HLA-DRB1*0102 is associated with TINU syndrome and bilateral, sudden-onset anterior uveitis but not with interstitial nephritis alone.
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).


CONCLUSIONS
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.
Interdisciplinary Uveitis Center, University Eye Hospital, INF 400, 69120 Heidelberg, Germany. mackensen@uveitiszentrum.de
F
F
Mackensen
F
F
David
V
V
Schwenger
L K
LK
Smith
R
R
Rajalingam
R D
RD
Levinson
C R
CR
Austin
D
D
Houghton
T M
TM
Martin
J T
JT
Rosenbaum
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics* / Q000378:metabolism; D059811:HLA-DRB1 Chains; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D058889:Molecular Typing; D009395:Nephritis, Interstitial / Q000235:genetics; D013577:Syndrome; D014605:Uveitis / Q000235:genetics; D014606:Uveitis, Anterior / Q000235:genetics*; D055815:Young Adult
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains