PMID- 33421092 OWN - NLM STAT- MEDLINE DCOM- 20210927 LR - 20221005 IS - 1365-2249 (Electronic) IS - 0009-9104 (Print) IS - 0009-9104 (Linking) VI - 204 IP - 1 DP - 2021 Apr TI - Behcet disease, new insights in disease associations and manifestations: a next-generation sequencing study. PG - 144-151 LID - 10.1111/cei.13571 [doi] AB - Behcet disease is a multi-system disease associated with human leukocyte antigen (HLA) class I polymorphism. High-resolution next-generation sequencing (NGS) with haplotype analysis has not been performed previously for this disease. Sixty Egyptian patients diagnosed according to the International Study Group (ISG) criteria for Behcet disease and 160 healthy geographic and ethnic-matched controls were genotyped for HLA class I loci (HLA-A, B, C). For HLA class II loci (DRB1, DRB3/4/5, DQA1, DQB1, DPA1, DPB1), 40 control samples were genotyped. High-resolution HLA genotyping was performed using NGS and the results were analyzed. Clinical manifestations were oral ulcers (100%), genital ulcers (100%), eye (55%) and neurological (28%) and vascular involvement (35%). HLA-B*51:08 [odds ratio (OR) = 19.75, 95% confidence interval (CI) = 6.5-79; P < 0.0001], HLA-B*15:03 (OR = 12.15, 95% CI = 3.7-50.7; P < 0.0001), HLA-C*16:02 (OR = 6.53, 95% CI = 3-14; P < 0.0001), HLA-A*68:02 (OR = 3.14, 95% CI = 1.1-8.9; P < 0.01) were found to be associated with Behcet disease, as were HLA-DRB1*13:01 and HLA-DQB1*06:03 (OR = 3.39, 95% CI = 0.9-18.9; P = 0.04 for both). By contrast, HLA-A*03:01 (OR = 0.13, 95% CI = 0-0.8; P = 0.01) and HLA-DPB1*17:01 were found to be protective (OR = 0.27, 95% CI = 0.06-1.03; P = 0.02). We identified strong linkage disequilibrium between HLA-B*51:08 and C*16:02 and A*02:01 in a haplotype associated with Behcet disease. HLA-B*51:08 was significantly associated with legal blindness (OR = 2.98, 95% CI = 1.06-8.3; P = 0.01). In Egyptian Behcet patients, HLA-B*51:08 is the most common susceptibility allele and holds poor prognosis for eye involvement. CI - (c) 2021 British Society for Immunology. FAU - Elfishawi, M AU - Elfishawi M AUID- ORCID: 0000-0002-4795-8991 AD - Division of Rheumatology, Mayo Clinic College of Medicine, Rochester, MN, USA. FAU - Mossallam, G AU - Mossallam G AD - BMT Lab Unit, Clinical Pathology Deptartment, National Cancer Institute, Cairo University, Cairo, Egypt. FAU - Augusto, D G AU - Augusto DG AD - Department of Neurology, University of California San Francisco, San Francisco, CA, USA. FAU - Montero-Martin, G AU - Montero-Martin G AD - Department of Pathology, Stanford University School of Medicine, Palo Alto, CA, USA. FAU - de Bruin, H AU - de Bruin H AD - GenDx, Utrecht, the Netherlands. FAU - Van de Pasch, L AU - Van de Pasch L AD - GenDx, Utrecht, the Netherlands. FAU - Norman, P J AU - Norman PJ AD - Division of Personalized Medicine and Department of Immunology and Microbiology, University of Colorado School of Medicine, Denver, CO, USA. FAU - Rozemuller, E AU - Rozemuller E AD - GenDx, Utrecht, the Netherlands. FAU - Fernandez-Vina, M AU - Fernandez-Vina M AD - Department of Pathology, Stanford University School of Medicine, Palo Alto, CA, USA. FAU - Abrudescu, A AU - Abrudescu A AD - Department of Medicine, New York City Health + Hospitals: Queens, Icahn School of Medicine at Mount Sinai, New York, NY, USA. FAU - Hollenbach, J A AU - Hollenbach JA AD - Department of Neurology, University of California San Francisco, San Francisco, CA, USA. FAU - Zaky, K AU - Zaky K AD - Rheumatology and Rehabilitation, Faculty of Medicine, Al-Azhar University, Cairo, Egypt. FAU - Elfishawi, S AU - Elfishawi S AD - BMT Lab Unit, Clinical Pathology Deptartment, National Cancer Institute, Cairo University, Cairo, Egypt. LA - eng GR - U01 AI090905/AI/NIAID NIH HHS/United States GR - This work was made possible through collaboration during the 17th International Histocompatibility and Immunogenetics Workshop (IHIWS), in the disease association component, and with support from GenDx Inc, Utrecht, The Netherlands./ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210203 PL - England TA - Clin Exp Immunol JT - Clinical and experimental immunology JID - 0057202 RN - 0 (HLA Antigens) RN - 0 (HLA-B Antigens) RN - 0 (HLA-C Antigens) RN - 0 (HLA-D Antigens) SB - IM MH - Adult MH - Alleles MH - Behcet Syndrome/*genetics/pathology MH - Egypt MH - Female MH - Gene Frequency MH - Genotype MH - HLA Antigens/*genetics MH - HLA-B Antigens/*genetics MH - HLA-C Antigens/*genetics MH - HLA-D Antigens/*genetics MH - Haplotypes MH - High-Throughput Nucleotide Sequencing/*methods MH - Humans MH - Male MH - Middle Aged MH - Polymorphism, Genetic PMC - PMC7944360 OTO - NOTNLM OT - Behcet disease OT - epidemiology OT - genetics OT - next-generation sequencing OT - susceptibility COIS- M. E., G. M. , D. G. A., G. M.-M., P. J. N., M. F.-V., A. A., J. H., K. Z. and S. E. have nothing relevant to disclose. H. de B., L. V. de P. and E. R. are employees of GenDx and E. R. is a stockholder in GenDx. All the authors included in the article meet the journal's criteria for authorship. This manuscript has not been submitted or is not being submitted simultaneously elsewhere and is not, at the time of submission, under consideration by another journal or other publication and no portion of the data have been or will be published elsewhere while the manuscript is under review by the journal. EDAT- 2021/01/10 06:00 MHDA- 2021/09/28 06:00 PMCR- 2022/04/01 CRDT- 2021/01/09 17:08 PHST- 2020/11/21 00:00 [received] PHST- 2020/12/20 00:00 [revised] PHST- 2020/12/21 00:00 [accepted] PHST- 2021/01/10 06:00 [pubmed] PHST- 2021/09/28 06:00 [medline] PHST- 2021/01/09 17:08 [entrez] PHST- 2022/04/01 00:00 [pmc-release] AID - CEI13571 [pii] AID - 10.1111/cei.13571 [doi] PST - ppublish SO - Clin Exp Immunol. 2021 Apr;204(1):144-151. doi: 10.1111/cei.13571. Epub 2021 Feb 3.