Biomedical subjects

Nima Rezaei

Publications and source records attributed to Nima Rezaei.

At least 19 recordsLinked to original sources

PubMed2006

HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease).

Autosomal recessive severe congenital neutropenia (SCN) constitutes a primary immunodeficiency syndrome associated with increased apoptosis in myeloid cells, yet the underlying genetic defect remains unknown. Using a positional cloning approach and candidate gene evaluation, we identified a recurrent homozygous germline mutation in HAX1 in three pedigrees. After further molecular screening of individuals with SCN, we identified 19 additional affected individuals with homozygous HAX1 mutations, including three belonging to the original pedigree described by Kostmann. HAX1 encodes the mitochondrial protein HAX1, which has been assigned functions in signal transduction and cytoskeletal control. Here, we show that HAX1 is critical for maintaining the inner mitochondrial membrane potential and protecting against apoptosis in myeloid cells. Our findings suggest that HAX1 is a major regulator of myeloid homeostasis and underline the significance of genetic control of apoptosis in neutrophil development.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Mortality and morbidity in common variable immunodeficiency.

Common variable immunodeficiency (CVID) is a heterogeneous group of disorders, characterized by hypogammaglobulinemia, defective specific-antibody production resulting in recurrent bacterial infections. Delay in diagnosis and inadequate treatment result in increased irreversible complications and mortality. To determine persistent morbidities, mortality rate and survival in Iranian patients with CVID, hospital records of 72 (39 males and 33 females) diagnosed CVID patients were reviewed. Probabilities of survival after diagnosis of CVID were estimated from Kaplan-Meier life tables. Studied patients were enrolled over a 20-year period (1984-2005). The most commonly observed complication was bronchiectasis (24 cases), followed by splenomegaly, intestinal villous atrophy (11 cases), and failure to thrive (10 cases). Post-diagnosis survival was estimated as 65% for the first 6.5 years, which remains the same until 14 years after diagnosis when the survival curve drops to nearly 45%. The mortality rate among patients who had no regular visits and did not receive periodical IVIG was more remarkable when compared with those who had been followed up timely (p-value = 0.001). The most common cause of death was respiratory failure. Based on our observation, it can be highlighted that all patients with CVID, even under regular immunoglobulin replacement, need close monitoring for early detection of complications and introduction of appropriate management.

Adolescent↗

PubMed2006

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

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

Adolescent↗

PubMed2006

Clinical, immunological and molecular characteristics of 37 Iranian patients with X-linked agammaglobulinemia.

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.

Adolescent↗

PubMed2006

Therapeutic targeting of pattern-recognition receptors.

Innate immune system could recognize the pathogen-associated molecular patterns by pattern-recognition receptors like Toll-like receptor (TLR) and nucleotide-binding oligomerisation domain (NOD) protein. Information regarding the structure and signalling pathways of TLRs and NODs could provide opportunities for new therapeutic approaches to modulate the innate immunity. Therapeutic targeting could be done by prevention of ligand binding to leucine-rich repeats domains of receptors, blocking the interactions between receptors (like Toll/interleukin-1 receptor domains of TLRs) and adaptors in signalling pathways, blocking the enzymes in signalling pathways, and immunostimulation with vaccine adjuvants. These therapeutic approaches could be useful in the treatment of different human diseases like immunological disorders, infections, and cancers. Further research on these receptors and their signalling pathways could help scientists to identify new candidates for therapeutic targeting.

Adjuvants, Immunologic↗

PubMed2006

TNF-receptor-associated periodic syndrome (TRAPS): an autosomal dominant multisystem disorder.

