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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 &lt; 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.

the journal of immunology/the journal of immunology

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