scholarly journals Visual outcomes and choroidal thickness associated with human leukocyte antigen DRB1*04 in unclassifiable uveitis in Japanese patients

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Norihiko Misawa ◽  
Mizuki Tagami ◽  
Atsushi Sakai ◽  
Takeya Kohno ◽  
Shigeru Honda

Abstract Purpose Human leukocyte antigen (HLA) and immunity are related. Uveitis is also closely related to immunity. For example, the common presence of human leukocyte antigen (HLA)-DRB1*04 in the immune response is well known. The aim of this study was to investigate the relationship between visual prognosis and various HLA alleles before and after therapy in patients with unclassifiable uveitis, excluding those with Vogt-Koyanagi-Harada (VKH) disease. Methods This retrospective case series included 42 eyes from 22 consecutive patients with unclassifiable uveitis, excluding those with VKH disease. Visual acuity (VA), sex, refractive error, central retinal thickness (CRT), central choroidal thickness (CCT), and duration from onset to treatment were measured at initial and 6-month visits. Mean values of parameters were compared at each visit. Genotyping was performed by polymerase chain reaction amplification with sequence-specific primers. Results DRB1*04 showed a dominant change. No significant difference was observed in the other alleles. In DRB1*04, The mean differences in initial CCT, 6-month CCT, and 6-month VA showed statistically significant difference was found in best-corrected visual acuity (BCVA) between DRB1*04+ and DRB1*04− at the first visit. BCVA values at baseline and at the final visit were 0.13 ± 0.29 and 0.20 ± 0.36 in the DRB1*04+ and 0.00045 ± 0.20 and − 0.058 ± 0.11 in the DRB1*04− groups(p = 0.00465). Central Choroidal Thickness (CCT) values pretreatment and at the final visit after treatment were (pretreatment:361.00 ± 361.0 μm,after treatment: 286.00 ± 106.53 μm, p = 0.0174) in the DRB1*04+ group, and (pretreatment:281.3 ± 139.68 μm,after treatment:223.85 ± 99.034 μm, p = 0.0426) in the DRB1*04− group, respectively, indicating changes between baseline and the final visit. CCT was significantly greater in the DRB1*04+ group at both the initial visit and at 6 months. Multivariate analysis showed a significant difference between the presence or absence of DRB1*04 and sex. Conclusion HLA-DRB1*04 allele may affect visual prognosis and CCT in unclassifiable uveitis.

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Norihiko Misawa ◽  
Mizuki Tagami ◽  
Takeya Kohno ◽  
Shigeru Honda

Abstract Background The common presence of human leukocyte antigen (HLA)-DRB1*04 in Vogt-Koyanagi-Harada (VKH) disease is well known. The aim of this study was to investigate the relationship between visual prognosis and HLA-DRB1*04 alleles during systemic corticosteroid therapy in patients with VKH disease. Methods This retrospective case series included 57 eyes from 29 consecutive patients with treatment-naïve VKH disease who received systemic corticosteroid therapy. Visual acuity, sex, refractive error, central retinal thickness (CRT), central choroidal thickness (CCT), and duration from onset to treatment were measured at initial and final visits. Mean values of parameters were compared with each visit. Genotyping was performed by polymerase chain reaction amplification with sequence-specific primer. Results Linear regression showed significant differences in logMAR best-corrected visual acuity between the three groups of homozygotes, heterozygotes, and normal subjects at baseline (p < 0.01), at 3 months after treatment (p < 0.01). There was no significant differences at 6 months after treatment (p = 0.257). No significant differences were detected between the three groups in age, sex, refractive error, CRT, CCT, or duration from onset to treatment. Conclusion Alleles of HLA-DRB1*04 might affect visual prognosis and be related to early response after initiation of treatment in VKH disease.


2019 ◽  
Author(s):  
Norihiko Misawa ◽  
Mizuki Tagami ◽  
Takeya Kohno ◽  
Shigeru Honda

Abstract Abstract Background: The common presence of human leukocyte antigen (HLA)-DRB1*04 in Vogt-Koyanagi-Harada (VKH) disease is well known. The aim of this study was to investigate the relationship between visual prognosis and HLA-DRB1*04 alleles during systemic corticosteroid therapy in patients with VKH disease. Methods: This retrospective case series included 57 eyes from 29 consecutive patients with treatment-naïve VKH disease who received systemic corticosteroid therapy. Visual acuity, sex, refractive error, central retinal thickness (CRT), central choroidal thickness (CCT), and duration from onset to treatment were measured at initial and final visits. Mean values of parameters were compared with each visit. Genotyping was performed by polymerase chain reaction amplification with sequence-specific primer. Results: Linear regression showed significant differences in logMAR best-corrected visual acuity between the three groups of homozygotes, heterozygotes, and normal subjects at baseline ( p <0.01), at three months after treatment ( p <0.01).There was no significant differences at six months after treatment ( p =0.257). No significant differences were detected between the three groups in age, sex, refractive error, CRT, CCT, or duration from onset to treatment. Conclusion: Alleles of HLA-DRB1*04 might affect visual prognosis and be related to early response after initiation of treatment in VKH disease.


2019 ◽  
Author(s):  
Norihiko Misawa ◽  
Mizuki Tagami ◽  
Takeya Kohno ◽  
Shigeru Honda

Abstract Background: The common presence of human leukocyte antigen (HLA)-DRB1*04 in Vogt-Koyanagi-Harada (VKH) disease is well known. The aim of this study was to investigate the relationship between visual prognosis and HLA-DRB1*04 alleles during systemic corticosteroid therapy in patients with VKH disease. Methods: This retrospective case series included 57 eyes from 29 consecutive patients with treatment-naïve VKH disease who received systemic corticosteroid therapy. Visual acuity, sex, refractive error, central retinal thickness (CRT), central choroidal thickness (CCT), and duration from onset to treatment were measured at initial and final visits. Mean values of parameters were compared with each visit. Genotyping was performed by polymerase chain reaction amplification with sequence-specific primer. Results: Linear regression showed significant differences in logMAR best-corrected visual acuity between the three groups of homozygotes, heterozygotes, and normal subjects at baseline ( p <0.01), at three months after treatment ( p <0.01).There was no significant differences at six months after treatment ( p =0.257). No significant differences were detected between the three groups in age, sex, refractive error, CRT, CCT, or duration from onset to treatment. Conclusion: Alleles of HLA-DRB1*04 might affect visual prognosis and be related to early response after initiation of treatment in VKH disease.


2019 ◽  
Author(s):  
Norihiko Misawa ◽  
Mizuki Tagami ◽  
Takeya Kohno ◽  
Shigeru Honda

Abstract Abstract Background: The common presence of human leukocyte antigen (HLA)-DRB1*04 in Vogt-Koyanagi-Harada (VKH) disease is well known. The aim of this study was to investigate the relationship between visual prognosis and HLA-DRB1*04 alleles during systemic corticosteroid therapy in patients with VKH disease. Methods: This retrospective case series included 57 eyes from 29 consecutive patients with treatment-naïve VKH disease who received systemic corticosteroid therapy. Visual acuity, sex, refractive error, central retinal thickness (CRT), central choroidal thickness (CCT), and duration from onset to treatment were measured at initial and final visits. Mean values of parameters were compared with each visit. Genotyping was performed by polymerase chain reaction amplification with sequence-specific primer. Results: Linear regression showed significant differences in logMAR best-corrected visual acuity between the three groups of homozygotes, heterozygotes, and normal subjects at baseline ( p <0.01), at three months after treatment ( p <0.01).There was no significant differences at six months after treatment ( p =0.257). No significant differences were detected between the three groups in age, sex, refractive error, CRT, CCT, or duration from onset to treatment. Conclusion: Alleles of HLA-DRB1*04 might affect visual prognosis and be related to early response after initiation of treatment in VKH disease.


2019 ◽  
Author(s):  
Norihiko Misawa ◽  
Mizuki Tagami ◽  
Takeya Kohno ◽  
Shigeru Honda

Abstract Abstract Background: The common presence of human leukocyte antigen (HLA)-DRB1*04 in Vogt-Koyanagi-Harada (VKH) disease is well known. The aim of this study was to investigate the relationship between visual prognosis and HLA-DRB1*04 alleles during systemic corticosteroid therapy in patients with VKH disease. Methods: This retrospective case series included 57 eyes from 29 consecutive patients with treatment-naïve VKH disease who received systemic corticosteroid therapy. Visual acuity, sex, refractive error, central retinal thickness (CRT), central choroidal thickness (CCT), and duration from onset to treatment were measured at initial and final visits. Mean values of parameters were compared with each visit. Genotyping was performed by polymerase chain reaction amplification with sequence-specific primer. Results: Linear regression showed significant differences in logMAR best-corrected visual acuity between the three groups of homozygotes, heterozygotes, and normal subjects at baseline ( p <0.01), at three months after treatment ( p <0.01).There was no significant differences at six months after treatment ( p =0.257). No significant differences were detected between the three groups in age, sex, refractive error, CRT, CCT, or duration from onset to treatment. Conclusion: Alleles of HLA-DRB1*04 might affect visual prognosis and be related to early response after initiation of treatment in VKH disease.


2019 ◽  
Author(s):  
Norihiko Misawa ◽  
Mizuki Tagami ◽  
Takeya Kohno ◽  
Shigeru Honda

Abstract Background Human leukocyte antigen (HLA)-DRB1*04 is well known to be associated with the course of Vogt-Koyanagi-Harada (VKH) disease. The aim of this study was to investigate the relationship between visual prognosis and HLA-DRB1*04 alleles during systemic corticosteroid therapy in patients with VKH disease. Methods This retrospective case series included 47 eyes from 29 consecutive treatment-naïve patients who received systemic corticosteroid therapy. Visual acuity sex, refractive error, central retinal thickness (CRT), central choroidal thickness (CCT), and duration from onset to treatment were measured at initial and final visits. Mean values of parameters were compared with each visit. Typing was performed by polymerase chain reaction amplification with sequence-specific primers. Results Linear regression showed significant differences in logMAR best-corrected visual acuity among the three groups of homozygotes, heterozygotes, and normal subjects between baseline (p<0.01) and final visit (p=0.012). No significant difference was detected between the three groups in age, sex, refractive error, CRT, CCT, or duration from onset to treatment. Conclusions The present study revealed a correlation between HLA04 allele type and visual acuity logMAR before and after initiating systemic corticosteroid therapy in treatment-naïve patients with VKH disease.


2008 ◽  
Vol 68 (1) ◽  
pp. 107-109 ◽  
Author(s):  
K A Guthrie ◽  
N R Tishkevich ◽  
J L Nelson

Objectives:Some patients with rheumatoid arthritis (RA) lack RA-associated human leukocyte antigen (HLA) alleles. Prior studies investigated non-inherited maternal HLA alleles (NIMA) in RA risk with conflicting results.Methods:We examined NIMA in a large cohort of families from the North American Rheumatoid Arthritis Consortium (NARAC).Results:Among 620 patients with 1 or both parents having a HLA genotype, patients with RA informative for analysis included 176 without HLA-DRB1*04 and 86 without the HLA shared epitope (SE). The frequency of NIMA encoding HLA-DR4 or the SE was compared to the non-inherited paternal allele (NIPA). DR4-encoding NIMA vs NIPA revealed no significant difference (27% vs 20%). However, parity is known to modulate RA risk and analyses stratified by sex and age of onset showed significant variation among women. Interestingly, among women with onset <45 years DR4-encoding NIMA was increased compared to NIPA; among women ⩾45 years at onset the reverse was observed (31% vs 16% compared to 10% vs 60%, p = 0.008). DR4 encoding NIMA vs NIPA did not differ in men. The SE did not differ in men or women.Conclusions:Risk of RA was associated with HLA-DR4 encoding NIMA in younger-onset women but not in older-onset women or men. These observations could help explain conflicting prior results of NIMA in RA.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3083-3083
Author(s):  
Charlene Marie Fares ◽  
Amy Lauren Cummings ◽  
Matthew Karl Theisen ◽  
Jaklin Gukasyan ◽  
Jackson P Lind-Lebuffe ◽  
...  

