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1. T-Cell Epitopes Shared Between Immunizing HLA and Donor HLA Associate With Graft Failure After Kidney Transplantation

Author

Peereboom, E.T.M., Matern, B.M., Tomosugi, T., Niemann, M., Drylewicz, J., Joosten, I., Allebes, W.A., Meer, A. van der, Hilbrands, L.B., Baas, M.C., Reekum, F.E. van, Verhaar, M.C., Kamburova, E.G., Seelen, M.A., Sanders, J.S., Hepkema, B.G., Lambeck, A.J.A., Bungener, L.B., Roozendaal, C., Tilanus, M.G., Voorter, C.E.M., Wieten, L., Duijnhoven, E.M. van, Gelens, M., Christiaans, M.H., Ittersum, F.J. van, Nurmohamed, A., Lardy, N.M., Swelsen, W., Pant, Karlijn A.M.I. van der, Weerd, N.C. van der, Berge, I.J. Ten, Bemelman, F.J., Vries, A.P.J de, Fijter, J.W. de, Betjes, M. G. H., Roelen, D.L., Claas, F.H.J., Otten, H.G., Heidt, S., Zuilen, A.D. van, Kobayashi, T., Geneugelijk, K., Spierings, E, Peereboom, E.T.M., Matern, B.M., Tomosugi, T., Niemann, M., Drylewicz, J., Joosten, I., Allebes, W.A., Meer, A. van der, Hilbrands, L.B., Baas, M.C., Reekum, F.E. van, Verhaar, M.C., Kamburova, E.G., Seelen, M.A., Sanders, J.S., Hepkema, B.G., Lambeck, A.J.A., Bungener, L.B., Roozendaal, C., Tilanus, M.G., Voorter, C.E.M., Wieten, L., Duijnhoven, E.M. van, Gelens, M., Christiaans, M.H., Ittersum, F.J. van, Nurmohamed, A., Lardy, N.M., Swelsen, W., Pant, Karlijn A.M.I. van der, Weerd, N.C. van der, Berge, I.J. Ten, Bemelman, F.J., Vries, A.P.J de, Fijter, J.W. de, Betjes, M. G. H., Roelen, D.L., Claas, F.H.J., Otten, H.G., Heidt, S., Zuilen, A.D. van, Kobayashi, T., Geneugelijk, K., and Spierings, E

Abstract

Contains fulltext : 241482.pdf (Publisher’s version ) (Open Access), CD4(+) T-helper cells play an important role in alloimmune reactions following transplantation by stimulating humoral as well as cellular responses, which might lead to failure of the allograft. CD4(+) memory T-helper cells from a previous immunizing event can potentially be reactivated by exposure to HLA mismatches that share T-cell epitopes with the initial immunizing HLA. Consequently, reactivity of CD4(+) memory T-helper cells toward T-cell epitopes that are shared between immunizing HLA and donor HLA could increase the risk of alloimmunity following transplantation, thus affecting transplant outcome. In this study, the amount of T-cell epitopes shared between immunizing and donor HLA was used as a surrogate marker to evaluate the effect of donor-reactive CD4(+) memory T-helper cells on the 10-year risk of death-censored kidney graft failure in 190 donor/recipient combinations using the PIRCHE-II algorithm. The T-cell epitopes of the initial theoretical immunizing HLA and the donor HLA were estimated and the number of shared PIRCHE-II epitopes was calculated. We show that the natural logarithm-transformed PIRCHE-II overlap score, or Shared T-cell EPitopes (STEP) score, significantly associates with the 10-year risk of death-censored kidney graft failure, suggesting that the presence of pre-transplant donor-reactive CD4(+) memory T-helper cells might be a strong indicator for the risk of graft failure following kidney transplantation.

Published
2021

2. Toward a Sensible Single-antigen Bead Cutoff Based on Kidney Graft Survival

Author

Wisse, B.W., Kamburova, E.G., Joosten, I., Allebes, W.A., Meer, A. van der, Hilbrands, L.B., Baas, M.C., Spierings, E., Hack, C.E., Reekum, F.E. van, Zuilen, A.D. van, Verhaar, M.C., Bots, M.L., Drop, A., Plaisier, L., Seelen, M.A., Stephan Sanders, J., Hepkema, B.G., Lambeck, A.J.A., Bungener, L.B., Roozendaal, C., Tilanus, M.G., Voorter, C.E.M., Wieten, L., van Duijnhoven, E.M., Gelens, M., Christiaans, M.H., van Ittersum, F.J., Nurmohamed, S.A., Lardy, N.M., Swelsen, W., Pant, K. van der, Weerd, N.C. van der, Berge, I.J. ten, Bemelman, F.J., Hoitsma, A.J., Boog, P.J. van der, Fijter, J.W. de, Betjes, M.G., Heidt, S., Roelen, D.L., Claas, F.H., Otten, H.G., Wisse, B.W., Kamburova, E.G., Joosten, I., Allebes, W.A., Meer, A. van der, Hilbrands, L.B., Baas, M.C., Spierings, E., Hack, C.E., Reekum, F.E. van, Zuilen, A.D. van, Verhaar, M.C., Bots, M.L., Drop, A., Plaisier, L., Seelen, M.A., Stephan Sanders, J., Hepkema, B.G., Lambeck, A.J.A., Bungener, L.B., Roozendaal, C., Tilanus, M.G., Voorter, C.E.M., Wieten, L., van Duijnhoven, E.M., Gelens, M., Christiaans, M.H., van Ittersum, F.J., Nurmohamed, S.A., Lardy, N.M., Swelsen, W., Pant, K. van der, Weerd, N.C. van der, Berge, I.J. ten, Bemelman, F.J., Hoitsma, A.J., Boog, P.J. van der, Fijter, J.W. de, Betjes, M.G., Heidt, S., Roelen, D.L., Claas, F.H., and Otten, H.G.

Abstract

Contains fulltext : 204258.pdf (publisher's version ) (Open Access), BACKGROUND: There is no consensus in the literature on the interpretation of single-antigen bead positive for a specific HLA antibody. METHODS: To inform the debate, we studied the relationship between various single-antigen bead positivity algorithms and the impact of resulting donor-specific HLA antibody (DSA) positivity on long-term kidney graft survival in 3237 deceased-donor transplants. RESULTS: First, we showed that the interassay variability can be greatly reduced when working with signal-to-background ratios instead of absolute median fluorescence intensities (MFIs). Next, we determined pretransplant DSA using various MFI cutoffs, signal-to-background ratios, and combinations thereof. The impact of the various cutoffs was studied by comparing the graft survival between the DSA-positive and DSA-negative groups. We did not observe a strong impact of various cutoff levels on 10-year graft survival. A stronger relationship between the cutoff level and 1-year graft survival for DSA-positive transplants was found when using signal-to-background ratios, most pronounced for the bead of the same HLA locus with lowest MFI taken as background. CONCLUSIONS: With respect to pretransplant risk stratification, we propose a signal-to-background ratio-6 (using the bead of the same HLA-locus with lowest MFI as background) cutoff of 15 combined with an MFI cutoff of 500, resulting in 8% and 21% lower 1- and 10-year graft survivals, respectively, for 8% DSA-positive transplants.

