Interleukins and interleukin receptors in rheumatoid arthritis: Research, diagnostics and clinical implications

Rheumatoid arthritis(RA) is an autoimmune disease, resulting in a chronic, systemic inflammatory disorder. It may affect many tissues and organs, but it primarily affects the flexible joints. In clinical practice patient care generates many questions about diagnosis, prognosis, and treatment. It is challenging for health care specialists to keep up to date with the medical literature. This review summarizes the pathogenesis, the polymorphisms of interleukin and interleukin genes and the standard available and possible future immunologictargets for RA treatment. The identification of diseaseassociated interleukin and interleukin receptor genes can provide precious insight into the genetic variations prior to disease onset in order to identify the pathways important for RA pathogenesis. The knowledge of the complex genetic background may prove useful for developing novel therapies and making personalized medicine based on the individual's genetics.

Susceptibility to ulcerative colitis in Hungarian patients determined by gene-gene interactions

AIM:To study the inflammatory bowel disease-5 locus(IBD5)and interleukin-23 receptor(IL23R)gene variants in UC patients and test for gene-gene interaction.METHODS:The study population(n=625)was comprised of 320 unrelated ulcerative colitis(UC)patients with Caucasian origin and 316 age-and gendermatched,healthy controls.Five variants in the IBD5 locus(IGR2198a_1 rs11739135,IGR2096a_1 rs12521868,IGR2230a_1 rs17622208,SLC22A4 rs1050152 and SLC22A5 rs2631367)and two of the IL23R gene(rs1004819,rs2201841)were analysed.PCR and restriction fragment length polymorphism methods were used for genotyping,the SLC22A4 rs1050152 genotypes were determined by direct sequencing.Interactions and specific genotype combinations of the seven variants were tested by binary logistic regression analysis.The IL23R genotypes were stratified by IBD5 genotypes for further interaction analyses.RESULTS:For the IL23R rs1004819 A allele we found significantly higher allele frequency(P=0.032)in UC patients compared to control subjects.The SNP rs1004819 showed significant association with UC risk for carriers(P=0.004,OR=1.606;95%CI:1.160-2.223)and the SNP rs2201841 for homozygotes(P=0.030,OR=1.983;95%CI:1.069-3.678).Individually none of the IBD5 markers conferred risk to UC development.There was no evidence for statistical interaction either between IBD5 loci and IL23R genes using logistic regression analysis.After genotype stratification,we could detect a positive association on the background of rs1004819 A allele for SLC22A4 T,SLC22A5 C,IGR2198a_1 C or IGR2096a_1 T allele,the highest OR was calculated in the presence of SLC22A4T allele(P=0.005,OR=2.015;95%CI:1.230-3.300).There was no association with UC for any combinations of rs1004819 and IGR2230a_1.The IL23R rs2201841homozygous genotype and IBD5 carrier status together did not confer susceptibility for UC.CONCLUSION:The present study has shown that UC susceptibility genes are likely to act in a complex interactive manner similar to CD.