Higher circulating levels of chemokine CCL20 in patients with multiple sclerosis: evaluation of the influences of chemokine gene polymorphism, gender, treatment and disease pattern.

Chemokines play an important role in the autoimmune diseases. The aim of this study was to investigate the levels of CCL20 and a polymorphism [-786C > T (rs6749704)] in the chemokine gene in patients with multiple sclerosis (MS). The blood samples were collected from 135 MS patients and 135 healthy subjects as a control group. The patients have relapsing-remitting (RRMS; n = 65), primary progressive (PPMS; n = 47), secondary progressive (SPMS; n = 35) or progressive relapsing (PRMS; n = 14) patterns. The serum levels of CCL20 were measured by ELISA. The DNA was analyzed for CCL20 polymorphism using PCR-RLFP. The mean serum levels of CCL20 in the MS group were significantly higher than in the healthy group (P < 0.001). In patients with a SPMS pattern, the frequency of CT genotype at rs6749704 (24.3 %) was significantly lower as compared to patients with other patterns (42.8 %; P < 0.04). No significant differences were observed between subjects with different genotypes in rs6749704 regarding the CCL20 levels. The mean serum levels of CCL20 in both newly diagnosed and previously diagnosed patients was significantly higher than in the healthy group (P < 0.05 and 0.001, respectively). The mean serum levels of CCL20 in patients with RRMS, SPMS and PPMS patterns were significantly higher than in the healthy group (P < 0.004, P < 0.04, and 0.05, respectively). The levels of CCL20 in untreated patients and in patients who received interferon-ß, methylprednisolone or the combination of interferon-ß plus methylprednisolone were higher as compared to the control group (P < 0.05, P < 0.03, P < 0.005, and P < 0.05, respectively). These results showed higher levels of CCL20 in patients that represent that the chemokine may play an important role in the pathogenesis of MS. The rs6749704 polymorphism was an associated SPMS pattern. The levels of CCL20 were not influenced by gender, disease pattern and treatment.

Lower serum levels of Th2-related chemokine CCL22 in women patients with multiple sclerosis: a comparison between patients and healthy women.

Chemokines play a major role in autoimmune diseases such as multiple sclerosis (MS). Gender also affects the susceptibility and course of MS. The aim of this study was to investigate the serum levels of the macrophage-derived chemokine (CCL22) in women and men patients with MS. Blood samples were collected from 135 healthy subjects (35 men and 100 women) and 135 MS patients (29 men and 136 women; 47 newly diagnosed and 88 treated patients and have relapsing-remitting (RRMS; n = 65), secondary progressive (SPMS; n = 37), primary progressive (PPMS; n = 19), or progressive relapsing (PRMS; n = 14) patterns). The serum levels of CCL22 were measured by ELISA. The difference of the mean serum levels of CCL22 between the newly diagnosed MS men and healthy men was not significant, but in newly diagnosed MS women, the mean serum levels of CCL22 were significantly lower than those in treated MS women and healthy women (P < 0.006 and P < 0.0001, respectively). The differences of the mean CCL22 levels between men patients with different treatment programs were not significant, but the mean CCL22 levels were significantly higher in women treated with interferon-ß or the combination of interferon-ß plus methylprednisolone as compared to untreated women patients (P < 0.01 and P < 0.05, respectively). The CCL22 levels were also significantly higher in women with RRMS and PRMS patterns in comparison to healthy women (P < 0.05 and P < 0.01, respectively). These results showed lower levels of CCL22 in women patients which represents that the reduction in CCL22 levels may play an important role in the pathogenesis of the disease in women. In women patients, the levels of CCL22 were influenced by disease pattern and treatment.

Hybridization of 2'-ribose modified mixed-sequence oligonucleotides: thermodynamic and kinetic studies.

In this study, we characterize the thermodynamics of hybridization, binding kinetics and conformations of four ribose-modified (2'-fluoro, 2'-O-propyl, 2'-O-methoxyethyl and 2'-O-aminopropyl) decameric mixed-sequence oligonucleotides. Hybridization to the complementary non-modified DNA or RNA decamer was probed by fluorescence and circular-dichroism spectroscopy and compared to the same duplex formed between two non-modified strands. The thermal melting points of DNA-DNA duplexes were increased by 1.8, 2.2, 0.3 and 1.3 degrees C for each propyl, methoxyethyl, aminopropyl and fluoro modification, respectively. In the case of DNA-RNA duplexes, the melting points were increased by 3.1, 4.1 and 1.0 degrees C for each propyl, methoxyethyl and aminopropyl modification, respectively. The high stability of the duplexes formed with propyl-, methoxyethyl- and fluoro-modified oligonucleotides correlated with high preorganization in these single-strands. Despite higher thermodynamic duplex stability, hybridization kinetics to complementary DNA or RNA was slower for propyl- and methoxyethyl-modified oligonucleotides than for the non-modified control. In contrast, the positively-charged aminopropyl-modified oligonucleotide showed rapid binding to the complementary DNA or RNA.