C-terminal domain (C208 β-CND) were produced and studied. Depending on the C- or N- 29 terminal position of inserted cysteine, each dimeric β-CN contains one polar/apolar region at the centre and 30 two external hydrophobic/hydrophilic ends. Consequently, such casein dimers have radically different 31 polarities/hydrophobicities on their outside surfaces. Dynamic light scattering (DLS) measurements indicate 32 that these dimeric casein molecules form micelles of different sizes depending on arrangement of polar 33 fragments of the β-CN mutants in their constrained dimers. Non-aggregated dimers have different 34 hydrodynamic diameters that could be explained by their different geometries. Measurements of 35 fluorescence showed more hydrophobic environment of Trp residues of C208 β-CND, while in similar 36 experimental conditions Trp residues of C4 β-CND and native β-CN were more exposed to the polar medium. 37 Both fluorescence and DLS studies showed greater propensity for micellisation of the dimeric β-CNs, 38 suggesting that the factors inducing the formation of micelles are stronger in the bi-amphiphilic dimers. 1-39 Anilino-naphthalene-8-sulfonate (ANS) binding studies showed different binding of ANS by these dimers as 40 well as different exposition of ANS binding (hydrophobic) regions in the micellar states. The differences in 41 fluorescence resonance energy transfer (FRET) profiles of C4 β-CND and C208 β-CND can be explained by 42 differences of distances and/or by differences of relative orientations of the donor (Trp) and acceptor (ANS), 43 as well as by differences in quenching properties of the disulfide bridges and intra-molecular hydrophobic 44 interactions. The immunoreactivity assays showed somewhat lower IgE response to C208 β-CND than to C4 45 β-CND. Thus, dimerization of C208 β-CN, connecting two C-terminal hydrophobic domains of two monomers 46 doubling long-range hydrophobic interactions, possibly may hide a part of epitopes in the hydrophobic 47 interface/core of C208 β-CND that is consistent with the results of DLS and fluorescence studies. The 48 obtained results indicate structural differences of dimers – possibly the formation of Y- and U-shaped 49 structures for C208 β-CND and C4 β-CND, respectively. This study not only demonstrated the importance of 50 the organization of polar and hydrophobic regions during micellisation of the constrained and oriented β-CN 51 dimers but also confirmed a possible role of C-terminal hydrophobic domain in the immunoreactivity profile 52 of native β-CN.

Adverse drug reactions (ADRs) are a major cause of hospital admission and inpatient morbidity. The department of internal medicine is not an exception to this issue. This study was performed to determine the nature and frequency of ADRs in an internal medicine ward in Iran.This survey was a prospective observational study based on admissions of 400 patients to the internal medicine ward over a 15-week period. Patients were intensively followed in order to assess any ADR as a cause of admission or occurring during hospitalization. Any suspicious ADR was confirmed by a pharmacist/pharmacologist.There were 47 patients of 400 patients (11.75%) that experienced at least one ADR. ADR leading to the admission was seen in seven cases (1.75%) and in 40 (10%) it occurred during hospitalization. ADRs were identified as preventable reactions in 50% of cases and as predictable in 94.3%. The severity of 18.6% of the ADRs was identified as mild, 62.9% as moderate, 14.3% as severe and 4.3% as lethal. Gastrointestinal system disorders (44.3%) represented the most frequent ADRs. The therapeutic groups that most commonly associated with suspected ADRs were antineoplastic, immunosuppressive and medicines used in palliative care (54.8%).ADRs are common among hospitalized patients in department of internal medicine and can be severe and even lethal. Since most ADRs occurred during hospitalization in studied patients and half of them were preventable, prevention strategies should be considered in hospitals. Also, our findings confirmed the role of hospital pharmacists in the reducing ADRs.

Common Variable Immunodeficiency (CVID) is a heterogeneous group of disorders characterized by hypogammaglobulinemia and an increased susceptibility to recurrent infections as well as autoimmunity and malignancies. Idiopathic Thrombocytopenic Purpura (ITP) and Autoimmune Hemolytic Anemia (AIHA) are two autoimmune disorders which may be seen in association with CVID. Among 85 CVID patients, seven cases had ITP and/or AIHA (8%). Four of these patients had one or more episodes of ITP, one patient had AIHA, and two patients had both ITP and AIHA (Evans syndrome). Almost, all patients experienced chronic and recurrent infections mostly in respiratory and gastrointestinal systems during the course of the disease. Among the seven patients, five presented their underlying disease with recurrent respiratory and/or gastrointestinal tract infections, while in two remaining patients, CVID was presented with ITP. Three patients died until now; two because of hepatic failure and one due to pulmonary hemorrhage. As CVID is prone to autoimmune disorders, it should be considered as a differential diagnosis of adult-onset ITP and possibly in children. Chronic and recurrent ITP, especially in the presence of propensity to respiratory and gastrointestinal infections mandate the evaluation for an underlying immune dysregulation such as CVID.

