Single nucleotide polymorphisms of the genes encoding IL-10 and TGF-ß1 in Iranian children with atopic dermatitis.

BACKGROUND: Atopic dermatitis is an inflammatory skin disease in which both genetic and environmental factors interact to determine the susceptibility and severity of the disease. OBJECTIVE: The aim of this study was to determine the association between atopic dermatitis and IL-10 and TGF-ß1 gene polymorphisms. METHODS: The allele and genotype frequencies of genes encoding for IL-10 and TGF-ß1 were investigated in 89 patients with atopic dermatitis in comparison with 138 in the control group using the PCR-SSP method. RESULTS: A significant increase was found in the frequency of the TGF-ß1 codon 10/C allele among patients (p<0.001, OR=6.77), whereas a significant decrease was observed in the frequency of the T allele at the same position (p<0.001, OR=0.14). The frequency of the TGF-ß1 codon 25/G allele in the control group was significantly higher than among patients (p<0.001, OR=0.08). A significant positive correlation was seen between CC (p<0.001, OR=15.10) and CG (p<0.001) genotypes and AD at codons 10 and 25, respectively. The most frequent haplotypes among patients was TGF-ß1 CG which was significantly higher than in the control subjects (50% in patients vs. 39.9% in controls, p=0.042). A significant increase was found in the frequency of TGF-ß CC (36% in patients vs. 7.6% in controls, p<0.001) and TC (14% in patients vs. 0% in controls, p<0.001) haplotypes among patients compared to controls. By contrast, the TGF-ß1 TG haplotype was significantly lower in patients than controls (0% in patients vs. 52.5% in controls, p<0.001). There were no significant differences in the frequency of alleles, genotypes and haplotypes of the IL-10 gene. CONCLUSIONS: We found a strong association between the polymorphisms of the TGF-ß1 gene at codon 10 and codon 25 positions and atopic dermatitis.

Promoter hypermethylation of BCL11B gene correlates with downregulation of gene transcription in ankylosing spondylitis patients.

Methylation of DNA is one of the important regulatory mechanisms of gene transcription. B-cell chronic lymphocytic leukemia/lymphoma 11B (BCL11B) plays a key role in the development, proliferation, differentiation, and survival of T cells. The aim of this study was to evaluate promoter methylation of BCL11B gene and its mRNA level in peripheral blood mononuclear cells (PBMCs) of ankylosing spondylitis (AS) patients in relation to healthy controls and evaluate their correlation with diseases clinical indices. Fifty AS patients and 50 healthy controls entered in this study. PBMCs were isolated from whole blood and RNA and DNA contents of leukocytes were extracted. The expression level of BCL11B gene was measured through real-time PCR assay using SYBR Green Master Mix, and PCR products of bisulfite-treated DNA were sequenced to determine the methylation level of promoter. Decreased transcript and increased promoter methylation levels of BCL11B gene were identified in AS patients compared with healthy controls. Hypermethylation of CpG3 and CpG5 was associated with increased AS risk. Promoter hypermethylation and mRNA overexpression correlated with each other but not with clinical manifestations. We identified aberrancies in expression and methylation of BCL11B gene in AS patients compared with healthy control group; however, they might not impress the clinical face of AS.

Single nucleotide polymorphisms of IL-2, but not IL-12 and IFN-γ, are associated with increased susceptibility to chronic spontaneous urticaria.

BACKGROUND: A clear picture of interaction of Th1/Th2 cytokines in pathogenesis of chronic spontaneous urticaria (CSU), remains elusive. Impaired IFN-γ production and decreased levels of IL-2 have been reported. The aim of this study was to evaluate the association of Th1 cytokines; IL-2, IL-12 and IFN-γ polymorphisms with CSU. METHODS: 90 patients with CSU and 140 age-sex matched subjects were included in this study. DNA samples were evaluated through PCR-SSP assay in order to detect single nucleotide polymorphisms of IL-12 (A/C -1188) or (rs3212227), IFN-γ (A/T UTR5644) or (rs2069717) and IL-2 (G/T -330 and G/T +166) or (rs2069762 and rs2069763). RESULTS: G allele at -330 at promoter region of IL-2 gene was overrepresented in CSU. Heterozygotes (GT) at this locus and heterozygotes at +166 of IL-2 gene (GT) were more prevalent in CSU group. Additionally, the haplotype GT for loci -330 and +166 of IL-2 gene was powerfully associated with CSU (OR (95%CI)=57.29 (8.43-112.7)). CONCLUSIONS: SNP at position -330 and +166 of IL-2 gene are differently expressed in CSU. The haplotype GT of IL-2 at -330 and +166 might confer vulnerability to a number of immunological disorders in Iranian region.

