AUTHOR=Yu Hongyan , Lin Yueling , Xu Yufen , Chen Kaining , Wang Yishuai , Fu Lanyan , Zhou Huazhong , Pi Lei , Che Di , Qiu Xiantao , Gu Xiaoqiong 

TITLE=Association between Rab31/rs9965664 polymorphism and immunoglobulin therapy resistance in patients with Kawasaki disease

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.944508

DOI=10.3389/fcvm.2022.944508

ISSN=2297-055X

ABSTRACT=<sec><title>Background</title><p>Kawasaki disease (KD) is an acute febrile systemic vasculitis affecting infants and young children. A high dose of intravenous immunoglobulin (IVIG) is the first-line strategy for patients with KD to reduce persistent inflammation and the risk of coronary artery aneurysm (CAA) formation. Unfortunately, 10–20% of the patients showed no response to the treatment and were defined as resistant to IVIG. <italic>Rab31</italic> has been reported to regulate innate immunity in several human diseases. However, whether single nucleotide polymorphism (SNP) in <italic>Rab31</italic> gene could predispose to IVIG therapy response in KD was uncovered.</p></sec><sec><title>Methods</title><p><italic>Rab31/</italic>rs9965664 polymorphism was genotyped in 1,024 Chinese patients with KD through TaqMan assay. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of association between <italic>Rab31/</italic>rs9965664 polymorphism and IVIG therapeutic effects.</p></sec><sec><title>Results</title><p>Our results showed that <italic>Rab31/</italic>rs9965664 AA/GA genotype was significantly associated with an increased risk of IVIG resistance compared to GG genotype (GA vs. GG: <italic>p</italic> = 0.0249; AA vs. GG: <italic>p</italic> = 0.0016; AA/GA vs. GG: <italic>p</italic> = 0.0039; and AA vs. GG/GA: <italic>p</italic> = 0.0072). Moreover, the KD individuals carrying the rs9965664 A allele displayed lower Rab31 protein levels, and the expression level of Rab31 in the IVIG-resistant group was decreased significantly when compared to that observed in the response group. A mechanical study demonstrated that Rab31 modulated IVIG response through NLRP3 and p38 pathways.</p></sec><sec><title>Conclusion</title><p>These results suggested that <italic>Rab31/</italic>rs9965664 polymorphism might be associated with an increased risk of IVIG resistance in southern Chinese patients with KD. The possible mechanism is that <italic>Rab31</italic> regulates the NLRP3 pathway negatively to inhibit IVIG response.</p></sec>