The aim of this study was to determine the frequency of adverse reactions to antibiotics by organ system in hospitalized children in the infectious ward of a pediatric diseases referral center in Iran.All patients treated with antibiotics were evaluated daily for the presence of ADRs during a 5-month period. For each suspected ADR, a specialized questionnaire was completed in order to obtain the information necessary for analysis of ADRs.Among 300 patients, 65 ADRs were seen in 36 patients (12%) during their hospitalization. Pneumonia was the most common reason for administering antibiotics; ceftriaxone and rifampin were the most frequently implicated antibiotics in ADRs. There was a significant relationship between the number of drugs used and the rate of ADRs (p=0.0001). The most commonly affected organ systems were skin and appendages, and the gastrointestinal system. Maculopapular rashes were the most frequent skin ADRs.As antibiotics are the most frequently used drugs in children, and also because of significant relationship between the number of drugs used and ADRs, limited use and careful selection of type and dose of antibiotics as well as close clinical observation are very important in minimizing ADRs.

Huntington disease (HD) is a genetically dominant condition caused by expanded CAG repeats which code for glutamine in the HD gene product, huntingtin. Huntingtin is expressed in almost all tissues, so abnormalities outside the brain can also be expected. Involvement of nuclei and mitochondria in HD pathophysiology has been suggested. In fact mitochondrial dysfunction is reported in brains of patients suffering from HD. The tRNA gene mutations are one of hot spots that can cause mitochondrial disorders. In this study, possible mitochondrial DNA (mtDNA) damage was evaluated by screening for mutations in the tRNA(leu/lys) and ATPase 6 genes of 20 patients with HD, using PCR and automated DNA sequencing. Mutations including an A8656G mutation in one patient were observed, which may be causal to the disease. Understanding the role of mitochondria in the pathogenesis of neurodegenerative diseases could potentially be important for the development of therapeutic strategies in HD.

Atopic dermatitis (AD) is a common skin condition. The aim of this study was to evaluate the impact of AD on the quality of life of children or adults and to identify the area of patients' lives most affected by the disease.Eighty six patients with AD who were referred to an immunology clinic and 98 patients (4 years old) attending a general clinic acting as controls (without any chronic or severe disease) participated in this survey. A physician filled the Children's Dermatology Life Quality Index (CDLQI) questionnaire for 4-16 year old children and the Dermatology Life Quality Index (DLQI) questionnaire for individuals more than 16 years via face-to-face interview.There were significant differences between the mean of CDLQI score and DLQI score in case and control groups (p0.001). For children and adults with AD, the mean score of each question was significantly higher than in the control group (p0.001).This study agreed with previous findings that AD has a major impact on physical well-being. The individuals dealing with AD and their families need more than just the physical treatment of symptoms. Educational and psychological support for patients and their families in addition to medical treatment of AD may improve their long-term physical outcomes.

Objective:One hundred and nine patients with primary antibody deficiencies were selected in order to determine the frequency of ENT complications.Method:Demographic information and ENT medical histories were collected for each patient. Duration of study for each patient was divided into two periods of before diagnosis and after diagnosis and the initiation of treatment.Results:Eighty-two of 109 patients (75.2 per cent) experienced ENT infections during the course of the disease (63: otitis media, 75: sinusitis and nine: mastoiditis). At the time of diagnosis, 52 (47.7 per cent) out of 109 patients presented with an ENT symptom. The frequencies of episodes were 27 for sinusitis and 25 for otitis media (one complicated with mastoiditis). After immunoglobulin replacement therapy the incidence of otitis media was reduced from 1.75 before treatment to 0.39 after treatment per patient per year (p = 0.008). The incidence of sinusitis also significantly decreased from 2.38 to 0.78 (p value = 0.011).Conclusion:ENT infections are common medical problems in primary antibody deficiency patients. Persistent and recurrent ENT infections should be suspected as originating from a possible underlying immunodeficiency.

Chediak - Higashi Syndrome (CHS) is a rare, primary Immunodeficiency disorder with an autosomal recessive (AR) inheritance and characterized by re¬current infection, partial occulocutaneous albinism and an accelerated phase. In this report we describe clinical and laboratory findings from 6 CHS pa¬tients. Clinical and laboratory information of six patients who were referred to our center during the last 20 years (from 1983 - 2003) were reviewed. Onset age of disease was between 3 months to 10 years. All patients had history of consanguineous parents and two patients were siblings. All patients had oculocutaneous albinism, nystagmus, recurrent infections which included upper and lower respiratory tract (U&LRT) infections, stomatitis, thrush, and skin ab¬scesses and hepatitis. In laboratory findings, all patients had neutropenia and normal immunoglobulins and normal CD3, CD4, CD8and CD 19 lymphocyte by flowcytometry and three of the four patients had chemotatic defect. Five patients certainly had giant granule in bone marrow neutrophil and in one patient it was equiovocal. Three patients had an accelerated phase, and for one patient bone marrow transplantation was done that was tolerated well and had been well after 7 years. We emphasize the need for early diagnosis on basis of characteristic facies and diagnostic laboratory examinations and early bone marrow transplantation (BMT) in patients.