FOXP3, RORγt and IL-10 cytokine profile in chronic heart failure.

BACKGROUND: Distinct subsets of T cells play crucial regulatory roles in inflammatory processes of chronic heart failure (CHF). Retinoic acid receptor-related orphan receptor-γt (Ror-γt) and Forkhead box P3 (Foxp3) have been defined as the "master regulators" of Th17 cells and Treg cells, respectively. At the same time, anti-inflammatory cytokines such as IL-10 may neutralize inflammation in CHF. The current study was designed to compare FOXP3, RORγt and IL-10 protein expression in the blood and IL-10 in supernatant PBMCs in CHF patients versus normal subjects. PATIENTS AND METHODS: Our study population consisted of 42 patients with CHF in four different function classes and 42 healthy subjects who served as controls. RNA extraction and cDNA synthesis was performed and mRNA expression for genes FOXP3, RORγt, IL-10 was determined by RT-PCR. The amount of IL-10 protein in supernatant of PBMCs was measured by ELISA technique. RESULTS: There was no significant difference in FOXP3, RORγt, IL-10 protein expression and supernatant PBMCs IL-10 in CHF patients as compared to control. The level of Foxp3 was significantly lower in CHF patients with ischemic vs non-ischemic cause (p = 0.04). DISCUSSION: Although inflammation plays a central role in the pathophysiology of CHF, the roles of FOXp3, RORγt, and IL-10 remain to be determined (Tab. 3, Ref. 33).

Gene polymorphisms of interleukin-10 and transforming growth factor beta in allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is a polygenic inflammatory disorder of the upper respiratory airway with an increasing prevalence worldwide. Interleukin-10 (IL-10) and transforming growth factor-beta (TGF-ß), as two cytokines with pleiotropic effects on both innate and adaptive immunity, play important roles in allergic responses. Therefore, this study was performed to evaluate the associations of five polymorphisms of IL-10 and TGF-ß genes with AR. MATERIALS AND METHODS: Ninety-eight patients with AR along with 140 healthy volunteers with no history of AR and with the same ethnicity of the patients were recruited in this study. Genotyping was done for three polymorphisms in promoter region of IL-10 gene (rs1800896, rs1800871, rs1800872), and two polymorphisms in the exonic region of TGF-ß1 gene (rs1982037, rs1800471) using PCR sequence-specific-primers method. RESULTS: A allele and AA genotype in rs1800896 of IL-10 and TT genotype in rs1982037 in TGF-ß were significantly less frequent in the patients than in controls. While the C allele and the CG genotype in rs1800471 in TGF-ß1 were associated with a higher susceptibility to AR. C/C and T/C haplotypes (rs1982037, rs1800471) in TGF-ß1 gene and A/C/A, A/T/C and G/C/A haplotypes (rs1800896, rs1800871, rs1800872) in IL-10 gene were found with higher frequencies in patients than controls. Patients with CC genotype in rs1800871 in Il-10 had significantly lower levels of IgE. CONCLUSION: We found that certain genetic variants in IL-10 and TGF-ß polymorphisms were associated with susceptibility to AR as well as some clinical parameters in the patients with AR.

Association of interleukin 1 gene cluster and interleukin 1 receptor gene polymorphisms with ischemic heart failure.

