Combined Analysis of HLA Class II Eplet Mismatch and Tacrolimus Levels for the Prediction of De Novo Donor Specific Antibody Development in Kidney Transplant Recipients
We investigated whether HLA class II eplet mismatch was related to dnDSA development and analyzed its combined impact with tacrolimus levels for kidney transplantation outcomes. A total of 347 kidney transplants were included. HLA Matchmaker was used for the single molecular eplet, total eplet, anti...
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| Veröffentlicht in: | International journal of molecular sciences 2022-07, Vol.23 (13), p.7357 |
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| creator | Lee, Hyeyoung Min, Ji Won Kang, Hyunhye Lee, Hanbi Eum, Sang Hun Park, Yohan Yang, Chul Woo Chung, Byung Ha Oh, Eun-Jee |
| description | We investigated whether HLA class II eplet mismatch was related to dnDSA development and analyzed its combined impact with tacrolimus levels for kidney transplantation outcomes. A total of 347 kidney transplants were included. HLA Matchmaker was used for the single molecular eplet, total eplet, antibody (Ab)-verified eplet mismatch analyses, and Ab-verified single molecular analysis to identify HLA-DR/DQ molecular thresholds for the risk of dnDSA development. A time-weighted tacrolimus trough level (TAC-C0) of 5 ng/mL and a TAC-C0 time-weighted coefficient variability (TWCV) of 20% were applied to find the combined effects on dnDSA development. A high level of mismatch for single molecular eplet (DQ ≥ 10), total eplet (DQ ≥ 12), Ab-verified eplet (DQ ≥ 4), and Ab-verified single molecular eplet (DQ ≥ 4) significantly correlated with HLA class II dnDSA development. Class II dnDSA developed mostly in patients with low TAC-C0 and high eplet mismatch. In the multivariable analyses, low TAC-C0 and high eplet mismatch showed the highest hazard ratio for the development of dnDSA. No significant combined effect was observed in dnDSA development according to TWCV. In conclusion, the determination of HLA class II eplet mismatch may improve the risk stratification for dnDSA development, especially in conjunction with tacrolimus trough levels. |
| doi_str_mv | 10.3390/ijms23137357 |
| format | Article |
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A total of 347 kidney transplants were included. HLA Matchmaker was used for the single molecular eplet, total eplet, antibody (Ab)-verified eplet mismatch analyses, and Ab-verified single molecular analysis to identify HLA-DR/DQ molecular thresholds for the risk of dnDSA development. A time-weighted tacrolimus trough level (TAC-C0) of 5 ng/mL and a TAC-C0 time-weighted coefficient variability (TWCV) of 20% were applied to find the combined effects on dnDSA development. A high level of mismatch for single molecular eplet (DQ ≥ 10), total eplet (DQ ≥ 12), Ab-verified eplet (DQ ≥ 4), and Ab-verified single molecular eplet (DQ ≥ 4) significantly correlated with HLA class II dnDSA development. Class II dnDSA developed mostly in patients with low TAC-C0 and high eplet mismatch. In the multivariable analyses, low TAC-C0 and high eplet mismatch showed the highest hazard ratio for the development of dnDSA. No significant combined effect was observed in dnDSA development according to TWCV. In conclusion, the determination of HLA class II eplet mismatch may improve the risk stratification for dnDSA development, especially in conjunction with tacrolimus trough levels.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms23137357</identifier><identifier>PMID: 35806362</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Antibodies ; Antigens ; Histocompatibility antigen HLA ; Impact analysis ; Kidney transplants ; Patients ; Tacrolimus ; Transplants ; Transplants & implants</subject><ispartof>International journal of molecular sciences, 2022-07, Vol.23 (13), p.7357</ispartof><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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A total of 347 kidney transplants were included. HLA Matchmaker was used for the single molecular eplet, total eplet, antibody (Ab)-verified eplet mismatch analyses, and Ab-verified single molecular analysis to identify HLA-DR/DQ molecular thresholds