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1. Incidence, risk factors and clinical outcome of leukemia relapses with loss of the mismatched HLA after partially incompatible hematopoietic stem cell transplantation

Author

Crucitti, L, Crocchiolo, R, Toffalori, C, Mazzi, B, Greco, R, Signori, A, Sizzano, F, Chiesa, L, Zino, E, Lupo Stanghellini, M T, Assanelli, A, Carrabba, M G, Marktel, S, Marcatti, M, Bordignon, C, Corti, C, Bernardi, M, Peccatori, J, Bonini, C, Fleischhauer, K, Ciceri, F, and Vago, L

Published
2015
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10. T cell neoepitope discovery in colorectal cancer by high throughput profiling of somatic mutations in expressed genes

Author

Mennonna, D, Maccalli, C, Romano, M, Garavaglia, C, Capocefalo, F, Bordoni, R, Severgnini, M, De Bellis, G, Sidney, J, Sette, A, Gori, A, Longhi, R, Braga, M, Ghirardelli, L, Baldari, L, Orsenigo, E, Albarello, L, Zino, E, Fleischhauer, K, Mazzola, G, Ferrero, N, Amoroso, A, Casorati, G, Parmiani, G, Dellabona, P, Mennonna, Daniele, Maccalli, Cristina, Romano, Michele C., Garavaglia, Claudio, Capocefalo, Filippo, Bordoni, Roberta, Severgnini, Marco, De Bellis, Gianluca, Sidney, John, Sette, Alessandro, Gori, Alessandro, Longhi, Renato, Braga, Marco, Ghirardelli, Luca, Baldari, Ludovica, Orsenigo, Elena, Albarello, Luca, Zino, Elisabetta, Fleischhauer, Katharina, Mazzola, Gina, Ferrero, Norma, Amoroso, Antonio, Casorati, Giulia, Parmiani, Giorgio, Dellabona, Paolo, Mennonna, D, Maccalli, C, Romano, M, Garavaglia, C, Capocefalo, F, Bordoni, R, Severgnini, M, De Bellis, G, Sidney, J, Sette, A, Gori, A, Longhi, R, Braga, M, Ghirardelli, L, Baldari, L, Orsenigo, E, Albarello, L, Zino, E, Fleischhauer, K, Mazzola, G, Ferrero, N, Amoroso, A, Casorati, G, Parmiani, G, Dellabona, P, Mennonna, Daniele, Maccalli, Cristina, Romano, Michele C., Garavaglia, Claudio, Capocefalo, Filippo, Bordoni, Roberta, Severgnini, Marco, De Bellis, Gianluca, Sidney, John, Sette, Alessandro, Gori, Alessandro, Longhi, Renato, Braga, Marco, Ghirardelli, Luca, Baldari, Ludovica, Orsenigo, Elena, Albarello, Luca, Zino, Elisabetta, Fleischhauer, Katharina, Mazzola, Gina, Ferrero, Norma, Amoroso, Antonio, Casorati, Giulia, Parmiani, Giorgio, and Dellabona, Paolo

Abstract

Objective Patient-specific (unique) tumour antigens, encoded by somatically mutated cancer genes, generate neoepitopes that are implicated in the induction of tumour-controlling T cell responses. Recent advancements in massive DNA sequencing combined with robust T cell epitope predictions have allowed their systematic identification in several malignancies. Design We undertook the identification of unique neoepitopes in colorectal cancers (CRCs) by using high-throughput sequencing of cDNAs expressed by standard cancer cell cultures, and by related cancer stem/initiating cells (CSCs) cultures, coupled with a reverse immunology approach not requiring human leukocyte antigen (HLA) allele-specific epitope predictions. Results Several unique mutated antigens of CRC, shared by standard cancer and related CSC cultures, were identified by this strategy. CD8+ and CD4+ T cells, either autologous to the patient or derived from HLA-matched healthy donors, were readily expanded in vitro by peptides spanning different cancer mutations and specifically recognised differentiated cancer cells and CSC cultures, expressing the mutations. Neoepitope-specific CD8+ T cell frequency was also increased in a patient, compared with healthy donors, supporting the occurrence of clonal expansion in vivo. Conclusions These results provide a proof-of-concept approach for the identification of unique neoepitopes that are immunogenic in patients with CRC and can also target T cells against the most aggressive CSC component.

Published
2017

11. ENHANCED ALLOREACTIVITY TO BI-DIRECTIONAL NON-PERMISSIVE HLA-DPB1 MISMATCHES SUPPORTS NON-HIERARCHICAL T-CELL EPITOPE GROUP DIVERSITY AS UNDERLYING BIOLOGICAL MECHANISM

Author

Zito, L., Sizzano, F., Crivello, P., Toffalori, C., Zino, E., Vago, L., Crocchiolo, R., Sacchi, N., Rambaldi, A., Ciceri, F., Claas, F.H.J., Oudshoorn, M., Fleischhauer, K., Zito, L, Sizzano, F, Crivello, P, Toffalori, C, Zino, E, Vago, L, Crocchiolo, R, Sacchi, N, Rambaldi, A, Ciceri, F, Claas, Fhj, Oudshoorn, M, and Fleischhauer, K

Published
2013

13. Incidence, Risk Factors and Clinical Outcome Of Leukemia Relapses Due To Loss Of The Mismatched HLA Haplotype After Partially-Incompatible Hematopoietic Stem Cell Transplantation

Author

Crucitti L, Crocchiolo R, Toffalori C, Stanghellini MTL, Assanelli A, Carrabba M, Mazzi B, Zino E, Marktel S, Marcatti M, Corti C, Bernardi M, Peccatori J, Bordignon C, Bonini C, Fleischhauer K, Ciceri F, Vago L, Crucitti, L, Crocchiolo, R, Toffalori, C, Stanghellini, Mtl, Assanelli, A, Carrabba, M, Mazzi, B, Zino, E, Marktel, S, Marcatti, M, Corti, C, Bernardi, M, Peccatori, J, Bordignon, C, Bonini, C, Fleischhauer, K, Ciceri, F, and Vago, L

Published
2013

14. Loss of mismatched HLA at leukaemia relapse after haematopoietic stem cell transplantation is significantly associated with clinical and immunogenetic hallmarks of donor-versus-host alloreactivity

Author

Crucitti L, Crocchiolo R, Toffalori C, Stanghellini MTL, Assanelli A, Carrabba M, Mazzi B, Zino E, Marktel S, Marcatti M, Corti C, Bernardi M, Peccatori J, Bordignon C, Bonini C, Fleischhauer K, Ciceri F, Vago L, Crucitti, L, Crocchiolo, R, Toffalori, C, Stanghellini, Mtl, Assanelli, A, Carrabba, M, Mazzi, B, Zino, E, Marktel, S, Marcatti, M, Corti, C, Bernardi, M, Peccatori, J, Bordignon, C, Bonini, C, Fleischhauer, K, Ciceri, F, and Vago, L

Published
2013

15. Changing the Face of Modern Medicine: Stem Cell and Gene Therapy Organized Jointly by the European Society of Gene & Cell Therapy (ESGCT), International Society for Stem Cell Research (ISSCR) and the French Society of Gene and Cell Therapy (SFTCG) Lausanne, Switzerland October 16–19, 2018 Abstracts

Author

Champion, K M, Albertini, P, Visigalli, I, Cecere, F, Carriglio, N, Hernandez, R J, De Simone, M, Vezzoli, M, Monti, L, Zino, E, Alfonso, E, Sanvito, F, Mauro, V, Norata, R, Acquati, S, Redaelli, D, Dionisio, F, De Mattia, F, Scaramuzza, S, and Rossi, C

Published
2018
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16. Loss of Mismatched HLA At Leukemia Relapse After Hematopoietic Stem Cell Transplantation Is Significantly Associated with Clinical and Immunogenetic Hallmarks of Donor-Versus-Host Alloreactivity

