International Journal of Immunogenetics最新文献

{"title":"Association of PADI4 Gene Polymorphisms With Susceptibility to Rheumatoid Arthritis: Evidence From 24 Case-Control Studies.","authors":"Mohammad Karimian, Fatemeh Zahra Mohammadzadeh","doi":"10.1111/iji.12701","DOIUrl":"https://doi.org/10.1111/iji.12701","url":null,"abstract":"<p><p>This study aims to investigate the association of rs11203366, rs11203367, rs874881, rs2240340 and rs1748033 polymorphisms of protein-arginine deiminase type 4 (PADI4) gene with the risk of rheumatoid arthritis (RA) through a meta-analysis that was followed with a bioinformatics approach. The data were collected from reputable articles and underwent quantitative analysis, followed by in silico analysis using some bioinformatics tools. The results showed that rs874881 polymorphism in Latino (G vs. C: OR = 1.35, 95% CI = 1.11-1.65, p = 0.003; GG + CG vs. CC: OR = 2.02, 95% CI = 1.41-2.89, p = 0.0001; CG vs. CC + GG: OR = 1.38, 95% CI = 1.04-1.83, p = 0.027; GG vs. CC: OR = 2.09, 95% CI = 1.35-3.23, p = 0.001; CG vs. CC: OR = 1.98, 95% CI = 1.36-2.87, p = 0.00033) and rs1748033 in Caucasian population (T vs. C: OR = 1.25, 95% CI = 1.07-1.45, p = 0.005; TT vs. CT + CC: OR = 1.34, 95% CI = 1.09-1.64, p = 0.005, TT + CT vs. CC: OR = 1.26, 95% CI = 1.09-1.44, p = 0.001; TT vs. CC: OR = 1.59, 95% CI = 1.13-2.23, p = 0.007; CT vs. CC: OR = 1.20, 95% CI: 1.04-1.39, p = 0.015) are associated with increased risk of RA. Moreover, rs11203366 (G vs. A: OR = 1.46, 95% CI = 1.19-1.78, p = 0.0002, GG vs. AG + AA: OR = 1.42, 95% CI = 1.01-2.01, p = 0.043; GG + AG vs. AA: OR = 2.03, 95% CI = 1.45-2.86, p = 0.00004; GG vs. AA: OR = 2.29, 95% CI = 1.49-3.51, p = 0.0002; AG vs. AA: OR = 1.93, 95% CI = 1.35-2.76, p = 0.0003) and rs11203367 (T vs. C: OR = 1.50, 95% CI = 1.23-1.83, p = 0.00007; TT vs. CT + CC: OR = 1.56, 95% CI = 1.12-2.18, p = 0.009; TT + CT vs. CC: OR = 2.02, 95% CI = 1.43-2.84, p = 0.00007, TT vs. CC: OR = 2.43, 95% CI = 1.59-3.71, p = 0.0004; CT vs. CC: OR = 1.86, 95% CI = 1.30-2.68, p = 0.0007) had an impact in the Latino population. Bioinformatics tools showed the effect of these polymorphisms on gene function. These findings suggest that rs11203366, rs11203367, rs874881 and rs1748033 polymorphisms may be genetic risk factors for RA. Moreover, differences between populations suggest that ethnicity may play an important role in the effect of these polymorphisms on RA risk.</p>","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations Between Interleukin-10 Polymorphisms and Susceptibility to Sjögren's Syndrome: A Meta-Analysis.","authors":"Young Ho Lee, Gwan Gyu Song","doi":"10.1111/iji.12702","DOIUrl":"https://doi.org/10.1111/iji.12702","url":null,"abstract":"<p><p>This study sought to investigate the association between interleukin-10 (IL10) polymorphisms and susceptibility to Sjögren's syndrome. A systematic search of the Medline, Embase and Web of Science databases was conducted to identify relevant articles from inception to April 2024. No restrictions were placed on race, ethnicity or geographic area, but only studies published in English were included. A meta-analysis was conducted to evaluate the association among the IL10-1082 G/A (rs1800896), -819 C/T (rs1800871) and -592 C/A (rs1800872) polymorphisms, as well as their haplotypes and the risk of developing Sjögren's syndrome. The included studies involved 998 Sjögren's syndrome patients and 1576 controls. Ten studies were included in the meta-analysis. Meta-analysis of the IL10-1082 G/A polymorphism revealed no significant association with Sjögren's syndrome (odds ratio [OR] = 1.115, 95% confidence interval [CI]: 0.888-1.401, p = 0.343), with stratification by ethnicity yielding consistent results for Europeans and Latin Americans. Similarly, the IL10-819 C/T polymorphism was not associated with Sjögren's syndrome in any study subjects (OR = 0.859, 95% CI: 0.648-1.138, p = 0.290). The IL10-592 C allele also exhibited no association with Sjögren's syndrome (OR = 1.131, 95% CI: 0.776-1.646, p = 0.522). However, the GCC carrier status demonstrated a significant association with Sjögren's syndrome across all study subjects (OR = 1.496, 95% CI: 1.200-1.865, p < 0.001), particularly in Europeans (OR = 1.444, 95% CI: 1.085-1.921, p = 0.012) and Latin Americans (OR = 1.324, 95% CI: 1.115-2.366, p = 0.012). A significant protective effect of the homozygous ATA/ATA haplotype on Sjögren's syndrome was found in Europeans (OR = 0.320, 95% CI: 0.121-0.846, p = 0.022). This meta-analysis indicates a significant link between carrying the GCC haplotype of the IL10-1082 G/A, -819 C/T and -592 C/A polymorphisms and an increased susceptibility to Sjögren's syndrome. Conversely, the homozygous ATA/ATA haplotype appears to confer protection against the risk of Sjögren's syndrome, particularly in European populations.