3083 Background: Recent evidence suggests efficacy of immune checkpoint blockade may be influenced by human leukocyte antigen (HLA)-B. HLA-B27 supertype has an electronegative binding pocket which favorably binds and displays neoepitopes harboring positively charged amino acids (AAs). Based on immune surveillance, we postulate that B27 tumors that have favorable neoepitopes should face negative selective pressure, and B27 tumors with favorable neoepitopes that develop could be more likely to upregulate immune escape mechanisms. Here we evaluate the relationship between prevalence of B27 and positively charged neoepitopes and assess association between positively charged neoepitopes and expression of PD-L1. Methods: TCGA datasets from head and neck squamous cell (HNSC), lung squamous cell (LUSC), and melanoma (SKCM) patients were evaluated. HLA alleles were determined with OptiType and supertype was based on 2008 criteria. Nonsynonymous mutations were annotated with Ensembl VEP and VAtools. pVAC-Seq using NetMHCpan algorithm predicted neoepitopes 9 AAs in length. Favorable B27 neoepitopes were defined as those having new positively charged AA substitutions (H/K/R) from negative or uncharged wildtype AAs. RNA-seq data for the PD-L1 gene were normalized on transcripts per million and log2 transformed. Linear regression tests were performed between PD-L1 gene expression values and fraction of nonsynonymous mutations resulting in neoepitopes with new positively charged AAs in patients with B27. Results: Data from 497 HNSC, 494 LUSC, and 468 SKCM patients were analyzed. B27 was observed in 20.1%, 23.2%, and 26.5% of HNSC, LUSC, and SKCM patients, respectively, with a significant difference seen between HNSC and SKCM by chi-square test (χ² = 5.14, p = .023). Of new charged AAs resulting from nonsynonymous mutations, 76.3% in HNSC, 74.0% in LUSC, and 72.0% in SKCM were positively charged (p < .05 between all histologies, paired t-tests). In B27 patients, association between PD-L1 gene expression and fraction of neoepitopes with new positively charged AAs was seen in HNSC (r = 0.25 p = .036) and SKCM (r = 0.30 p = .007), but not LUSC (r = -0.12 p = .296). Conclusions: With increasing fraction of positively charged neoepitopes, a decrease in prevalence of B27 was observed, suggesting improved binding and immune elimination of tumors with favorable neoepitopes. In B27 tumors that develop despite having favorable neoepitopes, upregulation of PD-L1 could be a putative mechanism to evade immune detection.


2020 ◽  
Vol 10 (4) ◽  
pp. e34-e34
Author(s):  
Mahsa Mohammadi ◽  
Mohsen Rajabnia ◽  
Mohammad Saad Forghani ◽  
Khaled Rahmani ◽  
Mohammad Bahadoram

