RESUMEN
Interleukin 6 (IL-6) is a pro-inflammatory cytokine involved in the development of rheumatoid arthritis (RA). The present study aimed to determine the possible association of the IL6 (rs1800795, G > C) polymorphism with RA susceptibility, disease progression and protein serum levels. Distribution of IL6 alleles and genotypes was similar in RA patients and controls. As expected, patients before induction of anti-tumour necrosis factor agents had significantly higher IL-6 levels as compared with controls (P = 0.002). The CC homozygous patients were characterised with the highest average concentrations of this pro-inflammatory cytokine before treatment (P = 0.028), and they also more frequently presented with more active disease (P = 0.048). These results imply that the IL6 rs1800795 CC homozygosity may play a rather unfavourable role in RA.
Asunto(s)
Artritis Reumatoide/genética , Predisposición Genética a la Enfermedad , Homocigoto , Interleucina-6/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Alelos , Antirreumáticos/uso terapéutico , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/inmunología , Estudios de Casos y Controles , Femenino , Expresión Génica , Frecuencia de los Genes , Humanos , Interleucina-6/sangre , Interleucina-6/inmunología , Masculino , Persona de Mediana Edad , Polonia , Índice de Severidad de la Enfermedad , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
The CXCL12 [chemokine (C-X-C motif) ligand 12] is a member of the CXC family of chemokines and interacts with its CXCR4 receptor. The CXCL12/CXCR4 axis is involved in regulation of proliferation, survival and trafficking of hematopoietic stem cells, including B lymphocytes and disruption within this signaling pathway has been implicated in pathogenesis of chronic lymphocytic leukemia (CLL). The aim of this study was to determine a potential association of the CXCL12 rs1801157 G > A polymorphism with susceptibility to CLL, the disease course and efficacy of therapy. Also, expression of the CD74 and CD38 proteins on B cells was analyzed in relation to clinical parameters and genotyping results. A total of 124 patients with CLL and 75 healthy controls were studied. CXCL12 genotyping was performed using polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) method. The CD74 and CD38 surface expression was determined using flow cytometry. There was a significantly increased frequency of the A allele and AA genotype in CLL patients compared with control group (P < 0.001 in both cases). In addition, the A allele was overrepresented among patients with worse response to therapy in comparison to other genotypes (P < 0.001). On the contrary, patients carrying the A allele displayed lower grade of the disease at diagnosis more frequently than patients homozygous for the G allele (P = 0.037). Moreover, the AA homozygosity correlated with lower CD74 expression on B cells (P = 0.007). In conclusion, data from this study indicate that the CXCL12 rs1801157 G > A polymorphism may affect CLL development, disease progression as well as response to treatment.
Asunto(s)
Antígenos de Diferenciación de Linfocitos B/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/genética , Quimiocina CXCL12/genética , Predisposición Genética a la Enfermedad , Antígenos de Histocompatibilidad Clase II/genética , Leucemia Linfocítica Crónica de Células B/genética , Polimorfismo de Nucleótido Simple , ADP-Ribosil Ciclasa 1/genética , ADP-Ribosil Ciclasa 1/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Antígenos de Diferenciación de Linfocitos B/inmunología , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Linfocitos B/patología , Biomarcadores de Tumor/inmunología , Estudios de Casos y Controles , Quimiocina CXCL12/inmunología , Femenino , Expresión Génica , Genotipo , Antígenos de Histocompatibilidad Clase II/inmunología , Homocigoto , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/inmunología , Leucemia Linfocítica Crónica de Células B/patología , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/inmunología , Persona de Mediana Edad , Clasificación del Tumor , Receptores CXCR4/genética , Receptores CXCR4/inmunología , Resultado del TratamientoRESUMEN
Involvement of the non-classical human leucocyte antigen-E (HLA-E) in both innate and acquired immune response suggests its possible role in development of autoimmune pathologies. This study was undertaken to investigate relationships between the HLA-E gene single nucleotide polymorphisms (SNPs) and a risk of rheumatoid arthritis (RA), as well as to evaluate a potential of these polymorphisms to modulate clinical outcome of anti-tumour necrosis factor (TNF) treatment in female patients. A total of 223 female patients with RA receiving anti-TNF biological therapy and 134 female healthy subjects were enrolled into the study. Genotypings for two SNPs within the HLA-E gene (rs1264457 HLA-E*01:01/01:03; rs1059510 HLA-E*01:03:01/01:03:02) were performed using a polymerase chain reaction (PCR) amplification employing LightSNiP assays. Clinical response was evaluated according to the European League Against Rheumatism (EULAR) criteria at 12 and 24 weeks after initiation of the therapy. The frequency of the HLA-E*01:01/01:01 genotype was decreased significantly in RA patients in comparison to controls (P = 0.031). The presence of the HLA-E*01:01/01:01 genotype in patients correlated with better EULAR response after 12 weeks of anti-TNF treatment, while 01:03 allele carriers were generally unresponsive to the treatment (P = 0.014). The HLA-E*01:03/01:03 genotype was also over-represented among non-responding patients in comparison to HLA-E*01:01/01:01 homozygotes (P = 0.021). With respect to the HLA-E rs1059510 variation, a better response after 12 weeks was observed more frequently in patients carrying the HLA-E*01:03:01/01:03:01 genotype than other genotypes (P = 0.009). The results derived from this study imply that HLA-E polymorphisms may influence RA susceptibility and affect clinical outcome of anti-TNF therapy in female RA patients.
Asunto(s)
Artritis Reumatoide , Predisposición Genética a la Enfermedad , Genotipo , Antígenos de Histocompatibilidad Clase I , Polimorfismo de Nucleótido Simple , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Artritis Reumatoide/inmunología , Femenino , Antígenos de Histocompatibilidad Clase I/genética , Antígenos de Histocompatibilidad Clase I/inmunología , Humanos , Persona de Mediana Edad , Factores de Tiempo , Factor de Necrosis Tumoral alfa/inmunología , Antígenos HLA-ERESUMEN
PURPOSE: To determine whether donor oocyte cytoplasm transferred into the oocytes of women < or = 40 years or with diminished ovarian reserve would enhance embryo quality, implantation, or pregnancy rates. METHODS: Study subjects included women > or = 40 years (15) or with abnormal FSH levels (3). Healthy volunteers (18) produced oocytes for cryopreservation. Donor oocytes were thawed and cytoplasm from surviving oocytes was injected with a single sperm into the cytoplasm of recipient oocytes. Outcome measures included embryo quality scores, implantation, and pregnancy rates. RESULTS: Eighteen donors produced 213 oocytes for cryopreservation and 39/171 (22.8%) survived thawing. Eighteen recipients initiated 25 IVF cycles with embryo transfer in 20 cycles after cytoplasmic transfer (CT). Four cycles resulted in three biochemical losses and one aneuploid clinical loss. Embryo quality did not improve with CT compared to pre-CT IVF cycles in six recipients. CONCLUSIONS: CT with cryopreserved donor oocyte cytoplasm did not enhance success in women with advanced reproductive age or low ovarian reserve.