■类风湿性关节炎(RA)是一种遗传倾向,系统性,慢性,炎症性疾病。免疫系统失调和遗传易感性多态性表明,这种类型的变异是功能性的,可能有助于预测疾病易感性和开发新的治疗策略。抗TNF-α(TNF-α)药物是非常有效的RA治疗方法,但并不是所有的病人都有同样的反应.研究RA危险等位基因是否能识别和预测RA患者的抗TNF-α反应性具有重要意义。
■检查NLR家族pyrin结构域包含3(NLRP3)和caspase募集结构域家族成员8(CARD8)基因多态性及其在RA患者和明显健康对照中的病态基因型和等位基因的功能。此外,它们在疾病易感性中的作用,严重程度,以及对抗TNF-α治疗的反应。此外,研究单核苷酸多态性(SNP)如何影响血清促炎细胞因子的水平,如TNF-α和白细胞介素(IL)-1β。
■100名RA患者(88名女性,12名男性)和100名明显健康的人(86名女性,14名男性)进行了检查。检测血清TNF-α和IL-1β,使用Elabscience夹心ELISA试剂盒。伊拉克生物技术,火鸡DNA提取试剂盒用于从全血提取基因组DNA。使用安捷伦对CARD8(rs2043211)和NLRP3(rs4612666)进行基因分型,AriaMx,美国,通过基于Tri-PlexSYBRGreen的实时PCR等位基因鉴别分析。有天赋的软件,版本2019.2.2,用于从已发布的序列设计引物(GenBank登录号。GCA009914755.1)。通过NCBI的BLAST测定引物特异性。
■研究发现细胞因子血清水平与28关节疾病活动评分(DAS-28)之间存在关联。TNF-α水平随着DAS-28的升高而升高(r2=0.45,P<0.0001)。此外,IL-1β水平随着DAS-28的升高而升高(r2=0.51,P<0.0001)。RA患者与对照组之间的CARD8SNPrs2043211和NLRP3SNPrs4612666基因型分布(分别为P=0.17和0.08)及其等位基因(分别为P=0.059和0.879)无统计学差异。CARD8(rs2043211)TT基因型在DAS-28较高(P<0.0001)和TNF-α和IL-1β血清水平较高(两者均P<0.0001)的患者中更为常见。此外,NLRP3(rs4612666)TT基因型在DAS-28较高(P<0.0001)和TNF-α和IL-1β血清水平较高(两者均P<0.0001)的患者中更为常见。有趣的是,这项研究表明,CARD8(rs2043211)和NLRP3(rs4612666)变异基因型与抗TNF-α药物的低反应相关。
■血清TNF-α和IL-1β与DAS-28和疾病活动相关。无应答者的TNF-α和IL-1β升高。CARD8rs2043211和NLRP3rs4612666变异多态性与高血清TNF-α和IL-1β相关,活跃的疾病过程,疾病结局差,抗TNF-α治疗反应低。
UNASSIGNED: Rheumatoid arthritis (RA) is a genetically predisposed, systemic, chronic, inflammatory disease. Immune system dysregulation and inherited susceptibility polymorphisms suggest that this type of variation is functional and may help predict disease susceptibility and develop new therapeutic strategies. Anti-TNF-alpha (TNF-α) drugs are highly effective RA treatments, but not all patients respond the same way. It\'s important to figure out whether RA risk alleles can identify and predict anti-TNF-α-responsiveness in RA patients.
UNASSIGNED: Examine the function of the NLR family pyrin domain containing 3 (NLRP3) and caspase recruitment domain family member 8 (
CARD8) genes polymorphisms and their morbid genotypes and alleles in RA patients and apparently healthy controls. In addition, their role in disease susceptibility, severity, and response to anti-TNF-α therapy. Also, examine how single nucleotide polymorphisms (SNPs) affect serum levels of pro-inflammatory cytokines like TNF-α and interleukin (IL)-1β.
UNASSIGNED: 100 RA patients (88 females, 12 males) and 100 apparently healthy people (86 females, 14 males) were examined. To measure serum TNF-α and IL-1β, Elabscience sandwich ELISA kits were used. Iraq Biotech, Turkey DNA extraction kit was used to extract genomic DNA from whole blood.
CARD8 (rs2043211) and NLRP3 (rs4612666) were genotyped using Agilent, AriaMx, USA, through Tri-Plex SYBR Green-based real-time PCR allelic discrimination assays. Geneious software, version 2019.2.2, used to design primers from published sequences (GenBank accession no. GCA 009914755.1). Primer specificity was determined by NCBI\'s BLAST.
UNASSIGNED: Study found that there is association between cytokines serum level and 28-joints disease activity score (DAS-28). The level of TNF-α increases with the higher DAS-28 (r2 = 0.45, P < 0.0001). Also, IL- 1β level increases with higher DAS-28 (r2 = 0.51, P < 0.0001). There were no statistically significant variations between patients with RA and the control group in the distribution of CARD8 SNP rs2043211 and NLRP3 SNP rs4612666 genotypes (P = 0.17 and 0.08 respectively) as well their alleles (P = 0.059 and 0.879 respectively).
CARD8 (rs2043211) TT genotype was more frequent in patients with higher DAS-28 (P < 0.0001) and higher TNF-α and IL-1β serum levels (P < 0.0001 for both). Also, NLRP3 (rs4612666) TT genotype was more frequent in patients with higher DAS-28 (P < 0.0001) and higher TNF-α and IL- 1β serum levels (P < 0.0001 for both). Interestingly, this study revealed that
CARD8 (rs2043211) and NLRP3 (rs4612666) variant genotypes are associated with lower response to anti-TNF-α drugs.
UNASSIGNED: Serum TNF-α and IL-1β correlate with DAS-28 and disease activity. Non-responders have elevated TNF-α and IL-1β.
CARD8 rs2043211 and NLRP3 rs4612666 variant polymorphisms are associated with high serum TNF-α and IL-1β, active disease course, poor disease outcomes, and low response to anti-TNF-α therapy.