Introduction: Diabetic nephropathy (diabetic kidney disease) is one of the microvascular complications of diabetes mellitus. The human leukocyte antigen (HLA) is a group of genes that is related to autoimmune diseases, infections and inflammation. Studies regarding the association of type 2diabetes and HLA-II are negligible. Objectives: The aim of this study is to determinate association between diabetic nephropathy and HLA II-DQ1 in diabetes type 2 patients. Patients and Methods: In this study, 120 diabetes type 2 patients were divided into two groups of diabetic nephropathy (case group) and without diabetic nephropathy (control group). Blood samples were taken and DNA was isolated. Asymmetric polymerase chain reaction (PCR) was used to amplify the HLA II-DQ1 exon 2 and exon 3. PCR products were hybridized and labeled with probes on the chip. Determination of HLAII-DQ1 gene typing was conducted by scanning hybrid products and analyzed with PerkinElmer ScanArray software. Results: The results of chi-square test showed no significant difference between expression levels of HLA in the two groups (P<0.05). Conclusion: There was no significant difference between expression levels of HLA in two groups of patients. Various factors such as demographic characteristics, lifestyle, geographic region, and race are the factors influencing the relationship between diabetic nephropathy and DQ1-HLA II. Since this study is conducted in one region and one race and with limited population, it is suggested that future studies should be considered and the association between the mentioned variables with HLA should be considered.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2463-2463
Author(s):  
Qiong Liao Master ◽  
Yan Zhang ◽  
Xiao Li ◽  
Zheng Zhang ◽  
Shaoxu Ying ◽  
...  

Abstract We investigate the frequency of the human leukocyte antigen DR15 (HLA-DR15) allele in patients with myelodysplastic syndromes (MDS). We used polymerase chain reaction-sequence-specific primers (PCR-SSP) to detect HLA-DR15 in the peripheral blood of patients with MDS(n = 76) and healthy controls (n = 227). The frequency of HLA-DR15 in MDS patients (40.8%) was significantly higher than in controls (13.7%; P &lt; 0.01). The diagnoses of refractory anemia/refractory anemia with ring sideroblasts (RA/RARS) accounted for 77.4% (24/31) and 62.2% (28/45) of the DR15-positive and the DR15-negative patients, respectively (difference not statistically significant). Although no statistically significant difference was observed, some trends were observed: IPSS low-risk MDS (IPSS score, ≤1) accounted for 80.6% of the DR15-positive patients compared to 64.4% among the DR15-negative patients. However, the difference between the numbers of DR15-positive and DR15-negative patients with chromosomal abnormalities was not statistically significant. Nevertheless, poor risk chromosome abnormalities (according to IPSS), were present in only 1 DR15-positive patient, while such abnormalities were present in 8 DR15-negative patients. In addition, the proportions of DR15-positive and DR15-negative patients with more than 5% blasts in marrow were 19.4% and 31.1%, respectively. Peripheral blood pancytopenia occurred in 51.6% of DR15-positive, and in 40.0% of DR15-negative patients. Although the HLA-DR15 allele appeared to be present more frequently in patients less than 60 years of age, this association was not significant. The frequency of HLA-DR15 was significantly higher in patients with MDS than in healthy controls suggesting the possibility that HLA-DR15 is associated with an enhanced susceptibility to develop MDS. The fact that HLA-DR15 was predominantly noted in patients with RA/RARS and low IPSS scores, suggested that HLA-DR15 might be associated more with bone marrow failure and less with leukemic transformation. clinical/experimental characteristics in HLA-DR15 positive or negative MDS patients Cohort HLA-DR15 positive(n=31) HLA-DR15 negative(n=45) P value RA/RARS(case/%) 24/31(77.4) 28/45(62.2) 0.161 Low risk (IPSS≤1) (case/%) 25/31(80.6) 29/45(64.4) 0.126 Karyotype abnormal(case/%) 13/31(41.9) 18/45(40.0) 0.866 Poor chromosome(case/%) 1/31(3.2) 8/45(17.8) 0.117 Blast&gt;5%(case/%) 6/31(19.4) 14/45(31.1) 0.253 Pancytopenia(case/%) 16/31(51.6) 18/45(40.0) 0.317 Male patients(case/%) 17/31(54.8) 25/45(55.6) 0.951 age(&lt;60 years) (case/%) 20/31(64.5) 20/45(44.4) 0.085 Figure Figure Figure Figure


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