Published
2019

3. Allocation to highly sensitized patients based on acceptable mismatches results in low rejection rates comparable to nonsensitized patients

Author

Heidt, S., Haasnoot, G.W., Witvliet, M.D., Linden-van Oevelen, M.J.H. van der, Kamburova, E.G., Wisse, B.W., Joosten, I., Allebes, W.A., Meer, A. van der, Hilbrands, L.B., Baas, M.C., Spierings, E., Hack, C.E., Reekum, F.E. van, Zuilen, A.D. van, Verhaar, M.C., Bots, M.L., Drop, A., Plaisier, L., Seelen, M.A., Sanders, J.S., Hepkema, B.G., Lambeck, A.J.A., Bungener, L.B., Roozendaal, C., Tilanus, M.G., Voorter, C.E.M., Wieten, L., Duijnhoven, E.M. van, Gelens, M., Christiaans, M.H., Ittersum, F.J. van, Nurmohamed, S.A., Lardy, N.M., Swelsen, W., Pant, K. van der, Weerd, N.C. van der, Berge, I.J. Ten, Bemelman, F.J., Hoitsma, A., Boog, P.J. van der, Fijter, J.W. de, Betjes, M.G., Otten, H.G., Roelen, D.L., Claas, F.H., Heidt, S., Haasnoot, G.W., Witvliet, M.D., Linden-van Oevelen, M.J.H. van der, Kamburova, E.G., Wisse, B.W., Joosten, I., Allebes, W.A., Meer, A. van der, Hilbrands, L.B., Baas, M.C., Spierings, E., Hack, C.E., Reekum, F.E. van, Zuilen, A.D. van, Verhaar, M.C., Bots, M.L., Drop, A., Plaisier, L., Seelen, M.A., Sanders, J.S., Hepkema, B.G., Lambeck, A.J.A., Bungener, L.B., Roozendaal, C., Tilanus, M.G., Voorter, C.E.M., Wieten, L., Duijnhoven, E.M. van, Gelens, M., Christiaans, M.H., Ittersum, F.J. van, Nurmohamed, S.A., Lardy, N.M., Swelsen, W., Pant, K. van der, Weerd, N.C. van der, Berge, I.J. Ten, Bemelman, F.J., Hoitsma, A., Boog, P.J. van der, Fijter, J.W. de, Betjes, M.G., Otten, H.G., Roelen, D.L., and Claas, F.H.

Abstract

Contains fulltext : 208426.pdf (publisher's version ) (Open Access), Whereas regular allocation avoids unacceptable mismatches on the donor organ, allocation to highly sensitized patients within the Eurotransplant Acceptable Mismatch (AM) program is based on the patient's HLA phenotype plus acceptable antigens. These are HLA antigens to which the patient never made antibodies, as determined by extensive laboratory testing. AM patients have superior long-term graft survival compared with highly sensitized patients in regular allocation. Here, we questioned whether the AM program also results in lower rejection rates. From the PROCARE cohort, consisting of all Dutch kidney transplants in 1995-2005, we selected deceased donor single transplants with a minimum of 1 HLA mismatch and determined the cumulative 6-month rejection incidence for patients in AM or regular allocation. Additionally, we determined the effect of minimal matching criteria of 1 HLA-B plus 1 HLA-DR, or 2 HLA-DR antigens on rejection incidence. AM patients showed significantly lower rejection rates than highly immunized patients in regular allocation, comparable to nonsensitized patients, independent of other risk factors for rejection. In contrast to highly sensitized patients in regular allocation, minimal matching criteria did not affect rejection rates in AM patients. Allocation based on acceptable antigens leads to relatively low-risk transplants for highly sensitized patients with rejection rates similar to those of nonimmunized individuals.

Published
2019

4. A paired kidney analysis on the impact of pre-transplant anti-HLA antibodies on graft survival

Author

Michielsen, L.A., Wisse, B.W., Kamburova, E.G., Verhaar, M.C., Joosten, I., Allebes, W.A., Meer, A. van der, Hilbrands, L.B., Baas, M.C., Spierings, E, Hack, C.E., Reekum, F.E. van, Bots, M.L., Drop, A., Plaisier, L., Seelen, M.A., Sanders, J.F., Hepkema, B.G., Lambeck, A.J.A., Bungener, L.B., Roozendaal, C., Tilanus, M.G., Voorter, C.E.M., Wieten, L., Duijnhoven, E.M. van, Gelens, M., Christiaans, M.H., Ittersum, F.J. van, Nurmohamed, S.A., Lardy, N.M., Swelsen, W., Pant, K.A. van der, Weerd, N.C. van der, Berge, I.J. ten, Bemelman, F.J., Hoitsma, A.J., Boog, P.J. van der, Fijter, J.W. de, Betjes, M.G., Heidt, S., Roelen, D.L., Claas, F.H., Otten, H.G., Zuilen, A.D. van, Michielsen, L.A., Wisse, B.W., Kamburova, E.G., Verhaar, M.C., Joosten, I., Allebes, W.A., Meer, A. van der, Hilbrands, L.B., Baas, M.C., Spierings, E, Hack, C.E., Reekum, F.E. van, Bots, M.L., Drop, A., Plaisier, L., Seelen, M.A., Sanders, J.F., Hepkema, B.G., Lambeck, A.J.A., Bungener, L.B., Roozendaal, C., Tilanus, M.G., Voorter, C.E.M., Wieten, L., Duijnhoven, E.M. van, Gelens, M., Christiaans, M.H., Ittersum, F.J. van, Nurmohamed, S.A., Lardy, N.M., Swelsen, W., Pant, K.A. van der, Weerd, N.C. van der, Berge, I.J. ten, Bemelman, F.J., Hoitsma, A.J., Boog, P.J. van der, Fijter, J.W. de, Betjes, M.G., Heidt, S., Roelen, D.L., Claas, F.H., Otten, H.G., and Zuilen, A.D. van

