Fundación Lolita Rubial 
Premios Morosoli Morosoli 2004
Morosoli de Oro 2004
Prof. Dr. Guillermo Dighiero
Médico, Inmunólogo, docente e investigador de trayectoria ejemplar.
• Doctor en Medicina - Universidad de la República - Montevideo - Uruguay.
• Ex Profesor Adjunto de la Clínica Semiológica - Facultad de Medicina - Montevideo - Uruguay.
• Profesor Asociado de la Facultad de Medicina Paris VI - Paris - Francia.
• Profesor del Instituto Pasteur - Francia.
• Presidente del Grupo Francés para el estudio de la Leucemia Linfoide Crónica - Francia.
• Miembro de la Academia de Medicina de Francia.
• Doctor Honoris Causa - Universidad de la República - Montevideo - Uruguay.
Nació un 21 de Mayo de 1941 en la ciudad de Montevideo, Uruguay.
I Datos Académicos
- Ingreso a la Facultad de Medicina, Universidad de la República, Montevideo, Uruguay, 1960.
- Practicante Interno del Laboratorio Central del Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay, 1964.
- Practicante Interno del Ministerio de Salud Pública, Montevideo, Uruguay, 1968.
- Doctor en Medicina, Facultad de Medicina, Universidad de la República Oriental del Uruguay, 1969.
- Asistente de la Clínica Semiológica de la Facultad de Medicina, Universidad de la República, Montevideo, Uruguay, 1971.
- Profesor Adjunto de la Clínica Semiológica de la Facultad de Medicina, Universidad de la República, Montevideo, Uruguay, 1975.
- Profesor Asociado de la Facultad de Medicina Paris VI, Paris, Francia, 1975.
- Docteur ès sciences, Paris, Francia, 1978.
- Ingreso al CNRS, Francia, 1979.
- Jefe de la Unidad de Inmuhematología e Inmunopatología del Instituto Pasteur, Francia, 1984.
- Director de Investigaciones de Primera Clase en el CNRS, Francia, 1991.
- Profesor del Instituto Pasteur, Francia, 1996.
- Director del Departamento de Fisiopatología del Instituto Pasteur, Francia, 1997.
- Presidente del Grupo Francés para el estudio de la Leucemia Linfoide Crónica, Francia, 1999.
- Doctor Honoris Causa de la Universidad de la República, Montevideo, Uruguay, 2002.
- Miembro de la Academia de Medicina de Francia, Paris, Francia, 2003.
II Contribución Científica
Durante los últimos 30 años, el Profesor Dighiero se ha concentrado en el estudio de dos temas mayores:
1) Los auto-anticuerpos naturales (AAN) y
2) La Leucemia Linfoide Crónica (LLC).
En el laboratorio de Stratis Avrameas del Instituto Pasteur, pudo demostrar que una parte substancial de las inmunoglobulinas normales y del repertorio de los linfocitos B, correspondían a auto-anticuerpos naturales (AAN). La existencia e importancia de este repertorio contradecía las hipótesis dominantes en esa época sobre la tolerancia, que predecían que esta era la consecuencia de un proceso de selección clonal de los clonos auto-reactivos que ocurría durante la vida fetal.
Durante los últimos 30 años, su trabajo en relación a la Leucemia Linfoide Crónica (LLC) estuvo consagrado al estudio de la biología y la clínica de esta enfermedad. Desde el punto de vista biológico, permitió de demostrar 3 características principales del linfocito B, que prolifera en esta enfermedad:
1) este linfocito sub-expresa en forma muy marcada el receptor para el antígeno. Esta característica es única entre las hemopatías malignas del linfocito B,
2) el linfocito que prolifera en esta enfermedad es una célula auto-reactiva y
3) este linfocito expresa genes de inmunoglobulina en configuración germinal o mutada, lo que es hoy en día un parámetro esencial para establecer el pronóstico de la LLC.
Su trabajo en la clínica de la enfermedad dio lugar a:
1) la descripción de una clasificación pronostica de la enfermedad, que es utilizada como clasificación de referencia en el mundo, y
2) al estudio de la historia natural de la enfermedad y una mejor definición de las indicaciones terapéuticas.
Es coautor, en colaboración con otros importantes científicos, de más de un centenar de trabajos originales, los que han sido publicados en Revistas Científicas Arbitradas de nivel internacional.
Sus trabajos y estudios son citados en las principales revistas científicas internacionales (3.881 citas presentes entre 1980 y el 2000).
El Dr. Dighiero ha sido el Jefe de Proyecto -de parte del Instituto Pasteur de París- para la instalación de un Instituto Pasteur en Montevideo. En su laboratorio en Francia se han formado numerosos científicos uruguayos. Ha apoyado en forma permanente desde Francia, el desarrollo de la Ciencia y la Medicina en el Uruguay.
Citas de los trabajos científicos (1980-2000)
| 1) | Guilbert B, Dighiero G, Avrameas S | |
| J. of Immunol. 128:2779-1982 (Ref. 24) | 498 | |
| 2) | Dighiero G, Guilbert B, Avrameas S | |
| J. of Immunol. 128:2788-1982 (Ref. 25) | 152 | |
| 3) | Dighiero G y Col., | |
| J. of Immunol. 131:2267-1983 (Ref. 27) | 266 | |
| 4) | Dighiero G y Col., | |
| Blood. 62:264-1983 (Ref. 26) | 154 | |
| 5) | Dighiero G y col., | |
| J. of Immunol. 134:765-1985 (Ref. 29) | 340 | |
| 6) | Dighiero G, y col., | |
| Ann. N.Y. Ac. Sci. 475:135-1986 (Ref.31) | 73 | |
| 7) | Lymbery P, Dighiero G y col., | |
| Eur. J. of Immunol. 15:702-1985 (Ref. 30) | 83 | |
| 8) | Binet JL, Auquier A, Dighiero G y col., | |
| Cancer 48:198-1981 (Ref. 20) | 373 | |
| 9) | Ternynck T, Dighiero G y col., | |
| Blood 43: 789,1974 (Ref. 1) | 61 | |
| 10) | Dighiero G y col. | |
| Blood 48: 559, 1976 (Ref. 3) | 29 | |
| 11) | Binet JL, Catovsky D, Chandra P, Dighiero G y col., | |
| Br. J. Haematol. 48:365-1981 (Ref. 21) | 159 | |
| 12) | Binet JL, Leporrier M, Dighiero G y col., | |
| Cancer 40:855-1977 (Ref. 5) | 136 | |
| 13) | Dighiero G y col., | |
| Br. J. Haematol. 41:169-1979 (Réf. 14) | 46 | |
| 14) | Otras publicaciones | 1511 |
| TOTAL | 3881 | |
| - Número de citaciones por año | 195 | |
| - Número de citaciones por artículo | 36 | |
| - Número de citaciones de los 10 artículos más citados | 2234 |
Publicaciones originales en revistas arbitradas de nivel internacional
1- T. Ternynck, G. Dighiero, J. Follezou and J.L. Binet.
Comparison of normal and CLL lymphocyte surface Ig determinants using peroxidase-labeled antibodies.I - Detection and quantitation of light chain determinants. Blood, 43:789-795 (1974).
2- J.L. Binet, G. Dighiero, Ph. d'Athis,M. Feinermann, F. de Montaut and J. Seroude.
Volumetric determinations of blood cells in acute lymphoblastic leukemia. Blood Cells, 1:95-97 (1975).
3- G. Dighiero, J.Y. Follezou, J.P. Roisin, T. Ternynck and J.L. Binet.
Comparison of normal and chronic lymphocytic leukemia lymphocyte surface Ig determinants using peroxidase-labeled antibodies. II -Quantification of light chain determinants in atypical lymphocytic leukemia. Blood, 48:559-567 (1976).
4- J.L. Binet, G. Vaugier, G. Dighiero, Ph. d'Athis and D. Charron.
Investigation of a new parameter in chronic lymphocytic leukemia: The percentage of large peripheral lymphocytes determined by the Hemalog D. The American Journal of Medicine, 63:683-688 (1977).
5- J.L. Binet, M. Leporrier, G. Dighiero, D. Charron, Ph. d'Athis, G. Vaugier, H. Merle-Béral, J.C. Natali,M. Raphaël, B. Nizet and J.Y. Follezou.
A clinical staging system for chronic lymphocytic leukemia. Prognostic significance. Cancer, 40:855-864 (1977).
6- G. Dighiero, G. Vaugier, D. Charron, Ph. d'Athis and J.L. Binet.