Chronic Granulomatous Disease (CGD) represents a group of inherited disorders of phagocytic system, manifesting recurrent infections at different sites. The present study was accomplished in order to determine the gastrointestinal manifestations of CGD patients. Fifty-seven patients (38 males and 19 females) with CGD, who had been referred to three immunodeficiency referral centers in Iran, were studied during a 24-year period (1980-2004). The median age at the time of study was 14.5 years old (1-56 years). The median onset age of symptoms was 5 months (1 month- 13.75 years), and that of diagnostic age was 5 years (2 months- 54.1 years), with a diagnostic delay of 33 months, on average. Seven patients were presented with acute diarrhea, 3 with oral candidiasis, and 2 with liver abscesses as the first chief complaints. Twenty-four cases (42.1%) had been complicated by gastrointestinal manifestations during their course of the disease. Of those, 12 cases (21.1%) had diarrhea, 7 (12.3%) oral candidiasis, 5 (8.8%) hepatitis, 4 (7.0%) hepatic abscess, and 2 cases (3.5%) gastric outlet obstruction. Also, failure to thrive was detected in 6 patients (10.5%). Four patients died (7%). CGD should be excluded in any patient with gastrointestinal manifestations especially chronic diarrhea, hepatic abscess, and gastric outlet obstruction.

Neutropenia is characterized by decrease in the absolute number of circulating neutrophils and an increase susceptibility to infections. The current study was performed in order to explain the clinical and laboratory findings of patients with antibody deficiency disorders associated neutropenia. The patients' records of 19 neutropenic cases out of 207 patients with antibody deficiencies, who had been referred to Children's Medical Center and enrolled in Iranian primary immunodeficiency registry, were reviewed. Nineteen cases (14 male and 5 female), with a mean age of 10.7+/-5.7 years, were associated with neutropenia (9.2%). The disorders with associated neutropenia were Hyper IgM syndromes (3 of 8), Common variable immunodeficiency (13 of 109), and X-linked agammaglobulinemia (3 of 45). The median age for the onset of disease and diagnosis age were 15 months (1-134) and 3.8 years (6 months-13 years), respectively. The most common infections during the course of illness were pneumonia (13 cases), diarrhea (12 cases), oral candidiasis (9 cases), otitis media (6 cases), sinusitis (6 cases), cutaneous infections (5 cases), and abscess (5 cases). Other less frequent infections were: conjunctivitis, oral ulcers, meningitis, and osteomyelitis. Three neutropenic patients died because of recurrent infections. Neutropenia may occur in any of the primary immunodeficiency disorders. Persistent or severe infections always pose a supposition, which deserves further evaluation for detecting an underlying immune deficiency syndrome and neutropenia, since a delay in diagnosis may result in a serious organ damage or even death of the patient.

Primary immunodeficiencies (PID) are a group of disorders, characterized by an unusual susceptibility to infections. Delay in diagnosis results in increased morbidity and mortality in affected patients. The purpose of this study was to determine the mortality rate of Iranian immunodeficient patients referred to Children Medical Center Hospital affiliated to Tehran University of Medical Sciences over a period of 20 years. In this study, records of 235 (146 males, 89 females) patients with immunodeficiency who were diagnosed and followed in our center, during 22 years period (1979-2001) were reviewed. The diagnosis of immunodeficiency was based on the standard criteria. The cause of death was determined by review of death certificates. Antibody deficiency was the most common diagnosis made in our patients. The overall five-year survival rate was 22.7% in our studied patient group; this was greatest in antibody deficiency. During the 22 year period of study, 32 patients died. As some of the patients could not be located, the true mortality rate ranged between 13.6% and 17.5%. The main leading cause of death were lower respiratory tract involvement in 14 cases (44%). The most common pathogenic microorganisms causing fatal infections were psudomonas and staphylococcus in 9 cases (28.1%) followed by E. coli in 7 (21.9%), tuberculosis in 13 (40.6%) and salmonella in 1 (3.1%). Based on our study, delay in diagnosis in patients with PID results in tissue and organ damage and several complications. Mortality and morbidity are increased in undiagnosed patients.

