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HLA-DRB1*0102 is associated with TINU syndrome and bilateral, sudden-onset anterior uveitis but not with interstitial nephritis alone
  1. F Mackensen1,
  2. F David1,
  3. V Schwenger2,
  4. L K Smith3,
  5. R Rajalingam4,
  6. R D Levinson5,
  7. C R Austin3,
  8. D Houghton6,
  9. T M Martin3,
  10. J T Rosenbaum3
  1. 1Interdisciplinary Uveitis Center, University of Heidelberg, Heidelberg, Germany
  2. 2Nephrology, Internal Medicine, University of Heidelberg, Heidelberg, Germany
  3. 3Ophthalmology, Oregon Health & Science University, Portland, Oregon, USA
  4. 4UCLA Immunogenetics Center, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA
  5. 5Ocular Inflammatory Disease Center, Jules Stein Eye Institute, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA
  6. 6Pathology, Oregon Health & Science University, Portland, Oregon, USA
  1. Correspondence to Dr Friederike Mackensen, Interdisciplinary Uveitis Center, University Eye Hospital, INF 400, 69120 Heidelberg, Germany; mackensen{at}


Background Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare form of uveitis. Previously, the authors had demonstrated a strong association of human leukocyte antigen (HLA) DRB1*0102 with TINU. Here, the authors performed HLA analysis on subjects with isolated bilateral sudden-onset uveitis (as in the TINU subtype) or with isolated tubulointerstitial nephritis (TIN).

Methods Patients with sudden onset, anterior, bilateral uveitis not fulfilling a diagnosis of TINU were identified. Pathology reports were reviewed to identify subjects with biopsy-proven TIN. Molecular typing of the HLA-DRB1 gene was performed by the Luminex technology-based sequence-specific oligonucleotide (SSO) hybridisation method (One Lambda, Canoga Park, California). HLA-DRB1 allele frequencies were compared with normal published controls ( dbMHC Europe cohort) and the published TINU cohort (n=18).

Results The authors included 28 subjects with uveitis and 14 with TIN. There was a significantly higher frequency of DRB1*0102 in the isolated uveitis cohort versus in normal controls (10.7% vs 0.6%, respectively, p<0.0001; RR 14.3 (6.9–29.8)). None of the nephritis patients showed this HLA subtype. Another association with HLA-DRB1*08 was seen in the isolated uveitis cohort with an allele frequency of 10.7% versus 2.7% in normal controls (p=0.0019; RR 4.0 (1.8–9.0)). In contrast, the HLA-DRB1*08 was not different from controls in the TINU cohort (allele frequency 2.8%, p=not significant).

Conclusion The incidence of HLA-DRB1*0102 is increased in sudden-onset bilateral anterior uveitis, as seen in patients with TINU. The same allele does not appear to occur in increased frequency in patients with isolated TIN. HLA DRB1*0102 might predispose to this subset of uveitis.

  • Uveitis
  • interstitial nephritis
  • TINU
  • HLA
  • genetics
  • Iris
  • inflammation
  • diagnostic tests/investigation

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  • Funding NIH EY013139 and EY0105712, Research to Prevent Blindness awards to TMM and the Casey Eye Institute; the Stan and Madelle Rosenfeld Family Trust; the William and Mary Bauman Foundation; the Fund for Arthritis and Infectious Disease Research; the Mac Donald Family Foundation.

  • Competing interests None.

  • Ethics approval Ethics approval was provided by the OHSU, UCLA and University of Heidelberg IRBs.

  • Provenance and peer review Not commissioned; externally peer reviewed.