HLA-DR, DQ Class II DNA Typing in Pediatric Panuveitis and Tubulointerstitial Nephritis and Uveitis

Reddy, Ashvini K.; Hwang, Yih Shiou; Mandelcorn, Efrem D.; Davis, Janet L.

doi:10.1016/j.ajo.2013.12.006

Cited by 41 publications

(31 citation statements)

References 25 publications

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“…Loss of T-cell tolerance in the pathogenesis of TINU is suggested by multiple studies identifying a strong link between TINU and certain class II human leukocyte antigen (HLA) subtypes, such as HLA-DQA1*01, HLA-DQB1*05, and HLA-DRB1*01, with a relative risk as high as 167.1 for HLA-DRB1*0102 [12,13,38]. The latter HLA gene is an independent risk factor for TINU, particularly of younger onset [38].…”

Section: Pathogenesismentioning

confidence: 99%

“…The latter HLA gene is an independent risk factor for TINU, particularly of younger onset [38]. These HLA subtypes confer variable risks based on the population studied [13,39,40]. Since HLA class II molecules are involved with exogenous antigen presentation to CD4+ T-helper cells [41], molecular mimicry between exogenous infectious antigens and ocular antigens could explain the HLA association with this disease [42].…”

Section: Pathogenesismentioning

confidence: 99%

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Tubulointerstitial nephritis and uveitis

Pakzad-Vaezi

Pepple

2017

Current Opinion in Ophthalmology

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Purpose of review Tubulointerstitial nephritis and uveitis (TINU) is an important yet under-recognized ocular inflammatory syndrome. This review summarizes key historical publications that identified and defined the syndrome, and more recent literature that reveal the importance of urinary beta-2 microglobulin testing and kidney biopsy in the diagnostic evaluation of patients with TINU. Additionally, research studies providing new insights into disease pathogenesis are highlighted. Recent findings In contrast with initial reports of TINU manifesting exclusively as an anterior uveitis in pediatric patients, more recent reports have identified TINU in patients of all ages with a wide range of ocular manifestations. Urinary beta-2 microglobulin has emerged as a sensitive and specific laboratory screening test, and the role of kidney biopsy in differentiating TINU from sarcoidosis continues to evolve. Genetic studies have identified HLA-DQA1*01, HLA-DQB1*05, and HLA-DRB1*01 as high risk alleles and the identification of anti-mCRP antibodies suggests a role for humoral immunity in disease pathogenesis. Management strategies have evolved to include systemic anti-inflammatory treatment as a result of important outcome studies in patients with significant renal and ocular disease. Summary With greater recognition, understanding, and treatment of this syndrome, both ocular inflammation and renal disease can be better addressed.

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Section: Pathogenesismentioning

confidence: 99%

Section: Pathogenesismentioning

confidence: 99%

Tubulointerstitial nephritis and uveitis

Pakzad-Vaezi

Pepple

2017

Current Opinion in Ophthalmology

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“…Some of these markers are: HLA-DRB1*01, HLA DRB1*0102, HLA-DQA1*01, and HLA-DQB1*05. [6][7][8][9] Definite TINU syndrome is diagnosed when acute interstitial nephritis is firmly established and the patient has bilateral anterior uveitis of sudden onset, which is the most common ocular presentation in reported cases, and well-established acute interstitial nephritis. 1 For definite TINU syndrome, acute interstitial nephritis is diagnosed either by histologic examination of renal biopsy specimens, or by all three of the following criteria for AIN: 1) abnormal renal function, usually mildly elevated creatinine or creatinine clearance, 2) abnormal findings on urinalysis consistent with AIN, and 3) history of acute systemic illness lasting for at least 2 weeks, characterized by the typical signs, symptoms, and laboratory findings.…”

Section: Diagnosismentioning

confidence: 99%

“…8 Bilateral panuveitis with chorioretinal lesions in pediatric patients was found to be associated with the HLA-DR, DQ class II type, in TINU syndrome . 9 Mandeville determined the diagnostic criteria for TINU syndrome characterized by the presence of histopathologically confirmed acute interstitial nephritis (AIN) and typical bilateral anterior non-granulomatous uveitis. 2 Clinical manifestations can be nonspecific (fever, abdominal pain, weight loss, fatigue, malaise, anorexia, and headache), and generally, renal involvement is mild.…”

Section: Introductionmentioning

confidence: 99%

Tubulointerstitial Nephritis and Uveitis Syndrome: Case Report and Review of the Literature

Aguilar¹,

Lonngi²,

de-la-Torre

2015

Ocular Immunology and Inflammation

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Purpose:To review the literature on tubulointerstitial nephritis and uveitis (TINU) syndrome, and to report a case of a patient with relapsing polychondritis (RP) and TINU syndrome. Method: TINU syndrome is a rare oculo-renal inflammatory disorder. It is more common in young women with autoimmune conditions, infections, systemic disease, and previous use of medications. We report the case of a 62-year-old woman with relapsing polychondritis and a 2-year history of acute, recurrent, asymmetric, bilateral, anterior, nongranulomatous uveitis accompanied by tubulointerstital nephritis. The patient was diagnosed with TINU syndrome associated with relapsing polychondritis. No cases of this association have been reported in the literature. The clinical features of TINU syndrome are discussed based on the published works. Conclusion: TINU is an uncommon syndrome; only about 200 cases have been reported in the literature related to infections, systemic disease, and previous use of medications such as antibiotics and non-steroidal anti-inflammatory drugs. We found that it can be associated with relapsing polychondritis; therefore, it is important to investigate symptoms of this disease since TINU syndrome can co-exist with it.

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“…HLA genes have extremely high levels of polymorphism and heterozygosity and are associated with most autoimmune disorders (4,5). Over the past decade, HLA alleles conferring genetic susceptibility to TINU syndrome have been revealed in small case series by researchers from Finland (HLA-DQA1*0104, -DRB1*14) (6), Spain (HLA-DQB1*01, -DR*14) (7,8), Italy (HLA-DQA1*0102, -DQB1*0503) (9, 10), the US (HLA-DRB1*0102,-DQB1*05) (11)(12)(13), Australia (HLA-DQA1*01, -DQB1*05) (14), Germany (HLA-DQB1*0503,-DRB1*1401) (15), Japan (HLA-DQB1*050101, -DQB1*050201) (16,17), the U.K. (HLA-DR*14), (18) and China (HLA-DQB1*0503) (19) (Supplemental Table I). These reports provided evidence for the relevance of HLA-DQA1, -DQB1, and -DRB1 to TINU syndrome in different populations.…”

mentioning

confidence: 99%

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

Jia

et al. 2018

The Journal of Immunology

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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 < 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.

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HLA-DR, DQ Class II DNA Typing in Pediatric Panuveitis and Tubulointerstitial Nephritis and Uveitis

Cited by 41 publications

References 25 publications

Tubulointerstitial nephritis and uveitis

Tubulointerstitial nephritis and uveitis

Tubulointerstitial Nephritis and Uveitis Syndrome: Case Report and Review of the Literature

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

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