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Machteld Oudshoorn - One of the best experts on this subject based on the ideXlab platform.

  • LBOR03: ASSOCIATION BETWEEN CTL PRECURSOR FREQUENCY TO HLA-C MISMATCHES AND HLA-C Antigen CELL SURFACE EXPRESSION
    Human Immunology, 2015
    Co-Authors: Moshe Israeli, Dave L. Roelen, Mary Carrington, Effie W. Petersdorf, Frans H.j. Claas, Geert W. Haasnoot, Machteld Oudshoorn
    Abstract:

    Aim Previous studies showed the relevanCe of the CytotoxiC T Cell preCursor frequenCy assay (CTLp) for prediCtion of the outCome of HLA mismatChed hematopoietiC Cell transplantation (HCT). ReCently it has been shown that HLA-C Cell surfaCe expression is Correlated with virus speCifiC CytotoxiC T Cell responses and viremia Control in HIV patients. The aim of the Current study was to investigate the assoCiation between HLA-C Antigen expression and the CTLp frequenCy to the mismatChed HLA-C Antigen. Methods In total 115 reCipient–donor pairs, for whom a suCCessful CTLp assay was performed, were evaluated in this pilot study. All donor–reCipient pairs were matChed at 9/10 alleles with a single mismatCh at the HLA-C loCus. Antigen expression level of the mismatChed HLA-C allele for eaCh reCipient and donor was based on the MFI values as desCribed by Apps et al. (SCienCe, 2013). Results The Cell surfaCe expression of reCipient’s mismatChed C Antigen was signifiCantly lower among CTLp negative ( n  = 59) Compared to CTLp positive ( n  = 56) pairs (154 and 193 MFI units, respeCtively; p  = 0.0031). This differenCe was more pronounCed in donor–reCipient pairs that were mismatChed for residue-116 loCated in the groove of the HLA-C Antigen, suggesting the importanCe of peptide binding in the allo-reCognition. Furthermore, in the Case of low expression of the reCipient mismatChed HLA-C Antigen (MFI  n  = 26), while in CTLp positive Cases ( n  = 15) the median MFI of donor’s HLA-C Antigen was 193. ( P  = 0.0093). ConClusion We ConClude that the expression level of the donor and reCipient mismatChed HLA-C Antigens affeCt CTLp outCome. HLA-C Antigen expression levels in Combination with the CTLp assay may prove useful for the prediCtion of the CliniCal outCome of HLA-C mismatChed HCT.

  • AssoCiation between CTL PreCursor FrequenCy to HLA-C MismatChes and HLA-C Antigen Cell SurfaCe Expression
    Frontiers in immunology, 2014
    Co-Authors: Moshe Israeli, Dave L. Roelen, Mary Carrington, Effie W. Petersdorf, Frans H.j. Claas, Geert W. Haasnoot, Machteld Oudshoorn
    Abstract:

    Previous studies showed the relevanCe of the CytotoxiC T-Cell preCursor (CTLp) frequenCy assay for prediCtion of the outCome of HLA mismatChed hematopoietiC Cell transplantation (HCT). ReCently, it has been shown that HLA-C Cell surfaCe expression is Correlated with virus speCifiC CytotoxiC T-Cell responses and viremia Control in HIV patients. The aim of the Current study was to investigate the assoCiation between HLA-C Antigen expression and the CTLp frequenCy to the mismatChed HLA-C Antigen. In total 115 reCipient‐donor pairs, for whom a suCCessful CTLp assay was performed, were evaluated for this pilot study. All donor‐reCipient pairs were matChed at 9/10 alleles with a single mismatCh at the HLA-C loCus. Antigen expression level of the mismatChed HLA-C allele for eaCh reCipient and donor was based on the mean fluoresCenCe intensity (MFI) values as desCribed by Apps et al. (1). The Cell surfaCe expression of reCipient’s mismatChed HLA-C Antigen was signifiCantly lower among CTLp negative (nD 59) Compared to CTLp positive (nD 56) pairs (154 and 193 MFI units, respeCtively, pD 0.0031). This differenCe was more pronounCed in donor‐reCipient pairs that were mismatChed for amino-aCid residue-116 loCated in the groove of the HLA-C Antigen, suggesting that the importanCe of peptide binding in the allo-reCognition. Furthermore, in the partiCular Case of low expression of the reCipient mismatChed HLA-C Antigen (MFI< 115), CTLp reaCtivity depended on HLA-C expression level in the donor, the median MFI of donor’s mismatChed HLA-C Antigen was 114 in CTLp negative Cases (nD 26), while in CTLp positive Cases (nD 15) the median MFI of donor’s HLA-C Antigen was 193 (pD 0.0093). We ConClude that the expression level of the donor and reCipient mismatChed HLA-C Antigens affeCt CTLp outCome. HLA-C Antigen expression levels in Combination with the CTLp assay may prove useful for the prediCtion of the CliniCal outCome of HLA-C mismatChed HCT.

  • HLA-C Antigen mismatCh is assoCiated with worse outCome in unrelated donor peripheral blood stem Cell transplantation.
    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2010
    Co-Authors: Ann E. Woolfrey, Effie W. Petersdorf, Machteld Oudshoorn, John P. Klein, Michael Haagenson, Stephen R. Spellman, James Gajewski, Gregory A. Hale, John T. Horan, Minoo Battiwalla
    Abstract:

    The assoCiation between HLA matChing and outCome in unrelated-donor peripheral blood stem Cell (PBSC) transplantation has not yet been established. In the present study, a total of 1933 unrelated donor–reCipient pairs who underwent PBSC transplantation between 1999 and 2006 for aCute myelogenous leukemia, aCute lymphoblastiC leukemia, myelodysplastiC syndrome, or ChroniC myelogenous leukemia and reCeived high-resolution HLA typing for HLA-A, -B, -C, -DRB1, -DQA1, and -DQB1 were inCluded in the analysis. OutComes were Compared between HLA-matChed and HLA-mismatChed pairs, adjusting for patient and transplant CharaCteristiCs. MatChing for HLA-A, -B, -C, and -DRB1 alleles (8/8 matCh) was assoCiated with better survival at 1 year Compared with 7/8 HLA-matChed pairs (56% vs 47%). Using 8/8 HLA–matChed patients as the baseline (n = 1243), HLA-C Antigen mismatChes (n = 189) were statistiCally signifiCantly assoCiated with lower leukemia-free survival (relative risk [RR], 1.36; 95% ConfidenCe interval [CI], 1.13-1.64; P = .0010), and inCreased risk for mortality (RR, 1.41; 95% CI, 1.16-1.70; P = .0005), treatment-related mortality (RR, 1.61; 95% CI, 1.25-2.08; P = .0002), and grade III-IV graft-versus-host disease (RR, 1.98; 95% CI, 1.50-2.62; P

H T Kim - One of the best experts on this subject based on the ideXlab platform.

  • Antigen Level MatChing at HLA-C Improves Long-Term OutComes after Double UmbiliCal Cord Blood Transplantation
    Blood, 2015
    Co-Authors: Claudio G. Brunstein, C Cutler, Todd E. Defor, Thomas R. Spitzer, Nelli Bejanyan, Alfred L. Garfall, Michael R. Verneris, Yi-bin Chen, Erica D. Warlick, H T Kim
    Abstract:

    MatChing at HLA-C has been shown to influenCe outComes and has been inCorporated in seleCtion of unrelated adult donors. In Contrast, seleCtion of UCB grafts has historiCally Considered HLA-A and B at Antigen and DRB1 at allele level resolution. ReCent data in single, myeloablative pediatriC UCB transplantation demonstrated that Antigen level matChing at HLA-C was assoCiated with lower NRM and improved survival in patients reCeiving better HLA-matChed units. Whether or not these same prinCiples apply in the setting of double UCB (dUCB) transplantation has not been addressed. Thus, we retrospeCtively studied whether HLA-C matChing would influenCe outComes in 490 patients with hematologiCal malignanCies at two Centers undergoing myeloablative and reduCed intensity dUCB transplantation. We Considered the worst HLA-matChing of the 2 donor units with 316 (64%) patients reCeiving at least one 4/6 matChed unit and 144 (29%) one or two 5/6 units, and 30 (6%) reCeiving two 6/6 HLA-matChed units. Patients were sCored Considering the number of HLA-C Antigen matChes as 0-1 (23%), 2 (40%), 3 (18%), and 4 (19%), of 4 possible matChes. The median age was 47 yrs. (range, 2-72), 59% were male, 285 (58%) had aCute leukemia, 291 (59%) were CMV seropositive, 319 (66%) reCeived RIC regimen, and 400 (82%) had CsA/MMF immunosuppression. In the overall study population, we observed no signifiCant influenCe of HLA-C matChing on the risk of death, treatment failure, non-relapse death, relapse, GVHD and hematopoietiC reCovery. However, we reCognized an interaCtion between Conventional HLA-matChing at A, B, and DRB1 and number of matChes at HLA-C in the survival endpoints. Thus, we analyzed two groups based on Conventional HLA-matChing at A, B and DRB1: those reCeiving at least one 4/6 HLA-matChed unit (4/6 & 4-6/6; n=316) or those reCeiving ≥ 5-6/6 matChed unit (5/6 & 5-6/6; n=174). In the ≥5/6 UCB transplants, there was no signifiCant influenCe of HLA-C matChing on the risk of death, treatment failure, non-relapse death, and relapse. However, in 4/6 & 4-6/6 transplants, better matChing at HLA-C was assoCiated with lower risk of death, treatment failure, and non-relapse death (Table), but there remained no assoCiation with risk of relapse. These data Contrast with those reported with single UCB grafts and suggest that with 4/6 HLA-matChed UCB units, additional matChing at HLA-C reduCes treatment failure and improves survival, and should be inCluded in the matCh strategy. In better matChed (≥5/6) dUCB grafts further matChing at HLA-C offers no additional benefit. DisClosures Chen: Bayer: ConsultanCy, ResearCh Funding. Miller: Coronado: Speakers Bureau; BioSCienCes: Speakers Bureau; Celegene: Speakers Bureau. Antin: Gentium SpA/Jazz PharmaCeutiCals: Membership on an entity9s Board of DireCtors or advisory Committees.

  • HLA-C mismatCh is assoCiated with inferior survival after unrelated donor non-myeloablative hematopoietiC stem Cell transplantation
    Bone Marrow Transplantation, 2006
    Co-Authors: H T Kim, D Liney, E Milford, J Gribben, C Cutler, S J Lee, J H Antin, R J Soiffer, E P Alyea
    Abstract:

    HLA-C matChing is an important determinant of outCome after myeloablative unrelated donor (URD) hematopoietiC stem Cell transplantation. However, its importanCe in non-myeloablative stem Cell transplantation (NST) is not known. We report a retrospeCtive analysis of 111 patients who underwent URD NST, of whom 78 were 10/10 matChed at HLA-A, B, C, DRB1, DQB1 and 33 were mismatChed at one or more HLA-C Antigen/allele (24 HLA-C only; nine HLA-C+other loCus mismatCh). Patients were Conditioned with busulfan (0.8 mg/kg/day i.v. × 4 days) and fludarabine (30 mg/m^2/day i.v. × 4 days). Graft-versus-host disease prophylaxis inCluded CyClosporine/prednisone- or taCrolimus/mini-methotrexate-based regimens. HLA-C disparity did not impair engraftment. Median marrow donor Chimerisms were ⩾90% donor at day+30 and +100 in both groups. Overall survival at 2 years was 30% in HLA-C-mismatChed and 51% in 10/10-matChed patients ( P =0.008). In Cox regression, HLA-C mismatCh was an independent prediCtor of death (hazard ratio 1.85, P =0.04). Treatment-related mortality was higher in the HLA-C-mismatChed group: 48 versus 16% ( P =0.0001). Cumulative relapse inCidenCe was 35% in the HLA-C-mismatChed and 55% in the 10/10-matChed Cohort, P =0.09. HLA-C mismatCh is assoCiated with inferior survival after URD NST.

  • HLA-C MismatCh Is AssoCiated with Inferior OutCome after Unrelated Donor Non-Myeloablative HematopoietiC Stem Cell Transplantation.
    Blood, 2005
    Co-Authors: H T Kim, D Liney, J Gribben, C Cutler, S J Lee, J H Antin, Sarah Windawi, Edgar L. Milford, R J Soiffer
    Abstract:

    Donor-reCipient disparity at HLA-C is an important determinant of CliniCal outCome after myeloablative unrelated donor (URD) hematopoietiC stem Cell transplantation, but its importanCe in URD non-myeloablative stem Cell transplantation (NST) is less Clear. Methods: We performed a retrospeCtive analysis of 111 patients who underwent unrelated donor NST for hematologiC malignanCies from 2000–2004. Of these, 78 were 10/10 matChed at HLA-A, B, C, DRB1, DQB1, and 33 were mismatChed at one or more HLA-C Antigen/allele (21 single C, 3 double C, 9 single C + other HLA loCus mismatCh). A majority (78%) of the mismatChes at HLA-C were deteCtable at the Antigen level. Diseases inCluded AML (24), ALL (3), MDS (17), CML (10), CLL (23), NHL (22), and HD (12). All patients reCeived non-myeloablative Conditioning with intravenous busulfan (0.8mg/kg/d x 4 days) and fludarabine (30mg/m 2 /d x 4 days). Graft-versus-host disease (GVHD) prophylaxis inCluded CyClosporine plus prednisone or taCrolimus plus low-dose methotrexate based regimens. Stem Cell sourCe was primarily G-CSF mobilized PBSC. Results: Median time to neutrophil engraftment (ANC > 500/ul) among patients who nadired was 12 days (range 8–21 days) in both groups. Median unfraCtionated marrow donor Chimerism were ≥ 90% donor at day+30 and day +100 in both groups. There was one late graft failure in the C-mismatChed Cohort, and one early graft rejeCtion in the 10/10 matChed Cohort. HLA-C disparity was assoCiated with an inCreased risk for grade III-IV aCute GVHD (33% vs. 12%, p = 0.01) in univariate and multivariate logistiC regression analyses (odds ratio 3.6, p = 0.03). This finding remained signifiCant even when baseline differenCes in GVHD prophylaxis between the 2 Cohorts were taken into Consideration. Cumulative relapse inCidenCe was not statistiCally different: 35% in the C-mismatChed group, versus 55% in the 10/10 matChed Cohort, p = 0.09. There was a higher inCidenCe of treatment related mortality in the C-mismatChed group: 48% versus 16% ( p = 0.001). Overall survival at 2 years was 27% in C-mismatChed, vs. 47% in 10/10 matChed patients ( p = 0.009). In Cox regression model, HLA-C disparity was an independent faCtor for poor survival (hazard ratio 1.85, p = 0.04). ConClusions: Donor reCipient disparity at HLA-C does not influenCe engraftment or donor Chimerism after URD NST, but is assoCiated with inCreased aCute GVHD and inferior survival. HLA-C is an important transplantation Antigen and should be Considered in the seleCtion of unrelated donors for NST.

E P Alyea - One of the best experts on this subject based on the ideXlab platform.

  • HLA-C mismatCh is assoCiated with inferior survival after unrelated donor non-myeloablative hematopoietiC stem Cell transplantation
    Bone Marrow Transplantation, 2006
    Co-Authors: H T Kim, D Liney, E Milford, J Gribben, C Cutler, S J Lee, J H Antin, R J Soiffer, E P Alyea
    Abstract:

    HLA-C matChing is an important determinant of outCome after myeloablative unrelated donor (URD) hematopoietiC stem Cell transplantation. However, its importanCe in non-myeloablative stem Cell transplantation (NST) is not known. We report a retrospeCtive analysis of 111 patients who underwent URD NST, of whom 78 were 10/10 matChed at HLA-A, B, C, DRB1, DQB1 and 33 were mismatChed at one or more HLA-C Antigen/allele (24 HLA-C only; nine HLA-C+other loCus mismatCh). Patients were Conditioned with busulfan (0.8 mg/kg/day i.v. × 4 days) and fludarabine (30 mg/m^2/day i.v. × 4 days). Graft-versus-host disease prophylaxis inCluded CyClosporine/prednisone- or taCrolimus/mini-methotrexate-based regimens. HLA-C disparity did not impair engraftment. Median marrow donor Chimerisms were ⩾90% donor at day+30 and +100 in both groups. Overall survival at 2 years was 30% in HLA-C-mismatChed and 51% in 10/10-matChed patients ( P =0.008). In Cox regression, HLA-C mismatCh was an independent prediCtor of death (hazard ratio 1.85, P =0.04). Treatment-related mortality was higher in the HLA-C-mismatChed group: 48 versus 16% ( P =0.0001). Cumulative relapse inCidenCe was 35% in the HLA-C-mismatChed and 55% in the 10/10-matChed Cohort, P =0.09. HLA-C mismatCh is assoCiated with inferior survival after URD NST.

Effie W. Petersdorf - One of the best experts on this subject based on the ideXlab platform.

  • LBOR03: ASSOCIATION BETWEEN CTL PRECURSOR FREQUENCY TO HLA-C MISMATCHES AND HLA-C Antigen CELL SURFACE EXPRESSION
    Human Immunology, 2015
    Co-Authors: Moshe Israeli, Dave L. Roelen, Mary Carrington, Effie W. Petersdorf, Frans H.j. Claas, Geert W. Haasnoot, Machteld Oudshoorn
    Abstract:

    Aim Previous studies showed the relevanCe of the CytotoxiC T Cell preCursor frequenCy assay (CTLp) for prediCtion of the outCome of HLA mismatChed hematopoietiC Cell transplantation (HCT). ReCently it has been shown that HLA-C Cell surfaCe expression is Correlated with virus speCifiC CytotoxiC T Cell responses and viremia Control in HIV patients. The aim of the Current study was to investigate the assoCiation between HLA-C Antigen expression and the CTLp frequenCy to the mismatChed HLA-C Antigen. Methods In total 115 reCipient–donor pairs, for whom a suCCessful CTLp assay was performed, were evaluated in this pilot study. All donor–reCipient pairs were matChed at 9/10 alleles with a single mismatCh at the HLA-C loCus. Antigen expression level of the mismatChed HLA-C allele for eaCh reCipient and donor was based on the MFI values as desCribed by Apps et al. (SCienCe, 2013). Results The Cell surfaCe expression of reCipient’s mismatChed C Antigen was signifiCantly lower among CTLp negative ( n  = 59) Compared to CTLp positive ( n  = 56) pairs (154 and 193 MFI units, respeCtively; p  = 0.0031). This differenCe was more pronounCed in donor–reCipient pairs that were mismatChed for residue-116 loCated in the groove of the HLA-C Antigen, suggesting the importanCe of peptide binding in the allo-reCognition. Furthermore, in the Case of low expression of the reCipient mismatChed HLA-C Antigen (MFI  n  = 26), while in CTLp positive Cases ( n  = 15) the median MFI of donor’s HLA-C Antigen was 193. ( P  = 0.0093). ConClusion We ConClude that the expression level of the donor and reCipient mismatChed HLA-C Antigens affeCt CTLp outCome. HLA-C Antigen expression levels in Combination with the CTLp assay may prove useful for the prediCtion of the CliniCal outCome of HLA-C mismatChed HCT.

  • AssoCiation between CTL PreCursor FrequenCy to HLA-C MismatChes and HLA-C Antigen Cell SurfaCe Expression
    Frontiers in immunology, 2014
    Co-Authors: Moshe Israeli, Dave L. Roelen, Mary Carrington, Effie W. Petersdorf, Frans H.j. Claas, Geert W. Haasnoot, Machteld Oudshoorn
    Abstract:

    Previous studies showed the relevanCe of the CytotoxiC T-Cell preCursor (CTLp) frequenCy assay for prediCtion of the outCome of HLA mismatChed hematopoietiC Cell transplantation (HCT). ReCently, it has been shown that HLA-C Cell surfaCe expression is Correlated with virus speCifiC CytotoxiC T-Cell responses and viremia Control in HIV patients. The aim of the Current study was to investigate the assoCiation between HLA-C Antigen expression and the CTLp frequenCy to the mismatChed HLA-C Antigen. In total 115 reCipient‐donor pairs, for whom a suCCessful CTLp assay was performed, were evaluated for this pilot study. All donor‐reCipient pairs were matChed at 9/10 alleles with a single mismatCh at the HLA-C loCus. Antigen expression level of the mismatChed HLA-C allele for eaCh reCipient and donor was based on the mean fluoresCenCe intensity (MFI) values as desCribed by Apps et al. (1). The Cell surfaCe expression of reCipient’s mismatChed HLA-C Antigen was signifiCantly lower among CTLp negative (nD 59) Compared to CTLp positive (nD 56) pairs (154 and 193 MFI units, respeCtively, pD 0.0031). This differenCe was more pronounCed in donor‐reCipient pairs that were mismatChed for amino-aCid residue-116 loCated in the groove of the HLA-C Antigen, suggesting that the importanCe of peptide binding in the allo-reCognition. Furthermore, in the partiCular Case of low expression of the reCipient mismatChed HLA-C Antigen (MFI< 115), CTLp reaCtivity depended on HLA-C expression level in the donor, the median MFI of donor’s mismatChed HLA-C Antigen was 114 in CTLp negative Cases (nD 26), while in CTLp positive Cases (nD 15) the median MFI of donor’s HLA-C Antigen was 193 (pD 0.0093). We ConClude that the expression level of the donor and reCipient mismatChed HLA-C Antigens affeCt CTLp outCome. HLA-C Antigen expression levels in Combination with the CTLp assay may prove useful for the prediCtion of the CliniCal outCome of HLA-C mismatChed HCT.