The TNF-receptor-associated periodic syndrome (TRAPS) is an autosomal dominant auto-inflammatory disorder, characterized by recurrent febrile attacks and localized inflammation. TRAPS is caused by mutations in the gene encoding the TNF Receptor Super Family 1A (TNFRSF1A) on chromosome 12p13. However, the incomplete penetrance and genetic heterogeneity have been reported in this syndrome. Although the ethnic diversity and clinical heterogeneity may propose the role of other genes in the pathogenesis of TRAPS, some low-penetrance TNFRSF1A variants contribute to atypical inflammatory responses in other autoimmune diseases. Furthermore, molecular studies on TRAPS and other auto-inflammatory disorders could be suggested to identify additional genes coding the molecules in the TNF signalling process.

Chromosomes, Human, Pair 12↗

PubMed2006

The clinical and laboratory survey of Iranian patients with hyper-IgE syndrome.

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.

Adolescent↗

PubMed2006

Lymphoma of mucosa-associated lymphoid tissue in common variable immunodeficiency.

Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency characterized by reduced levels of all major immunoglobuline classes and recurrent c infections. The risk of non-Hodgkin's lymphoma (NHL) among patients with CVID was found to be increased in different studies. Mucosa-associated lymphoid tissue (MALT) lymphomas are a recently recognized sub-set of low-grade B-cell NHL composed of marginal zone-related cells. MALT lymphomas appear in the lymphoid tissues as a result of chronic inflammatory or autoimmune stimulation. This study briefly reviews previously published cases and reports a patient suffering from CVID with a history of chronic diarrhea and recurrent sinopulmonary infections. Despite treatment with intravenous immunoglobulin, chronic cough and wheezing progressed. Open lung biopsy showed a MALT lymphoma. Although a rare complication, pulmonary low grade B-cell lymphoma is a diagnosis that must be kept in mind in CVID patients with chronic pulmonary symptoms unresponsive to conventional therapies.

Adolescent↗

PubMed2006

Consanguinity in primary immunodeficiency disorders; the report from Iranian Primary Immunodeficiency Registry.

PROBLEM: Primary Immunodeficiency Disorders (PiD) are a heterogeneous group of genetic disorders, with different modes of inheritance. This study was accomplished in order to determine the frequency of consanguineous marriages in the families of patients with PiD. METHOD: In this study, the records 515 Iranian PiD patients were reviewed during a 25-year period. RESULTS: The mean proportion of consanguineous marriages was 65.6% among PiD patients, while the overall rate was 38.6% in the country. The rate of consanguinity was 77.8% in cellular immunodeficiencies, 75.8% in combined immunodeficiencies, 72.5% in defects of phagocytic function, 58.6% in other immunodefiiencies, 54.1% in predominantly antibody deficiencies, and 50% in complement deficiencies. Moreover all patients with immunodeficiency associated with other diseases had consanguineous parents. Such marriages were most common in the parents of patients with Chediak-Higashi syndrome, severe combined immunodeficiencies, primary CD4 deficiency, ataxia-telangiectasia, selective IgG class deficiencies, chronic granulomatous disease, and Schwachman syndrome. CONCLUSIONS: It is important to inform the general population about the dangers of consanguinity, which is very common in some areas such as Iran. Premarital examination to avoid genetic diseases could be suggested, especially in a community where the rate of consanguineous marriage is high.

Adolescent↗

PubMed2006

Effect of regular intravenous immunoglobulin therapy on prevention of pneumonia in patients with common variable immunodeficiency.

BACKGROUND AND PURPOSE: 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. METHODS: 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. RESULTS: 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 (p<0.0005). CONCLUSIONS: Regular IVIG therapy can significantly reduce the incidence of pneumonia and hospital admission due to infections in patients with CVID.

Adolescent↗

PubMed2006

Cytokine single nucleotide polymorphisms in Iranian patients with pulmonary tuberculosis.

