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1.
Immunobiology ; 229(4): 152807, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38821752

ABSTRACT

The study aimed to explore the pontential impact of 10 polymorphisms within IFN-α, IFN-ß1, IFN-γ and TLR3 genes on SLE phenotype and susceptibility and to study the relationship between specific genotypes and clinics. Whole blood samples from SLE patients and healthy controls was obtained. DNA was extracted from the peripheral blood by the QIAamp DNA Blood Mini Kit (Qiagen). The quality and quantity of isolated DNA was estimated by the Quawell Q5000 spectrophotometer. We genotyped SLE patients and healthy subjects using real-time PCR (QuantStudio 5 thermocycler). The study suggests that IFN-γ rs2069705, IFN-γ rs2069718 and IFN-α rs3758236 polymorphisms have a protective role in SLE. We observed relations between TLR3 rs3775292, IFN-ß1 rs7873167, IFN-γ rs2069705, TLR3 rs3775291 and TLR3 rs5743305 polymorphisms and clinical picture of SLE patients. We found associations between the IFN-α rs3758236, IFN-γ rs2069705, IFN-γ rs2069718, IFN-γ rs1861493 and IFN-ß1 rs10964831 polymorphisms and the clinical manifestation of the SLE and/or its comorbidities. We perceived links between IFN-γ rs2069705, IFN-γ rs2069718, IFN-γ rs1861493, TLR3 rs3775291, TLR3 rs3775292 and TLR3 rs5743305 polymorphisms and the occurrence of autoantibodies. Our study presented the relationship between IFN and TLR gene polymorphisms with SLE susceptibility, phenotype and autoantibodies profile. This study propose that polymorphisms within interferons and TLR3 genes can be engaged in the SLE pathogenesis and course.


Subject(s)
Genetic Predisposition to Disease , Genotype , Lupus Erythematosus, Systemic , Polymorphism, Single Nucleotide , Toll-Like Receptor 3 , Humans , Lupus Erythematosus, Systemic/genetics , Toll-Like Receptor 3/genetics , Female , Male , Adult , Middle Aged , Gene Frequency , Alleles , Case-Control Studies , Interferons/genetics , Genetic Association Studies
2.
Clin Exp Immunol ; 204(1): 49-63, 2021 04.
Article in English | MEDLINE | ID: mdl-33336388

ABSTRACT

We investigated Toll-like receptor (TLR)-3/-7/-8/-9 and interferon (IFN)-α/ß/γ mRNA expression in whole blood and serum IFN-α/ß/γ levels in patients with mixed connective tissue disease (MCTD), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) and in healthy subjects to assess the association between the TLR-IFN expression and severity of and susceptibility to diseases, and identify potential biomarkers. Expression of the IFN-γ, TLR-3 and TLR-8 was detected only in SLE patients. TLR-7, IFN-α and IFN-ß expression was highest in SLE, while TLR-9 expression was highest in SSc patients. In SLE and MCTD patients a strong correlation was observed between TLR-7 and IFN-α expression and IFN-ß and IFN-α expression. In MCTD patients, negative correlation between IFN-α and TLR-9 and TLR-7 and TLR-9 was revealed. TLR-9 expression in anti-U1-70k-negative, anti-C negative and anti-SmB-negative MCTD patients was higher than in MCTD-positive patients. We observed negative correlations between serum IFN-α levels and TLR-7 expression and C3 and C4 levels in SLE patients. In SLE patients we observed that with increased IFN-γ, TLR-3 and TLR-8 expression increased the value of C3 and C4. Our results confirmed that the endosomal TLR-IFN pathway seems to be more important in SLE than in MCTD or SSc, and that IFN-α and IFN-ß may be possible biomarkers for SLE.