Abstract

Item does not contain fulltext, BACKGROUND: Pre-transplant donor-specific anti-human leucocyte antigen (HLA) antibodies (DSAs) are associated with impaired kidney graft survival while the clinical relevance of non-donor-specific anti-HLA antibodies (nDSAs) is more controversial. The aim of the present paired kidney graft study was to compare the clinical relevance of DSAs and nDSAs. METHODS: To eliminate donor and era-dependent factors, a post hoc paired kidney graft analysis was performed as part of a Dutch multicentre study evaluating all transplantations between 1995 and 2005 with available pre-transplant serum samples. Anti-HLA antibodies were detected with a Luminex single-antigen bead assay. RESULTS: Among 3237 deceased donor transplantations, we identified 115 recipient pairs receiving a kidney from the same donor with one recipient being DSA positive and the other without anti-HLA antibodies. Patients with pre-transplant DSAs had a significantly lower 10-year death-censored graft survival (55% versus 82%, P=0.0001). We identified 192 pairs with one recipient as nDSA positive (against Class I and/or II) and the other without anti-HLA antibodies. For the patients with nDSAs against either Class I or II, graft survival did not significantly differ compared with patients without anti-HLA antibodies (74% versus 77%, P = 0.79). Only in patients with both nDSAs Class I and II was there a trend towards a lower graft survival (58%, P = 0.06). Lastly, in a small group of 42 recipient pairs, 10-year graft survival in recipients with DSAs was 49% compared with 68% in recipients with nDSAs (P=0.11). CONCLUSION: This paired kidney analysis confirms that the presence of pre-transplant DSAs in deceased donor transplantations is a risk marker for graft loss, whereas nDSAs in general are not associated with a lower graft survival. Subgroup analysis indicated that only in broadly sensitized patients with nDSAs against Class I and II, nDSAs may be a risk marker for graft loss in the long term.

Published
2019

5. Antibodies against ARHGDIB are associated with long-term kidney graft loss

Author

Kamburova, E.G., Gruijters, M.L., Kardol-Hoefnagel, T., Wisse, B.W., Joosten, I., Allebes, W.A., Meer, A. van der, Hilbrands, L.B., Baas, M.C., Spierings, E., Hack, C.E., Reekum, F.E. van, Zuilen, A.D. van, Verhaar, M.C., Bots, M.L., Drop, A., Plaisier, L., Melchers, R.C., Seelen, M.A., Sanders, J.S., Hepkema, B.G., Lambeck, A.J.A., Bungener, L.B., Roozendaal, C., Tilanus, M.G., Voorter, C.E.M., Wieten, L., Duijnhoven, E.M. van, Gelens, M., Christiaans, M.H., Ittersum, F.J. van, Nurmohamed, S.A., Lardy, N.M., Swelsen, W., Pant, K. van der, Weerd, N.C. van der, Berge, I.J. Ten, Hoitsma, A., Boog, P.J. van der, Fijter, J.W. de, Betjes, M.G., Heidt, S., Roelen, D.L., Claas, F.H., Bemelman, F.J., Otten, H.G., Kamburova, E.G., Gruijters, M.L., Kardol-Hoefnagel, T., Wisse, B.W., Joosten, I., Allebes, W.A., Meer, A. van der, Hilbrands, L.B., Baas, M.C., Spierings, E., Hack, C.E., Reekum, F.E. van, Zuilen, A.D. van, Verhaar, M.C., Bots, M.L., Drop, A., Plaisier, L., Melchers, R.C., Seelen, M.A., Sanders, J.S., Hepkema, B.G., Lambeck, A.J.A., Bungener, L.B., Roozendaal, C., Tilanus, M.G., Voorter, C.E.M., Wieten, L., Duijnhoven, E.M. van, Gelens, M., Christiaans, M.H., Ittersum, F.J. van, Nurmohamed, S.A., Lardy, N.M., Swelsen, W., Pant, K. van der, Weerd, N.C. van der, Berge, I.J. Ten, Hoitsma, A., Boog, P.J. van der, Fijter, J.W. de, Betjes, M.G., Heidt, S., Roelen, D.L., Claas, F.H., Bemelman, F.J., and Otten, H.G.

Abstract

Contains fulltext : 215571.pdf (publisher's version ) (Open Access), The clinical significance of non-HLA antibodies on renal allograft survival is a matter of debate, due to differences in reported results and lack of large-scale studies incorporating analysis of multiple non-HLA antibodies simultaneously. We developed a multiplex non-HLA antibody assay against 14 proteins highly expressed in the kidney. In this study, the presence of pretransplant non-HLA antibodies was correlated to renal allograft survival in a nationwide cohort of 4770 recipients transplanted between 1995 and 2006. Autoantibodies against Rho GDP-dissociation inhibitor 2 (ARHGDIB) were significantly associated with graft loss in recipients transplanted with a deceased-donor kidney (N = 3276) but not in recipients of a living-donor kidney (N = 1496). At 10 years after deceased-donor transplantation, recipients with anti-ARHGDIB antibodies (94/3276 = 2.9%) had a 13% lower death-censored covariate-adjusted graft survival compared to the anti-ARHGDIB-negative (3182/3276 = 97.1%) population (hazard ratio 1.82; 95% confidence interval, 1.32-2.53; P = .0003). These antibodies occur independently from donor-specific anti-HLA antibodies (DSA) or other non-HLA antibodies investigated. No significant relations with graft loss were found for the other 13 non-HLA antibodies. We suggest that pretransplant risk assessment can be improved by measuring anti-ARHGDIB antibodies in all patients awaiting deceased-donor transplantation.

Published
2019

6. Allocation to highly sensitized patients based on acceptable mismatches results in low rejection rates comparable to nonsensitized patients

Author

Heidt, P.J. (Peter), Haasnoot, G.W. (Geert), Witvliet, M.D. (Marian), van der Linden-van Oevelen, M.J.H. (Marissa J. H.), Kamburova, E.G., Wisse, B.W., Joosten, I. (Irma), Allebes, W.A. (Wil), van der Meer, A., Hilbrands, L.B. (Luuk), Baas, M.C. (Marije), Spierings, E. (E.), Hack, C.E. (Erik), van Reekum, F., van Zuilen, A.D. (Arjan D.), Verhaar, M.C. (Marianne), Bots, M.L. (Michiel), Drop, A.C.A.D., Plaisier, L., Seelen, M.A.J., Sanders, J.S.F., Hepkema, B.G. (Bouke), Lambeck, A.J.A. (Annechien J.A.), Bungener, L.B., Roozendaal, C., Tilanus, M.G.J. (Marcel), Voorter, C.E.M. (C. E M), Wieten, L., van Duijnhoven, E., Gelens, M., Christiaans, M.H. (Maarten), van Ittersum, F., Nurmohamed, S.A. (Shaikh Azam), Lardy, N.M. (Neubury), Swelsen, W.T., van der Pant, K.A., Weerd, N.C. (Neelke) van der, Berge, I.J.M. (Ineke) ten, Bemelman, F.J. (Fréderike), Hoitsma, A.J. (Andries), van der Boog, P.J.M., Fijter, J.W. (Johan) de, Betjes, M.G.H. (Michiel), Otten, H.G. (Henderikus), Roelen, D.L. (Dave), Claas, F.H.J. (Frans), Heidt, P.J. (Peter), Haasnoot, G.W. (Geert), Witvliet, M.D. (Marian), van der Linden-van Oevelen, M.J.H. (Marissa J. H.), Kamburova, E.G., Wisse, B.W., Joosten, I. (Irma), Allebes, W.A. (Wil), van der Meer, A., Hilbrands, L.B. (Luuk), Baas, M.C. (Marije), Spierings, E. (E.), Hack, C.E. (Erik), van Reekum, F., van Zuilen, A.D. (Arjan D.), Verhaar, M.C. (Marianne), Bots, M.L. (Michiel), Drop, A.C.A.D., Plaisier, L., Seelen, M.A.J., Sanders, J.S.F., Hepkema, B.G. (Bouke), Lambeck, A.J.A. (Annechien J.A.), Bungener, L.B., Roozendaal, C., Tilanus, M.G.J. (Marcel), Voorter, C.E.M. (C. E M), Wieten, L., van Duijnhoven, E., Gelens, M., Christiaans, M.H. (Maarten), van Ittersum, F., Nurmohamed, S.A. (Shaikh Azam), Lardy, N.M. (Neubury), Swelsen, W.T., van der Pant, K.A., Weerd, N.C. (Neelke) van der, Berge, I.J.M. (Ineke) ten, Bemelman, F.J. (Fréderike), Hoitsma, A.J. (Andries), van der Boog, P.J.M., Fijter, J.W. (Johan) de, Betjes, M.G.H. (Michiel), Otten, H.G. (Henderikus), Roelen, D.L. (Dave), and Claas, F.H.J. (Frans)

Abstract

Whereas regular allocation avoids unacceptable mismatches on the donor organ, allocation to highly sensitized patients within the Eurotransplant Acceptable Mismatch (AM) program is based on the patient's HLA phenotype plus acceptable antigens. These are HLA antigens to which the patient never made antibodies, as determined by extensive laboratory testing. AM patients have superior long-term graft survival compared with highly sensitized patients in regular allocation. Here, we questioned whether the AM program also results in lower rejection rates. From the PROCARE cohort, consisting of all Dutch kidney transplants in 1995-2005, we selected deceased donor single transplants with a minimum of 1 HLA mismatch and determined the cumulative 6-month rejection incidence for patients in AM or regular allocation. Additionally, we determined the effect of minimal matching criteria of 1 HLA-B plus 1 HLA-DR, or 2 HLA-DR antigens on rejection incidence. AM patients showed significantly lower rejection rates than highly immunized patients in regular allocation, comparable to nonsensitized patients, independent of other risk factors for rejection. In contrast to highly sensitized patients in regular allocation, minimal matching criteria did not affect rejection rates in AM patients. Allocation based on acceptable antigens leads to relatively low-risk transplants for highly sensitized patients with rejection rates similar to those of nonimmunized individuals.

Published
2019
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9. Differential effects of donor-specific HLA antibodies in living versus deceased donor transplant

Author

Kamburova, E.G., Wisse, B.W., Joosten, I. (Irma), Allebes, W.A. (Wil), van der Meer, A., Hilbrands, L.B. (Luuk), Baas, M.C. (Marije), Spierings, E. (E.), Hack, C.E. (Erik), van Reekum, F., van Zuilen, A.D. (A. D.), Verhaar, M.C. (Marianne), Bots, M.L. (M. L.), Drop, A.C.A.D., Plaisier, L., Seelen, M.A.J., Sanders, J.S.F., Hepkema, B.G. (Bouke), Lambeck, A.J.A. (Annechien J.A.), Bungener, L.B., Roozendaal, C., Tilanus, M.G.J. (Marcel), Voorter, C.E.M. (C. E M), Wieten, L., van Duijnhoven, E., Gelens, M., Christiaans, M.H. (Maarten), van Ittersum, F., Nurmohamed, S.A. (Shaikh Azam), Lardy, N.M. (Neubury), Swelsen, W.T., van der Pant, K.A., Weerd, N.C. (Neelke) van der, Berge, I.J.M. (Ineke) ten, Bemelman, F.J. (Fréderike), Hoitsma, A.J. (Andries), van der Boog, P.J.M., Fijter, J.W. (Johan) de, Betjes, M.G.H. (Michiel), Heidt, P.J. (Peter), Roelen, D.L. (Dave), Claas, F.H.J. (Frans), Otten, H.G. (Henderikus), Kamburova, E.G., Wisse, B.W., Joosten, I. (Irma), Allebes, W.A. (Wil), van der Meer, A., Hilbrands, L.B. (Luuk), Baas, M.C. (Marije), Spierings, E. (E.), Hack, C.E. (Erik), van Reekum, F., van Zuilen, A.D. (A. D.), Verhaar, M.C. (Marianne), Bots, M.L. (M. L.), Drop, A.C.A.D., Plaisier, L., Seelen, M.A.J., Sanders, J.S.F., Hepkema, B.G. (Bouke), Lambeck, A.J.A. (Annechien J.A.), Bungener, L.B., Roozendaal, C., Tilanus, M.G.J. (Marcel), Voorter, C.E.M. (C. E M), Wieten, L., van Duijnhoven, E., Gelens, M., Christiaans, M.H. (Maarten), van Ittersum, F., Nurmohamed, S.A. (Shaikh Azam), Lardy, N.M. (Neubury), Swelsen, W.T., van der Pant, K.A., Weerd, N.C. (Neelke) van der, Berge, I.J.M. (Ineke) ten, Bemelman, F.J. (Fréderike), Hoitsma, A.J. (Andries), van der Boog, P.J.M., Fijter, J.W. (Johan) de, Betjes, M.G.H. (Michiel), Heidt, P.J. (Peter), Roelen, D.L. (Dave), Claas, F.H.J. (Frans), and Otten, H.G. (Henderikus)

Abstract

The presence of donor-specific anti-HLA antibodies (DSAs) is associated with increased risk of graft failure after kidney transplant. We hypothesized that DSAs against HLA class I, class II, or both classes indicate a different risk for graft loss between deceased and living donor transplant. In this study, we investigated the impact of pretransplant DSAs, by using single antigen bead assays, on long-term graft survival in 3237 deceased and 1487 living donor kidney transplants with a negative complement-dependent crossmatch. In living donor transplants, we found a limited effect on graft survival of DSAs against class I or II antigens after transplant. Class I and II DSAs combined resulted in decreased 10-year graft survival (84% to 75%). In contrast, after deceased donor transplant, patients with class I or class II DSAs had a 10-year graft survival of 59% and 60%, respectively, both significantly lower than the survival for patients without DSAs (76%). The combination of class I and II DSAs resulted in a 10-year survival of 54% in deceased donor transplants. In conclusion, class I and II DSAs are a clear risk factor for graft loss in deceased donor transplants, while in living donor transplants, class I and II DSAs seem to be associated with an increased risk for graft failure, but this could not be assessed due to their low prevalence.

Published
2018
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10. PIRCHE-II is related to graft failure after kidney transplantation

Author

Geneugelijk, K. (Kirsten), Niemann, M. (Matthias), Drylewicz, J. (Julia), van Zuilen, A.D. (Arjan D.), Joosten, I. (Irma), Allebes, W.A. (Wil), van der Meer, A., Hilbrands, L.B. (Luuk), Baas, M.C. (Marije), Hack, C.E. (Erik), van Reekum, F., Verhaar, M.C. (Marianne), Kamburova, E.G., Bots, M.L. (Michiel L.), Seelen, M.A.J., Sanders, J.S.F., Hepkema, B.G. (Bouke), Lambeck, A.J.A. (Annechien J.A.), Bungener, L.B., Roozendaal, C., Tilanus, M.G.J. (Marcel), Vanderlocht, J. (Joris), Voorter, C.E.M. (C. E M), Wieten, L., van Duijnhoven, E., Gelens, M., Christiaans, M.H. (Maarten), van Ittersum, F., Nurmohamed, A., Lardy, J.N.M. (Junior N.M.), Swelsen, W.T., van der Pant, K.A., Weerd, N.C. (Neelke) van der, Berge, I.J.M. (Ineke) ten, Bemelman, F.J. (Fréderike), Hoitsma, A.J. (Andries), van der Boog, P.J.M., Fijter, J.W. (Johan) de, Betjes, M.G.H. (Michiel), Heidt, P.J. (Peter), Roelen, D.L. (Dave), Claas, F.H.J. (Frans), Otten, H.G. (Henderikus), Spierings, E. (E.), Geneugelijk, K. (Kirsten), Niemann, M. (Matthias), Drylewicz, J. (Julia), van Zuilen, A.D. (Arjan D.), Joosten, I. (Irma), Allebes, W.A. (Wil), van der Meer, A., Hilbrands, L.B. (Luuk), Baas, M.C. (Marije), Hack, C.E. (Erik), van Reekum, F., Verhaar, M.C. (Marianne), Kamburova, E.G., Bots, M.L. (Michiel L.), Seelen, M.A.J., Sanders, J.S.F., Hepkema, B.G. (Bouke), Lambeck, A.J.A. (Annechien J.A.), Bungener, L.B., Roozendaal, C., Tilanus, M.G.J. (Marcel), Vanderlocht, J. (Joris), Voorter, C.E.M. (C. E M), Wieten, L., van Duijnhoven, E., Gelens, M., Christiaans, M.H. (Maarten), van Ittersum, F., Nurmohamed, A., Lardy, J.N.M. (Junior N.M.), Swelsen, W.T., van der Pant, K.A., Weerd, N.C. (Neelke) van der, Berge, I.J.M. (Ineke) ten, Bemelman, F.J. (Fréderike), Hoitsma, A.J. (Andries), van der Boog, P.J.M., Fijter, J.W. (Johan) de, Betjes, M.G.H. (Michiel), Heidt, P.J. (Peter), Roelen, D.L. (Dave), Claas, F.H.J. (Frans), Otten, H.G. (Henderikus), and Spierings, E. (E.)

Abstract

Individual HLA mismatches may differentially impact graft survival after kidney transplantation. Therefore, there is a need for a reliable tool to define permissible HLA mismatches in kidney transplantation. We previously demonstrated that donor-derived Predicted Indirectly ReCognizable HLA Epitopes presented by recipient HLA class II (PIRCHE-II) play a role in de novo donor-specific HLA antibodies formation after kidney transplantation. In the present Dutch multi-center study, we evaluated the possible association between PIRCHE-II and kidney graft failure in 2,918 donor-recipient couples that were transplanted between 1995 and 2005. For these donors-recipients couples, PIRCHE-II numbers were related to graft survival in univariate and multivariable analyses. Adjusted for confounders, the natural logarithm of PIRCHE-II was associated with a higher risk for graft failure [hazard ratio (HR): 1.13, 95% CI: 1.04-1.23, p = 0.003]. When analyzing a subgroup of patients who had their first transplantation, the HR of graft failure for ln(PIRCHE-II) was higher compared with the overall cohort (HR: 1.22, 95% CI: 1.10-1.34, p < 0.001). PIRCHE-II demonstrated both early and late effects on graft failure in this subgroup. These data suggest that the PIRCHE-II may impact graft survival after kidney transplantation. Inclusion of PIRCHE-II in donor-selection criteria may eventually lead to an improved kidney graft survival.

Published
2018
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11. Pretransplant C3d-Fixing Donor-Specific Anti-HLA Antibodies Are Not Associated with Increased Risk for Kidney Graft Failure

Author

Kamburova, E.G., Wisse, B.W., Joosten, I., Allebes, W.A., Meer, A. van der, Hilbrands, L.B., Baas, M.C., Spierings, E., Hack, C.E., Reekum, F.E. van, Zuilen, A.D. van, Verhaar, M.C., Bots, M.L., Drop, A.C., Plaisier, L., Seelen, M.A., Sanders, J.S., Hepkema, B.G., Lambeck, A.J.A., Bungener, L.B., Roozendaal, C., Tilanus, M.G., Voorter, C.E.M., Wieten, L., Duijnhoven, E.M. van, Gelens, M.A., Christiaans, M.H., Ittersum, F.J. van, Nurmohamed, S.A., Lardy, N.M., Swelsen, W., Pant, Karlijn A.M.I. van der, Weerd, N.C. van der, Berge, I.J. Ten, Bemelman, F.J., Hoitsma, A.J., Boog, P.J. van der, Fijter, J.W. de, Betjes, M.G., Heidt, S., Roelen, D.L., Claas, F.H., Otten, H.G., Kamburova, E.G., Wisse, B.W., Joosten, I., Allebes, W.A., Meer, A. van der, Hilbrands, L.B., Baas, M.C., Spierings, E., Hack, C.E., Reekum, F.E. van, Zuilen, A.D. van, Verhaar, M.C., Bots, M.L., Drop, A.C., Plaisier, L., Seelen, M.A., Sanders, J.S., Hepkema, B.G., Lambeck, A.J.A., Bungener, L.B., Roozendaal, C., Tilanus, M.G., Voorter, C.E.M., Wieten, L., Duijnhoven, E.M. van, Gelens, M.A., Christiaans, M.H., Ittersum, F.J. van, Nurmohamed, S.A., Lardy, N.M., Swelsen, W., Pant, Karlijn A.M.I. van der, Weerd, N.C. van der, Berge, I.J. Ten, Bemelman, F.J., Hoitsma, A.J., Boog, P.J. van der, Fijter, J.W. de, Betjes, M.G., Heidt, S., Roelen, D.L., Claas, F.H., and Otten, H.G.

Abstract

Item does not contain fulltext

Published
2018

12. PIRCHE-II: A NOVEL TOOL TO IDENTIFY PERMISSIBLE HLA MISMATCHES IN KIDNEY TRANSPLANTATION

Author

Geneugelijk, K., Niemann, M., Drylewicz, J., Zuilen, A.D. van, Joosten, I., Allebes, W.A., Meer, A. van der, Hilbrands, L.B., Baas, M.C., Hack, C.E., Reekum, F.E. van, Verhaar, M., Kamburova, E.G., Bots, M.L., Seelen, M.A.J., Sanders, J.S.F., Hepkema, B.G., Lambeck, A.J., Bungener, L.B., Roozendaal, C., Tilanus, M.G.J., Vanderlocht, J., Voorter, C.E.M., Wieten, L., Duijnhoven, E.M. van, Gelens, M., Christiaans, M.H.L., Ittersum, F.J. van, Nurmohamed, A., Lardy, N.M., Swelsen, W., Pant, K.A. van der, Weerd, N.C. van der, Berge, I.J.M. ten, Bemelman, F.D.J., Hoitsma, A., Boog, P.J.M. van der, Fijter, J.W. de, Betjes, M.G.H., Heidt, S., Roelen, D.L., Claas, F.H.J., Otten, H.G., and Spierings, E.

Published
2017

13. DIFFERENTIAL EFFECT OF DONOR-SPECIFIC HLA ANTIBODIES IN LIVING VERSUS DECEASED DONOR KIDNEY TRANSPLANTATION

Author

Kamburova, E.G., Wisse, B.W., Joosten, I., Allebes, W.A., Meer, A. van der, Hilbrands, L.B., Baas, M.C., Spierings, E., Hack, C.E., Reekum, F. van, Zuilen, A. van, Verhaar, M.C., Bots, M.L., Drop, A.C.A.D., Plaisier, L., Seelen, M.A.J., Sanders, J.S.F., Hepkema, B.G., Lambeck, A.J., Bungener, L.B., Roozendaal, C., Tilanus, M.G.J., Voorter, C.E.M., Wieten, L., Duijnhoven, E.M. van, Gelens, M., Christiaans, M.H.L., Ittersum, F.J. van, Nurmohamed, A., Lardy, N.M., Swelsen, W., Pant, K.A. van der, Weerd, N.C. van der, Berge, I.J.M. ten, Bemelman, F.J., Hoitsma, A., Boog, P.J.M. van der, Fijter, H. de, Betjes, M.G.H., Heidt, S., Roelen, D.L., Claas, F.H.J., and Otten, H.G.

Published
2017

14. The increase of the global donor inventory is of limited benefit to patients of non-Northwestern European descent

Author

Walraven, S.M. van, Brand, A., Bakker, J.N., Heemskerk, M.B., Nillesen, S., Bierings, M.B., Bungener, L.B., Hepkema, B.G., Lankester, A., Meer, A. van der, Sintnicolaas, K., Somers, J.A., Spierings, E., Tilanus, M.G., Voorter, C.E.M., Cornelissen, J.J., Oudshoorn, M., Walraven, S.M. van, Brand, A., Bakker, J.N., Heemskerk, M.B., Nillesen, S., Bierings, M.B., Bungener, L.B., Hepkema, B.G., Lankester, A., Meer, A. van der, Sintnicolaas, K., Somers, J.A., Spierings, E., Tilanus, M.G., Voorter, C.E.M., Cornelissen, J.J., and Oudshoorn, M.

Abstract

Contains fulltext : 170602.pdf (publisher's version ) (Open Access), Between 2001 and 2012, the number of unrelated donors registered worldwide increased from 7 to 21 million, and the number of public cord blood units increased to over 500,000. We addressed the question of whether this expansion resulted in higher percentages of patients reaching transplantation. Unrelated donor searches were evaluated for 3,124 eligible patients in the Netherlands in two cohorts (2001-2006, n=995; 2007-2012, n=2129), comparing results for patients of Northwestern European and non-Northwestern European origin. Endpoints were 'donor found' and 'transplantation reached'. The substantial growth of the donor inventory over the period studied did not increase the median number of potential unrelated donors (n=7) for non-Northwestern European patients, but almost doubled the number for Northwestern European patients from 42 to 71. Before and after 2007, an unrelated donor or cord blood was identified for 91% and 95%, respectively, of Northwestern European patients and for 65% and 82% of non-Northwestern European patients (P<0.0001). Non-Northwestern European patients more often needed a cord blood transplant. The degree of HLA matching was significantly lower for non-Northwestern European patients (P<0.0006). The time needed to identify a donor decreased for both populations. The percentage of Northwestern European patients reaching transplantation increased from 77% to 83% and for non-Northwestern European patients from 57% to 72% (P=0.0003). The increase of the global inventory resulted in more transplants for patients lacking a family donor, although the quality and quantity of (potential) haematopoietic cell grafts for patients of a non-Northwestern European descent remained inferior, indicating the need for adaptation of recruitment.

Published
2017

15. The increase of the global donor inventory is of limited benefit to patients of non-northwestern european descent

Author

Walraven, S.M. (S.) van, Brand, A. (Anneke), Bakker, J.N.A. (Jack N. A.), Heemskerk, M.B.A. (Martin), Nillesen, S. (Suzan), Bierings, M. (Marc), Bungener, L.B. (Laura B.), Hepkema, B.G. (Bouke), Lankester, A.C. (Arjan), van der Meer, A. (Arnold), Sintnicolaas, K. (Krijn), Somers, J.A.E. (J. A E), Spierings, E. (E.), Tilanus, M.G.J. (Marcel), Voorter, C.E.M. (Christien E. M.), Cornelissen, J.J. (Jan), Oudshoorn, M. (Machteld), Walraven, S.M. (S.) van, Brand, A. (Anneke), Bakker, J.N.A. (Jack N. A.), Heemskerk, M.B.A. (Martin), Nillesen, S. (Suzan), Bierings, M. (Marc), Bungener, L.B. (Laura B.), Hepkema, B.G. (Bouke), Lankester, A.C. (Arjan), van der Meer, A. (Arnold), Sintnicolaas, K. (Krijn), Somers, J.A.E. (J. A E), Spierings, E. (E.), Tilanus, M.G.J. (Marcel), Voorter, C.E.M. (Christien E. M.), Cornelissen, J.J. (Jan), and Oudshoorn, M. (Machteld)