BACKGROUND: Proinflammatory cytokines have been known to play a considerable part in the pathomechanisms of chronic heart failure (CHF). Given the importance of proinflammatory cytokines in the context of the failing heart, we assessed whether the polymorphisms of interleukin (IL)-1 gene cluster, including IL-1α, IL-1ß, and IL-1 receptor antagonist (IL-1RA) and IL-1R gene are predictors of CHF due to ischemic heart disease. METHODS: Forty- three patients with ischemic heart failure were recruited in this study as patients group and compared with 140 healthy unrelated control subjects. Using polymerase chain reaction with sequence-specific primers method, the allele and genotype frequency of 5 single nucleotide polymorphisms (SNPs) within the IL-1α (-889), IL-1ß (-511, +3962), IL-1R (psti 1970), and IL-1RA (mspa1 11100) genes were determined. RESULTS: The frequency of the IL-1ß -511/C allele was significantly higher in the patient group compared to that in the control group (p = 0.031). The IL-1ß (-511) C/C genotype was significantly overrepresented in patients compared to controls (p = 0.022). CONCLUSIONS: Particular allele and genotype in IL-1ß gene were overrepresented in patients with ischemic heart failure, possibly affecting the individual susceptibility to this disease (Tab. 1, Ref. 27).

Association study of interleukin-1 family and interleukin-6 gene single nucleotide polymorphisms in recurrent aphthous stomatitis.

Recurrent aphthous stomatitis (RAS) is a common painful, ulcerative oral inflammatory disorder with unknown aetiology. Immune system and aberrant cytokine cascade deemed to be critical in outbreaks of RAS ulcers. Interleukin-1 (IL-1) and IL-6 are the most potent pro-inflammatory cytokines. Single nucleotide polymorphisms (SNPs) of IL-1 and IL-6 genes can affect the secretion of these cytokines. The aim of this study was to investigate the association between RAS and IL-6 and IL-1 in Iranian subjects with minor RAS. Genomic DNA was obtained from 64 Iranian patients with RAS. IL-1α C -889 T, IL-1ß C -511 T, IL-1ß C +3962 T, IL-1R C pst-I 1970 T, IL-1Ra C Mspa-I11100 T, IL-6 C -174 G and IL-6 A nt +565 G polymorphisms were determined using polymerase chain reaction with sequence-specific primers (PCR-SSP). The frequency of C -174 C genotype in the patients group was significantly different from the healthy control. No other significant differences were found in genotype and alleles frequencies between the two groups. These results indicate that certain SNPs of IL-6 gene at position -174 which located in promoter have association with predisposition of individuals to RAS.

IL-1A rs1800587, IL-1B rs1143634 and IL-1R1 rs2234650 polymorphisms in Iranian patients with systemic sclerosis.

Systemic Sclerosis (SSc) is a systemic autoimmune disorder, with ambiguous pathogenesis. Genetic and environmental factors were proved to be correlated with SSc aetiology. Single nucleotide polymorphisms (SNPs) in cytokine genes can alter the structure and function of the cytokines and consequently may increase the susceptibility to a specific disease. In this study, we investigated SNPs of the IL-1 gene cluster in Iranian SSc patients. We obtained blood samples from 170 SSc patients and 213 healthy individuals. Cytokine genotyping results were obtained by polymerase chain reaction with sequence-specific primers (PCR-SSP). IL-1A rs1800587, IL-1B rs1143634 and IL-1R1 rs2234650 were evaluated for SNP study. The frequency of the IL-1B rs1143634 CT genotype was significantly lower in SSc patients compared to the controls (OR = 0.584; 95% CI = 0.385-0.886; P-value = 0.023), so we propose that CT genotype of this allele might be protective. According to our haplotype analysis, CCC haplotype frequency is higher in the control group compared to SSc patients (OR = 1.575; 95% CI = 1.176-2.111; P-value = 0.008) and in contrast, CTC haplotype frequency is lower in the control group compared to SSc patients (OR = 0.152; 95% CI = 0.047-0.484; P-value = 0.002), so they might decrease and increase the susceptibility of having SSc, respectively. In addition, we reported two significant diplotypes frequency differences among SSc patients and healthy individuals. It is highly important that there is not much resemblance between the IL-1 gene cluster polymorphism in different populations, so we can indicate that SNPs may play critical roles when they are combined with other genetic and environmental factors.

IgG anti-IgA antibodies in paediatric antibody-deficient patients receiving intravenous immunoglobulin.

