{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:01:10Z","timestamp":1790794870125,"version":"4.1.0"},"reference-count":48,"publisher":"JMIR Publications Inc.","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JMIR Res Protoc"],"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n The incidence of end-stage renal disease (ESRD) continues to increase globally, including in Indonesia, representing a significant public health burden. Genetic factors, particularly variations in human leukocyte antigen (HLA) alleles, have been suggested to contribute to ESRD susceptibility, either indirectly through their association with underlying immune-mediated diseases or directly through their involvement in immune regulation and renal injury pathways. Studies have shown varying results due to HLA polymorphisms, ethnicity, and environmental influences. HLA polymorphisms are suspected of influencing HLA antibody production, which in turn impacts kidney transplant outcomes. Although ethnicity is one of the factors that determine HLA allele variation in the population, research on HLA alleles has not been widely conducted in Indonesia.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n This study aims to analyze the role HLA alleles play in the occurrence of ESRD and their association with HLA antibody production.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n This observational case-control study incorporates both retrospective and prospective data collection at Dr Sardjito General Hospital, Yogyakarta. Retrospective HLA typing and HLA antibody data were obtained from the medical records of patients with ESRD and healthy controls between January 2020 and May 2026. Additional participants in both groups are being prospectively recruited between June and December 2026 according to predefined eligibility criteria. The case group will comprise participants aged 18 years or older with ESRD, complete HLA typing data for 8 loci, and available HLA antibody results, excluding those who have undergone kidney transplantation. The control group will comprise individuals aged 18 years or older with normal kidney function. HLA allele typing will be performed using a molecular method, namely, polymerase chain reaction sequence\u2013specific oligonucleotide probes. HLA antibody testing will be performed using a solid-phase assay-based technology, specifically a Luminex single-antigen bead assay (DiaSorin), and both the HLA allele typing and HLA antibody testing will be analyzed using a LABScan3D analyzer (One Lambda Inc). The HLA antibody results will be subsequently categorized into positive and negative calculated panel reactive antibody (cPRA) statuses. Statistical analysis using odds ratio (OR) calculation will be performed to determine the association between specific HLA alleles and the occurrence of ESRD as well as HLA antibody production, with a 95% CI.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Participant recruitment and data collection began after approval of ethical considerations and are anticipated to be completed by December 2026. Dissemination of the study findings is planned for mid-2027.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n This study will evaluate the role of HLA class I and class II allele patterns in the development of ESRD and anti-HLA antibody production, as well as the influence of demographic characteristics, sensitization-related factors (including blood transfusion, pregnancy, and autoimmune disease), and clinical comorbidities on HLA antibody production and susceptibility to ESRD.<\/jats:p>\n <\/jats:sec>","DOI":"10.2196\/107508","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:41:18Z","timestamp":1790793678000},"page":"e107508-e107508","source":"Crossref","is-referenced-by-count":0,"title":["The Role of Human Leukocyte Antigen (HLA) Allele Patterns in the Incidence of End-Stage Renal Disease and HLA Antibody Production: Protocol for a Case-Control Study"],"prefix":"10.2196","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1402-7397","authenticated-orcid":false,"given":"Ira","family":"Puspitawati","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5319-945X","authenticated-orcid":false,"given":"Nyoman","family":"Kertia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8848-1336","authenticated-orcid":false,"given":"Teguh","family":"Triyono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1010","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"R1","unstructured":"Laporan