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1.
Pediatr Blood Cancer ; 64(6)2017 06.
Article in English | MEDLINE | ID: mdl-27873456

ABSTRACT

Mutations of the IL12B and IL12RB1 genes underlie the development of IL-12 p40 and IL-12Rß1 deficiencies, respectively, both of which cause predisposition to infection with weakly virulent mycobacteria and Salmonella. Infections with other intramacrophagic organisms have only been rarely observed. We identified two patients with visceral leishmaniasis who had autosomal recessive IL-12 p40 and IL-12Rß1 deficiencies, respectively. This finding demonstrates the importance of IFN-γ immunity in the control of leishmaniasis. We also searched the literature for similar reports in patients with these and other primary immunodeficiencies.


Subject(s)
Genetic Diseases, Inborn , Immunologic Deficiency Syndromes , Interleukin-12 Subunit p40/deficiency , Leishmaniasis, Visceral , Receptors, Interleukin-12/deficiency , Adolescent , Child , Female , Genetic Diseases, Inborn/genetics , Genetic Diseases, Inborn/immunology , Genetic Diseases, Inborn/pathology , Humans , Immunologic Deficiency Syndromes/genetics , Immunologic Deficiency Syndromes/immunology , Immunologic Deficiency Syndromes/pathology , Leishmaniasis, Visceral/genetics , Leishmaniasis, Visceral/immunology , Leishmaniasis, Visceral/pathology , Male
2.
Emerg Infect Dis ; 22(10): 1712-9, 2016 10.
Article in English | MEDLINE | ID: mdl-27648512

ABSTRACT

Widespread use of oral poliovirus vaccine has led to an ≈99.9% decrease in global incidence of poliomyelitis (from ≈350,000 cases in 1988 to 74 cases in 2015) and eradication of wild-type poliovirus serotypes 2 and 3. However, patients with primary immunodeficiency might shed vaccine-derived polioviruses (VDPVs) for an extended period, which could pose a major threat to polio eradication programs. Since 1995, sixteen VDPV populations have been isolated from 14 patients with immunodeficiency in Iran. For these patients, vaccine-associated paralysis, mostly in >1 extremity, was the first manifestation of primary immunodeficiency. Seven patients with humoral immunodeficiency cleared VDPV infection more frequently than did 6 patients with combined immunodeficiencies. Our results raise questions about manifestations of VDPVs in immunodeficient patients and the role of cellular immunity against enterovirus infections. On the basis of an association between VDPVs and immunodeficiency, we advocate screening of patients with primary immunodeficiency for shedding of polioviruses.


Subject(s)
Immunologic Deficiency Syndromes/immunology , Poliomyelitis/immunology , Poliovirus Vaccine, Inactivated/immunology , Poliovirus Vaccine, Oral/immunology , Poliovirus/isolation & purification , Virus Shedding/immunology , Adolescent , Adult , Child , Feces/virology , Female , Follow-Up Studies , Humans , Immunocompromised Host/immunology , Immunologic Deficiency Syndromes/complications , Immunologic Deficiency Syndromes/virology , Iran , Male , Poliomyelitis/etiology , Poliomyelitis/mortality , Poliomyelitis/virology , Poliovirus/immunology , Poliovirus Vaccine, Inactivated/adverse effects , Poliovirus Vaccine, Oral/adverse effects , Treatment Outcome , Young Adult
3.
Mol Cell Biochem ; 350(1-2): 113-8, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21153685

ABSTRACT

The K121Q polymorphism of the ectoenzyme nucleotide pyrophosphate phosphodiesterase 1 (ENPP1) gene has been variably associated with insulin resistance and type 2 diabetes (T2D) in several populations. However, this association has not been studied in Iranian subjects and we hypothesized that the K121Q variant might be associated with T2D and related metabolic traits in this population. The K121Q genotypes were determined by PCR-restriction fragment length polymorphism in 377 normoglycemic controls and 155 T2D patients. T2D patients had significantly higher values for systolic and diastolic blood pressure, BMI, glucose, cholesterol, triglyceride, LDL, apoB, insulin, and HOMA-IR, and lower levels of HDL than the normoglycemic subjects. The frequency of the Q allele did not differ between T2D and normoglycemic subjects (OR 0.96, 95% CI 0.90-2.00, P = 0.70). The Q allele frequency was 16.5% in T2D and 15.2% in normoglycemic subjects. The ENPP1 genotype (KQ + QQ) was not associated with the systolic and diastolic blood pressure, glucose, triglyceride, cholesterol, LDL-C and HDL-C, apo B, BMI, HOMA-IR, and insulin levels in both normoglycemic and T2D groups. Our results suggest that the ENPP1 121Q allele might not be associated with T2D and related metabolic traits among Iranian subjects.