BACKGROUND: Immunoglobulin replacement therapy is an effective route of management for both infections and non-infectious complications in predominantly antibody deficiency (PAD). Trace levels of IgA (ranged from 0.4 to 2500 mg/ml), which exist in all immunoglobulin products, could lead to an increased susceptibility for adverse reactions in PAD patients. Furthermore, the exact mechanism which stimulates the anti-IgA antibody production in PAD is still unknown. The aim of this study was to evaluate IgG anti-IgA antibodies in PAD patients receiving intravenous immunoglobulin (IVIg) and its predisposing factors. METHODS: Available patients with confirmed diagnosis of PAD, who underwent regular IVIg replacement therapy in our centre, were enrolled in the study. Control group included 24 healthy individuals as the negative control and eight symptomatic patients with IgA deficiency as the positive control groups. IgG anti-IgA antibodies level was measured by the ELISA method. RESULTS: A significant difference was observed between Anti-IgA level of common variable immunodeficiency (CVID) and other PAD groups (p=0.02). Moreover, six CVID patients were seropositive for the IgG anti-IgA antibody, with higher susceptibility to the adverse reactions (p<0.001). IgG anti-IgA level has a negative relationship with serum IgA level (r=-0.06) and IVIg treatment duration (r=-0.006). CONCLUSION: Our data suggested that there was a significant association between anti-IgA antibody presence and the adverse reactions, especially in CVID patients with higher susceptibility to produce this constitutional antibody.

Association of single nucleotide polymorphisms of interleukin-1 family with atopic dermatitis.

BACKGROUND: Interleukin-1 (IL-1) seems to have an important role in early reactions towards microbes, while its genetic variability could affect this role in atopic patients who have a distressed immunity towards dermatological infections. METHODS: Eighty-nine patients with atopic dermatitis (AD), who were referred to a main referral paediatric hospital, were enrolled in this study. Single nucleotide polymorphisms (SNP) of the following IL-1 cluster genes were assessed in this group of patients: IL-1α -889, IL-1ß -511, IL-1ß +3962, IL-1R Pst-I 1970, and IL-1RA Mspa-I 11100. The results were compared with a group of 140 healthy subjects from the same region. RESULTS: Fourteen percent of the controls had TT homozygous genotype in IL-1R at position Pst-I 1970, while only 2% of the patients with AD had this genotype (p=0.005, OR: 0.14, 95%CI: 0.02-0.64). The CC homozygous genotype was the most common genotype in IL-1α position -889 and IL-1ß at position +3962 in both groups of patients with AD and the controls, while the TC heterozygous genotype was the most common genotype in IL-1ß at position -511 and IL-1R at position Pst-I 1970, with no significant difference between the two groups. CONCLUSIONS: This study showed a significant negative association in the IL-1R Mspa-I 11100 TT homozygous genotype in the patients with AD.

AICDA single nucleotide polymorphism in common variable immunodeficiency and selective IgA deficiency.

BACKGROUND: Primary antibody deficiencies (PADs) are a heterogeneous group of disorders, characterised by increased susceptibility to recurrent bacterial infections. Common variable immunodeficiency (CVID) is the most important PAD from the clinical point of view and selective IgA deficiency (IgAD) is the most common PAD. However, the underlying gene defect in both is still unknown. As a recent study in Europe showed an association between a single nucleotide polymorphism (SNP) of AICDA gene with PADs, this study was performed to evaluate such an association in Iranian patients. METHODS: Fifty-eight patients with PAD, including 39 CVID and 19 IgAD, as well as 34 healthy volunteers, were enrolled in this study. Genotyping was done in all groups for an intronic SNP in AICDA (rs2580874), using real-time PCR genotyping assay. RESULTS: The less frequent genotype of AICDA in IgAD patients was AA, seen in 10.5% of the patients, which was much lower than the 30.8% in CVID patients and 38.2% in the controls. However, these differences were not significant. Indeed the GG genotype in the patients with PADs was seen in 20.7%, compared to 8.8% in the controls without any significant difference. CONCLUSIONS: There was no significant association between the previously reported genetic variant of AICDA gene and the development of CVID or IgAD, but further multi-center studies are also needed.

