RESUMO
OBJECTIVE: Interleukin-33 is an IL-1 family cytokine which signals via its T1/ST2 receptor, and acts as a key regulator of inflammation, notably the type-2 response implicated in asthma. This study aims to measure the expression of soluble ST2 (sST2) and IL-33 in asthmatic children, depending on disease activity. METHODS: Thirty-seven children with well-defined asthma (20 moderate and 17 mild asthmatics) were studied. IL-33 and sST2 were measured by ELISA in serum and induced sputum (IS) samples, and compared with 22 age- and sex-matched healthy controls. Real-time quantitative PCR was used to determine IL-33 and TNF-α mRNA expression in IS. RESULTS: sST2 and IL-33 levels in IS and serum were significantly higher in patients compared with healthy controls (p = 0.0001). The increase in sST2 and IL33 was significantly more important in moderate cases than in mild asthma. A significant correlation was observed between serum and IS IL-33 levels (r = 0.497; p = 0.0018). Higher levels of IL-33 mRNA were detected in IS from asthmatics than those observed in controls. A significant correlation was found between TNF-α and IL-33 mRNA expression in the asthmatic subjects (r = 0.772, p = 0.0001). CONCLUSIONS: Values of sST2 and IL-33 observed in IS were found to correlate with disease activity. Elevated IL-33 mRNA expression in IS and its correlation with TNF-α reflected the inflammatory process observed in the lung of young asthmatics.
Assuntos
Asma/imunologia , Interleucinas/imunologia , Receptores de Superfície Celular/imunologia , Escarro/imunologia , Fator de Necrose Tumoral alfa/imunologia , Adolescente , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Inflamação/imunologia , Proteína 1 Semelhante a Receptor de Interleucina-1 , Interleucina-33 , Masculino , RNA Mensageiro/química , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Estatísticas não Paramétricas , Fator de Necrose Tumoral alfa/genéticaRESUMO
BACKGROUND: A positive association between genetic polymorphism and asthma may not be extrapolated from one ethnic group to another based on intra- and interethnic allelic and genotype frequencies differences. OBJECTIVE: We assessed whether polymorphisms of GST genes (GSTM1, GSTT1, and GSTP1) are associated with asthma and atopy among Tunisian children. METHODS: 112 unrelated healthy individuals and 105 asthmatic (73 atopic and 32 nonatopic) children were studied. Genotyping the polymorphisms in the GSTT1 and GSTM1 genes was performed using the multiplex PCR. The GSTP1 ILe105Val polymorphism was determined using PCR-RFLP. RESULTS: GSTM1 null genotype was significantly associated with the increased risk of asthma (P = .002). Asthmatic children had a higher prevalence of the GSTP1Ile105 allele than the control group (43.8% and 33.5%, respectively; P = .002). Also, the presence of the GSTP1 homozygote Val/Val was less common in subjects with asthma than in control group. We have found that GSTT1 null genotype (GSTT1 *0/*0) was significantly associated with atopy (P = .008). CONCLUSION: Polymorphisms within genes of the GST superfamily were associated with risk of asthma and atopy in Tunisia.
Assuntos
Asma/genética , Predisposição Genética para Doença/genética , Glutationa Transferase/genética , Polimorfismo Genético , Adolescente , Criança , Pré-Escolar , Feminino , Frequência do Gene , Genótipo , Glutationa S-Transferase pi/genética , Humanos , Masculino , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , TunísiaRESUMO
BACKGROUND: Previous studies have reported an association between polymorphisms in Il17A and IL17F genes and the prevalence of rheumatoid arthritis (RA) in Caucasian populations. The aim of the current study was to investigate that polymorphisms in both genes may affect RA susceptibility in the Tunisian population and to study the relation between serum IL-17 levels and synovial fluid (SF) levels and risk in RA patients. We suggested also that these polymorphisms may influence response to treatment in Tunisian RA patients. METHODS: We studied IL17A-152 G/A (rs2275913), IL17F 7488 A/G (rs763780) and IL17F 7383 A/G polymorphisms in a Tunisian population. The genotypic and allelic distributions of IL-17A and IL-17F genes polymorphisms were analyzed by Polymerase Chain-Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) for 108 patients and 202 healthy controls. IL-17 levels were measured in synovial fluid (SF) and in serum of both 108 patients and 47 controls (pg/ml) using enzyme-linked immunosorbent assay (ELISA) technique. RESULTS: Our results indicated that IL17F 7488 A/G and IL17F 7383 A/G polymorphisms were significantly associated with RA risk in the whole population. However, IL17A-152 G/A polymorphism did not show any significant association with RA prevalence in the Tunisian population. Stratification according to demographic and clinical features revealed differential significant associations of IL17A-152 G/A, IL17F 7488 A/G and IL17F 7383 A/G polymorphisms within different subgroups and subtypes of clinical-pathologic features in RA patients. IL17A-152 G/A polymorphism was associated with an enhanced response to biologic and MTX treatment. IL17F 7383 A/G polymorphism was associated with an enhanced response to biologic treatment. The IL17F 7488 A/G polymorphism decreased significantly good response to biologic treatment, but enhanced response to MTX treatment. The expression of IL-17 in serum and synovial fluid (SF) in RA patients was significantly higher than that observed in healthy controls (P<0.0001) and their levels depend on RA severity. The mean IL-17 levels in the anti-TNF α treated patients decreased significantly at 0 week, 14 weeks and 30 weeks (P=0.0032 and P<0.0001, respectively). CONCLUSIONS: Our results confirmed IL17A and IL17F as potential candidate genes involved in RA. They play pivoting roles in the susceptibility and in clinical features of RA disease. Responses to RA treatments are differently conditioned by polymorphisms in IL17A and IL17F genes.