</p>","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nomenclature for factors of the HLA system, update July, August and September 2024","authors":"Steven G. E. Marsh,&nbsp;for the WHO Nomenclature Committee for Factors of the HLA System","doi":"10.1111/iji.12699","DOIUrl":"10.1111/iji.12699","url":null,"abstract":"<p>The following sequences have been submitted to the Nomenclature Committee since the April, May and June 2024 nomenclature update (Marsh, <span>2024</span>) and, following agreed policy, have been assigned official allele designations (Marsh et al., <span>2010</span>). Full details of all sequences will be published in a forthcoming report.</p><p>Below are listed the newly assigned sequences (Table 1) and confirmations of previously reported sequences (Table 2). The accession number of each sequence is given, and these can be used to retrieve the sequence files from the EMBL, GenBank or DDBJ data libraries. Although accession numbers have been assigned by the data libraries and most sequences are already available, there is still the possibility that an author may not yet have allowed the sequence to be released; in such a case, you will have to contact the submitting author directly. Additional information pertaining to new sequences is often included in the publications describing these alleles; a listing of recent publications that describe new HLA sequences is given in Table 3. An additional 221 alleles were recently published but have not been included in Table 3 due to space considerations (French et al., <span>2024</span>; Lucas et al, <span>2024</span>).</p><p>All new and confirmatory sequences should now be submitted directly to the WHO Nomenclature Committee for Factors of the HLA System via the IPD-IMGT/HLA Database using the sequence submission tool provided (Barker et al., <span>2023</span>; Robinson et al., <span>2024</span>). The IPD-IMGT/HLA Database may be accessed via the World Wide Web at www.ebi.ac.uk/ipd/imgt/hla.</p>","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":"51 6","pages":"397-432"},"PeriodicalIF":2.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iji.12699","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of C–C chemokine receptor type 5 in pathogenesis of malaria and its severe forms","authors":"Marina Ziliotto,&nbsp;Joel Henrique Ellwanger,&nbsp;Bruna Kulmann-Leal,&nbsp;Alessandra Pontillo,&nbsp;José Artur Bogo Chies","doi":"10.1111/iji.12700","DOIUrl":"10.1111/iji.12700","url":null,"abstract":"<p>Malaria is a mosquito-borne disease caused by <i>Plasmodium</i> parasites, responsible for a significant impact on public health in several tropical and sub-tropical countries. The majority of infection cases are classified as uncomplicated malaria, causing mild symptoms such as fever and headache. However, the disease may progress to severe malaria and death if the infection is not properly treated. Furthermore, malaria poses a major concern for children, pregnant women and immunosuppressed individuals. Exacerbated inflammation is characteristic of severe malaria cases. The C–C chemokine receptor type 5 (CCR5) is an important molecule for leukocyte migration and regulation of inflammation. Although widely known as an HIV-1 co-receptor, CCR5 also affects the susceptibility and progression of autoimmune and inflammatory diseases. There is evidence supporting the participation of CCR5 in malaria manifestations, with the evaluation of <i>CCR5</i> gene expression levels suggested as a marker to monitor malaria severity. Certain genetic variants in the <i>CCR5</i> gene affect CCR5 expression, potentially altering CCR5-mediated inflammatory responses during malaria infection. However, the complex influences of CCR5 on malaria remain underexplored. Therefore, this review examines and updates the role of CCR5 in various contexts of malaria infection, including uncomplicated malaria, <i>Plasmodium</i>/HIV co-infection, pregnancy and severe (cerebral) malaria.</p>","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":"51 6","pages":"369-379"},"PeriodicalIF":2.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iji.12700","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does HLA-DQA1*05 carriage have a greater impact on the outcome of infliximab therapy for isolated small-bowel Crohn's disease?","authors":"Juan Wu,&nbsp;Nannan Zhu,&nbsp;Jing Hu,&nbsp;Chenyu Zhang,&nbsp;Yuanyuan Fang,&nbsp;Yumei Wu,&nbsp;Yongrong Shi,&nbsp;Qiuyuan Liu,&nbsp;Hao Ding,&nbsp;Qiao Mei,&nbsp;Bingqing Bai,&nbsp;Wei Han","doi":"10.1111/iji.12696","DOIUrl":"10.1111/iji.12696","url":null,"abstract":"<p>Carriage of HLA-DQA1*05 is thought to increase the formation of anti-tumour necrosis factor alpha (TNF-α) antibodies, reducing the drug efficacy in Crohn's disease (CD) patients. However, little data are currently available for small-bowel Crohn's disease (SB-CD). A specific assessment of the impact of HLA-DQA1*05 on the clinical response to treatment with infliximab (IFX), a TNF-α antagonists, in SB-CD patients is necessary. We conducted a single-center retrospective study that included 106 SB-CD patients treated with IFX. The serum samples were collected for antibodies to infliximab (ATI) testing and HLA-DQA1*05 genotyping. Double-balloon enteroscopy (DBE) was performed following the IFX treatment, with endoscopic outcomes evaluated using the partial simple endoscopic score for CD (pSES-CD), whereas the clinical response was assessed with the Crohn's disease activity index (CDAI). Multivariate logistic regression and multivariate COX regression analyses were employed to analyze the correlation of the HLA-DQA1*05 genotypes with other clinical variables. In this study, 30.2% of SB-CD patients carried the HLA-DQA1*05 allele, which significantly increased their risk of ATI generation (odds ratio [OR] = 2.337, p = .043), but it was not associated with the clinical response to IFX and drug persistence (OR = 2.356, p = .145; OR = 0.457, p = .249). The endoscopic remission rates were 40.6% (13/32) and 55.4% (41/74) in HLA-DQA1*05 carriers and non-carriers, respectively. HLA-DQA1*05 was not associated with endoscopic remission (OR = 0.684, p = .414). The HLA-DQA1*05 variant is identified as a significant risk factor of ATI formation in Chinese patients with SB-CD, but is not associated with the clinical response of IFX treatment and endoscopic remission of SB lesions.</p>","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":"51 6","pages":"380-387"},"PeriodicalIF":2.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigations of associations between TNF-α promoter polymorphisms and genetic susceptibility to type 2 diabetes mellitus: A cross-sectional study in Chinese Han population","authors":"Wenyu Tao,&nbsp;Xiaoling Wang,&nbsp;Man Yang,&nbsp;Xing Zhou,&nbsp;Mingliu Yin,&nbsp;Ying Yang,&nbsp;Yiping Li","doi":"10.1111/iji.12698","DOIUrl":"10.1111/iji.12698","url":null,"abstract":"<p>Type 2 diabetes (T2DM) is characterised by insulin resistance and a relative shortage of insulin secretion. Tumour necrosis factor-α (TNF-α) plays an important role in insulin resistance by impairing insulin signal transduction. The variants of the TNF-α promoter region are considered to influence its transcription and are associated with the TNF-α level. Therefore, it is worth detecting the association of the variants in the TNF-α gene with the development of T2DM. The aim of this study was to investigate the association of five variants (rs1799964, rs1800630, rs1799724, rs1800629 and rs361525) in the TNF-α gene promoter region with T2DM in a Chinese Han population. A total of 713 subjects with T2DM and 751 nondiabetic subjects were genotyped using the TaqMan method. The associations of the five variants with the development of T2DM were evaluated. The associations of the five variant genotypes with metabolic traits in nondiabetic subjects were analysed. Our data showed that the A allele of rs1800629 