nasional riskesdas [Report in Indonesian]. Badan Penelitian dan Pengembangan Kesehatan; 2018. URL: https:\/\/www.badankebijakan.kemkes.go.id\/repositori\/id\/eprint\/3514\/1\/Laporan%20Riskesdas%202018%20Nasional.pdf [Accessed 18-09-2026]"},{"issue":"7","key":"R2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2019.05.843","article-title":"MON-055 the growing burden of end stage renal disease in Indonesia: ten years of the Indonesian Renal Registry reports","volume":"4","author":"Abdurahman","journal-title":"Kidney Int Rep"},{"key":"R3","unstructured":"13th Annual Report Of Indonesian Renal Registry. Indonesian Renal Registry; 2020. URL: https:\/\/www.indonesianrenalregistry.org\/media\/laporan%20IRR%202020.pdf [Accessed 18-09-2026]"},{"issue":"4, Supplement","key":"R4","first-page":"S117","volume":"105","author":"Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group","journal-title":"Kidney Int"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1177\/2054358118789368","article-title":"Opportunities and challenges for genetic studies of end-stage renal disease in Canada","volume":"5","author":"Kalatharan","journal-title":"Can J Kidney Health Dis"},{"issue":"10","key":"R6","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1038\/s41581-018-0057-8","article-title":"HLA and kidney disease: from associations to mechanisms","volume":"14","author":"Robson","journal-title":"Nat Rev Nephrol"},{"issue":"2","key":"R7","doi-asserted-by":"publisher","first-page":"77","DOI":"10.4103\/GJTM.GJTM_45_17","article-title":"The human leukocyte antigen system \u2026 simplified","volume":"2","author":"Deshpande","journal-title":"Glob J Transfus Med"},{"issue":"10","key":"R8","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1038\/nri3523","article-title":"The immune system and kidney disease: basic concepts and clinical implications","volume":"13","author":"Kurts","journal-title":"Nat Rev Immunol"},{"issue":"9","key":"R9","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1038\/ki.2011.217","article-title":"Renal microenvironments and macrophage phenotypes determine progression or resolution of renal inflammation and fibrosis","volume":"80","author":"Anders","journal-title":"Kidney Int"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/4219822","article-title":"Evaluation of human leukocyte antigen class I and class II in end-stage renal disease occurrence in Indonesian transplantation patients","volume":"2021","author":"Susianti","journal-title":"Int J Nephrol"},{"issue":"11","key":"R11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0111403","article-title":"HLA class I and class II associations with ESRD in Saudi Arabian population","volume":"9","author":"Hamdi","journal-title":"PLoS One"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1186\/s12882-015-0165-7","article-title":"Association between human leucocyte antigen subtypes and risk of end stage renal disease in Taiwanese: a retrospective study","volume":"16","author":"Dai","journal-title":"BMC Nephrol"},{"issue":"6","key":"R13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0090869","article-title":"HLA polymorphism and susceptibility to end-stage renal disease in Cantonese patients awaiting kidney transplantation","volume":"9","author":"Cao","journal-title":"PLoS One"},{"issue":"3","key":"R14","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.24251","article-title":"Association of end-stage renal disease with HLA phenotypes and panel reactive antibodies in patients awaiting renal transplantation in Hunan Province","volume":"36","author":"Long","journal-title":"J Clin Lab Anal"},{"issue":"6","key":"R15","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1016\/j.humimm.2016.04.017","article-title":"HLA-A, -B, and -DRB1 allele and haplotype diversity in a cohort of Brazilian renal transplant candidates","volume":"77","author":"Ravazzi-Gauch","journal-title":"Hum Immunol"},{"issue":"17","key":"R16","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241713383","article-title":"Association between human leukocyte antigen and end-stage renal disease in patients from Transylvania, Romania","volume":"24","author":"Iancu Loga","journal-title":"Int J Mol Sci"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.14792","article-title":"Association