The primary immunodeficiency (PI) disorders are abnormalities in development and maturation of the immune system. Individuals with PI disease may experience frequent infections, which limit their abilities to exhibit physical and psychological well-being secondary to their illness. In this survey we compared health-related quality of life of primary immune deficient patients with healthy children. The case-control study was designed for patients with PI disease who were referred to Children Medical Center in 2004-2005. Demographic information was taken and Pediatric Quality Of Life (PEDQOL) questionnaire were filled for 50 PI patients and 100 healthy children. The mean age in PI patients was 12.62+/- 3.65 (range from 8 to 18) years and in the control group was 11.04+/- 3.3 years. In PI patients 68% were male and 32% female .Most patients with PI disease had a diagnosis of common variable immunodeficiency (54%) or X-linked agammaglobulinemia (24%). Patients with PI disease had great limitations in physical functioning and psychological well-being (p0.001 and p0.001 respectively) compared with children without a chronic health condition. Patients had lower PEDQOL scores in all age groups compared with normal sample (p0.001). Long duration of disease significantly correlated with low psychological score. (r =-3.23. P= 0.03) Children with PI disease experience poorer health related quality of life than healthy children, indicating more attention should be paid to early diagnosis and treatment of PI disease, as well as more attention to their social limitation. PI patients may need psychological consultation for better coping with their illness.

As with chromosomal DNA, the mitochondrial DNA (mtDNA) can contain mutations that are highly pathogenic . In fact, many diseases of the central nervous system are known to be caused by mutations in mtDNA. Dysfunction of the mitochondrial Respiratory Chain (RC) has been shown in patients with neurological disease including Alzheimer's disease (AD), Parkinson's disease (PD) and Multiple sclerosis (MS). MS is a demyelinating disease of central nervous system characterized by morphological hallmarks of inflammation, demyelination and axonal loss. Considering this importance, we decided to investigate several highly mutative parts of mtDNA for point mutations as MT-LTI (tRNA(Leucine1(UUA/G))), MT-NDI (NADH Dehydrogenase subunit 1), MT-COII (Cytochrome c oxidase subunit II), MT-TK (tRNA(Lysine)), MT-ATP8 (ATP synthase subunit F0 8) and MT-ATP6 (ATP synthase subunit F0 6) in 20 Iranian MS patients and 80 age-matched control subjects by PCR and automated DNA sequencing to evaluate any probable point mutations. Our results revealed that 15 (75%) out of 20 MS patients had point mutations. Some of point mutations were newly found in this study. This study suggested that point mutation occurred in mtDNA might be involved in pathogenesis of MS.

Ataxia-telangiectasia is a multisystem disorder characterized by progressive neurologic impairment, variable immunodeficiency, impaired organ maturation, x-ray hypersensitivity, oculocutaneous telangiectasia, and a predisposition to malignancy. To evaluate clinical and immunologic features of Iranian patients with ataxia-telangiectasia, the records of 104 patients with ataxia-telangiectasia (54 male, 50 female) with the age range of 1.6-23.5 years were reviewed. The Iranian Primary Immunodeficiency Registry was used as the data source. Progressive ataxia was seen in all the patients. Other symptoms were eye movement disorders (n = 84), slurred speech (n = 70), mental retardation (n = 10), and ocular (n = 87) and cutaneous (n = 73) telangiectasia. Three patients developed leukemia and lymphoma, and 17 patients had family history of malignancy. Positive correlation was seen between clinical immunologic symptoms and immunoglobulin deficiencies (P = 0.004). The predominant infections were sinopulmonary and acute and recurrent infections (78 cases). Infections included pneumonia (56 patients), otitis media (34 patients), and sinusitis (50 patients). Average serum alpha-fetoprotein level was 149 +/- 137 ng/dL. The incidence of ataxia-telangiectasia in Iran is high, possibly due to familial marriages. Treatment should be focused on supportive management to prolong survival.

In order to determine the clinical and laboratory findings of Iranian patients with presumed hyper-immunoglobulin E syndrome (HIES), the medical records of 22 patients from 21 unrelated families, who had been registered in the Iranian Primary Immunodeficiency Registry, were observed. The median age of patients at the time of first symptom and at the time of diagnosis was 1 month and 52.5 months, respectively, with a median diagnosis delay of 70 months. 13 families had consanguineous marriages. IgE level was higher than 2000 IU/ml in all patients, ranging from >2000 to 80,000 IU/ml. The most commonly occurring manifestations were: eczema and dermatitis, pneumonia, upper respiratory tract infections, cutaneous abscesses, diarrhoea, deep abscesses, and otitis media. Other less frequent manifestations were: mucocutaneous candidiasis, sinusitis, cutaneous ulcers, Molluscum contagiosum, herpetic keratitis, onychomycosis, conjunctivitis, septic arthritis, and meningitis. Five patients were complicated by bronchiectasis due to recurrent pneumonia and 5 patients died because of severe infections and malignancy. The HIES is a multisystem disorder that affects especially cutaneous, respiratory, skeletal and the immune system. Although HIES is a rare condition, the recurrent infections should always raise a suspicion, which deserves further evaluation for detecting the syndrome.

