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HLA-DQA1, -DQB1, and -DRB1 Alleles Associated with Acute Tubulointerstitial Nephritis in a Chinese Population: A Single-Center Cohort Study.


ABSTRACT: Acute tubulointerstitial nephritis (ATIN) is a common cause of acute kidney injury with various origins. HLA-DQA1, -DQB1, and -DRB1 have been associated with development of tubulointerstitial nephritis and uveitis (TINU) syndrome in case reports and small case series, but information about HLA genetic susceptibility to drug hypersensitivity-related ATIN (D-ATIN) or other types of ATIN is limited. In this article, we genotyped 154 patients with ATIN of different causes and 200 healthy controls at HLA-DQA1, -DQB1, and -DRB1 loci. We found that there was no difference between patients with D-ATIN and TINU in the carrier's frequency of HLA-DQA1, -DQB1, or -DRB1 Patients with Sjogren's syndrome-ATIN and IgG4-related ATIN presented a different pattern of tested HLA alleles. HLA-DQA1*0104 (p value corrected by false discovery rate method [Pc] = 4.72 × 10-22, odds ratio [OR] = 13.81), -DQB1*0503 (Pc = 1.95 × 10-14, OR = 9.51), and -DRB1*1405 (Pc = 8.06 × 10-19, OR = 12.80) were significant risk alleles for the occurrence of D-ATIN and TINU. There were no significant associations between tested HLA alleles and ATIN induced by other causes. Patients with D-ATIN/TINU carrying HLA-DQA1*0104/DQB1*0503/DRB1*1405 had higher peak serum creatinine and more severe renal tubulointerstitial inflammatory impairment. They also had significantly higher levels of tubular HLA-DR and HLA-DQ expression, which were correlated with the numbers of interstitial CD4+ T lymphocytes (r = 0.975, p < 0.001 and r = 0.832, p = 0.005, respectively) and monocytes/macrophages (r = 0.721, p = 0.004 and r = 0.615, p = 0.02, respectively). In conclusion, patients with D-ATIN or TINU have genetic susceptibility in HLA-DQA1, -DQB1, and -DRB1 alleles. HLA-DQA1*0104/DQB1*0503/DRB1*1405 serves as a significant risk haplotype for development of D-ATIN and TINU, which might facilitate renal tubulointerstitial inflammation by enhancing Ag-presenting capacity of renal tubular cells.

SUBMITTER: Jia Y 

PROVIDER: S-EPMC6036232 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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<i>HLA-DQA1</i>, <i>-DQB1</i>, and <i>-DRB1</i> Alleles Associated with Acute Tubulointerstitial Nephritis in a Chinese Population: A Single-Center Cohort Study.

Jia Yan Y   Su Tao T   Gu Yanghui Y   Li Cui C   Zhou Xujie X   Su Jianqun J   Sun Pingping P   Tang Jiawei J   Yang Liu L   Liu Gang G   Yang Li L  

Journal of immunology (Baltimore, Md. : 1950) 20180601 2


Acute tubulointerstitial nephritis (ATIN) is a common cause of acute kidney injury with various origins. <i>HLA-DQA1</i>, <i>-DQB1</i>, and <i>-DRB1</i> have been associated with development of tubulointerstitial nephritis and uveitis (TINU) syndrome in case reports and small case series, but information about HLA genetic susceptibility to drug hypersensitivity-related ATIN (D-ATIN) or other types of ATIN is limited. In this article, we genotyped 154 patients with ATIN of different causes and 20  ...[more]

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