دورية أكاديمية

Utilizing principal component analysis in the identification of clinically relevant changes in patient HLA single antigen bead solid phase testing patterns.

التفاصيل البيبلوغرافية
العنوان: Utilizing principal component analysis in the identification of clinically relevant changes in patient HLA single antigen bead solid phase testing patterns.
المؤلفون: Cornaby C; Histocompatibility & Diagnostic Immunology Laboratory, Children's Hospital of Los Angeles, Los Angeles, California, United States of America.; Department of Pathology and Laboratory Medicine, University of Southern California Keck School of Medicine, Los Angeles, California, United States of America., Weimer ET; Molecular Immunology Laboratory, McLendon Clinical Laboratories, UNC Health, Chapel Hill, North Carolina, United States of America.; Department of Pathology & Laboratory Medicine, the University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States of America.
المصدر: PloS one [PLoS One] 2023 Oct 26; Vol. 18 (10), pp. e0288743. Date of Electronic Publication: 2023 Oct 26 (Print Publication: 2023).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Kidney Transplantation*/methods , Organ Transplantation*, Humans ; Principal Component Analysis ; Isoantibodies ; Graft Rejection ; HLA Antigens ; Histocompatibility Testing/methods
مستخلص: Background: HLA antibody testing is essential for successful solid-organ allocation, patient monitoring post-transplant, and risk assessment for both solid-organ and hematopoietic transplant patients. Luminex solid-phase testing is the most common method for identifying HLA antibody specificities, making it one of the most complex immunoassays as each panel contains over 90 specificities for both HLA class I and HLA class II with most of the analysis being performed manually in the vendor-provided software. Principal component analysis (PCA), used in machine learning, is a feature extraction method often utilized to assess data with many variables.
Methods & Findings: In our study, solid organ transplant patients who exhibited HLA donor-specific antibodies (DSAs) were used to characterize the utility of PCA-derived analysis when compared to a control group of post-transplant and pre-transplant patients. ROC analysis was utilized to determine a potential threshold for the PCA-derived analysis that would indicate a significant change in a patient's single antigen bead pattern. To evaluate if the algorithm could identify differences in patterns on HLA class I and HLA class II single antigen bead results using the optimized threshold, HLA antibody test results were analyzed using PCA-derived analysis and compared to the clinical results for each patient sample. The PCA-derived algorithm had a sensitivity of 100% (95% CI, 73.54%-100%), a specificity of 75% (95% CI, 56.30%-92.54%), with a PPV of 65% (95% CI, 52.50%-83.90%) and an NPV of 100%, in identifying new reactivity that differed from the patients historic HLA antibody pattern. Additionally, PCA-derived analysis was utilized to assess the potential over-reactivity of single antigen beads for both HLA class I and HLA class II antibody panels. This assessment of antibody results identified several beads in both the HLA class I and HLA class II antibody panel which exhibit over reactivity from 2018 to the present time.
Conclusions: PCA-derived analysis would be ideal to help automatically identify patient samples that have an HLA antibody pattern of reactivity consistent with their history and those which exhibit changes in their antibody patterns which could include donor-specific antibodies, de novo HLA antibodies, and assay interference. A similar method could also be applied to evaluate the over-reactivity of beads in the HLA solid phase assays which would be beneficial for lot comparisons and instructive for transplant centers to better understand which beads are more prone to exhibiting over-reactivity and impact patient care.
Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Eric T. Weimer is a consultant and Scientific Advisor for One Lambda, whose products were used in this study.
(Copyright: © 2023 Cornaby, Weimer. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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المشرفين على المادة: 0 (Isoantibodies)
0 (HLA Antigens)
تواريخ الأحداث: Date Created: 20231026 Date Completed: 20231030 Latest Revision: 20231112
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC10602234
DOI: 10.1371/journal.pone.0288743
PMID: 37883384
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0288743