BACKGROUND: Several genes coding for different cytokines may affect host susceptibility to tuberculosis. METHODS: In the present study, the allele and genotype frequencies of a number polymorphic genes coding for cytokines or cytokine receptors were investigated in Iranian patients with pulmonary tuberculosis (PTB). RESULTS: From the IL-1 cluster, a positive, significant difference was found at position -889, where the T/T genotype was over represented in PTB patients (p = 0.01); a positive, significant increase was found in the IL1R PstI 1970 C/C genotype, where the C allele was over represented in the PTB patients (p = 0.01). A significant negative association at codon 10 TGF-beta, T allele, was shown in our patients and the C allele and C/C genotype were over represented in the PTB patients (P<0.005). For TNF-alpha at position -238, we found a negative association for the G/A genotype and a positive association for the G/G genotype (p = 0.0009). Significant negative associations at position -590 IL-4, T allele and the T/T genotype were shown in our patients (p = 0.0007); also, the C allele and T/C genotype were significantly increased in our patients (P<0.05). With IL-6 at -174, G/G increased and G/C decreased significantly in the patients (P<0.005). CONCLUSION: Pro-inflammatory cytokines such as TNF-alpha and TGF-beta seem to be decreased, and IL-6 increased in PTB patients.

Case-Control Studies↗

PubMed2005

Epidemiology of tuberculosis in the Southeastern Iran.

In order to study the epidemiology of tuberculosis (TB) in Zabol, situated in the Southeast of Iran, this study was performed. Two thousand seven hundred and twenty-nine cases of tuberculosis disease were identified during 1998-2002. The notification rate was 135/100,000 population in 2002, which was higher than this rate in previous years. The notification rate of TB in Afghan population was significantly higher than Iranian population (202 cases/100,000 in Afghan and 122 cases/100,000 in Iranian population. The case notifications in 1998-2001 were 134, 131, 130, and 130 in 100,000 populations, respectively. The prevalence of smear-positive cases was 76/100,000 population in 2002 and the ratio of smear-positive cases to smear-negative and extrapulmonary cases was 1.46. This region remains high TB rates. It is necessary to pay attention to the detection of TB, by making their register in order to enhance the effectiveness and to reduce the cost of existing methods.

Adolescent↗

PubMed2005

Congenital neutropenia and primary immunodeficiency disorders: a survey of 26 Iranian patients.

Inherited neutropenia is characterized by a decrease in the absolute number of circulating neutrophils and an increased susceptibility to infections. The current study was performed to determine the clinical and laboratory findings of Iranian patients with inherited neutropenias. Records of 26 patients (14 male, 12 female) with inherited neutropenia were reviewed in this study. The patients had been referred to Children's Medical Center, a referral center for immunodeficiency disorders in Iran, during a 22-year period (1981-2003). Primary immunodeficiency disorders of these patients were as follows: cyclic neutropenia (8 patients), Shwachman-Diamond syndrome (7 patients), Kostmann syndrome (6 patients), and Chediak-Higashi syndrome (5 patients). The mean absolute neutrophil count of patients was 398.2 +/- 259.3 cells/mm (range 74-1,152/mm) at the first visit. Twenty-one patients showed severe, four moderate, and one mild neutropenia. Sixteen of these patients had leukopenia, seven anemia, two thrombocytopenia, and one monocytosis. The most common presenting complaints in these patients were oral ulcer, otitis, pneumonia, diarrhea, cutaneous abscess, and oral candidiasis. The patients first manifested symptoms of infection suggesting neutropenia at a median age of 7.5 months (range 1 month to 10 years). During follow-up, respiratory infections developed in 24 cases, oral manifestations in 20 patients. The most common infections, in descending order of frequency, were otitis media, abscesses, pneumonia, oral ulcers, acute diarrhea, cutaneous infections, oral candidiasis, and periodontitis. Less frequent infections were sinusitis, cystitis, conjunctivitis, meningitis, and osteomyelitis. Nonspecific symptoms (hepatomegaly and splenomegaly) were also detected in 10 patients and 1 patient, respectively. Three patients died of recurrent infections. The infectious manifestations both at presentation and during follow-up in inherited neutropenia were similar. Although inherited neutropenias are rare, recurrent infections always deserves further evaluation for detecting such disorders.

