Killer Immunoglobulin-like Receptor Genes in Uveitis

Levinson, Ralph D.

doi:10.3109/09273948.2010.538798

Cited by 23 publications

(19 citation statements)

References 39 publications

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“…Without ruling out a pathogenetic ERAP2-dependent epitope, the influence of ERAP1 on the A*29:02 peptidome may be more complex. For instance, killer cell immunoglobulin-like receptors are risk factors for BSCR in A*29:02 ϩ individuals (47,48). ERAP1 was recently suggested to modify, killer cell immunoglobulin-like receptor engagement to the MHC-I molecule by altering the affinity of MHC-I-bound peptides (49).…”

Section: Discussionmentioning

confidence: 99%

Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) Polymorphism Relevant to Inflammatory Disease Shapes the Peptidome of the Birdshot Chorioretinopathy-Associated HLA-A29:02 Antigen

Alvarez-Navarro

Martín-Esteban

Barnea

et al. 2015

Molecular & Cellular Proteomics

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Birdshot chorioretinopathy is a rare ocular inflammation whose genetic association with HLA-A*29:02 is the highest between a disease and a major histocompatibility complex (MHC) molecule. It belongs to a group of MHC-I-associated inflammatory disorders, also including ankylosing spondylitis, psoriasis, and Behç et's disease, for which endoplasmic reticulum aminopeptidases (ERAP) 1 and/or 2 have been identified as genetic risk factors. Since both enzymes are involved in the processing of MHC-I ligands, it seems reasonable that common peptide-mediated mechanisms may underlie the pathogenesis of these diseases. In this study, comparative immunopeptidomics was used to characterize >5000 A*29:02 ligands and quantify the effects of ERAP1 polymorphism and expression on the A*29:02 peptidome in human cells. The peptides predominant in an active ERAP1 context showed a higher frequency of nonamers and bulkier amino acid side chains at multiple positions, compared with the peptides predominant in a less active ERAP1 background. Thus, ERAP1 polymorphism has a large influence, shaping the A*29:02 peptidome through length-dependent and length-independent effects. These changes resulted in increased affinity and hydrophobicity of A*29:02 ligands in an active ERAP1 context. The results reveal the nature of the functional interaction between A*29:02 and ERAP1 and suggest that this enzyme may affect the susceptibility to birdshot chorioretinopathy by altering the A*29:02 peptidome.

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Section: Discussionmentioning

confidence: 99%

Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) Polymorphism Relevant to Inflammatory Disease Shapes the Peptidome of the Birdshot Chorioretinopathy-Associated HLA-A29:02 Antigen

Alvarez-Navarro

Martín-Esteban

Barnea

et al. 2015

Molecular & Cellular Proteomics

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“…While filling Scantron forms requires motor actions that reading does not, visual scanning is required to identify the circled answers and locate the corresponding answer bubbles. This engages oculomotor and visual skills in common with reading (eg, saccades, 1,2 accommodation, near vision). Therefore, reading-associated factors may be associated with performance on both tasks.…”

mentioning

confidence: 99%

Implications of Birdshot-Like Uveitis on the Pathogenesis of Birdshot Chorioretinopathy

2019

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“…NK cells are activated when there is an increase of activation signals, even if there is a combination of strong or weak inhibitory signals45. Yet, the absence of KIR3DS1 in the presence of its inhibitor homologue, KIR3DL1, was indicative of the inhibitory or protective role played by NK cells, which perhaps avoids subsequent immune responses that may trigger inflammation and autoimmunity.…”

Section: Discussionmentioning

confidence: 99%

Ocular toxoplasmosis: susceptibility in respect to the genes encoding the KIR receptors and their HLA class I ligands

Ayo

Frederico

Siqueira

et al. 2016

Sci Rep

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The objective of this study was to investigate the influence of the genes encoding the KIR receptors and their HLA ligands in the susceptibility of ocular toxoplasmosis. A total of 297 patients serologically-diagnosed with toxoplasmosis were selected and stratified according to the presence (n = 148) or absence (n = 149) of ocular scars/lesions due to toxoplasmosis. The group of patients with scars/lesions was further subdivided into two groups according to the type of ocular manifestation observed: primary (n = 120) or recurrent (n = 28). Genotyping was performed by PCR-SSOP. Statistical analyses were conducted using the Chi-square test, and odds ratio with a 95% confidence interval was also calculated to evaluate the risk association. The activating KIR3DS1 gene was associated with increased susceptibility for ocular toxoplasmosis. The activating KIR together with their HLA ligands (KIR3DS1-Bw4-80Ile and KIR2DS1+/C2++ KIR3DS1+/Bw4-80Ile+) were associated with increased susceptibility for ocular toxoplasmosis and its clinical manifestations. KIR-HLA inhibitory pairs -KIR2DL3/2DL3-C1/C1 and KIR2DL3/2DL3-C1- were associated with decreased susceptibility for ocular toxoplasmosis and its clinical forms, while the KIR3DS1−/KIR3DL1+/Bw4-80Ile+ combination was associated as a protective factor against the development of ocular toxoplasmosis and, in particular, against recurrent manifestations. Our data demonstrate that activating and inhibitory KIR genes may influence the development of ocular toxoplasmosis.

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Killer Immunoglobulin-like Receptor Genes in Uveitis

Abstract: KIR genetics are complex, as are the functions of KIR-bearing cells. Nonetheless, evidence for KIRs in the pathogenesis of uveitis has been found.

Cited by 23 publications

References 39 publications

Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) Polymorphism Relevant to Inflammatory Disease Shapes the Peptidome of the Birdshot Chorioretinopathy-Associated HLA-A29:02 Antigen

Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) Polymorphism Relevant to Inflammatory Disease Shapes the Peptidome of the Birdshot Chorioretinopathy-Associated HLA-A29:02 Antigen

Implications of Birdshot-Like Uveitis on the Pathogenesis of Birdshot Chorioretinopathy

Ocular toxoplasmosis: susceptibility in respect to the genes encoding the KIR receptors and their HLA class I ligands

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Killer Immunoglobulin-like Receptor Genes in Uveitis

Abstract: KIR genetics are complex, as are the functions of KIR-bearing cells. Nonetheless, evidence for KIRs in the pathogenesis of uveitis has been found.

Cited by 23 publications

References 39 publications

Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) Polymorphism Relevant to Inflammatory Disease Shapes the Peptidome of the Birdshot Chorioretinopathy-Associated HLA-A*29:02 Antigen*

Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) Polymorphism Relevant to Inflammatory Disease Shapes the Peptidome of the Birdshot Chorioretinopathy-Associated HLA-A*29:02 Antigen*

Implications of Birdshot-Like Uveitis on the Pathogenesis of Birdshot Chorioretinopathy

Ocular toxoplasmosis: susceptibility in respect to the genes encoding the KIR receptors and their HLA class I ligands

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Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) Polymorphism Relevant to Inflammatory Disease Shapes the Peptidome of the Birdshot Chorioretinopathy-Associated HLA-A29:02 Antigen

Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) Polymorphism Relevant to Inflammatory Disease Shapes the Peptidome of the Birdshot Chorioretinopathy-Associated HLA-A29:02 Antigen