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 (

Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder, which presents with hypogammaglobulinemia and recurrent bacterial infections. Patients with CVID have frequent and severe episodes of pneumonia. The standard intravenous immunoglobulins (IVIG) therapy has led to the reduction of pulmonary infections in these patients. The aim of this study was to evaluate the effectiveness of IVIG treatment in reducing the incidence of pneumonia in patients with CVID.Twenty six Iranian patients with CVID whose diseases had been diagnosed at the Children Medical Center and had received regular IVIG for at least 9 months were selected. The numbers of episodes of pneumonia and hospital admissions were documented before and during treatment with IVIG.Of 26 patients with CVID, 80.5% had experienced pneumonia at least once before receiving immunoglobulin and 88.5% required hospital admission. After starting treatment with IVIG (mean treatment period, 41.5 +/- 35.4 months), the annual incidence of pneumonia significantly decreased from 80.5% to 34.6% (p=0.0017), and the rate of hospitalization from 88.5% to 46% (p=0.0025) . The incidence of pneumonia requiring treatment or hospitalization fell from 3.4 to 0.7 per year (p0.0005).Regular IVIG therapy can significantly reduce the incidence of pneumonia and hospital admission due to infections in patients with CVID.

The primary immunodeficiency (PI) disorders are abnormalities in development and maturation of the immune system. Individuals with PI disease may experience frequent infections, which limit their abilities to exhibit physical and psychological well-being secondary to their illness. In this survey we compared health-related quality of life of primary immune deficient patients with healthy children. The case-control study was designed for patients with PI disease who were referred to Children Medical Center in 2004-2005. Demographic information was taken and Pediatric Quality Of Life (PEDQOL) questionnaire were filled for 50 PI patients and 100 healthy children. The mean age in PI patients was 12.62± 3.65 (range from 8 to 18) years and in the control group was 11.04± 3.3 years. In PI patients 68% were male and 32% female .Most patients with PI disease had a diagnosis of common variable immunodeficiency (54%) or X-linked agammaglobulinemia (24%). Patients with PI disease had great limitations in physical functioning and psychological well-being (p

Background: X-linked agammaglobulinemia (XLA) is a hereditary immunodeficiency characterized by an early onset of recurrent bacterial infections, a profound deficiency of all immunoglobulin isotypes and a markedly reduced number of peripheral B lymphocytes. Eighty-five percent of the patients with this phenotype have mutations in Bruton’s tyrosine kinase (BTK) gene. Methods: To provide an informative outlook of clinical and immunological manifestations of XLA in Iran, 37 Iranian male patients with an age range of 1–34 years, followed over a period of 25 years, were studied. Twenty-four of the 37 patients were screened for BTK gene mutation using PCR-SSCP followed by direct sequencing. BTK protein expression assay was done by flow cytometry in 9 families. Results: All patients first presented with infectious diseases, the most common of which were respiratory tract infections. Eighteen different mutations were identified, 13 of which were novel: IVS1+5G>C, 1896G>A, 349delA, 1618C>T, 1783T>C, 2084A>G, 1346delT, 1351delGAG, 587A>G, IVS14–1G>A, IVS3+2T>C, 1482G>A, 1975C>A. Conclusion: The fact that we found a great number of novel mutations in a relatively limited number of patients underlines the heterogeneity of BTK mutations in the Iranian population. The large number of new mutations indicates that extended studies in this region would be rewarding.

Neutropenia may occur in some of the primary immunodeficiency disorders. We reviewed the records of 56 neutropenic patients. The most common disorders were Shwachman-Diamond syndrome, cyclic neutropenia, Kostmann disease, Chediak-Higashi syndrome, hyper IgM syndromes, severe combined immunodeficiency, hyper IgE syndrome, and common variable immunodeficiency.

Neutropenia is characterized by decrease in the absolute number of circulating neutrophils and an increase susceptibility to infections. The current study was performed in order to explain the clinical and laboratory findings of patients with antibody deficiency disorders associated neutropenia. The patients' records of 19 neutropenic cases out of 207 patients with antibody deficiencies, who had been referred to Children's Medical Center and enrolled in Iranian primary immunodeficiency registry, were reviewed. Nineteen cases (14 male and 5 female), with a mean age of 10.7±5.7 years, were associated with neutropenia (9.2%). The disorders with associated neutropenia were Hyper IgM syndromes (3 of 8), Common variable immunodeficiency (13 of 109), and X-linked agammaglobulinemia (3 of 45). The median age for the onset of disease and diagnosis age were 15 months (1-134) and 3.8 years (6 months-13 years), respectively. The most common infections during the course of illness were pneumonia (13 cases), diarrhea (12 cases), oral candidiasis (9 cases), otitis media (6 cases), sinusitis (6 cases), cutaneous infections (5 cases), and abscess (5 cases). Other less frequent infections were: conjunctivitis, oral ulcers, meningitis, and osteomyelitis. Three neutropenic patients died because of recurrent infections. Neutropenia may occur in any of the primary immunodeficiency disorders. Persistent or severe infections always pose a supposition, which deserves further evaluation for detecting an underlying immune deficiency syndrome and neutropenia, since a delay in diagnosis may result in a serious organ damage or even death of the patient.

Ataxia-Telangiectasia (AT) is an autosomal recessive disorder involving cerebellar degeneration, immunodeficiency, radiation sensitivity and cancer predisposition. The ATM gene on human chromosome 11q22.3 has recently been identified as the gene responsible for ataxia-telangiectasia (AT). The gene mutated in AT, which has been designated as the ATM gene, encodes a large protein kinase with a PI-3 kinase-related domain. More than 100 mutations are broadly distributed throughout the ATM gene. The large size of the ATM gene (66 exons spanning ~150kb of genomic DNA) together with the diversity and broad distribution of mutations in AT patients, greatly limits the utility of direct mutation screening as a diagnostic tool. In this study, 20 families with at least one affected child clinically suspected to have ataxia-telangiectasia were examined and their DNA was extracted and amplified with standard methods. Sequencing methods were used to detect the new point mutation. Four exons which were hot spots for point mutations in ATM gene were detected by PCR-SSCP or PCR-RFLP.

In order to determine the clinical and laboratory features of X-linked agammaglobulinemia, the records of 33 male patients with XLA were reviewed during 22 years (1980-2002) in the Iranian referral center of primary immunodeficiency disorders. The patients' ages ranged from 20 to 360 months (median 113 months). The median age at the onset of the disease was 8 months and the median age of diagnosis was 48 months, with a median diagnosis delay of 33 months. Almost all of the patients presented common infectious diseases, which were: pneumonia, otitis, diarrhea, sinusitis, and arthritis. During the course of illness, infections in the respiratory tract, gastrointestinal tract, central nervous system, and musculoskeletal system were seen in 93.9%, 75.8%, 33.3%, and 21.2% of XLA patients, respectively. The most common complications of these patients were chronic infections in 75.8% of them, including: chronic otitis media, chronic sinusitis, chronic diarrhea, and bronchiectasis.

Local reference ranges of immunoglobulins are required for studies and clinical interpretation. In this study, serum levels of IgA, IgG, and IgM in 914 Iranian healthy adult blood donor volunteers, aged 18-55 years, were measured by nephelometry. Our data showed that serum reference intervals of IgA, IgG, and IgM in subjects were 72-375, 636-1518, and 39-283 mg/dL, respectively. Data analysis showed a significant difference between the male and female subjects only for IgM; thus, the means of IgM in females were higher than for males (p0.05). Correlation coefficient r for paired samples showed no statistically significant relationship between age and each Ig (p0.05). Comparison of this study with others demonstrated that results are similar; some differences are probably related to ethnic differences. Therefore, our results can be considered as a source of reliable local reference for use in laboratories.

Background: Chronic granulomatous disease (CGD) represents a group of inherited disorders of the phagocytic system, involving recurrent infections at different sites, especially the respiratory system. The present study was accomplished in order to determine the clinical spectrum of Iranian patients with CGD. Methods: Forty-one patients (29 males and 12 females) with CGD, who had already been referred to two immunodeficiency referral centers in Iran, were reviewed during a 22-year period (1980–2002). Results: These patients belonged to 34 families, and 56% of them were consanguineous. The median age at the time of study was 12 years (3 months to 22 years). The median age at onset of symptoms was 4 months (1 month to 12 years), and the median diagnostic age was 5.5 years (2 months to 20 years), with a diagnostic delay of 3 years on average. The most common presenting complaint in our CGD patients was lymphadenopathy (seen in 11 patients, 26.8%). The most common manifestations of CGD (in descending order) were lymphadenopathy (75.6%), pulmonary infections (65.9%) and skin involvement (63.4%) during their illness, followed by gastrointestinal (56.1%), skeletal (29.3%), upper respiratory tract (26.8%) and central nervous system (2.4%) involvement. Conclusions: Early diagnosis of the disease is crucial. In view of the possibility of timely treatment, i.e. prophylactic treatment of infection, CGD should be excluded in any patient with unexplained infections or granulomas.

