{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:10:17Z","timestamp":1788844217559,"version":"build-2803163510"},"reference-count":51,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Med. Sci.","Medical Sciences"],"abstract":"<jats:p>Antibody-mediated rejection (AMR) remains a major cause of kidney allograft injury and loss. Although donor-specific antibodies against human leukocyte antigens (HLA-DSAs) are central to humoral alloimmunity, they do not explain all cases of microvascular inflammation or graft dysfunction. This review critically evaluates non-HLA antibodies as potential mediators of allograft injury and markers of dysregulated humoral immunity by integrating functional, experimental, clinicopathological, and clinical evidence. Receptor-targeting antibodies, especially those against the angiotensin II type 1 receptor (AT1R) and the endothelin-1 type A receptor (ETAR), have the strongest evidence for direct pathogenicity. Antibodies against major histocompatibility complex class I-related chain A (MICA) and glutathione S-transferase theta-1 (GSTT1) reflect non-HLA alloimmunity, whereas antibodies targeting perlecan-derived LG3, vimentin, and injury-associated antigens may arise through secondary autoimmunity and mark broader humoral activation. We propose that selected pathogenic non-HLA antibodies participate in a feed-forward cycle of graft injury, antigen exposure, epitope spreading, and humoral amplification, although this model requires longitudinal validation. Crucially, non-HLA antibody positivity alone should neither establish AMR nor guide antibody-specific treatment. Its interpretation should be target-specific and integrated with HLA-DSAs, histopathology, molecular findings, graft function, and evidence of immune activation.<\/jats:p>","DOI":"10.3390\/medsci14050534","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T03:19:26Z","timestamp":1788232766000},"page":"534","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Non-HLA Antibodies in Kidney Transplantation: Mediators of Allograft Injury or Markers of Dysregulated Humoral Immunity?"],"prefix":"10.3390","volume":"14","author":[{"given":"Ariadni","family":"Fouza","sequence":"first","affiliation":[{"name":"5th Surgical Department, Hippokratio General Hospital, School of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece"},{"name":"Department of Transplant Surgery, Center for Research and Innovation in Solid Organ Transplantation, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3342-8711","authenticated-orcid":false,"given":"Maria","family":"Daoudaki","sequence":"additional","affiliation":[{"name":"Laboratory of Biological Chemistry, School of Medicine, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1056\/NEJMra1802677","article-title":"Antibody-mediated rejection of solid-organ allografts","volume":"379","author":"Loupy","year":"2018","journal-title":"N. 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