between human leukocyte antigen (HLA) and end-stage renal disease (ESRD): a meta-analysis","volume":"11","author":"Noureen","journal-title":"PeerJ"},{"issue":"2","key":"R18","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1111\/ajt.14625","article-title":"The Banff 2017 Kidney Meeting Report: Revised diagnostic criteria for chronic active T cell-mediated rejection, antibody-mediated rejection, and prospects for integrative endpoints for next-generation clinical trials","volume":"18","author":"Haas","journal-title":"Am J Transplant"},{"issue":"1","key":"R19","doi-asserted-by":"publisher","first-page":"182","DOI":"10.2215\/CJN.00700117","article-title":"Donor-specific antibodies in kidney transplant recipients","volume":"13","author":"Zhang","journal-title":"Clin J Am Soc Nephrol"},{"issue":"5","key":"R20","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1016\/j.kint.2024.07.030","article-title":"Transfusion-induced HLA sensitization in wait-list patients and kidney transplant recipients","volume":"106","author":"Willicombe","journal-title":"Kidney Int"},{"issue":"4","key":"R21","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1007\/s00467-014-2868-6","article-title":"HLA sensitisation: can it be prevented?","volume":"30","author":"Rees","journal-title":"Pediatr Nephrol"},{"issue":"9","key":"R22","doi-asserted-by":"publisher","first-page":"1825","DOI":"10.1111\/j.1537-2995.2009.02206.x","article-title":"Alloimmunization in blood donors: implications for a transfusion","volume":"49","author":"Triulzi","journal-title":"Transfusion"},{"issue":"3","key":"R23","doi-asserted-by":"publisher","DOI":"10.1016\/s0041-1345(00)00908-8","article-title":"Evaluation of HLA antibody synthesis due to blood transfusion in 314 patients from the Isfahan (Iran) Transplantation Center","volume":"32","author":"Adib","journal-title":"Transplant Proc"},{"issue":"8","key":"R24","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1016\/j.humimm.2015.06.013","article-title":"Pregnancy-induced HLA antibodies respond more vigorously after renal transplantation than antibodies induced by prior transplantation","volume":"76","author":"Higgins","journal-title":"Hum Immunol"},{"issue":"4","key":"R25","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1097\/TP.0000000000004420","article-title":"Pathways of antigen recognition by T cells in allograft rejection","volume":"107","author":"Carnel","journal-title":"Transplantation"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.3389\/ti.2024.13196","article-title":"Activation and regulation of indirect alloresponses in transplanted patients with donor specific antibodies and chronic rejection","volume":"37","author":"Basu","journal-title":"Transpl Int"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.831822","article-title":"Promiscuity of peptides presented in HLA-DP molecules from different immunogenicity groups is associated with T-cell cross-reactivity","volume":"13","author":"Laghmouchi","journal-title":"Front Immunol"},{"key":"R28","unstructured":"Sullivan KM Pezzullo JC Dean AG EpiInformatics.comMir RA . OpenEpi - sample size for umatched case-control studies. OpenEpi. URL: https:\/\/www.openepi.com\/SampleSize\/SSCC.htm"},{"key":"R29","unstructured":"CPRA calculator. Health Resources & Services Administration. 2025. URL: https:\/\/www.hrsa.gov\/optn\/data-calculators\/allocation-calculators\/cpra-calculator [Accessed 15-09-2026]"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0012.2001.00004.x","article-title":"HLA phenotypes of ESRD patients are risk factors in the panel-reactive antibody (PRA) response","volume":"15 Suppl 6","author":"Heise","journal-title":"Clin Transplant"},{"key":"R31","unstructured":"Single Antigen ExPlex Extended Single Antigen Bead Coverage. ThermoFisher Scientific. URL: https:\/\/www.thermofisher.com\/diagnostic-education\/dam\/one_lambda\/documents\/collateral\/TDX-MKT-0098.pdf [Accessed 18-09-2026]"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2018.06.002","article-title":"Cellular and molecular mechanisms of kidney fibrosis","volume":"65","author":"Djudjaj","journal-title":"Mol Aspects Med"},{"issue":"7","key":"R33","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1038\/ki.2008.350","article-title":"Chronic hypoxia as a mechanism of progression of chronic kidney diseases: from hypothesis to novel therapeutics","volume":"74","author":"Fine","journal-title":"Kidney Int"},{"issue":"11","key":"R34","doi-asserted-by":"publisher","first-page":"2974","DOI":"10.1681\/ASN.2006040377","article-title":"How does proteinuria cause progressive renal damage?","volume":"17","author":"Abbate","journal-title":"J Am Soc Nephrol"},{"issue":"3","key":"R35","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1007\/s00281-012-0309-9","article-title":"Roles for major histocompatibility complex glycosylation in immune function","volume":"34","author":"Ryan","journal-title":"Semin Immunopathol"},{"key":"R36","unstructured":"Murphy K Weaver C . Janeway\u2019s Immunobiology. 