Author

Crucitti L, Crocchiolo R, Toffalori C, Stanghellini MTL, Assanelli A, Carrabba M, Mazzi B, Zino E, Marktel S, Marcatti M, Consuelo C, Bernardi M, Peccatori J, Bordignon C, Bonini C, Fleischhauer K, Ciceri F, Vago L, Crucitti, L, Vago, L, Crocchiolo, R, Toffalori, C, Stanghellini, Mtl, Assanelli, A, Carrabba, M, Mazzi, B, Zino, E, Marktel, S, Marcatti, M, Corti, C, Bernardi, M, Peccatori, J, Bordignon, C, Bonini, C, Fleischhauer, K, Ciceri, F, and Consuelo, C

Published
2012

19. Timing and rate of success in transplant of matched unrelated donor (MUD) searches through bone marrow donors worldwide (BMDW): the case of San Raffaele Institute in 2006-2009

Author

Forno B, Mazzi B, Zino E, Lupo Stanghellini MT, Vago L, Guggiari E, Coppola M, Piemontese S, Claudiani S, Lunghi F, Marktel S, Bernardi M, Corti C, Peccatori J, CICERI, FABIO, Fleischhauer K, Marcatti M., BONINI , MARIA CHIARA, Forno, B, Mazzi, B, Zino, E, Lupo Stanghellini, Mt, Vago, L, Guggiari, E, Coppola, M, Piemontese, S, Claudiani, S, Lunghi, F, Marktel, S, Bernardi, M, Corti, C, Bonini, MARIA CHIARA, Peccatori, J, Ciceri, Fabio, Fleischhauer, K, and Marcatti, M.

Published
2010

20. Bone marrow morphology and cytogenetics in donors provide additional safety in allogeneic haematopoietic stem cell transplantation: results in 460 healthy candidates

Author

Lupo Stanghellini MT, Gattillo S, Ronchi P, Guggiari E, Fomo B, Sala E, Lorentino F, Malato S, Bruno Ventre M, Piemontese S, Girlanda S, Tassara M, Zino E, Mazzi B, Bellio L, Malabarba L, Corti C, Bernardi M, Peccatori J, Fleischhauer K, Marcatti M, Rossini S., CICERI , FABIO, Lupo Stanghellini, Mt, Gattillo, S, Ronchi, P, Guggiari, E, Fomo, B, Sala, E, Lorentino, F, Malato, S, Bruno Ventre, M, Piemontese, S, Girlanda, S, Tassara, M, Zino, E, Mazzi, B, Bellio, L, Malabarba, L, Corti, C, Bernardi, M, Peccatori, J, Fleischhauer, K, Marcatti, M, Ciceri, Fabio, and Rossini, S.

Published
2010

21. HLA-DPB1 T cell epitope 4-group matching is significantly predictive of survival after unrelated hematopoietic stem cell transplantation in onco-hematologic patients from Italy: an updated analysis

Author

Crocchiolo R, Oneto R, Bruno B, Pollichieni S, Sacchi N, Fanin R, Garbarino L, Miotti V, Bandini G, Bosi A, Zino E, Bacigalupo A, Fleischhauer K., CICERI , FABIO, Crocchiolo, R, Oneto, R, Bruno, B, Pollichieni, S, Sacchi, N, Fanin, R, Garbarino, L, Miotti, V, Bandini, G, Bosi, A, Ciceri, Fabio, Zino, E, Bacigalupo, A, and Fleischhauer, K.

Published
2010

22. Nonpermissive HLA-DPB1 disparity is a significant independent risk factor for mortality after unrelated hematopoietic stem cell transplantation

