Dataset Information

KIR and HLA Genotypes Implicated in Reduced Killer Lymphocytes Immunity Are Associated with Vogt-Koyanagi-Harada Disease.

ABSTRACT: Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells are killer lymphocytes that provide defense against viral infections and tumor transformation. Analogous to that of CTL, interactions of killer-cell immunoglobulin-like receptors (KIR) with specific human leukocyte antigen (HLA) class I ligands calibrate NK cell education and response. Gene families encoding KIRs and HLA ligands are located on different chromosomes, and feature variation in the number and type of genes. The independent segregation of KIR and HLA genes results in variable KIR-HLA interactions in individuals, which may impact disease susceptibility. We tested whether KIR-HLA combinations are associated with Vogt-Koyanagi-Harada (VKH) disease, a bilateral granulomatous panuveitis that has strong association with HLA-DR4. We present a case control study of 196 VKH patients and 209 controls from a highly homogeneous native population of Japan. KIR and HLA class I genes were typed using oligonucleotide hybridization method and analyzed using two-tailed Fisher's exact probabilities. The incidence of Bx-KIR genotypes was decreased in VKH patients (odds ratio [OR] 0.58, P = 0.007), due primarily to a decrease in centromeric B-KIR motif and its associated KIRs 2DS2, 2DL2, 2DS3, and 2DL5B. HLA-B22, implicated in poor immune response, was increased in VKH (OR = 4.25, P = 0.0001). HLA-Bw4, the ligand for KIR3DL1, was decreased in VKH (OR = 0.59, P = 0.01). The KIR-HLA combinations 2DL2+C1/C2 and 3DL1+Bw4, which function in NK education, were also decreased in VKH (OR = 0.49, P = 0.012; OR = 0.59, P = 0.013). Genotypes missing these two inhibitory KIR-HLA combinations in addition to missing activating KIRs 2DS2 and 2DS3 were more common in VKH (OR = 1.90, P = 0.002). These results suggest that synergistic hyporesponsiveness of NK cells (due to poor NK education along with missing of activating KIRs) and CTL (due to HLA-B22 restriction) fail to mount an effective immune response against viral-infection that may trigger VKH pathogenesis in genetically susceptible individuals, such as HLA-DR4 carriers.

SUBMITTER: Levinson RD

PROVIDER: S-EPMC4973954 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:PurposeAs an autoimmune disease, Vogt‒Koyanagi‒Harada disease (VKHD) is a main type of uveitis in many countries and regions, significantly impacting patient vision. At present, information regarding VKHD is still limited, and further research is needed. We conducted a bibliometric analysis to characterize the overall status, current trends, and current focus of VKHD research.MethodLiterature published from 1975 to 2022 was obtained from the Web of Science core collection and analysed with the R-language packages Bibliometrix, VOSviewer, and CiteSpace software.ResultsA total of 1050 papers on VKHD were retrieved from 261 journals, and 16,084 references were obtained from the papers in the original search. The average annual number of published articles was approximately 21.9, and the number of publications rapidly increased after 2004. The journal Ocular Immunology and Inflammation published the most papers on VKHD, while the American Journal of Ophthalmology has the highest citation frequency. The leading countries were Japan, China (PRC), and the United States of America (USA). Yang PZ from Chongqing Medical University was the most prolific and cited author. The most frequently cited study discussed revision of VKHD diagnostic criteria. An analysis of the highest frequency keywords showed that most research focused on the treatment, diagnosis, and pathogenesis of VKHD and its relationship with other related diseases. At present, the most urgent research direction is in the relationship between COVID-19 or COVID-19 vaccines and VKHD and the corresponding mechanisms underlying it.ConclusionUtilizing dynamic and visualization tools, bibliometrics provides a clear depiction of the research history, development trends, and research hotspots in VKHD It serves as a valuable tool for identifying research gaps and areas that necessitate further exploration. Our study revealed potential directions for future VKHD research, including investigating specific molecular mechanisms underlying the disease, exploring the clinical utility of optical coherence tomography angiography and other diagnostic techniques, and conducting clinical research on novel therapeutic drugs.

Project description:ImportanceTo our knowledge, a set of well-defined diagnostic criteria is not yet developed for the diagnosis of Vogt-Koyanagi-Harada (VKH) disease.ObjectiveTo develop and evaluate a set of diagnostic criteria for VKH disease using data from Chinese patients.Design, setting, and participantsThis case-control study reviewed medical records of patients from a tertiary referral center between October 2011 and October 2016. Data from 634 patients with VKH disease and 623 patients with non-VKH uveitis from southern China were used to develop the Diagnostic Criteria for VKH Disease (DCV). Data from an additional group of 537 patients with a definite VKH disease diagnosis and 525 patients with non-VKH uveitis from northern China were used to evaluate the diagnostic criteria.Main outcomes and measuresSensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristic.ResultsOf the 1257 patients used to construct the DCV, 665 (52.9%) were male, and the mean (SD) age at disease onset was 38.6 (13.6) years. The 3-class model and 21 clinical findings were selected by latent class analysis. Variables with a high positive rate in the early-phase or late-phase VKH group or high specificity constituted essential parameters. Constellations of these essential parameters constructed the DCV. The sensitivity and NPV of the DCV were higher than those of the Revised Diagnostic Criteria for VKH Disease (RDC) (sensitivity: 94.6% vs 71.9%; difference, 22.7%; 95% CI, 18.5-27.0; NPV: 94.3% vs 76.6%; difference, 17.7%; 95% CI, 13.9-21.5). The specificity and PPV of the DCV were not different from that of the RDC (specificity: 92.2% vs 93.9%; difference, 1.7%; 95% CI, -1.4 to 4.8; PPV: 89.3% vs 92.3%; difference, 3.0%; 95% CI, -1.4 to 4.8). The area under the receiver operating characteristic curve of the DCV and the RDC were 0.934 (95% CI, 0.917-0.951) and 0.829 (95% CI, 0.803-0.855), respectively.Conclusions and relevanceThe DCV were developed and evaluated using data from Chinese patients with VKH disease and showed a high sensitivity, NPV, and area under the receiver operating characteristic curve in comparison with the RDC. However, they were developed using a retrospective analysis and should be evaluated in prospective studies in other racial/ethnic populations.

Dataset Information

KIR and HLA Genotypes Implicated in Reduced Killer Lymphocytes Immunity Are Associated with Vogt-Koyanagi-Harada Disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets