ABSTRACT
Background: Inflammatory cytokines have been known to be associated with Chronic Heart Failure [CHF]. Given the importance of cytokines in the context of the failing heart, the prevalence of Interleukin-2 [IL-2] and Interferon-gamma [IFN-Gamma] polymorphisms was studied in patients with CHF due to ischemic heart disease in a casecontrol study
Methods: Fifty-six Iranian patients with CHF were enrolled in this study as the case group and compared with 139 healthy subjects, using polymerase chain reaction with sequence-specific primers method, so as to determine the frequency of alleles, genotypes and haplotypes of IFN-Gamma [+874 A/T] and IL-2 [-330 G/T, +166 G/T] SNPs
Results: The GG genotype at IL-2 -330 in patients with CHF was significantly overrepresented in comparison with the control group [p=0.013]. Such a positive genotypic association was also observed for IL-2 +166/TT [p=0.022]. Meanwhile, the GT genotype frequency at IL-2 -330/GT in the patient group was significantly lower than the one in healthy controls [p=0.049]. No significant association was detected between the IFN-Gamma gene polymorphisms and individuals' susceptibility to CHF
Conclusion: Certain genotypes in IL-2 gene were overrepresented in patients with CHF, which could render individuals more vulnerable to this disease
ABSTRACT
Background: Proinflammatory cytokines have been known to be elevated in patients with Chronic Heart Failure [CHF]. Given the importance of proinflammatory cytokines in the context of the failing heart, the prevalence of Tumor Necrosis Factor-alpha [TNF-alpha], Interleukin [IL]-6 polymorphisms in patients with CHF was studied due to ischemic heart disease
Methods: Forty three patients with ischemic heart failure were enrolled in this study and compared with 140 healthy individuals. The allele and genotype frequency of four Single Nucleotide Polymorphisms [SNPs] within the IL-6 [-174, nt565] and TNF-alpha [-308, -238] genes were determined, using Polymerase Chain Reaction with Sequence-Specific Primers [PCR-SSP] assay
Results: The frequency of the TNF-alpha [-238] A/A genotype was significantly higher in patients comparing to controls [p=0.043], while TNF-alpha G/A genotype at the same position decreased significantly, in comparison with controls [p=0.018]. The most frequent haplotype for TNF-alpha was A/A in the patient group in comparison with controls [p=0.003]. There was no significant difference in allele and genotype frequencies of IL-6 at positions -174 and nt565, and TNF-alpha at position -308
Conclusion: Certain alleles, genotypes, and haplotypes in TNF-alpha, but not IL-6, gene were overrepresented in patients with ischemic heart failure, which may, in turn, predispose individuals to this disease
ABSTRACT
The CD30 antigen seems to play a costimulatory role in maintaining the physiological balance between T-helper [Th] l/Th2 immune responses. In this study, plasma and in vitro soluble CD30 [sCD30] secretion was investigated in patients with coronary artery disease [CAD] as a plausible marker of dysregulated immune response. Twenty one patients with angiographically confirmed CAD and 31 healthy controls took part in this study. The levels of the activation marker sCD30 were determined in plasma and phytohaemagglutinin [PHA]-stimulated and unstimulated peripheral blood mononuclear cell cultures by ELISA. Plasma sCD30 levels did not differ significantly between the patients and controls. However, spontaneous sCD30 secretion was significantly lower in patients with CAD compared to controls [p < 0.001]. The soluble CD30 levels were significantly increased in the supernatant of PHA-stimulated PBMCs compared to unstimulated cultures in both groups of patients and controls [p < 0.001]. PHA-stimulated sCD30 secretion was found to be lower in patients compared to controls; however, the difference was not statistically significant. Plasma sCD30 levels were not statistically different in patients with chronic stable CAD, a well-known Thl-mediated disease, compared to controls; whereas decreased spontaneous and PHA-stimulated sCD30 secretion in patients with CAD might indicate the progressive shift towards a Thl immune response
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Coronary Artery Disease/immunology , T-Lymphocytes/immunology , Chronic Disease , Phytohemagglutinins/pharmacology , Cells, Cultured , Ki-1 Antigen/physiology , SolubilityABSTRACT
Atherosclerosis, a chronic inflammatory disease of the vessel wall is characterized by local and systemic immune responses to a variety of antigens. Oxidized low-density lipoprotein [oxLDL] is considered as an important determining factor in the pathogenesis of atherosclerosis. The purpose of this study was to investigate the degree of peripheral blood mononuclear cells [PBMC] vulnerability to in vitro oxLDL-induced cytotoxicity from atherosclerotic patients in comparison to healthy individuals. Thirty patients with atherosclerotic lesions, confirmed by angiography, and 30 matched healthy individuals were investigated. PBMC was prepared from individuals' blood samples which were further stimulated with low dose [1 micro g/mL] and high dose [50 micro g/mL] of extensively oxidized LDL. MTT assay was utilized to measure cell viability and proliferation. Stimulation index [SI] was calculated as mean ratio of optical density [OD] of the stimulated cells divided by OD of untreated cells. Low dose oxLDL treatment caused no significant proliferative or cytotoxic effect in the control group; however, similar treatment caused significant cytotoxic effect in the patient group compared to the controls [p=0.026]. High dose oxLDL treatment induced more significant cytotoxicity in the patient compared to the control group [p=0.006]. Comparison of the SI between the two groups of patients and controls showed significantly lower index by either the low [p=0.03] or the high dose [p<0.001] oxLDL in the patients compared to the controls. PBMC from patients with atherosclerosis showed increased susceptibility to oxLDL-induced cytotoxicity. Our results imply that prolonged exposure to elevated levels of circulating oxLDL could weaken the cellular defense mechanisms by progressive depletion of the pool of antiapoptotic proteins, rendering the cells more vulnerable to oxLDL-induced cell death
Subject(s)
Humans , Male , Female , Lymphocytes , Cytotoxicity, Immunologic , Cytokine-Induced Killer Cells , Lipoproteins, LDLABSTRACT
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
ABSTRACT
Cyclic neutropenia is a rare immunodeficiency syndrome, characterized by regular periodic oscillations in the circulating neutrophil count from normal to neutropenic levels through 3 weeks period, and lasting for 3-6 days. In order to determine the clinical features of cyclic neutropenia, this study was performed. Seven patients with cyclic neutropenia [3 males and 4 females], who experienced neutropenic periods every 3 weeks [5 with severe and 2 with moderate neutropenia], were investigated in this study. They had been referred to Iranian Primary Immunodeficiency Registry during 23 years [1980-2003]. The range of patients' ages was from 7 to 13 years [median 11 years]. The median age at the onset of the disease was 12 months [1 month- 2 years] and the median age of diagnosis was 2 [1.5-5] years, with a median diagnosis delay of 1 year [2 months- 5 years]. Neutropenia was associated with leukopenia [3 patients], anemia [3 patients], and thrombocytopenia [1 patient]. Patients were asymptomatic in healthy phase, but during the episode of neutropenia suffered from aphthous ulcers, abscesses and overwhelming infections. The most commonly occurred manifestations were: otitis media [6 cases], oral ulcers [5 cases], abscesses [4 cases], pneumonia [3 cases], diarrhea [3 cases], oral candidiasis [3 cases], cutaneous infections [2 cases], and periodontitis [2 cases]. One of these patients subsequently died because of recurrent infections. Unusual, persistent or severe infections should be the initiating factors to search for an immune deficiency syndrome such as cyclic neutropenia, because a delay in diagnosis may result in chronic infection, irretrievable end-organ damage or even death of the patient
ABSTRACT
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
ABSTRACT
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