Author

Crocchiolo, R., Zino, E., Vago, L., Oneto, R., Bruno, B., Pollichieni, S., Sacchi, N., Sormani, M. P., Marcon, J., Lamparelli, T., Fanin, R., Garbarino, L., Miotti, V., Bandini, G., Bosi, A., Ciceri, F., Bacigalupo, A., Fleischhauer, K., Midollo Osseo Gruppo Italiano Trapianto, D. I., Terapia Cellulare, Cellule Staminali Ematopoietiche Cse E., Italian Bone Marrow Donor Registry Collaboratori, Scalari P., Bontempelli, M., Prinoth, O., Carcassi, C., Marceno, R., Porfirio, Rombola, G., Lombardo, Ferrioli, G., Poli, F., Scalamogna, M., Mazzi, B., Rossi, F., Mascaretti, L., Albergoni, Salvaneschi, L., Salvaneschi, M., Valentini, Nesci, S., Papola, F., Scatena, Mariotti, Perrone, Laurenti, Grammatico, Paola, Mariani, M., Favoino, B., Guizzardi, Pontiero, Leoni, P., Rambaldi, A., Casini, M., Angelucci, E., Baronciani, D., La Nasa, G., Milone, G., Guidi, S., Van Lint, M. T., Dini, G., Corradini, P., Milani, R., Morra, E., Marenco, P., Deliliers, Lambretenghi G., Onida, F., Marcatti, M., Castagna, L., Pioltelli, P., Selleri, C., Zanesco, L., Scime, R., Musso, M., Alessandrino, E. P., Locatelli, F., Visani, G., Di Bartolomeo, P., Papineschi, F., Favre, C., Iori, A. P., Foa, Roberto, Locasciulli, A., Majolino, I., Majolino, P., Leone, G., Arcese, W., Cerretti, R., Carella, A. M., Cascavilla, N., Lauria, F., Mazza, P., Cerno, M., Benedetti, F., Crocchiolo, R, Zino, E, Vago, L, Oneto, R, Bruno, B, Pollichieni, S, Sacchi, N, Sormani, Mp, Marcon, J, Lamparelli, T, Fanin, R, Garbarino, L, Miotti, V, Bandini, G, Bosi, A, Ciceri, F, Bacigalupo, A, and Fleischhauer, K

Subjects
Adult, Disease-Free Survival, Donor Selection, Female, HLA-DRB1 Chains, Hematologic Neoplasms, Humans, Italy, Male, Middle Aged, Recurrence, Registries, Retrospective Studies, Risk Factors, Survival Rate, Transplantation, Homologous, Algorithms, HLA-DR Antigens, Hematopoietic Stem Cell Transplantation, Tissue Donors, Biochemistry, Immunology, Hematology, Cell Biology, Homologous, medicine.medical_treatment, Human leukocyte antigen, Hematopoietic stem cell transplantation, Medicine, Risk factor, Survival rate, Transplantation, HLA-DPB1, business.industry, Hazard ratio, Confidence interval, business, Settore MED/15 - Malattie del Sangue
Abstract

The importance of donor-recipient human leukocyte antigen (HLA)-DPB1 matching for the clinical outcome of unrelated hematopoietic stem cell transplantation (HSCT) is controversial. We have previously described an algorithm for nonpermissive HLA-DPB1 disparities involving HLA-DPB1*0901,*1001,*1701,*0301,*1401,*4501, based on T-cell alloreactivity patterns. By revisiting the immunogenicity of HLA-DPB1*02, a modified algorithm was developed and retrospectively tested in 621 unrelated HSCTs facilitated through the Italian Registry for onco-hematologic adult patients. The modified algorithm proved to be markedly more predictive of outcome than the original one, with significantly higher KaplanMeier probabilities of 2-year survival in permissive compared with nonpermissive transplantations (55% vs 39%, P = .005). This was the result of increased adjusted hazards of nonrelapse mortality (hazard ratio [HR] = 1.74; confidence interval [CI], 1.19-2.53; P = .004) but not of relapse (HR = 1.02; CI, 0.73-1.42; P = .92). The increase in the hazards of overall mortality by nonpermissive HLA-DPB1 disparity was similar in 10 of 10 (HR = 2.12; CI, 1.23-3.64; P = .006) and 9 of 10 allele-matched transplantations (HR = 2.21; CI, 1.28-3.80; P = .004), both in early-stage and in advanced-stage disease. These data call for revisiting current HLA matching strategies for unrelated HSCT, suggesting that searches should be directed up-front toward identification of HLA-DPB1 permissive, 10 of 10 or 9 of 10 matched donors. (Blood. 2009; 114:1437-1444) RI Porfirio, Berardino/I-1988-2012

Published
2009

23. Non-permissive HLA-DPB1 disparity is a significant independent risk factor for mortality after unrelated hematopoietic stem cell transplantation

