Why birdshot retinochoroiditis should rather be called ‘HLA-A29 uveitis’?

Herbort, Carl P.; Pavésio, Carlos; LeHoang, Phuc; Bodaghi, Bahram; Fardeau, Christine; Kestelyn, Philippe; Neri, Piergiorgio; Papadia, Marina

doi:10.1136/bjophthalmol-2016-309764

Cited by 65 publications

(68 citation statements)

References 34 publications

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“…A previous genome-wide association study in Birdshot highlighted strong involvement of the ERAP region on chromosome 5q15 [20]. The unique (diagnostic) prerequisite of HLA-A29 [19] and ERAP association classifies Birdshot patients within the MHC-I-opathy cluster and provides an attractive model to define the genetic architecture of this superfamily of conditions [18]. Therefore, we mapped ERAP1 allotypes and other key variants at 5q15 across two European populations of 130 cases and 2,993 controls, and interrogated their downstream implications using transcriptomic data, molecular cloning and functional assays.…”

Section: Introductionmentioning

confidence: 96%

Functionally distinct ERAP1 and ERAP2 are a hallmark of HLA-A29-(Birdshot) Uveitis

Kuiper

Setten

Devall

et al. 2018

Preprint

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Birdshot Uveitis (Birdshot) is a rare eye condition that affects HLA-A29-positive individuals and could be considered a prototypic member of the recently proposed "MHC-I-opathy" family. Genetic studies have pinpointed the ERAP1 and ERAP2 genes as shared associations across MHC-I-opathies, which suggests ERAP dysfunction may be a root cause for MHC-I-opathies. We mapped the ERAP1 and ERAP2 haplotypes in 84 Dutch cases and 890 controls. We identified association at variant rs10044354, which mediated a marked increase in ERAP2 expression.We also identified and cloned an independently associated ERAP1 haplotype (tagged by rs2287987) present in more than half of the cases; this ERAP1 haplotype is also the primary risk and protective haplotype for other MHC- 6)) replicated and showed consistent direction of effect in an independent Spanish cohort of 46 cases and 2,103 controls. In both cohorts, the combined rs2287987-rs10044354 haplotype associated with Birdshot more strongly than either SNP alone (meta-analysis: p=3.9 × 10(-9)). Finally, we observed that ERAP2 protein expression is dependent on the ERAP1 background across three European populations (n=3,353). In conclusion, a functionally distinct combination of ERAP1 and ERAP2 are a hallmark of Birdshot and provide rationale for strategies designed to correct ERAP function for treatment of Birdshot and MHC-I-opathies more broadly.

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Section: Introductionmentioning

confidence: 96%

Functionally distinct ERAP1 and ERAP2 are a hallmark of HLA-A29-(Birdshot) Uveitis

Kuiper

Setten

Devall

et al. 2018

Preprint

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“…Similarly, the disease‐associated allele HLA‐A*29 is used in the diagnosis of birdshot uveitis. Given that ≥95% of patients with the disease carry HLA‐A*29 , its absence can be used as an exclusion criterion in the diagnostic workup . HLA‐B*51 is associated with Behçet's disease, and testing for this allele can aid in disease diagnosis.…”

Section: Primer Sequences For Hla‐a*29 and Hla‐b*51 Ssp‐pcr And Intermentioning

confidence: 99%

“…Given that ≥95% of patients with the disease carry HLA-A*29, its absence can be used as an exclusion criterion in the diagnostic workup. 4 HLA-B*51 is associated with Behçet's disease, 5 and testing for this allele can aid in disease diagnosis. As a consequence, detection of these alleles is requested from diagnostic laboratories and is also of interest in a research context.…”

mentioning

confidence: 99%

An SSP‐PCR method for the rapid detection of disease‐associated alleles HLA‐A29* and HLA‐B51*

Amstutz

Schaerer

Andrey

et al. 2018

HLA

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HLA-A*29 and HLA-B*51 are associated with birdshot uveitis and Behçet's disease, respectively, and are used as a diagnostic criterion in patients with suspected disease, requiring their detection in diagnostic laboratories. While commercial tests for individual HLA alleles are available for other disease-associated HLA variants, no similar allele-specific assays are available for HLA-A*29 and HLA-B*51. Here, we report sequence-specific priming-polymerase chain reaction (SSP-PCR) methods for the detection of HLA-A*29 and HLA-B*51 using a single PCR reaction per allele. The assays were tested in 30 and 32 previously HLA-typed samples, respectively, representing >97% of HLA-A alleles and >93% of HLA-B alleles in a European population. A concordance of 100% was observed with previous typing results, validating these methods for use in a diagnostic or research context.

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“…BirdShot ChorioRetinopathy (BSCR) [1][2][3][4] is a non-infectious, bilateral, panuveitis associated with distinctive, widely distributed, yellow-white choroiditis spots. Women are affected slightly more often than men and virtually all patients are Caucasian adults.…”

mentioning

confidence: 99%

“…HLA-A29 positivity is essentially disease-defining, although the limited sensitivity of earlier antibody-based HLA typing techniques has been misinterpreted to indicate that roughly 5% of those with BSCR fail to express the HLA-A29 antigen. 4,5 Most patients will have diffuse retinal vasculitis, often producing cystoid macular edema (CME). A minority will have little or no leakage, what might be termed "dry BSCR," but can still develop diffuse outer retinal atrophy over time without treatment.…”

mentioning

confidence: 99%

Birdshot Chorioretinopathy

Cunningham

Levinson

Denniston

et al. 2017

Ocular Immunology and Inflammation

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Why birdshot retinochoroiditis should rather be called ‘HLA-A29 uveitis’?

Cited by 65 publications

References 34 publications

Functionally distinct ERAP1 and ERAP2 are a hallmark of HLA-A29-(Birdshot) Uveitis

Functionally distinct ERAP1 and ERAP2 are a hallmark of HLA-A29-(Birdshot) Uveitis

An SSP‐PCR method for the rapid detection of disease‐associated alleles HLA‐A29* and HLA‐B51*

Birdshot Chorioretinopathy

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Why birdshot retinochoroiditis should rather be called ‘HLA-A29 uveitis’?

Cited by 65 publications

References 34 publications

Functionally distinct ERAP1 and ERAP2 are a hallmark of HLA-A29-(Birdshot) Uveitis

Functionally distinct ERAP1 and ERAP2 are a hallmark of HLA-A29-(Birdshot) Uveitis

An SSP‐PCR method for the rapid detection of disease‐associated alleles HLA‐A*29 and HLA‐B*51

Birdshot Chorioretinopathy

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Product

Resources

About

An SSP‐PCR method for the rapid detection of disease‐associated alleles HLA‐A29* and HLA‐B51*