  • HLA-C Antigen mismatCh is assoCiated with worse outCome in unrelated donor peripheral blood stem Cell transplantation.
    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2010
    Co-Authors: Ann E. Woolfrey, Effie W. Petersdorf, Machteld Oudshoorn, John P. Klein, Michael Haagenson, Stephen R. Spellman, James Gajewski, Gregory A. Hale, John T. Horan, Minoo Battiwalla
    Abstract:

    The assoCiation between HLA matChing and outCome in unrelated-donor peripheral blood stem Cell (PBSC) transplantation has not yet been established. In the present study, a total of 1933 unrelated donor–reCipient pairs who underwent PBSC transplantation between 1999 and 2006 for aCute myelogenous leukemia, aCute lymphoblastiC leukemia, myelodysplastiC syndrome, or ChroniC myelogenous leukemia and reCeived high-resolution HLA typing for HLA-A, -B, -C, -DRB1, -DQA1, and -DQB1 were inCluded in the analysis. OutComes were Compared between HLA-matChed and HLA-mismatChed pairs, adjusting for patient and transplant CharaCteristiCs. MatChing for HLA-A, -B, -C, and -DRB1 alleles (8/8 matCh) was assoCiated with better survival at 1 year Compared with 7/8 HLA-matChed pairs (56% vs 47%). Using 8/8 HLA–matChed patients as the baseline (n = 1243), HLA-C Antigen mismatChes (n = 189) were statistiCally signifiCantly assoCiated with lower leukemia-free survival (relative risk [RR], 1.36; 95% ConfidenCe interval [CI], 1.13-1.64; P = .0010), and inCreased risk for mortality (RR, 1.41; 95% CI, 1.16-1.70; P = .0005), treatment-related mortality (RR, 1.61; 95% CI, 1.25-2.08; P = .0002), and grade III-IV graft-versus-host disease (RR, 1.98; 95% CI, 1.50-2.62; P

Frans H.j. Claas - One of the best experts on this subject based on the ideXlab platform.

  • LBOR03: ASSOCIATION BETWEEN CTL PRECURSOR FREQUENCY TO HLA-C MISMATCHES AND HLA-C Antigen CELL SURFACE EXPRESSION
    Human Immunology, 2015
    Co-Authors: Moshe Israeli, Dave L. Roelen, Mary Carrington, Effie W. Petersdorf, Frans H.j. Claas, Geert W. Haasnoot, Machteld Oudshoorn
    Abstract:

    Aim Previous studies showed the relevanCe of the CytotoxiC T Cell preCursor frequenCy assay (CTLp) for prediCtion of the outCome of HLA mismatChed hematopoietiC Cell transplantation (HCT). ReCently it has been shown that HLA-C Cell surfaCe expression is Correlated with virus speCifiC CytotoxiC T Cell responses and viremia Control in HIV patients. The aim of the Current study was to investigate the assoCiation between HLA-C Antigen expression and the CTLp frequenCy to the mismatChed HLA-C Antigen. Methods In total 115 reCipient–donor pairs, for whom a suCCessful CTLp assay was performed, were evaluated in this pilot study. All donor–reCipient pairs were matChed at 9/10 alleles with a single mismatCh at the HLA-C loCus. Antigen expression level of the mismatChed HLA-C allele for eaCh reCipient and donor was based on the MFI values as desCribed by Apps et al. (SCienCe, 2013). Results The Cell surfaCe expression of reCipient’s mismatChed C Antigen was signifiCantly lower among CTLp negative ( n  = 59) Compared to CTLp positive ( n  = 56) pairs (154 and 193 MFI units, respeCtively; p  = 0.0031). This differenCe was more pronounCed in donor–reCipient pairs that were mismatChed for residue-116 loCated in the groove of the HLA-C Antigen, suggesting the importanCe of peptide binding in the allo-reCognition. Furthermore, in the Case of low expression of the reCipient mismatChed HLA-C Antigen (MFI  n  = 26), while in CTLp positive Cases ( n  = 15) the median MFI of donor’s HLA-C Antigen was 193. ( P  = 0.0093). ConClusion We ConClude that the expression level of the donor and reCipient mismatChed HLA-C Antigens affeCt CTLp outCome. HLA-C Antigen expression levels in Combination with the CTLp assay may prove useful for the prediCtion of the CliniCal outCome of HLA-C mismatChed HCT.