Interleukin-6 and tumor necrosis factor-alpha gene polymorphisms in chronic idiopathic urticaria.

BACKGROUND: This study was performed to evaluate association of gene polymorphisms among proinflammatory cytokines and susceptibility to chronic idiopathic urticaria (CIU). METHODS: Ninety patients with prolonged urticaria more than 6 weeks were included as case group. Single nucleotide polymorphisms (SNPs) of IL-6 (G/C -174, G/A nt565) and TNF-α (G/A -308, G/A -238) were evaluated, using polymerase chain reaction (PCR); and the results were compared to the control group. RESULTS: G allele was significantly higher in the patients at locus of -238 of promoter of TNF-α gene (p<0.001). Frequency of following genotypes were significantly lower in patients with CIU, compared to controls: AG at -308 and GA at -238 of TNF-α gene (p<0.05 and p<0.001, respectively), CG at -174 and GG at +565 of IL-6 gene (p<0.05). Additionally, following genotypes were more common among patients with CIU: GG at -308 and -238 of TNF-α gene (p<0.05 and p<0.001, respectively), GG at -174 and GA at +565 of IL-6 gene (p<0.05). CONCLUSIONS: Pro-inflammatory cytokine gene polymorphisms can affect susceptibility to CIU. TNF-α promoter polymorphisms as well as IL-6 gene polymorphisms are associated with CIU.

HLA-DRB and HLA-DQA/HLA-DQB allele and haplotype frequencies in Iranian patients with aggressive periodontitis.

BACKGROUND AND OBJECTIVE: Genetic backgrounds play a key role in susceptibility to and protection against a spectrum of periodontal diseases. Like other infectious diseases, the human leukocyte antigen (HLA) have been found to be associated with periodontitis. This study aimed to investigate differences in allele and haplotype frequencies of HLA class II antigens in a sample of Iranian patients with aggressive periodontitis compared with a healthy control group. MATERIAL AND METHODS: Fifty unrelated patients with aggressive periodontitis and 130 healthy volunteers were enrolled in this study. HLA genotyping for HLA-DRB, HLA-DQA1 and HLA-DQB1 was performed using the PCR with sequence-specific primers. Allele and haplotype frequencies were compared across groups. RESULTS: The frequencies of HLA-DQA1*03:01, HLA-DQB1*03:02 and HLA-DQB1*03:05 alleles, as well as that of the HLA-DRB1*04:01 allele, were significantly higher in patients with aggressive periodontitis compared with control subjects (p = 0.01, p = 0.04, p = 0.05 and p = 0.04, respectively). In contrast, the frequency of the HLA-DQB1*0603 allele was significantly lower in patients with aggressive periodontitis compared with control subjects (p = 0.006; odds ratio = 0.20). With regard to haplotype association, a significantly higher frequency of two haplotypes - HLA-DRB1*04:01/HLA-DQA1*03:01/HLA-DQB1*03:02 and HLA-DRB1*16:01/HLA-DQA1*01:03/HLA-DQB1*05:01 - was observed in patients with aggressive periodontitis compared with healthy controls (p = 0.01, odds ratio = 2.56 and p = 0.05, odds ratio = 5.38, respectively). CONCLUSION: These results provide additional evidence that class II HLA polymorphisms, particularly in the DQ locus, are associated with protection against and susceptibility to aggressive periodontitis.

Single-nucleotide polymorphisms of TNFA and IL1 in allergic rhinitis.

BACKGROUND: Allergic rhinitis is a complex polygenic disorder of the upper respiratory tract. Given that proinflammatory cytokines such as tumor necrosis factor (TNF) and interleukin (IL) 1 seem to play a role in the development of allergic rhinitis, we evaluated the associations between various single-nucleotide polymorphisms (SNPs) of the TNF and IL1 genes in a case-control study. METHODS: The study population comprised 98 patients with allergic rhinitis. Genotyping was performed using polymerase chain reaction with sequence-specific primers for 2 TNFA promoter variants (rs1800629 and rs361525), 1 variant in the promoter region of IL1A (rs1800587), 2 SNPs in the IL1B gene (rs16944 and rs1 143634), 1 variant in the IL1 receptor (rs2234650), and 1 in IL1RA (rs315952). RESULTS: Patients who were homozygous for the T allele of rs16944 in IL1B had an 8.1-fold greater risk of allergic rhinitis than those with the C allele. In TNFA, a significant relationship was also detected between rs1800629 and rs361525 and allergic rhinitis. Except for rs1800587 in IL1A and rs315952 in IL1RA, significant differences were found between the patient and control groups for all other SNPs. CONCLUSIONS: We found that allelic variants in the TNFA and IL1 genes were not only associated with the risk of developing allergic rhinitis, but also affected disease course and severity.