Subject(s)
Gene Expression Profiling/methods , Interferons/genetics , Lupus Erythematosus, Systemic/genetics , Mixed Connective Tissue Disease/genetics , Scleroderma, Systemic/genetics , Toll-Like Receptors/genetics , Adult , Aged , Aged, 80 and over , Endosomes/genetics , Endosomes/metabolism , Female , Humans , Interferon-alpha/blood , Interferon-alpha/genetics , Interferon-alpha/metabolism , Interferon-beta/blood , Interferon-beta/genetics , Interferon-beta/metabolism , Interferon-gamma/blood , Interferon-gamma/genetics , Interferon-gamma/metabolism , Interferons/blood , Interferons/metabolism , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/metabolism , Male , Middle Aged , Mixed Connective Tissue Disease/blood , Mixed Connective Tissue Disease/metabolism , Scleroderma, Systemic/blood , Scleroderma, Systemic/metabolism , Toll-Like Receptor 3/blood , Toll-Like Receptor 3/genetics , Toll-Like Receptor 3/metabolism , Toll-Like Receptor 7/blood , Toll-Like Receptor 7/genetics , Toll-Like Receptor 7/metabolism , Toll-Like Receptor 8/blood , Toll-Like Receptor 8/genetics , Toll-Like Receptor 8/metabolism , Toll-Like Receptor 9/blood , Toll-Like Receptor 9/genetics , Toll-Like Receptor 9/metabolism , Toll-Like Receptors/blood , Toll-Like Receptors/metabolism , Young Adult
3.
Scand J Immunol ; 85(2): 147-154, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27896842

ABSTRACT

Rheumatoid arthritis (RA) is one of the autoimmune diseases, where different polymorphisms in cytokine genes play a pathogenic role. IL-12 is now recognized as a critical cytokine in terms of regulating the balance between Th1 and Th2 cells. We investigated the role of single nucleotide polymorphisms (SNPs) (rs3212227 (A/C) and rs17860508 (CTCTAA/GC)) of the IL-12B gene in the genetic susceptibility to RA and in the severity of the disease. Six hundred and thirty-four Caucasian RA patients and 341 healthy matched controls were studied using PCR-RFLP method and high-resolution melting analysis. Concentration of IL-12 cytokine level in serum was evaluated using ELISA. The genotype frequency did not deviate from HWE in each examined group. Frequencies of the rs3212227 CC genotype were statistically higher in patients with RA compared with the healthy control group in both codominant and recessive models (P = 0.037; P = 0.04, respectively). The frequency of rs3212227 C allele also showed similar tendency (P = 0.07). IL-12 level in serum was significantly higher in RA group compared with control (P < 0.0001). We observed that increased IL-12 serum level was correlated with higher number of tender and swollen joints, ExRA presence and higher levels of haemoglobin, CRP and PLT. Also higher IL-12 level in serum was observed within RA patients with hypertension. Present findings indicated that IL-12p40 + 1188A/C polymorphism as well as IL-12p70 protein levels may be associated with RA in the Polish population.


Subject(s)
Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/genetics , Genetic Predisposition to Disease/genetics , Interleukin-12 Subunit p40/genetics , Interleukin-12/blood , Polymorphism, Single Nucleotide , Adolescent , Adult , Aged , Aged, 80 and over , Arthritis, Rheumatoid/pathology , Enzyme-Linked Immunosorbent Assay , Female , Gene Frequency , Genotype , Humans , Logistic Models , Male , Middle Aged , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Severity of Illness Index , Young Adult
4.
Scand J Immunol ; 84(1): 49-60, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27059274