Author

Crocchiolo R, Zino E, Vago L, Oneto R, Bruno B, Pollicchieni S, Sacchi N, Sormani MP, Marcon J, Fanin R, Garbarino L, Miotti V, Bandini G, Bosi A, Bacigalupo A, Fleischhauer K., CICERI , FABIO, Crocchiolo, R, Zino, E, Vago, L, Oneto, R, Bruno, B, Pollicchieni, S, Sacchi, N, Sormani, Mp, Marcon, J, Fanin, R, Garbarino, L, Miotti, V, Bandini, G, Bosi, A, Ciceri, Fabio, Bacigalupo, A, and Fleischhauer, K.

Published
2009

24. Termporal, quantitative and functional characteristics of single-KIR positive alloreactive natural killer cell recovery account for impaired graft-versus-leukemia activity after haploidentical hematopoietic stem cell transplantation

Author

VAGO L, FORNO B, SORMANI M. P, CROCCHIOLO R, ZINO E, DI TERLIZZI S, LUPO STANGHELLINI M. T, MAZZI B, PERNA S. K, BONDANZA A, MIDDLETON D, PALINI A, BERNARDI M, BACCHETTA R, PECCATORI J, ROSSINI S, RONCAROLO M. G, BORDIGNON , CLAUDIO, BONINI C, CICERI, FABIO, AND K. FLEISCHHAUER, Vago, L, Forno, B, SORMANI M., P, Crocchiolo, R, Zino, E, DI TERLIZZI, S, LUPO STANGHELLINI M., T, Mazzi, B, PERNA S., K, Bondanza, A, Middleton, D, Palini, A, Bernardi, M, Bacchetta, R, Peccatori, J, Rossini, S, RONCAROLO M., G, Bordignon, Claudio, Bonini, C, Ciceri, Fabio, and AND K., Fleischhauer

Published
2008

25. The effect of donor-recipient KIR ligand incompatibility after haploidentical hematopoietic stem cell transplantation is overruled by biological characteristics of early reconstituting NK cells with impaired graft versus leukemia activity

Author

Vago L, Zino E, Di Terlizzi S, Forno B, Lupo Stanghellini MT, Mazzi B, Palini A, Rossini S, Roncarolo MG, BONINI , MARIA CHIARA, CICERI , FABIO, BORDIGNON, CLAUDIO, Fleischhauer K., Vago, L, Zino, E, Di Terlizzi, S, Forno, B, Lupo Stanghellini, Mt, Mazzi, B, Palini, A, Rossini, S, Roncarolo, Mg, Bonini, MARIA CHIARA, Ciceri, Fabio, Bordignon, Claudio, and Fleischhauer, K.

Published
2007

27. Temporal, quantitative and functional characteristics of Single-KIR positive alloreactive NK cell recovery account for impaired graft versus leukemia activity after haploidentical HSCT

Author

Vago L, Fomot B, Zino E, Di Terlizzi S, Stanghellini MTL, Crocchiolo R, Pema SK, BONDANZA , ATTILIO, Mazzi B, Peccatori J, Roncarolo MG, BORDIGNON, CLAUDIO, BONINI , MARIA CHIARA, CICERI , FABIO, Fleischhauer K., Vago, L, Fomot, B, Zino, E, Di Terlizzi, S, Stanghellini, Mtl, Crocchiolo, R, Pema, Sk, Bondanza, Attilio, Mazzi, B, Peccatori, J, Roncarolo, Mg, Bordignon, Claudio, Bonini, MARIA CHIARA, Ciceri, Fabio, and Fleischhauer, K.

Published
2007

28. Impaired GvL potential of natural killer cells early reconstituting following haploidentical HSCT

Author

Vago L, Zino E, Di Terlizzi S, Forno B, Stanghellini MTL, Pema SK, Mazzi B, Peccatori J, Rossini S, Roncarolo MG, Fleischhauer K., BONINI , MARIA CHIARA, CICERI , FABIO, BORDIGNON, CLAUDIO, Vago, L, Zino, E, Di Terlizzi, S, Forno, B, Stanghellini, Mtl, Pema, Sk, Mazzi, B, Peccatori, J, Rossini, S, Roncarolo, Mg, Bonini, MARIA CHIARA, Ciceri, Fabio, Bordignon, Claudio, and Fleischhauer, K.