Adolescent↗

PubMed2005

The prevalence of penoscrotal abnormalities and inguinal hernia in elementary-school boys in the west of Iran.

AIM: We designed a cross-sectional study in order to determine the prevalence of inguinal hernia and penoscrotal abnormalities in the Lorestan province, situated in the west of Iran. METHODS: We studied 3205 elementary-school boys, aged 6-12 years, who underwent clinical examinations of the groin and genitalia in 2002. RESULTS: Abnormalities were detected in 213 children (6.64%). The most frequent anomaly was indirect inguinal hernia, seen in 78 children (2.4%). The other abnormalities were retractile testes in 39 boys (1.22%), undescended testes in 36 boys (1.12%), hydrocele in 28 boys (0.87%) and hypospadiasis in 25 boys (0.78%). Also, three children had micropenises, two had epispadiasis and another two boys had varicoceles. Ambiguous genitalia and apenia were not seen in the present series. Most of the parents were not aware of their children's anomalies (60.1%). CONCLUSIONS: Education of the public and medical staff about these abnormalities and screening system are needed to improve the outcome.

Abnormalities, Multiple↗

PubMed2005

Clinical and immunological features of 65 Iranian patients with common variable immunodeficiency.

Common variable immunodeficiency (CVID) is a primary immunodeficiency disease characterized by hypogammaglobulinemia and recurrent bacterial infections. The records of 65 patients with CVID (37 males and 28 females) in the age range of 24 to 537 months were reviewed. By the year 2003, 11 patients had died and seven patients could not be located. The total follow-up period was 221 patient-years. The median diagnostic delay (time between onset and diagnosis) in our patient group was 60 months. At the time of diagnosis, the baseline serum immunoglobulin G (IgG), IgM, and IgA levels were below the level normal for the patients' age; the medians for this group were 120, 10, and 0 mg/dl, respectively. All of the patients presented with infectious diseases at the time of onset, the most common of which were otitis media, diarrhea, pneumonia, and sinusitis. Acute and recurrent infections were also found in almost all of the patients, particularly involving respiratory and gastrointestinal systems. The most common infections, before diagnosis and during follow-up, were pneumonia, acute diarrhea, acute sinusitis, and otitis media. CVID should be considered in any patient with a history of recurrent infections and decreased levels of all serum immunoglobulin isotypes.

Adolescent↗

PubMed2005

A six-year study on Vibrio cholerae in southeastern Iran.

Cholera continues to be an important public health problem among many poorer communities. In order to determine the epidemiology of Vibrio cholerae in southeastern Iran, 3,594 patients with watery diarrhea, who were referred to the hospitals from Zabol city and 45 neighboring rural populations of Sistan-Blouchestan province, were investigated over a period of 6 years (1997 - 2002). V. cholerae strains were isolated from 362 samples (10.07%). Isolation of V. cholerae in this sample decreased from 22.47% in 1997 to 0% in 2002. Individuals of all ages and social and economic strata were affected. Among the patients with cholera in the present study, only 24 (6.6%) lived in an urban area; 270 (74.6%) of the patients had been referred from rural areas, and the remaining 68 (18.8%) were from neighboring Afghanistan. V. cholerae O1 Ogawa and NAG vibrios were found in 92.8 and 7.2% of patients, respectively. Among the 362 samples, 244 were collected from inpatients and 118 were from outpatients. Twelve of these patients died because of the severity of their disease, severe dehydration and electrolytes imbalance. The priorities for cholera control remain public health interventions through improved water and sanitation, improved surveillance and access to health care facilities, and further development of appropriate vaccines.

Adolescent↗

PubMed2005

Neutropenia in Iranian patients with primary immunodeficiency disorders.

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.

Adolescent↗

PubMed2004

Chronic granulomatous disease: a clinical survey of 41 patients from the Iranian primary immunodeficiency registry.

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.

Adolescent↗