Association between the interleukin 6 genotype at position -174 and atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic skin disorder of unknown origin that usually manifests for the first time in early infancy. Different types of genetic predisposition and environmental factors seem to be associated with the disease. METHODS: This study was performed to evaluate the frequency of alleles, genotypes, and haplotypes of interleukin (IL) 6 single-nucleotide polymorphisms (SNPs) at positions -174 and nt565 in 89 Iranian children with AD and 139 healthy controls. RESULTS: The G allele was significantly more frequent at position -174 in IL6 in atopic patients than in the healthy controls (P < .001; OR, 2.82). Genotype GG was found at the same position in 71% of the patients; this frequency was significantly higher than the frequency of 30% recorded in the controls (P < .001; OR, 5.60). The GG haplotype of IL6 (-174, nt565) was significantly more frequent in the atopic patients than in the healthy controls (P < .001; OR, 2.99). CONCLUSIONS: A significant increase in the frequency of the G allele and GG genotype at position -174 of IL6 was found in patients with AD, thus suggesting that production of this cytokine is greater in atopic patients.

The influence of systemic therapy on the serum levels of IL-6 and IL-8 in pemphigus vulgaris.

BACKGROUND: The place of cell-mediated immunity and cytokines in the immunopathogenesis of pemphigus vulgaris (PV) has not been fully established. OBJECTIVE: To assess the serum levels of pro-inflammatory cytokines, Interleukine-6 (IL-6) and Interleukine-8 (IL-8), in PV patients before and after therapy, to evaluate the influence of therapy on the serum cytokine levels. METHODS: Sixty-six newly diagnosed PV patients enrolled into the study. The serum levels of IL-8 and IL-6 were measured in 66 and 64 patients, respectively. According to the extent of skin and mucosal involvement, the patients were divided into two groups namely mild and severe. The serum levels of cytokines were measured using enzyme-linked immunosorbent assay (ELISA) method before and after 4 weeks of prednisolone plus azathioprine therapy. RESULTS: In 64 patients studied for the serum level of IL-6, the median IL-6 level was significantly decreased from 1.6 to 0.9 pg/mL by therapy (P-value = 0.001). Segregating the patients according to the severity of the disease, the serum level of IL-6 did not differ significantly by therapy in patients with a mild disease. However, in patients with a severe disease the median serum level of IL-6 decreased significantly from 1.8 to 0.9 pg/mL after therapy (P-value = 0.001). No significant changes were found in the IL-8 level by treatment. CONCLUSION: The significant decrease in the IL-6 level after therapy suggests that blocking of IL-6 could have therapeutic benefits for the treatment of PV, particularly in severe forms.

Serum and salivary desmoglein 1 and 3 enzyme-linked immunosorbent assay in pemphigus vulgaris: correlation with phenotype and severity.