Subject(s)
Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/metabolism , Metabolic Diseases/genetics , Phosphoric Diester Hydrolases/genetics , Polymorphism, Single Nucleotide , Pyrophosphatases/genetics , Adult , Aged , Amino Acid Substitution/genetics , Amino Acid Substitution/physiology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Female , Gene Frequency , Genetic Predisposition to Disease , Genetics, Population , Genotype , Glutamic Acid/genetics , Humans , Insulin Resistance/genetics , Iran/epidemiology , Lysine/genetics , Male , Metabolic Diseases/epidemiology , Metabolic Diseases/etiology , Middle Aged , Phosphoric Diester Hydrolases/physiology , Polymorphism, Single Nucleotide/physiology , Pyrophosphatases/physiology , Young Adult
4.
J Clin Immunol ; 30(5): 756-60, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20549317

ABSTRACT

BACKGROUND: Leukocyte adhesion deficiency type 1 (LAD I) is an autosomal recessive disorder caused by mutations in the ITGB2 gene, encoding the beta2 integrin family. Severe recurrent infections, impaired wound healing, and periodontal diseases are the main features of disease. METHODS: In order to investigate clinical and molecular manifestations of new LAD I cases, 11 patients diagnosed in one center during 7 years were studied. Patients were screened for the ITGB2 gene mutations, using polymerase chain reaction, followed by single-strand conformation polymorphism and sequencing. RESULTS: The most common first presenting feature of the patients was omphalitis. The mean age of cord separation was 19.9 +/- 1 days. The most common clinical manifestations of the patients during the follow-up period included omphalitis, skin ulcers with poor healing, sepsis, and otitis media. During the follow-up, eight patients died. Eight homozygous changes, including seven novel mutations, were detected: two splicing (IVS4-6C>A, IVS7+1G>A), three missense (Asp128Tyr, Ala239Thr, and Gly716Ala), and three frameshift deletions (Asn282fsX41, Tyr382fsX9, and Lys636fsX22). CONCLUSION: Our results indicate that different mutations underlie the development of LAD I. Definitive molecular diagnosis is valuable for genetic counseling and prenatal diagnosis. Regarding clinical presentations, it seems that omphalitis is the most consistent finding seen in LAD I infants.


Subject(s)
Cytoskeletal Proteins/metabolism , Gram-Negative Bacterial Infections/genetics , Muscle Proteins/metabolism , Skin Ulcer/genetics , Umbilical Cord/immunology , Amino Acid Sequence , Animals , Cytoskeletal Proteins/genetics , DNA Mutational Analysis , Disease Progression , Female , Follow-Up Studies , Gram-Negative Bacterial Infections/etiology , Gram-Negative Bacterial Infections/physiopathology , Humans , Infant , Iran , Leukocyte-Adhesion Deficiency Syndrome/complications , Leukocyte-Adhesion Deficiency Syndrome/genetics , Leukocyte-Adhesion Deficiency Syndrome/physiopathology , Male , Molecular Sequence Data , Muscle Proteins/genetics , Mutation/genetics , Recurrence , Skin Ulcer/etiology , Skin Ulcer/physiopathology , Umbilical Cord/microbiology , Umbilical Cord/pathology
5.
Biochem Biophys Res Commun ; 396(2): 467-71, 2010 May 28.
Article in English | MEDLINE | ID: mdl-20417620

ABSTRACT

The factors responsible for up-regulation of PTP1B, a negative regulator of insulin signaling, in insulin resistance state are not well understood. We performed a series of experiments in C2C12 muscle cells to determine the role of palmitate and an inflammatory state in regulation of PTP1B. Palmitate (0.75mM) induced PTP1B mRNA and protein level only at 16h. The combination of palmitate and macrophages, accompanied by a great increase of TNF-alpha and IL-6 in the culture media, additively caused a higher level of PTP1B protein levels in the muscle. Higher concentrations of palmitate reduced insulin stimulated glucose uptake in myotubes. A specific inhibitor of PTP1B partly increased insulin stimulated glucose uptake in palmitate treated cells. In conclusion, our results showing the additive influence of palmitate and the inflammatory state in the expression of PTP1B imply the involvement of these factors in the overexpression of PTP1B in insulin resistance state. We further provided the evidence suggesting the mediatory role for PTP1B in palmitate induced insulin resistance in myotubes.


Subject(s)
Insulin Resistance , Muscle Fibers, Skeletal/enzymology , Palmitates/metabolism , Protein Tyrosine Phosphatase, Non-Receptor Type 1/biosynthesis , Animals , Culture Media/metabolism , Cytokines/metabolism , Gene Expression/drug effects , Glucose/metabolism , Inflammation/enzymology , Insulin/pharmacology , Macrophages/physiology , Mice , Palmitates/pharmacology , Protein Tyrosine Phosphatase, Non-Receptor Type 1/antagonists & inhibitors , Protein Tyrosine Phosphatase, Non-Receptor Type 1/genetics
6.
EJHaem ; 1(1): 334-337, 2020 Jul.
Article in English | MEDLINE | ID: mdl-35847695

ABSTRACT

Hemophagocytic lymphohistiocytosis (HLH) disease is a severe immune dysregulation caused by mutations in genes required for lymphocyte cytotoxicity function. However, HLH-like syndrome may develop secondary to infections, malignancy, and autoimmunity. Primary immunodeficiencies (PIDs) could predispose to HLH syndrome after uncontrolled infections. Mendelian susceptibility to mycobacterial disease (MSMD) is a PID characterized by a predisposition to clinical disease caused by weakly virulent mycobacteria, such as bacillus Calmette-Guérin (BCG). Inborn errors of interferon-γ immunity caused by mutations in 16 genes, underly MSMD development. Here, we report a case of fatal interferon-γ receptor 1 deficiency with disseminated BCG infection, which was initially diagnosed with HLH disease. We also include a review of cases reported in the literature.