Published
2006

32. Receptor repertoire reconstitution suggests acquisition of patient-specific tolerance by natural killer cells arising from hematopoietic progenitor stem cells after haploidentical transplantation

Author

Vago L, Terlizzi SD, Zino E, Magnani CF, Stanghellini MTL, Magnani Z, Mazzi B, Clerici D, BONDANZA , ATTILIO, Bregni M, Rossini S, Peccatori J, BONINI , MARIA CHIARA, CICERI , FABIO, BORDIGNON, CLAUDIO, Fleischhauer K., Vago, L, Terlizzi, Sd, Zino, E, Magnani, Cf, Stanghellini, Mtl, Magnani, Z, Mazzi, B, Clerici, D, Bondanza, Attilio, Bregni, M, Rossini, S, Peccatori, J, Bonini, MARIA CHIARA, Ciceri, Fabio, Bordignon, Claudio, and Fleischhauer, K.

Published
2005

38. Incidence, risk factors and clinical outcome of leukemia relapses with loss of the mismatched HLA after partially incompatible hematopoietic stem cell transplantation

Author

Crucitti, L, primary, Crocchiolo, R, additional, Toffalori, C, additional, Mazzi, B, additional, Greco, R, additional, Signori, A, additional, Sizzano, F, additional, Chiesa, L, additional, Zino, E, additional, Lupo Stanghellini, M T, additional, Assanelli, A, additional, Carrabba, M G, additional, Marktel, S, additional, Marcatti, M, additional, Bordignon, C, additional, Corti, C, additional, Bernardi, M, additional, Peccatori, J, additional, Bonini, C, additional, Fleischhauer, K, additional, Ciceri, F, additional, and Vago, L, additional

Published
2014
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39. Nonpermissive HLA-DPB1 disparity is a significant independent risk factor for mortality after unrelated hematopoietic stem cell transplantation

Author

Crocchiolo, R, Zino, E, Vago, L, Oneto, R, Bruno, B, Pollichieni, S, Sacchi, N, Sormani, Mp, Marcon, J, Lamparelli, T, Fanin, R, Garbarino, L, Miotti, V, Bandini, G, Bosi, A, Ciceri, F, Bacigalupo, A, Fleischhauer, K, Gruppo Italiano Trapianto di Midollo Osseo, Terapia Cellulare, Cellule Staminale Ematopoietiche e., Italian Bone Marrow Donor Registry, Scalari, P, Bontempelli, M, Prinoth, O, Carcassi, C, Marcenò, R, Porfirio, Rombolà, G, Lombardo, Ferrioli, G, Poli, F, Scalamogna, M, Mazzi, B, Rossi, F, Mascaretti, L, Albergoni, Salvaneschi, L, Martinetti, M, Valentini, Renzo, Nesci, S, Papola, F, Scatena, Mariotti, Perrone, Laurenti, Grammatico, P, Mariani, M, Favoino, B, Guizzardi, Pontiero, Leoni, P, Rambaldi, A, Casini, M, Angelucci, E, Baronciani, D, La Nasa, G, Milone, G, Guidi, S, Van Lint MT, Dini, G, Corradini, P, Milani, R, Morra, E, Marenco, P, Lambretenghi Deliliers, G, Onida, F, Marcatti, M, Castagna, L, Pioltelli, P, Selleri, C, Zanesco, L, Scimè, R, Musso, M, Alessandrino, Ep, Locatelli, F, Visani, G, Di Bartolomeo, P, Papineschi, Federico, Favre, C, Iori, Ap, Foà, R, Locasciulli, A, Majolino, I, Majolino, P, Leone, G, Arcese, W, Cerretti, R, Carella, Am, Cascavilla, N, Lauria, F, Mazza, P, Cerno, M, and Benedetti, F.

