HLA DRB1*0102, Which Is Associated With Tubulointerstitial Nephritis and Uveitis Syndrome (TINU) Is Also Frequent in Patients With Sudden Onset Anterior Bilateral Uveitis but Not in Patients With Tubulointerstitial Nephritis Alone

Abstract

Purpose: : Tubulointerstitial nephritis and uveitis (TINU) syndrome is rare even in specialized uveitis clinics, but is more frequent in patients with sudden onset anterior bilateral uveitis, especially when < 20 years of age. Earlier, we demonstrated a very strong association of HLA DRB1*0102 with definite, biopsy proven TINU. Here, we performed HLA analysis on subjects with isolated uveitis of this subtype or with isolated nephritis (TIN).

Methods: : IRB approval was obtained. Patients with sudden onset anterior bilateral uveitis (U) and inadequate criteria to meet a diagnosis of TINU were identified by database search in 2 centers. At the same time pathology reports were reviewed to identify subjects with biopsy proven TIN. Excluded were patients with other systemic diseases or patients with TIN and uveitis. HLA typing was performed on genomic DNA by a Luminex-based PCR-SSO typing method. HLA frequencies were compared to normal published controls (http://www.ncbi.nlm.nih.gov/projects/gv/mhc/ihwg.cgi) and to the previously published TINU cohort (n=20). p < 0.005 was used as cut-off for significance.

Results: : We included 28 subjects with U and 14 with TIN. As in the published TINU cohort (30%) there was a high allele frequency of HLA DRB1*0102 with 12.5% in the isolated U cohort versus 0.6% in normal controls (p <0.0001; RR 14.3 (8.3-32.0)). None of the TIN patients showed this HLA subtype. Another HLA class II association with HLA DRB1*08 was seen in the U 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 2.5%, p=ns).

Conclusions: : A significant number of patients with isolated sudden onset, anterior, bilateral uveitis have the same HLA class II genotype as patients with TINU. HLA DRB1*0102 might predispose to this subset of uveitis. Alternatively many patients with this uveitis might have a subclinical form of TINU. This latter conclusion is supported by observations from Japan demonstrating biopsy confirmed TINU in patients with normal renal function.

Keywords: uveitis-clinical/animal model • genetics • clinical research methodology