7.
Brain Dev ; 29(2): 124-6, 2007 Mar.
Article in English | MEDLINE | ID: mdl-16949240

ABSTRACT

Progressive multifocal leukoencephalopathy is a demyelinating disease caused by JC virus, an opportunistic infection of the central nervous system. Although the majority of cases are infected with the human immunodeficiency virus (HIV), other immunocompromised patients are also at risk. Purine nucleoside phosphorylase is an enzyme in the purine salvage pathway that reversibly converts inosine to hypoxanthine and guanosine to guanine. Purine nucleoside phosphorylase deficiency is a combined immunodeficiency with a profound cellular defect. Neurologic abnormalities are salient features of this syndrome. We describe for the first time a patient with this rare disorder presented with progressive multifocal leukoencephalopathy.


Subject(s)
Leukoencephalopathy, Progressive Multifocal/etiology , Purine-Nucleoside Phosphorylase/deficiency , Purine-Pyrimidine Metabolism, Inborn Errors/complications , Child , Humans , Leukoencephalopathy, Progressive Multifocal/pathology , Magnetic Resonance Imaging/methods , Male , Purine-Pyrimidine Metabolism, Inborn Errors/pathology
8.
Expert Rev Clin Immunol ; 13(5): 499-505, 2017 05.
Article in English | MEDLINE | ID: mdl-28162005

ABSTRACT

BACKGROUND: Ataxia telangiectasia (AT) is a primary immunodeficiency associated with recurrent infections. We aimed to investigate clinical and immunological classification in AT patients who suffer from a different spectrum of humoral immune defects. METHODS: AT patients were categorized according to the ability of class switching and patients with hyper IgM (HIgM) profile were defined as class switching defect (CSD). RESULTS: Serum immunoglobulin profile in 66 AT patients showed normal immunoglobulin level (22.8%), IgA deficiency (37.9%) and hypogammaglobulinemia (18.1%) in the majority of patients, while 21.2% had HIgM profile revealing CSD. CSD does not affect the frequency of infections, however, the frequency of lymphoproliferation (p < 0.001), and autoimmunity (p = 0.004) were significantly higher in this group. Neurologic symptoms in CSD patients are mild or appear after recurrent infections, therefore these patients were usually misdiagnosed as HIgM syndrome. CONCLUSIONS: Although most of AT patients have reduced IgA levels or normal immunoglobulin levels, but a fraction of these patients may show CSD ensuing HIgM-profile. CSD poses affected individuals at higher risk of non-infectious complications.


Subject(s)
Ataxia Telangiectasia/diagnosis , Hyper-IgM Immunodeficiency Syndrome/diagnosis , Infections/diagnosis , Ataxia Telangiectasia/immunology , Child , Child, Preschool , Consanguinity , Diagnosis, Differential , Female , Humans , Hyper-IgM Immunodeficiency Syndrome/immunology , Immunoglobulin A/blood , Immunoglobulin Class Switching , Immunoglobulin M/blood , Infections/immunology , Iran , Male , Retrospective Studies
9.
Expert Rev Clin Immunol ; 12(4): 479-86, 2016.
Article in English | MEDLINE | ID: mdl-26910880

ABSTRACT

OBJECTIVES: Impairment in early B-cell development can cause a predominantly antibody deficiency with severe depletion of peripheral B-cells. Mutations in the gene encoding for Bruton's-tyrosine-kinase (BTK) and the components of the pre-B-cell receptor complex or downstream signaling molecules have been related to this defect in patients with agammaglobulinemia. METHODS: Iranian patients with congenital agammaglobulinemia were included and the correlation between disease-causing mutations and parameters such as clinical and immunologic phenotypes were evaluated in available patients. RESULTS: Out of 87 patients, a molecular investigation was performed on 51 patients leading to identification of 39 cases with BTK (1 novel mutation), 5 cases of µ-heavy chain (3 novel mutations) and 1 case of Igα-deficiencies. CONCLUSION: Although there is no comprehensive correlation between type of responsible BTK mutation and severity of clinical phenotype, our data suggest that BTK-deficient and autosomal recessive agammaglobulinemia patients differ significantly regarding clinical/immunologic characteristics.


Subject(s)
Agammaglobulinemia/genetics , B-Lymphocytes/physiology , Genetic Diseases, X-Linked/genetics , Immunoglobulin A/genetics , Immunoglobulin mu-Chains/genetics , Protein-Tyrosine Kinases/genetics , Agammaglobulinaemia Tyrosine Kinase , Chromosome Disorders , Cohort Studies , DNA Mutational Analysis , Genetic Association Studies , Genotype , Iran , Mutation/genetics , Phenotype , Time Factors
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