Published
2009

42. Sequencing of a new subtype of HLA-A*32

Author

Zino E., Severini G., Mazzi B., Benazzi E., K. Fleischhauer, BORDIGNON , CLAUDIO, Zino, E., Severini, G., Mazzi, B., Bordignon, Claudio, Benazzi, E., and K., Fleischhauer

Published
1996

43. Therapeutic and diagnostic applications of minor histocompatibility antigen HA-1 and HA-2 disparities in allogeneic hematopoietic stem cell transplantation: A survey of different populations

Author

Di Terlizzi, S, Zino, E, Mazzi, B, Magnani, C, Tresoldi, C, Perna, S, Bregni, M, Rossini, S, Ciceri, F, Bordignon, C, Bonini, C, Fleischhauer, K, Fleischhauer, K., MAGNANI, CHIARA FRANCESCA, Di Terlizzi, S, Zino, E, Mazzi, B, Magnani, C, Tresoldi, C, Perna, S, Bregni, M, Rossini, S, Ciceri, F, Bordignon, C, Bonini, C, Fleischhauer, K, Fleischhauer, K., and MAGNANI, CHIARA FRANCESCA

Abstract

Minor histocompatibility antigens (mHags) HA-1 and HA-2 are encoded by biallelic loci, with immunogenic variants, HA-1H and HA-2V, which induce strong HLA-A2-restricted alloreactive T-cell responses, and nonimmunogenic counterparts, HA-1R and HA-2M, which represent functional null alleles that are poorly presented by HLA class I molecules. HA-1 and HA-2 are potential targets of selective graft-versus-leukemia and graft-versus-tumor reactivity after allogeneic hematopoietic stem cell transplantation (HSCT); however, these applications are restricted to a limited number of patients. Here, we show that a far more frequent application of HA-1 and HA-2 disparity relies on their use as markers for the state of host chimerism after allogeneic HSCT. We have determined allelic frequencies of 29.3% and 70.7% for HA-1H and HA-1R, respectively, and of 83.7% and 16.3% for HA-2V and HA-2M, respectively, in >200 healthy individuals from northern Italy. Similar frequencies were observed in nearly 100 patients affected by hematologic malignancies or solid tumors, thus showing that HA-1 and HA-2 variability are not associated with the presence of cancer. On the basis of these data, we predict that HA-1 and HA-2 can be used in 32.8% and 23.5% of Italian transplant patients, respectively, as markers for the state of host chimerism, whereas exploitation of disparity for these mHags for targeted immunotherapy will be possible in 10.7% and 1.1% of Italian patients, respectively. Retrospective HA-2 typing of bone marrow aspirates obtained from a patient during complete remission or recurrence of acute myeloid leukemia after haploidentical HSCT showed the feasibility of using HA-2 as a surrogate marker for disease monitoring. Because of an apparent north-south gradient for HA-1 allelic frequencies, with higher frequencies for the HA-1H variant reported in white populations from Southern Europe as compared with Northern Europe and North America, the diagnostic applicability of HA-1 disparity

Published
2006

50. Brief communication Rapid detection of all HLA-B*27 alleles (B*2701–B*2725) by group-specific polymerase chain reaction.

Author

Zino, E., Di Terlizzi, S., Carugo, C., Baggi, L., Galli, A., Bonini, C., Rossini, S., Mazzi, B., and Fleischhauer, K.

Subjects
*ANTIGENS, *RHEUMATISM, *ANKYLOSING spondylitis, *INFECTIOUS arthritis, *IMMUNOSPECIFICITY, *POLYMERASE chain reaction
Abstract

Human leucocyte antigen-B*27 is strongly associated with a number of rheumatic diseases, including ankylosing spondylitis and reactive arthritis. Targeted detection of the B*27 group by molecular methods is hampered by the extreme heterogeneity of the serological B*27 group. Here, we describe a simple, rapid sequence-specific primer-based method for detection of all 28 B*27 alleles defined to date. The method involves an initial screening with two sequence-specific polymerase chain reactions (PCRs), which has to be followed by two additional PCR amplifications in samples carrying a few rare subtypes of B*27, B*4202 or B*7301. The described protocol should be useful for laboratories involved in diagnostics and research of rheumatoid diseases. [ABSTRACT FROM AUTHOR]

Published
2004
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