could increase the risk of developing T2DM (<i>p</i> = .002, OR = 1.563; 95% CI: 1.18–2.08). According to inheritance mode analysis, compared with the G/G genotype, the G/A+2A/A genotype of rs1800629 showed a risk effect on T2DM in the log-additive mode (<i>p</i> = .002, OR = 1.56; 95% CI: 1.17–2.07). The haplotypes analysis identified that the rs1799724-rs1800629CA was associated with high risk of the development of T2DM (<i>p</i> = .002, OR = 1.559, 95% CI: 1.173–2.072). Conversely, the rs1799724-rs1800629CG was a protective haplotype of T2DM (<i>p</i> = .001, OR = 0.732, 95% CI: 0.607–0.884). Moreover, compared with the rs1799964 (T/T+C/T) genotype, the rs1799964 C/C genotype was associated with higher glycosylated haemoglobin (HbA1c) levels in nondiabetic subjects (<i>p</i> = .017). Our results revealed that the rs1800629 in the TNF-α gene promoter region was associated with T2DM in a Chinese Han population.</p>","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":"51 6","pages":"388-396"},"PeriodicalIF":2.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to Abstracts from the 34th BSHI Annual Conference (2024), 24 September 2024, Manchester","authors":"","doi":"10.1111/iji.12697","DOIUrl":"https://doi.org/10.1111/iji.12697","url":null,"abstract":"<p> (2024), Abstracts<i>. Int J Immunogenet</i>, 51: S3-S18. https://doi.org/10.1111/iji.12692</p><p>In Abstract O10 on page 56, there were minor typesetting errors in the title.</p><p>The incorrect title reads:</p><p>HLA INTRONIC MISMATCHES INCREASE GRADE <b>2−4AGVHD</b> RISK BUT DO NOT AFFECT OVERALL SURVIVAL, <b>AND IN</b> THE UNITED KINGDOM, UNRELATED DONOR HAEMATOPOIETIC CELL TRANSPLANTS FOR MALIGNANT DISEASES</p><p>The correct title should read:</p><p>HLA INTRONIC MISMATCHES INCREASE GRADE <b>2−4 aGvHD</b> RISK BUT DO NOT AFFECT OVERALL SURVIVAL, <b>IN</b> UK UNRELATED DONOR HAEMATOPOIETIC CELL TRANSPLANTS FOR MALIGNANT DISEASES</p><p>We apologise for this error.</p>","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":"51 6","pages":"433"},"PeriodicalIF":2.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iji.12697","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142588029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between a single-nucleotide polymorphism of the angiotensin-converting enzyme gene and susceptibility to systemic lupus erythematosus in the Hainanese population of China","authors":"Qi Zhang,&nbsp;Yanping Zhuang,&nbsp;Xuan Zhang,&nbsp;Guiling Lin,&nbsp;Huitao Wu,&nbsp;Ziman He,&nbsp;Zhe Wang,&nbsp;Wenlu Xu,&nbsp;Xiyu Yin,&nbsp;Linglan Su,&nbsp;Xiaokang Jia,&nbsp;Aimin Gong","doi":"10.1111/iji.12690","DOIUrl":"10.1111/iji.12690","url":null,"abstract":"<p>The angiotensin-converting enzyme (ACE) gene plays a significant role in regulating immune responses and inflammatory processes, thus impacting the susceptibility to systemic lupus erythematosus (SLE). Understanding how single-nucleotide polymorphisms (SNPs) within the ACE gene contribute to the genetic susceptibility to SLE is essential for comprehending the disease's aetiology. Therefore, exploring this relationship in the Hainan region of China is crucial for gaining insights into the pathogenesis of SLE. This study comprised 428 participants, including 214 SLE patients and 214 healthy controls. Clinical data were gathered, and blood samples were collected. Genotyping of three SNPs (<i>rs4459609</i>, <i>rs4309</i>, <i>rs1987692</i>) within the ACE gene was performed using SNaPshot technology. The frequencies of alleles and genotypes of these three SNPs were compared between the SLE and control groups. Combining different genetic models and haplotype analysis, the correlation between ACE gene polymorphisms and SLE was investigated. Both study groups exhibited conformity with the Hardy–Weinberg genetic equilibrium (<i>p</i> &gt; .05). Significant differences were observed in the genotype frequency distributions of ACE genes <i>rs4459609</i>, <i>rs4309</i> and <i>rs1987692</i> between the SLE and control groups (<i>p</i> = .009, .008, .032, respectively). The frequency of allele T at <i>rs4309</i> was significantly higher in the SLE group than in the control group, correlating significantly with increased SLE risk (odds ratio [OR] = 1.527, 95% confidence