ABSTRACT

To investigate the potential association between IL-12B and IL-27 gene polymorphisms and systemic lupus erythematosus (SLE), we performed a case-control study based on the Polish population. Patients with SLE and healthy individuals were examined for -6415 CTCTAA/GC (rs17860508) and +1188A/C (rs3212227) in IL-12B and -924A/G (rs153109) and 4730T/C (rs181206) in IL-27 gene polymorphisms using the high-resolution melting method, PCR-RFLP method and TaqMan SNP genotyping assay, respectively. An increased frequency of GC/GC genotype as well as GC allele of the IL-12B rs17860508 was found in patients with SLE, as compared with healthy subjects (P < 0.001). We did not find differences in genotype and allele frequencies of the IL-12B rs3212227 and IL-27 rs153109 and rs181206 variants between patients with SLE and controls. IL-27 haplotype rs181206C/rs153109G indicated higher risk for SLE (P = 0.002), whereas haplotype rs181206T/rs153109G indicated reduced risk for SLE (P = 0.005). The IL-12B rs3212227 A/C polymorphism was associated with the mean value of the platelets (PLT), urea and complement C3 level. Furthermore, IL-12B rs17860508 genetic variant showed correlation with PLT, prothrombin time, international normalized ratio and alkaline phosphatase. Our results revealed that IL-12B rs17860508 and IL-27 haplotype CG are genetic risk factors for SLE and that both IL-12B rs17860508 and rs3212227 predict disease phenotype.


Subject(s)
Blood Platelets/immunology , Interleukin-12 Subunit p40/genetics , Interleukins/genetics , Lupus Erythematosus, Systemic/genetics , Adult , Aged , Aged, 80 and over , Alkaline Phosphatase/metabolism , Case-Control Studies , Complement C3/metabolism , Gene Frequency , Genetic Association Studies , Genetic Predisposition to Disease , Genotype , Humans , Male , Middle Aged , Phenotype , Poland , Polymorphism, Single Nucleotide , Prothrombin/metabolism , Young Adult
5.
HLA ; 87(1): 13-8, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26818120

ABSTRACT

Mixed connective tissue disease (MCTD) is a systemic autoimmune disease, originally defined as a connective tissue inflammatory syndrome with overlapping features of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), polymyositis/dermatomyositis (PM/DM) and systemic sclerosis (SSc), characterized by the presence of antibodies against components of the U1 small nuclear ribonucleoprotein (U1snRNP). The aim of the study was to assess the frequency of (high-resolution-typed) DRB1 alleles in a cohort of Polish patients with MCTD (n = 103). Identification of the variants potentially associated with risk and protection was carried out by comparison with the DKMS Polish Bone Marrow Donor Registry (41306 alleles). DRB1*15:01 (odds ratio (OR): 6.06; 95% confidence interval (CI) 4.55-8.06), DRB1*04 (OR: 3.69; 95% CI 2.69-5.01) and *09:01 (OR: 8.12; 95% CI 2.15-21.75) were identified as risk alleles for MCTD, while HLA-DRB1*07:01 allele was found to be protective (OR: 0.50; 95% CI 0.28-0.83). The carrier frequency of the DRB1*01 was higher in MCTD patients compared with controls, although the differences were not statistically significant. Our results confirm the modulating influence of HLA-DRB1 genotypes on development of connective tissue diseases such as MCTD.


Subject(s)
Genetic Predisposition to Disease , HLA-DRB1 Chains/genetics , Mixed Connective Tissue Disease/diagnosis , Mixed Connective Tissue Disease/genetics , Registries , Alleles , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/pathology , Autoantibodies/blood , Autoantibodies/genetics , Case-Control Studies , Dermatomyositis/diagnosis , Dermatomyositis/genetics , Dermatomyositis/immunology , Dermatomyositis/pathology , Diagnosis, Differential , Female , Gene Expression , Gene Frequency , HLA-DRB1 Chains/immunology , Heterozygote , Humans , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/genetics , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/pathology , Male , Mixed Connective Tissue Disease/immunology , Mixed Connective Tissue Disease/pathology , Poland , Ribonucleoprotein, U1 Small Nuclear/genetics , Ribonucleoprotein, U1 Small Nuclear/immunology , Scleroderma, Systemic/diagnosis , Scleroderma, Systemic/genetics , Scleroderma, Systemic/immunology , Scleroderma, Systemic/pathology
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