BACKGROUND: To the best of our knowledge there is only one report about salivary desmoglein (Dsg) 1 and 3 enzyme-linked immunosorbent assay (ELISA) in pemphigus vulgaris (PV), whereas several studies have been performed on serum. AIMS: To find the sensitivity of serum and salivary anti-Dsg1 and 3 antibodies in the diagnosis of PV, and to determine the relationship between disease severity and phenotype with antibody levels. METHODS: Fifty new patients with PV were included in this study. The diagnosis of PV was confirmed by histopathology and direct immunofluorescence. Demographical data, disease severity and phenotypes were recorded on questionnaire sheets. Dsg1 and Dsg3 ELISA were performed on serum and salivary samples of patients and controls. RESULTS: Thirty-seven patients had mucocutaneous phenotype; whereas mucosal dominant and cutaneous dominant phenotypes were seen in 11 and 2 patients respectively. The sensitivities of serum anti-Dsg3 and anti-Dsg1 were 94% and 72% respectively. The sensitivities of salivary anti-Dsg3 and anti-Dsg1 antibodies were accordingly 94% and 70%. Compared with mucosal phenotype, serum and salivary anti-Dsg1 antibodies were significantly higher in the patients with mucocutaneous phenotype. Serum Dsg1 antibodies were related with cutaneous and serum Dsg3 antibodies with mucosal severity scores. Salivary Dsg1 antibodies were significantly correlated with mucosal severity (P=0.00); however there was no correlation between this antibody and cutaneous severity (P=0.07). Salivary Dsg3 antibodies were not correlated with mucosal severity (P=0.16). CONCLUSION: Saliva Dsg ELISA could be used for diagnosis of PV. Salivary Dsg1 antibodies had a significant correlation with mucosal severity.

Proinflammatory cytokine gene single nucleotide polymorphisms in common variable immunodeficiency.

Common variable immunodeficiency (CVID) is a heterogeneous group of primary immunodeficiency diseases. Cytokine production could be affected in CVID patients, whereas its alteration could be due to genetic polymorphisms within coding and promoter regions of the cytokine genes. This study was performed to analyse the proinflammatory cytokine single nucleotide polymorphisms in CVID. The allele and genotype frequencies of a number polymorphic genes coding tumour necrosis factor (TNF)-alpha, interleukin (IL)-1alpha, IL-1beta, IL-1R, IL-1RA and IL-6 were investigated and compared between two groups of CVID patients and controls. The IL-6 GA genotype at position nt565 was significantly over-represented in the patient group (P<0.001), while the IL-6 GG genotype at position -174 (P=0.006) and the GG genotype at position nt565 (P<0.001) were significantly lower than controls. The TNF-alpha AG genotype at position -308 in the patient group was increased significantly in comparison with controls (P=0.027), but the GG genotype at the same position was significantly decreased (P=0.011). IL-6 CA and GA haplotypes were the most frequent haplotypes in the patients (P<0.005), whereas TNF-alpha GA (P=0.002) and IL-6 GG (P<0.001) haplotypes were decreased significantly in the patients in comparison with controls. Cytokine single nucleotide polymorphisms could have a role in pathophysiology of CVID. High production of TNF-alpha is expected in some CVID patients based on the frequency of genotypes/haplotypes of these cytokine gene polymorphisms.

Polymorphisms in IL4 and iLARA confer susceptibility to asthma.

BACKGROUND: Asthma is a complex disease that is caused by genetic and environmental factors. The production of interleukin (IL)-4, which can influence mast cell responsiveness to immunoglobulin (Ig) E--mediated signaling, could be modified by genetic variants in the IL-4 promoter. OBJECTIVE: To investigate the association between the IL-4 and IL-4RA promoter polymorphisms and asthma in a sample of Iranian patients. METHODS: We used polymerase chain reaction with sequence-specific primers to investigate the allele and genotype frequencies of 2 polymorphic genes coding for IL-4 and IL-4RA in 59 Iranian patients with asthma and 139 healthy controls. RESULTS: The most frequent genotypes in the patient group were IL-4TC (-590), IL-4TC (-33), IL-4 GT (-1098), and IL-4RA GA (+1902). In contrast, the frequencies of IL-4 CC (-590), IL-4 CC (-33), IL-4TT (-1098), and IL-4RAAA (+1902) were significantly lower in the patient group than in the control group. The most frequent haplotypes in our patients were IL-4 TCT and GTC at positions -1098,-590,-33. The mean total serum IgE level in patients with the TTT/GCC genotype was 258.8 IU/mL, which was significantly higher than the 95.4 IU/mL observed for other genotypes. CONCLUSION: We showed a strong association between the polymorphisms of the IL-4 gene promoter at positions -590, -33 and -1098 and bronchial asthma. We also demonstrated an association between their haplotypes and serum total IgE.