Variations in lymphocyte counts four hours after administration of hydrocortisone in patients with chronic lymphocytic leukemia. Blood, 49:719-728 (1977).
7- J.Y. Follezou, J.M. Andrieux, J.P. Roisin, G. Dighiero and G. Schaison.
Quantification of surface membrane immunoglobulins by immunoperoxidase assay Immunology, 34:733-739 (1978).
8- G. Dighiero, J.Y. Follezou and J.L. Binet.
Surface immunoglobulins in lymphocytic leukemia. Blood, 50:179 (1977).
9- J.L. Binet, G. Dighiero, M. Leporrier, J.Y. Follezou, D. Charron and P. Debré.
Surveillance of chronic lymphocytic leukemia. Blood Cells, 3:651-653 (1977).
10- J.L. Binet, G. Dighiero, Y. Cayre, F. de Montaut and M.C. Couty.
Relevance of cell size to the monitoring of treatment efficacy in acute leukemia and chronic lymphocytic leukemia. Blood Cells, 3:687-689 (1977).
11- G. Dighiero, E. Karsenti, J.Y. Follezou and M. Bornens.
Visualization of tubulin in lymphocytes . I - Comparison of normal and chronic lymphocytic leukemia (CLL) lymphocytes Blood, 51:1031-1037 (1978).
12- J.Y. Follezou, G. Dighiero, J.P. Roisin and J.L. Binet.
Ontogeny of B lymphocytes in mice. Quantification of surface membrane immunoglobulins by immunoperoxidase assay. Immunology, 34:733-739 (1978). 13- D. Charron, G. Dighiero, M. Raphael and J.L. Binet. Bone-marrow patterns and clinical staging in chronic lymphocytic leukemia. The Lancet, 2:819 (1977).
14- G. Dighiero, D. Charron, P. Debré, M. Leporrier, G. Vaugier, J.Y. Follezou, L. Degos, Cl. Jacquillat and J.L. Binet.
Identification of pure splenic form of chronic lymphocytic leukaemia. British Journal of Haematology, 41:169-176 (1979).
15- M. Leporrier, G. Dighiero, M. Auzemery and J.L. Binet.
Detection and quantification of platelet-bound antibodies with immunoperoxydase. British Journal of Haematology, 42:605-611 (1979).
16- G. Dighiero, E. Bodega, R. Mayzner and J.L. Binet.
Individual cell-by-cell quantitation of lymphocyte surface membrane Ig in normal and CLL lymphocytes and during ontogeny of mouse B lymphocytes by immunoperoxydase assay. Blood, 55:93-100 (1980).
17- G. Dighiero, Cl. Lesty, M. Leporrier and M.C. Couty.
Computer analysis of platelet volumes. Blood Cells, 6:365-370 (1980).
18- G. Dighiero, E. Bodega, R. Mayzner and J.L. Binet.
Two new applications of the immunoperoxidase method: Cell-by-cell quantitation of surface immunoglobulins and automated recognition of B-lymphocytes. Blood Cells, 6:371-379 (1980).
19- J. Grellet, P. Curet, M.G. Leammel, P. Cazala, G. Dighiero and J.L. Binet.
Correlation between lymphographic grouping and anatomoc and clinical stages in chronic lymphoïd leukemia. American Journal of Roentgenology, 133:797-803 (1979).
20- J.L. Binet, A. Auquier, G. Dighiero, C. Chastang, H. Piguet, J. Goasguen, G. Vaugier, G. Potron, P. Colona, F. Oberling, M. Thomas, G. Tchernia, C. Jacquillat, P. Boivin, C. Lesty, M.T. Duault, M. Monconduit, S. Belabbes and F. Gremy.
A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer, 48:198-206 (1981).
21- J.L. Binet, D. Catovsky, P. Chandra, G. Dighiero, E. Montserrat, K. Rai and A. Sawitsky.
Chronic lymphocytic leukemia: A proposal for a revised prognostic staging system. British Journal of Haematology, 48:365-367 (1981).
22- S. Avrameas, B. Guilbert and G. Dighiero.
Natural antibodies against tubulin, actin, myoglobin, thyroglobulin, fetuin, albumin and transferrin are present in normal human sera and monoclonal immunoglobulins from multiple myeloma and Waldenström's macroglobulinemia may express similar antibody specificities (preliminary note). Annals of Immunology (Inst. Pasteur), 132 C:231-236 (1981).
