Anti-IL23A monoclonal antibody, clone 584Q20

Molecular analysis is key to a better understanding of drug resistance during therapy. The aim of this study was to evaluate changes in the expression of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-IL12A, IL12B, IL23A, interferon gamma (IFN-gamma) in psoriatic patients during 84 days of treatment and TNF-alpha on the protein level. The study group consisted of 32 psoriatic patients during cyclosporine A therapy. The molecular analysis was made by using real-time reverse transcription polymerase chain assay (RTqPCR) and MALDI ToF mass spectroscopy three times: after 0, 42, 84 days of treatment. Statistically significant differences (p < .05) in transcriptional activity were observed for genes: TNF-alpha (0 vs. 42nd days p = .006; 0 vs. 84th days p = .005), IL23A (0 vs. 42nd days p = .041), IFN-gamma (0 vs. 42th days p = .040; 0 vs. 84th days p = .041), IL17 (0 vs. 42nd p = .000003 0 vs. 84th p = .001650), IL12A (0 vs. 42nd p = .0047 vs. 84th p = .0063). The expression of TNF-alpha was down-regulated during therapy, IL23A was upregulated during CsA treatment, while the expression of IFN-gamma and IL17 were higher after 42 days and lower after 84 days compared to 0 days of CsA treatment. It seems that TNF-alpha, IL12A, IL23A, IFN-gamma, and IL17 can be useful complementary molecular markers to assess the efficacy of psoriasis treatment.

The concept of interferon-gamma (IFN-gamma) having a central role in cell-mediated immune defence to Mycobacterium tuberculosis has long been proposed. Observations made through early candidate gene studies of constituents of the IFN-gamma pathway have identified moderately associated variants associated with resistance or susceptibility to tuberculosis (TB). By analysing 20 major genes whose proteins contribute to IFN-gamma signalling we have assessed a large fraction of the variability in genes that might contribute to susceptibility to TB. Genetic variants were identified by sequencing the promoter regions and all exons of IFNG, IFNGR1, IFNGR2, IRF1, IL12A, IL12B, IL12RB1, IL12RB2, IL23A, IL23R, IL27, EBI3, IL27RA, IL6ST, SOCS1, STAT1, STAT4, JAK2, TYK2 and TBX21 in 69 DNA samples from Ghana. In addition, we screened all exons of IFNGR1 in a Ghanaian study group comprising 1999 TB cases and 2589 controls by high-resolution melting point analysis. The fine-mapping approach allows for a detailed screening of all variants, common and rare. Statistical comparisons of cases and controls, however, did not yield significant results after correction for multiple testing with any of the 246 variants selected for genotyping in this investigation. Gene-wise haplotype tests and analysis of rare variants did not reveal any significant association with susceptibility to TB in our investigation as well. Although this analysis was applied on a plausible set of IFN-gamma pathway genes in the largest African TB cohort available so far, the lack of significant results challenges the view that genetic marker of the IFN-gamma pathway have an important impact on susceptibility to TB.