Abstract

Between 2001 and 2012, the number of unrelated donors registered worldwide increased from 7 to 21 million, and the number of public cord blood units increased to over 500, 000. We addressed the question of whether this expansion resulted in higher percentages of patients reaching transplantation. Unrelated donor searches were evaluated for 3,124 eligible patients in the Netherlands in two cohorts (2001-2006, n=995; 2007-2012, n=2129), comparing results for patients of Northwestern European and non-Northwestern European origin. Endpoints were ‘donor found’ and ‘transplantation reached’. The substantial growth of the donor inventory over the period studied did not increase the median number of potential unrelated donors (n=7) for non-Northwestern European patients, but almost doubled the number for Northwestern European patients from 42 to 71. Before and after 2007, an unrelated donor or cord blood was identified for 91% and 95%, respectively, of Northwestern European patients and for 65% and 82% of non-Northwestern European patients (P<0.0001). Non-Northwestern European patients more often needed a cord blood transplant. The degree of HLA matching was significantly lower for non-Northwestern European patients (P<0.0006). The time needed to identify a donor decreased for both populations. The percentage of Northwestern European patients reaching transplantation increased from 77% to 83% and for non-Northwestern European patients from 57% to 72% (P=0.0003). The increase of the global inventory resulted in more transplants for patients lacking a family donor, although the quality and quantity of (potential) haematopoietic cell grafts for patients of a non-Northwestern European descent remained inferior, indicating the need for adaptation of recruitment.

Published
2017
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16. How can we reduce costs of solid-phase multiplex-bead assays used to determine anti-HLA antibodies?

Author

Kamburova, E.G., Wisse, B.W., Joosten, I., Allebes, W.A., Meer, A. van der, Hilbrands, L.B., Baas, M.C., Spierings, E., Hack, C.E., Reekum, F.E. van, Zuilen, A.D. van, Verhaar, M., Bots, M.L., Drop, A.C., Plaisier, L., Seelen, M.A., Sanders, J.S., Hepkema, B.G., Lambeck, A.J.A., Bungener, L.B., Roozendaal, C., Tilanus, M.G., Vanderlocht, J., Voorter, C.E.M., Wieten, L., Duijnhoven, E.M. van, Gelens, M., Christiaans, M.H., Ittersum, F.J. van, Nurmohamed, A., Lardy, N.M., Swelsen, W., Pant, K.A. van der, Weerd, N.C. van der, Berge, I.J. Ten, Bemelman, F.J., Hoitsma, A., Boog, P.J. van der, Fijter, J.W. de, Betjes, M.G., Heidt, S., Roelen, D.L., Claas, F.H., Otten, H.G., Kamburova, E.G., Wisse, B.W., Joosten, I., Allebes, W.A., Meer, A. van der, Hilbrands, L.B., Baas, M.C., Spierings, E., Hack, C.E., Reekum, F.E. van, Zuilen, A.D. van, Verhaar, M., Bots, M.L., Drop, A.C., Plaisier, L., Seelen, M.A., Sanders, J.S., Hepkema, B.G., Lambeck, A.J.A., Bungener, L.B., Roozendaal, C., Tilanus, M.G., Vanderlocht, J., Voorter, C.E.M., Wieten, L., Duijnhoven, E.M. van, Gelens, M., Christiaans, M.H., Ittersum, F.J. van, Nurmohamed, A., Lardy, N.M., Swelsen, W., Pant, K.A. van der, Weerd, N.C. van der, Berge, I.J. Ten, Bemelman, F.J., Hoitsma, A., Boog, P.J. van der, Fijter, J.W. de, Betjes, M.G., Heidt, S., Roelen, D.L., Claas, F.H., and Otten, H.G.

Abstract

Item does not contain fulltext, Solid-phase multiplex-bead assays are widely used in transplantation to detect anti-human leukocyte antigen (HLA) antibodies. These assays enable high resolution detection of low levels of HLA antibodies. However, multiplex-bead assays are costly and yield variable measurements that limit the comparison of results between laboratories. In the context of a Dutch national Consortium study we aimed to determine the inter-assay and inter-machine variability of multiplex-bead assays, and we assessed how to reduce the assay reagents costs. Fifteen sera containing a variety of HLA antibodies were used yielding in total 7092 median fluorescence intensities (MFI) values. The inter-assay and inter-machine mean absolute relative differences (MARD) of the screening assay were 12% and 13%, respectively. The single antigen bead (SAB) inter-assay MARD was comparable, but showed a higher lot-to-lot variability. Reduction of screening assay reagents to 50% or 40% of manufacturers' recommendations resulted in MFI values comparable to 100% of the reagents, with an MARD of 12% or 14%, respectively. The MARD of the 50% and 40% SAB assay reagent reductions were 11% and 22%, respectively. From this study, we conclude that the reagents can be reliably reduced at least to 50% of manufacturers' recommendations with virtually no differences in HLA antibody assignments.

Published
2016

17. RNA and protein expression of HLA-A∗23:19Q

Author

Gerritsen, K.E.H., primary, Voorter, C.E.M., additional, Joannes, M.O.R.F., additional, Senden-Gijsbers, B.L.M.G., additional, Agis, F., additional, Wieten, L., additional, and Tilanus, M.G.J., additional

Published
2015
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18. The PROCARE consortium: Toward an improved allocation strategy for kidney allografts

Author

Otten, H.G., Joosten, I., Allebes, W.A., Meer, A. van der, Hilbrands, L.B., Baas, M., Spierings, E., Hack, C.E., Reekum, F. van, Zuilen, A.D. van, Verhaar, M.C., Bots, M.L., Seelen, M.A., Sanders, J.S., Hepkema, B.G., Lambeck, A.J.A., Bungener, L.B., Roozendaal, C., Tilanus, M.G.J., Vanderlocht, J., Voorter, C.E.M., Wieten, L., Duijnhoven, E. van, Gelens, M., Christiaans, M., Ittersum, F. van, Nurmohamed, A., Lardy, N.M., Swelsen, W.T., Donselaar-van Pant, K.A., Weerd, N.C. van der, Berge, I.J. Ten, Bemelman, F.J., Hoitsma, A.J., Fijter, J.W. de, Betjes, M.G., Roelen, D.L., Claas, F.H., Otten, H.G., Joosten, I., Allebes, W.A., Meer, A. van der, Hilbrands, L.B., Baas, M., Spierings, E., Hack, C.E., Reekum, F. van, Zuilen, A.D. van, Verhaar, M.C., Bots, M.L., Seelen, M.A., Sanders, J.S., Hepkema, B.G., Lambeck, A.J.A., Bungener, L.B., Roozendaal, C., Tilanus, M.G.J., Vanderlocht, J., Voorter, C.E.M., Wieten, L., Duijnhoven, E. van, Gelens, M., Christiaans, M., Ittersum, F. van, Nurmohamed, A., Lardy, N.M., Swelsen, W.T., Donselaar-van Pant, K.A., Weerd, N.C. van der, Berge, I.J. Ten, Bemelman, F.J., Hoitsma, A.J., Fijter, J.W. de, Betjes, M.G., Roelen, D.L., and Claas, F.H.