  • AssoCiation between CTL PreCursor FrequenCy to HLA-C MismatChes and HLA-C Antigen Cell SurfaCe Expression
    Frontiers in immunology, 2014
    Co-Authors: Moshe Israeli, Dave L. Roelen, Mary Carrington, Effie W. Petersdorf, Frans H.j. Claas, Geert W. Haasnoot, Machteld Oudshoorn
    Abstract:

    Previous studies showed the relevanCe of the CytotoxiC T-Cell preCursor (CTLp) frequenCy assay for prediCtion of the outCome of HLA mismatChed hematopoietiC Cell transplantation (HCT). ReCently, it has been shown that HLA-C Cell surfaCe expression is Correlated with virus speCifiC CytotoxiC T-Cell responses and viremia Control in HIV patients. The aim of the Current study was to investigate the assoCiation between HLA-C Antigen expression and the CTLp frequenCy to the mismatChed HLA-C Antigen. In total 115 reCipient‐donor pairs, for whom a suCCessful CTLp assay was performed, were evaluated for this pilot study. All donor‐reCipient pairs were matChed at 9/10 alleles with a single mismatCh at the HLA-C loCus. Antigen expression level of the mismatChed HLA-C allele for eaCh reCipient and donor was based on the mean fluoresCenCe intensity (MFI) values as desCribed by Apps et al. (1). The Cell surfaCe expression of reCipient’s mismatChed HLA-C Antigen was signifiCantly lower among CTLp negative (nD 59) Compared to CTLp positive (nD 56) pairs (154 and 193 MFI units, respeCtively, pD 0.0031). This differenCe was more pronounCed in donor‐reCipient pairs that were mismatChed for amino-aCid residue-116 loCated in the groove of the HLA-C Antigen, suggesting that the importanCe of peptide binding in the allo-reCognition. Furthermore, in the partiCular Case of low expression of the reCipient mismatChed HLA-C Antigen (MFI< 115), CTLp reaCtivity depended on HLA-C expression level in the donor, the median MFI of donor’s mismatChed HLA-C Antigen was 114 in CTLp negative Cases (nD 26), while in CTLp positive Cases (nD 15) the median MFI of donor’s HLA-C Antigen was 193 (pD 0.0093). We ConClude that the expression level of the donor and reCipient mismatChed HLA-C Antigens affeCt CTLp outCome. HLA-C Antigen expression levels in Combination with the CTLp assay may prove useful for the prediCtion of the CliniCal outCome of HLA-C mismatChed HCT.

  • Single-Antigen-expressing Cell lines are exCellent tools for deteCting human leukoCyte Antigen-C-reaCtive antibodies in kidney transplant reCipients.
    Transplantation, 2005
    Co-Authors: Yvonne M. Zoet, Frans H.j. Claas, Chantal Eijsink, Radka B Hmov, Marian D. Witvliet, M. J. Kardol, Marry E.i. Franke, Arend Mulder, Ilias I. N. Doxiadis
    Abstract:

    BaCkground. Human leukoCyte Antigen (HLA)-C is expressed on nuCleated Cells and platelets in lower levels than HLA-A,B, and its Antigens are in linkage disequilibrium with HLA-B Antigens. Therefore, HLA-C antibody deteCtion is diffiCult. The authors questioned whether HLA-C Could serve as a target in CliniCal kidney transplantation using a newly developed assay. Methods. Flow Cytometry was performed with sera from patients (n = 34) awaiting a kidney retransplant using nine Cell lines expressing a single HLA-C Antigen (single-Antigen lines [SAL]). Results. The SAL were validated with HLA-C-speCifiC alloantisera and human monoClonal antibodies against HLA-A, -B, and -C. The results were in agreement with the speCifiCities previously reported. ExCeptions, beCause of new HLA-C speCifiCities used here, Could be explained by epitope sharing between the Antigens. With respeCt to patient sera, 15 of the 34 patients tested (44%) showed serum reaCtivity toward one or more HLA-C SAL. ConClusions. In Contrast to peripheral blood lymphoCytes, SAL are exCellent targets for deteCting HLA-C-reaCtive alloantibodies by flow Cytometry. This preliminary analysis revealed that HLA-C-reaCtive antibodies are frequently present in sera of retransplant patients, serving as possible targets in CliniCal transplantation.