Donor-Specific Antibody Is Associated with Increased Expression of Rejection Transcripts in Renal Transplant Biopsies Classified as No Rejection
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F21%3A00081724" target="_blank" >RIV/00023001:_____/21:00081724 - isvavai.cz</a>
Result on the web
<a href="https://jasn.asnjournals.org/content/jnephrol/32/11/2743.full.pdf?with-ds=yes" target="_blank" >https://jasn.asnjournals.org/content/jnephrol/32/11/2743.full.pdf?with-ds=yes</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1681/ASN.2021040433" target="_blank" >10.1681/ASN.2021040433</a>
Alternative languages
Result language
angličtina
Original language name
Donor-Specific Antibody Is Associated with Increased Expression of Rejection Transcripts in Renal Transplant Biopsies Classified as No Rejection
Original language description
BACKGROUND: Donor -specific HLA antibody (DSA) is present in many kidney transplant patients whose biopsies are classified as no rejection (NR). We explored whether in some NR kidneys DSA has subtle effects not currently being recognized. METHODS: We used microarrays to examine the relationship between standard-of-care DSA and rejection-related transcript increases in 1679 kidney transplant indication biopsies in the INTERCOMEX study (ClinicalTrials.gov NCT01299168), focusing on biopsies classified as NR by automatically assigned archetypal clustering. DSA testing results were available for 835 NR biopsies and were positive in 271 (32%). RESULTS: DSA positivity in NR biopsies was associated with mildly increased expression of antibody-mediated rejection (ABMR)-related transcripts, particularly IFNG-inducible and NK cell transcripts. We developed a machine learning DSA probability (DSA(Prob)) classifier based on transcript expression in biopsies from DSA-positive versus DSA-negative patients, assigning scores using 10-fold cross-validation. This DSA(Prob) classifier was very similar to a previously described "ABMR probability" classifier trained on histologic ABMR in transcript associations and prediction of molecular or histologic ABMR. Plotting the biopsies using Uniform Manifold Approximation and Projection revealed a gradient of increasing molecular ABMR-like transcript expression in NR biopsies, associated with increased DSA (P<2 × 10(-16)). In biopsies with no molecular or histologic rejection, increased DSA(Prob) or ABMR probability scores were associated with increased risk of kidney failure over 3 years. CONCLUSIONS: Many biopsies currently considered to have no molecular or histologic rejection have mild increases in expression of ABMR-related transcripts, associated with increasing frequency of DSA. Thus, mild molecular ABMR-related pathology is more common than previously realized.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30217 - Urology and nephrology
Result continuities
Project
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Continuities
N - Vyzkumna aktivita podporovana z neverejnych zdroju
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of the American Society of Nephrology
ISSN
1046-6673
e-ISSN
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Volume of the periodical
32
Issue of the periodical within the volume
11
Country of publishing house
US - UNITED STATES
Number of pages
16
Pages from-to
2743-2758
UT code for WoS article
000753515500013
EID of the result in the Scopus database
2-s2.0-85119127225