9th ed. Garland Science, Taylor & Francis Group; 2017. ISBN: 9780815345053"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1186\/1742-9994-2-16","article-title":"The importance of immune gene variability (MHC) in evolutionary ecology and conservation","volume":"2","author":"Sommer","journal-title":"Front Zool"},{"issue":"1","key":"R38","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/s40744-018-0100-z","article-title":"Role of human leukocyte antigens (HLA) in autoimmune diseases","volume":"5","author":"Bodis","journal-title":"Rheumatol Ther"},{"issue":"1","key":"R39","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1007\/s12016-011-8294-7","article-title":"Molecular mimicry as a mechanism of autoimmune disease","volume":"42","author":"Cusick","journal-title":"Clin Rev Allergy Immunol"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-091212-153455","article-title":"Major histocompatibility complex genomics and human disease","volume":"14","author":"Trowsdale","journal-title":"Annu Rev Genomics Hum Genet"},{"issue":"1","key":"R41","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03181-4","article-title":"Effector CD4 T cells recognize intravascular antigen presented by patrolling monocytes","volume":"9","author":"Westhorpe","journal-title":"Nat Commun"},{"issue":"389","key":"R42","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aai8708","article-title":"Phenome-wide scanning identifies multiple diseases and disease severity phenotypes associated with HLA variants","volume":"9","author":"Karnes","journal-title":"Sci Transl Med"},{"issue":"4","key":"R43","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1038\/ng.787","article-title":"Genome-wide association study identifies susceptibility loci for IgA nephropathy","volume":"43","author":"Gharavi","journal-title":"Nat Genet"},{"issue":"5","key":"R44","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1016\/j.transproceed.2008.02.086","article-title":"HLA polymorphisms as incidence factor in the progression to end-stage renal disease in Brazilian patients awaiting kidney transplant","volume":"40","author":"Crispim","journal-title":"Transplant Proc"},{"issue":"1","key":"R45","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.103664","article-title":"Feto-maternal microchimerism: memories from pregnancy","volume":"25","author":"C\u00f3mitre-Mariano","journal-title":"iScience"},{"issue":"9","key":"R46","doi-asserted-by":"publisher","first-page":"1785","DOI":"10.1111\/j.1600-6143.2011.03705.x","article-title":"Blood transfusions in organ transplant patients: mechanisms of sensitization and implications for prevention","volume":"11","author":"Scornik","journal-title":"Am J Transplant"},{"issue":"1","key":"R47","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1146\/annurev-pathol-012414-040318","article-title":"Pathobiology of transfusion reactions","volume":"10","author":"Zimring","journal-title":"Annu Rev Pathol: Mech Dis"},{"issue":"11","key":"R48","doi-asserted-by":"publisher","first-page":"2908","DOI":"10.1093\/ndt\/gft362","article-title":"Sensitization from transfusion in patients awaiting primary kidney transplant","volume":"28","author":"Yabu","journal-title":"Nephrol Dial Transplant"}],"container-title":["JMIR Research Protocols"],"original-title":[],"language":"en","deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:41:20Z","timestamp":1790793680000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.researchprotocols.org\/2026\/1\/e107508"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,30]]},"references-count":48,"URL":"https:\/\/doi.org\/10.2196\/107508","relation":{},"ISSN":["1929-0748"],"issn-type":[{"value":"1929-0748","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,30]]},"article-number":"v15i7e107508"}}