Agammaglobulinemia is characterized by failure of B-cell differentiation (hypogammaglobulinemia) and increased susceptibility to bacterial infections. The present study was set up in order to evaluate the effectiveness of intravenous immunoglobulin (IVIG) treatment on the incidence of pneumonia in patients with agammaglobulinemia. We carried out chart reviews of 23 patients with agammaglobulinemia (mean age 11.5+/-5.4 years), who had been observed in a 22-year period (July 1981-January 2003) in Iran's referral center for primary immunodeficiency disorders. Nineteen of these 23 (82.5%) had been infected with pneumonia at least once before receiving the immunoglobulin treatment and 11 of them had experienced multiple episodes. During treatment with gamma-globulin - over a mean period of 6.8+/-4.1 years (range: 0.8-15.3 years) - the incidence of pneumonia requiring treatment or hospitalization decreased from 0.82 to 0.12 per patient per year (P=0.006). During IVIG replacement, hospitalization due to pneumonia decreased from 0.58 to 0.05 per patient per year (P=0.08) and the immunoglobulin G level (mean+/-S.D.) changed from 66.2+/-63.9 (range: 0-210 mg dl(-1)) to 552.4+/-199.1 (range: 136-942 mg dl(-1)) (P

There is much evidence that allergic symptoms represent a major health problem in polluted cities. The aim of this research is to elucidate some microscopic effects of air pollutants on pollen structure, proteins, and allergenicity. A scanning electron microscopy study of pollen grains indicated that in polluted areas, airborne particles accumulate on the surface of pollen grains and change the shape and tectum of pollen. Also, many vesicles are released from polluted pollen grains and the pollen material agglomerates on the surface of pollen grains. SDS-PAGE revealed that different proteins exist in mature and immature pollen grains. There were no significant differences between protein bands of polluted and nonpolluted pollen grains, but in polluted pollen, protein content decreases in response to air pollution, causing the release of pollen proteins. The results indicate that mature pollen have more allergenicity than immature pollen. According to the experiments polluted pollen grains are more effective than nonpolluted pollen grains in inducing allergic symptoms. Air pollutants can cause allergic symptoms, but when associated with allergen pollen grains, their allergenicity power is increased.

Methods A survey was conducted of patients ≥ 6y rs. old with a diagnosis of asthma who were registered in Iranian Pediatric Asthma Registration program (IPAR) in Immunology,Asthma and Allergy Research Institute (IAARI), Tehran, Iran since 2008. Mangement practice and level of asthma control, according to GINA guidline, for 517 children were evaluated. Data were analyzed using the statistical package SPSS version 16. Univarite analysis were performed to identify association between influenza vaccination and asthma control. Results Among 172 well controlled patients, 59 one (34.3%) influenza vaccination was not current, 103 (59.54%) vaccination was current, and 10 patients didn’t receive vaccine. In group II (partly controlled+ uncontrolled) 301 patients were registered, in which 164 (34.55%) was current, 131 (43.52%) was not current, and 64 (21.26%) didn’ tr eceive vaccine. There was a significant relation between receiving vaccination and well-controlled asthma (p

Background: The hyper-IgE syndrome (HIES) is a primary immunodeficiency characterized by infections of the lung and skin, elevated serum IgE, and involvement of the soft and bony tissues. Recently, HIES has been associated with heterozygous dominant-negative mutations in the signal transducer and activator of transcription 3 (STAT-3) and severe reductions of T(H)17 cells. Objective: To determine whether there is a correlation between the genotype and the phenotype of patients with HIES and to establish diagnostic criteria to distinguish between STAT3 mutated and STAT3 wild-type patients. Methods: We collected clinical data, determined T(H)17 cell numbers, and sequenced STAT3 in 100 patients with a strong clinical suspicion of HIES and serum IgE > 1000 IU/mL. We explored diagnostic criteria by using a machine-learning approach to identify which features best predict a STAT3 mutation. Results: In 64 patients, we identified 31 different STAT3 mutations, 18 of which were novel. These included mutations at splice sites and outside the previously implicated DNA-binding and Src homology 2 domains. A combination of 5 clinical features predicted STAT3 mutations with 85% accuracy. T(H)17 cells were profoundly reduced in patients harboring STAT-3 mutations, whereas 10 of 13 patients without mutations had low (1000IU/mL plus a weighted score of clinical features >30 based on recurrent pneumonia, newborn rash, pathologic bone fractures, characteristic face, and high palate. Probable: These characteristics plus lack of T(H)17 cells or a family history for definitive HIES. Definitive: These characteristics plus a dominant-negative heterozygous mutation in STAT3. GlaxoSmithKline European consortium (EURO-PADnet HEALRH-F2-2008-201549) Brescia United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Library of Medicine (NLM) United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Allergy & Infectious Diseases (NIAID) United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI) (N01-CO-1240) MEXT-CT-2006-042316 OTKA49017 Fondazione Telethon United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Allergy & Infectious Diseases (NIAID) (ZIAAI000646) United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Library of Medicine (NLM) (ZIALM000097)

2005 contender Mostafa Moin talks about how the international science community can help Iran.

