Background/Purpose
We preliminarily found a SNP (A vs. C, rs6871626) in IL-12B region as a susceptibility gene to Takayasu arteritis (TAK) by genome-wide association study. IL-12Bencodes IL-12/IL-23 p40 that regulates differentiation and activation of Th1 and Th17. In the present study, we investigated the association of this SNP with clinical characteristics and pathophysiology of TAK.
Methods
We investigated 1) the association of the SNP with clinical features of 84 TAK patients who have visited Kyoto University Hospital and 2) the association of the SNP with expression levels of surface markers and intracellular cytokines in peripheral T cells sampled from 21 TAK patients and 15 healthy controls (HC). We obtained peripheral blood mononuclear cells from the TAK patients and HC, stained them with fluorescent antibodies, and analyzed them with flow cytometry.
Results
1) In 84 patients with TAK, 68 were the risk group (R-Group; AA+AC) and 16 were the non-risk group (NR-Group; CC). The complication rate of aortic regurgitation (AR) was 51% in R-Group, significantly higher than 13% in NR-Group (p<0.01). The ultrasound-evaluated severity of AR was higher in R-Group (p<0.01). eGFR tended to be lower in R-Group than in NR-Group (70.5 vs. 80.3 mL/min/1.73m2 , p=0.2). The complication rate of abdominal arterial lesions was 58% in R-Group, significantly higher than 27% in NR-Group (p<0.05). 2) In 21 patients with TAK analyzing T cells, 14 and 7 were R-Group and NR-Group, respectively. In CD4+ T cells, CXCR3+ (Th1) cells were 6.9% in patients (7.5% in R-Group and 5.7% in NR-Group), tended to be higher than 5.7% in HC (p=0.16), while CCR6+ (Th17) cells were 16.0% in patients (16.5% in R-Group and 15.4% in NR-Group), significantly higher than 8.3% in HC (p<0.01). In CD4+ T cells, IFN-γ+ cells in R-Group was significantly higher than in NR-Group (23% vs.7%, p=0.02), while IL-17+cells were not significantly different between R-Group and NR Group (0.7% vs. 1.4%, p=0.37).
Conclusion
In TAK patients with the risk allele of IL-12B, the complications of aortic valve and abdominal arteries were more frequent than in patients with the non-risk allele. TAK patients showed a tendency to have higher percentage of Th1 and Th17 cells than HC, and R-group had higher percentage of Th1 cells than NR-Group. The results suggested a possibility that this SNP may be involved in the pathophysiology of TAK through increased expression of cytokines.
Disclosure:
T. Nakajima,
None;
H. Yoshifuji,
None;
C. Terao,
None;
K. Kitagori,
None;
R. Nakashima,
None;
Y. Imura,
None;
N. Yukawa,
None;
K. Ohmura,
None;
T. Fujii,
None;
T. Mimori,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/association-of-a-single-nucleotide-polymorphism-snp-in-il-12b-region-with-clinical-features-and-peripheral-t-cell-profiles-of-patients-with-takayasu-arteritis/