for the risk of dnDSA development. A time-weighted tacrolimus trough level (TAC-C0) of 5 ng/mL and a TAC-C0 time-weighted coefficient variability (TWCV) of 20% were applied to find the combined effects on dnDSA development. A high level of mismatch for single molecular eplet (DQ ≥ 10), total eplet (DQ ≥ 12), Ab-verified eplet (DQ ≥ 4), and Ab-verified single molecular eplet (DQ ≥ 4) significantly correlated with HLA class II dnDSA development. Class II dnDSA developed mostly in patients with low TAC-C0 and high eplet mismatch. In the multivariable analyses, low TAC-C0 and high eplet mismatch showed the highest hazard ratio for the development of dnDSA. No significant combined effect was observed in dnDSA development according to TWCV. In conclusion, the determination of HLA class II eplet mismatch may improve the risk stratification for dnDSA development, especially in conjunction with tacrolimus trough levels.</description><subject>Antibodies</subject><subject>Antigens</subject><subject>Histocompatibility antigen HLA</subject><subject>Impact analysis</subject><subject>Kidney transplants</subject><subject>Patients</subject><subject>Tacrolimus</subject><subject>Transplants</subject><subject>Transplants & implants</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkstuEzEUhkcIREthxwMciQ0LAr5kZuwNUpQWGhEuguwtj32GOPLYU3smUt6Ix8SlFSqsbPn_zn8uPlX1kpK3nEvyzh2GzDjlLa_bR9U5XTK2IKRpHz-4n1XPcj4Qwjir5dPqjNeCNLxh59WvdRw6F9DCKmh_yi5D7OF6u4K11znDZgNXo8cJPrs86MnsQQcLO21S9G6YM2zxiD5DHxNMe4RvCa0zk4vh1ucS4Us8RriMoeg_RjSud6akmlwX7anoJTiOA4YJXIBPzgY8wS7pkEevy-P3EjG6Iufn1ZNe-4wv7s-Lavfhare-Xmy_ftysV9uF4UJOC9MZTnRNZV8jJVYKNII3lGtBl10rGcO6tz2nRJBaSN7YvhOcIiHWLmXX8ovq_Z3tOHcDWlNSJ-3VmNyg00lF7dS_SnB79TMelWRNS6ksBq_vDVK8mTFPanDZoC_tYJyzYo1oWyaIqAv66j_0EOdUvuEP1dCWEt4U6s0dVUaec8L-bzGUqNsNUA83gP8GYmCksA</recordid><startdate>20220701</startdate><enddate>20220701</enddate><creator>Lee, Hyeyoung</creator><creator>Min, Ji Won</creator><creator>Kang, Hyunhye</creator><creator>Lee, Hanbi</creator><creator>Eum, Sang Hun</creator><creator>Park, Yohan</creator><creator>Yang, Chul Woo</creator><creator>Chung, Byung Ha</creator><creator>Oh, Eun-Jee</creator><general>MDPI AG</general><general>MDPI</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9796-636X</orcidid><orcidid>https://orcid.org/0000-0001-5870-915X</orcidid><orcidid>https://orcid.org/0000-0001-8871-5091</orcidid><orcidid>https://orcid.org/0000-0001-7326-0602</orcidid><orcidid>https://orcid.org/0000-0003-0048-5717</orcidid></search><sort><creationdate>20220701</creationdate><title>Combined Analysis of HLA Class II Eplet Mismatch and Tacrolimus Levels for the Prediction of De Novo Donor Specific Antibody Development in Kidney Transplant Recipients</title><author>Lee, Hyeyoung ; 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A total of 347 kidney transplants were included. HLA Matchmaker was used for the single molecular eplet, total eplet, antibody (Ab)-verified eplet mismatch analyses, and Ab-verified single molecular analysis to identify HLA-DR/DQ molecular thresholds for the risk of dnDSA development. A time-weighted tacrolimus trough level (TAC-C0) of 5 ng/mL and a TAC-C0 time-weighted coefficient variability (TWCV) of 20% were applied to find the combined effects on dnDSA development. A high level of mismatch for single molecular eplet (DQ ≥ 10), total eplet (DQ ≥ 12), Ab-verified eplet (DQ ≥ 4), and Ab-verified single molecular eplet (DQ ≥ 4) significantly correlated with HLA class II dnDSA development. Class II dnDSA developed mostly in patients with low TAC-C0 and high eplet mismatch. In the multivariable analyses, low TAC-C0 and high eplet mismatch showed the highest hazard ratio for the development of dnDSA. No significant combined effect was observed in dnDSA development according to TWCV. 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| subjects | Antibodies Antigens Histocompatibility antigen HLA Impact analysis Kidney transplants Patients Tacrolimus Transplants Transplants & implants |
| title | Combined Analysis of HLA Class II Eplet Mismatch and Tacrolimus Levels for the Prediction of De Novo Donor Specific Antibody Development in Kidney Transplant Recipients |
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