23- G. Dighiero, R. Mayzner, J.P. Roisin and J.L. Binet.
Automated recognition of B and T lymphocytes by immunoperoxidase on the Hemalog D system and its application. Blood Cells, 8:447, (1982).
24- B. Guilbert, G. Dighiero and S. Avrameas.
Naturally occurring antibodies against nine common antigens in human sera. I - Detection, isolation and characterization. The Journal of Immunology, 128:2779-2787 (1982).
25- G. Dighiero, B. Guilbert and S. Avrameas.
Naturally occurring antibodies against nine common antigens in human sera. II - High incidence of monoclonal Ig exhibiting antibody activity against actin and tubulin and sharing antibody specificities with natural antibodies. The Journal of Immunology, 128:2788-2792 (1982).
26- G. Dighiero, B. Guilbert, J.P. Fermant, P. Lymberi, F. Danon and S. Avrameas.
Thirty-six human monoclonal immunoglobulins with antibody activity against cytoskeleton proteins, thyroglobulin and native DNA: Immunologic studies and clinical correlations. Blood, 62:264-270 (1983).
27- G. Dighiero, P. Lymberi, J.C. Mazié, S. Rouyre, G.S. Butler-Browne, R.G. Whalen and S. Avrameas.
Murine hybridomas secreting natural monoclonal antibodies reacting with self antigens. The Journal of Immunology, 131:2267-2272 (1983).
28- S. Avrameas, G. Dighiero, P. Lymberi, and B. Guilbert.
Studies on natural antibodies and autoantibodies. Annals of Immunology (Inst. Pasteur), 134D:103-113 (1983).
29- G. Dighiero,, P. Lymberi, D. Holmberg, I. Lundquist, A. Coutinho and S. Avrameas.
High frequency of natural autoantibodies in normal newborn mice. The Journal of Immunology, 134:765-771 (1985).
30- P. Lymberi, G. Dighiero, T. Ternynck and S. Avrameas.
A high incidence of cross reactive idiotypes among murine natural autoantibodies. European Journal of Immunology, 15:702-707 (1985).
31- G. Dighiero, P. Lymberi, B. Guilbert, T. Ternynck and S. Avrameas.
Natural autoantibodies constitute a substantial part of normal circulating immunoglobulins. Autoimmunity: Experimental and clinical aspects Annals of the New-York Academy of Sciences, 475:135-145 (1986).
32- G. Dighiero, P. Poncet, S. Rouyre and J.C. Mazié.
Newborn Xid mice carry the genetic information for the production of natural autoantibodies against DNA, cytoskeletal proteins, and TNP. Journal of Immunology, 136:4000-4005 (1986).
33- C. Chastang, P. Travade, J. Benichou, G. Dighiero, J.L. Binet, and the Cooperative Group on CLL of Société Française d'Hématologie.
Patient accrual and interim statistical analysis in long-term randomized clinical trials : The french chronic lymphocytic leukemia CLL 80 protocol as a case study. Statistics in Medicine, 5:465-473 (1986).
34- French Cooperative Group on Chronic Lymphocytic Leukemia.
Effectiveness of "CHOP" regimen in advanced untreated chronic lymphocytic leukaemia. The Lancet, June 14: 1346-1349 (1986).
36- G. Dighiero, L. Intrator, C. Cordonnier, P. Tortevoye and J.P. Vernant.
High levels of anti-cytoskeleton autoantibodies are frequently associated with chronic GVHD. British Journal of Haematology, 67:301-305 (1987).
37- G. Dighiero, Ch. Magnac, J. de Saint Martin and N. Abuaf.
Detection of anti-mitochondrial antibodies by ELISA and Western-blot techniques and identification by one and two-dimensional gel electrophoresis of M2 target antigens. Clinical and experimental Immunology, 70:640-648 (1987).
38- G. Dighiero, A. Lim, P. Poncet, A. Kaushik, X.R. Ge and J.C. Mazié.
Age-related natural antibody specificities among hybridoma clones originating from NZB spleen. Immunology, 62:341-347 (1987). 39- F. Vuillier, Cath. Lapresle and G. Dighiero. Comparative analysis of CD4-4B4 and CD4-2H4 lymphocyte subpopulations in HIV negative homosexual, HIV seropositive and healthy subjects. Clinical and experimental Immunology, 71:8-12 (1988).