interval [CI] = 1.147–2.035). Associations among ACE <i>rs4459609</i>, <i>rs4309</i> and <i>rs1987692</i> polymorphisms and increased susceptibility to SLE were found under co-dominant and dominant models (<i>p</i> &lt; .05, with OR values and 95% CI greater than 1). Linkage disequilibrium was observed among <i>rs4459609</i>, <i>rs4309</i> and <i>rs1987692</i>, and haplotype analysis revealed a significantly higher frequency of the CCA haplotype in the control group compared to the SLE group (<i>p</i> &lt; .001). The ACA and ATA haplotypes showed significantly higher frequencies in the SLE group than in the control group (<i>p</i> = .014, <i>p</i> = .013, respectively). ACE gene polymorphisms are associated with the genetic susceptibility to SLE. The AC and AA genotypes at the <i>rs4459609</i> locus, the TT genotype and T allele at the <i>rs4309</i> locus and the AC and CC genotypes at the <i>rs1987692</i> locus may serve as risk factors for the development of SLE.</p>","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":"51 5","pages":"319-329"},"PeriodicalIF":2.3,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iji.12690","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nomenclature for factors of the HLA system, update April, May and June 2024","authors":"Steven G. E. Marsh,&nbsp;for the WHO Nomenclature Committee for Factors of the HLA System","doi":"10.1111/iji.12691","DOIUrl":"10.1111/iji.12691","url":null,"abstract":"","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":"51 5","pages":"330-367"},"PeriodicalIF":2.3,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-resolution HLA sequencing and hypocretin receptor 2 autoantibodies in narcolepsy type 1 and type 2","authors":"Samia Hamdan,&nbsp;Pontus Wasling,&nbsp;Alexander Lind","doi":"10.1111/iji.12688","DOIUrl":"10.1111/iji.12688","url":null,"abstract":"<p>Narcolepsy is a sleep disorder caused by an apparent degeneration of orexin/hypocretin neurons in the lateral hypothalamic area and a subsequent decrease in orexin/hypocretin levels in the cerebrospinal fluid. Narcolepsy is classified into type 1 (NT1) and type 2 (NT2). While genetic associations in the human leukocyte antigen (HLA) region and candidate autoantibodies have been investigated in NT1 to imply an autoimmune origin, less is known about the pathogenesis in NT2. Twenty-six NT1 and 15 NT2 patients were included, together with control groups of 24 idiopathic hypersomnia (IH) patients and 778 general population participants. High-resolution sequencing was used to determine the alleles, the extended haplotypes, and the genotypes of HLA-<i>DRB3</i>, <i>-DRB4</i>, <i>-DRB5</i>, <i>-DRB1</i>, <i>-DQA1</i>, <i>-DQB1</i>, <i>-DPA1</i>, and <i>-DPB1</i>. Radiobinding assay was used to determine autoantibodies against hypocretin receptor 2 (anti-HCRTR2 autoantibodies). NT1 was associated with <i>HLA-DRB5*01:01:01</i>, <i>-DRB1*15:01:01</i>, <i>-DQA1*01:02:01</i>, <i>-DQB1*06:02:01</i>, <i>-DRB5*01:01:01</i>, <i>-DRB1*15:01:01</i>, <i>-DQA1*01:02:01</i>, <i>-DQB1*06:02:01</i> (odds ratio [OR]: 9.15; <i>p</i> = 8.31 × 10⁻⁴) and <i>HLA-DRB5*01:01:01</i>, <i>-DRB1*15:01:01</i>, <i>-DQA1*01:02:01</i>, <i>-DQB1*06:02:01</i>, <i>-DRB4*01:03:01</i>, <i>-DRB1*04:01:01</i>, <i>-DQA1*03:02//03:03:01</i>, <i>-DQB1*03:01:01</i> (OR: 23.61; <i>p</i> = 1.58 × 10⁻⁴) genotypes. Lower orexin/hypocretin levels were reported in the NT2 subgroup (<i>n</i> = 5) that was associated with the extended <i>HLA-DQB1*06:02:01</i> haplotype (<i>p</i> = .001). Anti-HCRTR2 autoantibody levels were not different between study groups (<i>p</i> = .8524). We confirmed the previous association of NT1 with <i>HLA-DQB1*06:02:01</i> extended genotypes. A subgroup of NT2 patients with intermediate orexin/hypocretin levels and association with <i>HLA-DQB1*06:02:01</i> was identified, indicating a possible overlap between the two distinct narcolepsy subtypes, NT1 and NT2. Low anti-HCRTR2 autoantibody levels suggest that these receptors might not function as autoimmune targets in either NT1 or NT2.</p>","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":"51 5","pages":"310-318"},"PeriodicalIF":2.3,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iji.12688","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}