mRNA level of ROCK1, RHOA, and LIMK2 as genes associated with apoptosis in evaluation of effectiveness of adalimumab treatment

Abstract

Background Psoriasis is a multifactorial autoimmune disease, which underlies the abnormalities of the apoptotic process. In cases of psoriasis and psoriatic arthritis, biological treatment is used. This study aimed to determine any changes in the expression of the genes associated with apoptosis in patients with psoriatic arthritis treated with adalimumab and to assess any phenotypic modifications based on changes in dermatological indexes. Methods The study included 20 patients with psoriatic arthritis treated biologically and 20 healthy volunteers. The research material consisted of peripheral blood mononuclear cells (PBMCs) from which the total RNA was isolated. Changes in the gene expression were determined using oligonucleotide microarrays and RT-qPCR. The clinical condition was assessed based on selected indicators: PASI, BSA [%], DAS28, and DLQI, which were determined every 3 months. Results There were changes in the expression of genes associated with apoptosis. Significant differences were found for ROCK1, RhoA, and LIMK2 expression profiles in PBMCs. At the initial stage of treatment, a decrease in the PASI and BSA rates was observed. At the later stages, the values of these indicators increased once again. There were correlations between the changes in these genes' expression and the dermatological markers. Conclusion Adalimumab influences the expression of genes related to apoptosis and the values of dermatological indicators of patients. Changes in the expression level of genes associated with apoptosis suggest that ROCK1, RhoA, and LIMK2 may be genes that can potentially be indicators of treatment effectiveness and lack of response to biological treatment.

Gene expression profile of mitogen-activated kinases and microRNAs controlling their expression in HaCaT cell culture treated with lipopolysaccharide A and cyclosporine A

“…Krawczyk et al assessed the transcriptional activity of MAPK pathway genes and noticed changes in the expression level of genes related to apoptosis in patients with psoriatic arthritis who were treated with adalimumab [ 39 ]. They showed a decrease in MAP3K1 gene expression in patients before and during adalimumab therapy [ 39 ]. Interestingly, they used the HG-U133A 2.0 oligonucleotide microarray technique, which is the same as in our study [ 39 ].…”

“…They showed a decrease in MAP3K1 gene expression in patients before and during adalimumab therapy [ 39 ]. Interestingly, they used the HG-U133A 2.0 oligonucleotide microarray technique, which is the same as in our study [ 39 ]. Tan et al showed a statistically significant decrease in the expression of the MAPK group genes using sequencing [ 40 ].…”

“…The work of Krawczyk et al [ 39 ] and Kjellerup et al [ 42 ] became the basis for our research, in which we assessed changes in the expression of MAPKs pathway genes under the influence of LPS and CsA in a human keratinocyte cell-line HaCaT [ 39 , 42 ]. We noticed changes in the expression profile of 6 mRNAs: DUSP1 , DUSP4 , MAP2K2 , MAP2K7 , MAP3K2 and MAPK9 in the HaCaT cell culture exposed to LPS and CsA compared to the control culture.…”

Expression profile of mRNAs and miRNAs related to mitogen-activated kinases in HaCaT cell culture treated with lipopolysaccharide a and adalimumab

“…In the context of psoriasis, MAPKs have demonstrated regulatory effects on the expression of genes responsible for pro-inflammatory cytokines [ 54 ]. Furthermore, our study built upon the research conducted by Krawczyk et al [ 55 ] and Kjellerup et al [ 56 ]. In our investigation, we assessed alterations in the gene expression of MAPKs pathway influenced by LPS and adalimumab in the HaCaT human keratinocyte cell line.…”

“…One of the more recent studies on selected MAPKs pathway transcripts conducted on a group of Polish patients with psoriatic arthritis treated with adalimumab is that of Krawczyk et al These authors reported a statistically significant decrease in the expression of genes encoding MAPKs family proteins associated with apoptosis [ 55 ]. Notably, the HG-U133A 2.0 oligonucleotide microarray technique, identical to the one employed in our study, was utilized by Krawczyk et al [ 55 ]. In turn, Tan et al observed a statistically significant reduction in the expression of MAPK genes through sequencing [ 57 ].…”