HLA-DRB1*0102 is associated with TINU syndrome and bilateral, sudden-onset anterior uveitis but not with interstitial nephritis alone
- F Mackensen1,
- F David1,
- V Schwenger2,
- L K Smith3,
- R Rajalingam4,
- R D Levinson5,
- C R Austin3,
- D Houghton6,
- T M Martin3,
- J T Rosenbaum3
- 1Interdisciplinary Uveitis Center, University of Heidelberg, Heidelberg, Germany
- 2Nephrology, Internal Medicine, University of Heidelberg, Heidelberg, Germany
- 3Ophthalmology, Oregon Health & Science University, Portland, Oregon, USA
- 4UCLA Immunogenetics Center, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA
- 5Ocular Inflammatory Disease Center, Jules Stein Eye Institute, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA
- 6Pathology, Oregon Health & Science University, Portland, Oregon, USA
- Correspondence to Dr Friederike Mackensen, Interdisciplinary Uveitis Center, University Eye Hospital, INF 400, 69120 Heidelberg, Germany;
- Accepted 26 September 2010
- Published Online First 7 November 2010
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 (http://www.ncbi.nlm.nih.gov/projects/gv/mhc/ihwg.cgi 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.
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.