Objective To investigate whether daily diet provides adequate selenium intake in healthy men and women living in Tehran, Iran. Method Serum level of selenium was determined in 184 healthy individuals of both genders. The samples were divided into two age groups, adults and children, for analysis. The serum level of selenium was determined using hydride generation and flame atomic absorption spectroscopy. Results The mean and standard deviation of serum selenium levels in children (1–16 years) was 84.3 ± 11 μg/l and there was no significant difference between genders in this group. In adults (older than 16 years) the mean serum selenium level was 100.6 ± 13 SD μg/l; among women the mean was 93.9 ± 14 SD μg/l and among men it was 102.2 ± 12 SD μg/l. The mean selenium level in men was higher than in women and data analysis showed a significant difference between them (p < 0.005). There was also a positive correlation between higher selenium serum concentration and age in men (P < 0.001). Daily intake of selenium in men and women was calculated to be 67 μg and 62.1 μg respectively. Conclusion Our results show that the serum concentration of selenium in an Iranian population is similar to other nationalities in the Middle East, particularly Saudi Arabia.

The present study was conducted to compare the physical and psychosocial functions of asthmatic patients presenting at different levels of asthma control to that of healthy children in Iran. The aim was to determine if a correlation could be made between the two thus suggesting that the level of asthma control can be used as an indirect indicator for the level of psychosocial impact. A case-control study involving 160 asthmatic children aged between 8 to 12 years-old, in comparison to an age-sex matched healthy control group was thus conducted. The result demonstrates that asthmatic children are more likely to have emotional dysfunction associated with their disease. This in turn resulted in significantly negative effects on the parents� daily working activities. The PedsQL scale which categorizes asthmatic children into three levels of asthma (controlled, partly-controlled and uncontrolled asthma) demonstrated significant differences in their Physical Function scale scores (p

Asthma is a complex, heterogeneous and chronic airway inflammatory disease with different clinical phenotypes caused by diverse triggers and pathophysi ological mechanisms. Asthma heritability has been established in many genetic studies but it is evident that only genetic elements are not responsible for the development of asthma. Increasing rate of asthma incidence during past decades has implicated the role of epigenetics in development of asthma. Environmental factors perform as initiator signals through epigenetic mechanisms. Three epigenetic mechanisms have been identified, including DNA methylation, histone modifications, and small noncoding RNAs. These mechanisms regulate the immune responses and inflammatory genes expression in asthma and allergy. This review explains the role of epigenetic modifications in controlling Th2 response and IgE production in asthma and also briefly overviews the role o f environmental factors such as pollutions, allergens, prenatal exposures and diet in developing asthma. Recognizing environmental risk factors and their effects on epigenetic mechanisms would be of great interest for prognostic and preventive aspect in t reatment of asthma.

Background Although long-term intravenous immunoglobulin infusion is an effective treatment for children with antibody deficiencies, it can be complicated by systemic adverse reactions. Objective To evaluate the adverse reactions of intravenous immunoglobulin therapy in patients with primary immunodeficiency. Methods Seventy-one immunodeficient patients receiving intravenous immunoglobulin were evaluated during a 7-year period (1995–2002) at Children's Medical Center in Tehran, Iran. Immunological diagnoses were as follows: common variable immunodeficiency (31 patients), X-linked agammaglobulinemia (25 patients), IgG subclass deficiency (5 patients), hyper-IgM syndrome (2 patients), and ataxia-telangiectasia (8 patients). Results One hundred fifty-two cases (12.35%) of adverse reactions occurred following 1,231 infusions in 35 patients. The most frequent immediate adverse reactions were mild reactions (131 infusions), including chills, fever, flushing, muscle pains, nausea, headache, and anxiety. Moderate reactions, such as vomiting, chest pain, and wheezing, occurred in 19 infusions. Two patients experienced severe adverse reactions. The highest proportion (23.06%) of reaction to injection was in patients with common variable immunodeficiency. Conclusions Intravenous immunoglobulin is a well tolerated medical agent for patients with antibody deficiency. However, to prevent occurrence of immediate adverse reactions during infusion in these patients, physicians should perform a detailed history and proper physical examination and check the titer of anti-IgA.

Results Eighty six patients with CMA (3month to 18 yrs) were entered this study Fifty three patients were males (61.1%). Median of age was 2.5 yrs (Mean=3.98) and most of CMA patients was under 2 yrs (45.1 %). Mean of total IgE was 343.39±93.63 (SE)(0.2-5000IU/ml). The symptoms of patients was as following: (respiratory symptoms: 62.8%, Skin symptoms: 56.4%, gastrointestinal symptoms: 19.2% & Anaphylaxis: 13.6%). Totally, positive Specific IgE to cow’s milk protein, a-lactalbumin, casein, b-lactoglobulin and bovin serum albumin were 89.2%, 78.3%, 75%, 63.4%, & 45.5%, respectively. Although a-lactalbumin & casein were the most allergenic protein, mean of specific IgE concentration to blactoglobulin was highest in patients with CMA. There was a significant correlation between positive specific IgE to b-lactalbumin & anaphylaxis (P=0.05) and also between respiratory symptoms and positive specific IgE to casein (P=0.01). There was significant difference between mean of specific IgE to casein between males and females (P=0.001) that was the more frequent in males.