Abstract

Item does not contain fulltext, Kidney transplantation is the best treatment option for patients with end-stage renal failure. At present, approximately 800 Dutch patients are registered on the active waiting list of Eurotransplant. The waiting time in the Netherlands for a kidney from a deceased donor is on average between 3 and 4years. During this period, patients are fully dependent on dialysis, which replaces only partly the renal function, whereas the quality of life is limited. Mortality among patients on the waiting list is high. In order to increase the number of kidney donors, several initiatives have been undertaken by the Dutch Kidney Foundation including national calls for donor registration and providing information on organ donation and kidney transplantation. The aim of the national PROCARE consortium is to develop improved matching algorithms that will lead to a prolonged survival of transplanted donor kidneys and a reduced HLA immunization. The latter will positively affect the waiting time for a retransplantation. The present algorithm for allocation is among others based on matching for HLA antigens, which were originally defined by antibodies using serological typing techniques. However, several studies suggest that this algorithm needs adaptation and that other immune parameters which are currently not included may assist in improving graft survival rates. We will employ a multicenter-based evaluation on 5429 patients transplanted between 1995 and 2005 in the Netherlands. The association between key clinical endpoints and selected laboratory defined parameters will be examined, including Luminex-defined HLA antibody specificities, T and B cell epitopes recognized on the mismatched HLA antigens, non-HLA antibodies, and also polymorphisms in complement and Fc receptors functionally associated with effector functions of anti-graft antibodies. From these data, key parameters determining the success of kidney transplantation will be identified which will lead to the identification

Published
2014

20. Identification of three new DRB1 alleles, DRB1*0107,*0425 and*13012 and confirmation of DRB4*01033

Author

Voorter, C.E.M., Hepkema, B.G., Lems, S.P.M., van den Berg-Loonen, E.M, Rijksuniversiteit Groningen, and Faculteit Medische Wetenschappen/UMCG

Subjects
musculoskeletal diseases, new allele, T-CELL-RECEPTOR, HLA-DR, DRB1*0425, POLYMERASE CHAIN-REACTION, DRB1*0107, POLYMORPHISM, DRB4*01033, immune system diseases, DRB1*13012, HLA-DRB, LOCUS, sequence-based typing, HLA-DR4 DRA-ASTERISK-0101, DRB1-ASTERISK-0401, CRYSTAL-STRUCTURE, PEPTIDE, skin and connective tissue diseases, RESTRICTION
Abstract

The characterization of three novel DRB1 alleles is described, DRB1*0107, DRB1*0425 and DRB1*13012 as well as confirmation of DRB4*01033. Two alleles, DRB1*0107 and *0425, showed amino acid differences with previously identified HLA molecules. In DRB1*0107, the glutamine at position 10 was substituted by a glutamic acid. DRB1*0425 showed one amino acid difference with DRB1*0418 (I to F) at position 67, and five amino acid differences with DRB1*04011 at positions 67 (L to F), 70 (Q to D), 71 (K to R), 74 (A to L) and 86 (G to V). The alleles DRB1*13012 and DRB4*01033 had protein sequences identical to DRB1*13011 and DRB4*01031/01032, respectively. Nucleotide differences were present at position 306 for DRB1*13012 and at position 321 for DRB4*01033

Published
2003

21. Identification of a new HLA-B*40 variant, B*4035

Author

Voorter, C.E.M., Hepkema, B.G., Lems, S.P.M., van den Berg-Loonen, E.M, Rijksuniversiteit Groningen, and Faculteit Medische Wetenschappen/UMCG

Subjects
B*4035, HLA-B, new allele, RESOLUTION, INTRON-1, sequence-based typing, ALLELES, ANTIGENS
Abstract

In this report, the novel allele B*4035(1) is presented. The allele was identified in a Caucasian individual by sequence-based typing. B*4035 is identical to B*4002 in exon 2, but differs in exon 3 at position 463, where it has an A in stead of a C. This results in an amino acid change from arginine to serine at codon 131 of the mature protein. The haplotype carrying the B*4035 was A3 B*4035 Cw2 DR11 DQ3

Published
2003

26. Helper and cytotoxic T cell precursor frequencies are not predictive for development of acute graft-versus-host disease after partially T cell depleted HLA-identical sibling BMT

Author

Meer, A. van der, Allebes, W.A., Voorter, C.E.M., Berg-Loonen, E.M. van den, Schattenberg, A.V.M.B., Witte, T.J.M. de, Joosten, I., Meer, A. van der, Allebes, W.A., Voorter, C.E.M., Berg-Loonen, E.M. van den, Schattenberg, A.V.M.B., Witte, T.J.M. de, and Joosten, I.

Abstract

Item does not contain fulltext

Published
1998

48. There is more to HLA-C than exons 2 and 3: sequencing of exons 1, 4 and 5.

Author

Voorter, C.E.M.

Subjects
*EXONS (Genetics), *HLA histocompatibility antigens, *HISTOCOMPATIBILITY testing
Abstract

HLA-C was shown to be a highly polymorphic gene which can be accurately typed for by sequencing methodologies. Most HLA-C sequence-based typing protocols described so far are based on analysis of sequence data of exons 2 and 3. Nonetheless, exons 1, 4 and 5 also contain nucleotide substitutions which contribute to the polymorphisms of the HLA-C locus. Ten alleles contain polymorphic positions in exons 1, 4 and 5, Cw*0701/06, Cw*12021/2, Cw*15051/2, Cw*1701/02, and Cw*1801/02. Here we describe a reliable solid-phase sequence-based typing strategy for sequencing exons 1, 4 and 5, which is an extended protocol of our previous HLA-C study. A panel of 16 individuals, carrying 27 different Cw-alleles, was typed for exons 1, 4 and 5 to check the newly designed primers. No allelic dropout or preferential amplification was noticed in these individuals. The panel was also sequenced in order to check the known polymorphisms present in exons 1, 4 and 5. For exon 5 the sequences of the alleles Cw*0302, *0501 and *07011 did not correspond with the published data. In addition, exons 1, 4 and 5 were sequence-based typing typed in 28, 17 and 59 individuals, respectively. Two new alleles were detected which contain polymorphic positions outside exons 2 and 3, Cw*07012 and Cw*1703. The unknown sequence data of exons 1, 4 and 5 of the alleles Cw*02024, *0308, *1506 and *16041 were elucidated. The described high-resolution sequence-based typing protocol for sequencing exons 1, 4 and 5 will be a valuable tool to study the HLA-C locus for polymorphisms outside exons 2 and 3 and for identification of the presently known HLA-C alleles with polymorphic positions in these exons. [ABSTRACT FROM AUTHOR]

Published
1999

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