40- T. Matthes and G. Dighiero.
Detection of private and recurrent idiotopes on natural anti-tubulin antibodies by monoclonal anti-idiotopic antibodies. The Journal of Immunology, 140:148-154 (1988).
41- A. Kaushik, A. Lim, P. Poncet, X.R. Ge and G. Dighiero.
Comparative analysis of natural antibody specificities among hybridomas originating from spleen and peritoneal cavity of adult NZB and BALB/c mice. Scandinavian Journal of Immunology, 27:461-471 (1988).
42- F. Vuillier, N.E. Bianco, L. Montagnier and G. Dighiero.
Selective depletion of low density CD8+, CD16+ lymphocytes during HIV infection. AIDS Research and Human Retroviruses, 4: 121 (1988).
43- P. Poncet, T. Matthes, A. Billecocq and G. Dighiero.
Immunochemical studies of polyspecific natural autoantibodies : Charge, lipid reactivity, Fab'2 fragments activity and complement fixation. Molecular Imunology, 25:981-989 (1988).
44- T. Matthes, A. Wolff, P. Soubiran, F. Gros and G. Dighiero.
Antitubulin antibodies. II: Natural autoantibodies and induced antibodies recognize different epitopes on the tubulin molecule. The Journal of Immunology, 141:3135-3141 (1988).
45- A. Kaushik, T. Matthes and G. Dighiero.
Do natural autoantibodies play an important role in the elimination of senescent or damaged red blood cells ? Blood Cells, 14:161-170 (1988).
46- G. Dighiero, A. Lim, M.P. Lembezat, A. Kaushik, L. Andrade and A. Freitas.
Comparative study of VH gene family usage by new-born Xid and non-Xid mice, new-born NZB and adult NZB mice and by splenic and peritoneal cavity B-cell compartments. European Journal of Immunology, 18:1979-1983 (1988).
47- French Cooperative Group on Chronic Lymphocytic Leukemia (protocol CLL 80).
Comparison of the A, B, C staging and the Rai's staging from a large prospective series (935 patients). Nouvelle Revue Française d'Hématologie, 30:363-368 (1988).
48- J.L. Binet, D. Catovsky, G. Dighiero, R.P. Gale, E. Montserrat, K.R. Rai, C. Rozman and A. Sawitsky.
Chronic lymphocytic leukemia: Recommendations for diagnosis, staging and response criteria. Annals of Internal Medicine, 110: 236-238 (1989).
49- E. Goshen, A. Livne, M. Krupp, L. Hammarström, G. Dighiero, H. Slor, and Y. Shoenfeld.
Antinuclear and related autoantibodies in sera of healthy subjects with IgA deficiency. Journal of Autoimmunity, 2:51-60 (1989).
50- P. Poncet, L. Reininger, A. Freitas, D. Holmberg, G. Dighiero, and A. Coutinho.
Expression of VH11 gene family in hybridoma collections from peritoneum and spleen: differential correlation with BrMRBC reactivity. Res. Immunol., 140:255-264 (1989).
51- J.L. Binet, D. Catovsky, C. Chastang, G. Dighiero, J. Fooks, D.A.G. Galton, A. Gates, T.J. Hamblin, T. Han, M.M. Hansen, M.J. Keating, E. Monserrat, G.A. Pangalis, A. Polliack, K.R. Rai, S. Richards, D.K. Rai, S. Richards, D.K. Tessman and P. Wyld.
Prognostic features of early chronic lymphocytic leukaemia. The Lancet, october 21:968-969 (1989).
52- French Cooperative Group on Chronic Lymphocytic Leukaemia.
Long-term results of the CHOP regimen in stage C chronic lymphocytic leukaemia. British Journal of Haematology, 73:334-340 (1989).
53- French Cooperative Group on Chronic Lymphocytic Leukaemia.
Effects of chlorambucil and therapeutic decision in initial forms of chronic lymphocytic leukemia (stage A): Results of a randomized clinical trial on 612 patients. Blood, 75: 1414-1421 (1990).
54- French Cooperative Group on Chronic Lymphocytic Leukaemia.
A randomized clinical trial of chlorambucil versus COP in stage B chronic lymphocytic leukemia. Blood, 75:1422-1425 (1990).
55- R. Mayer, T. Logtenberg, J. Strauchen, A. Dimitriu-Bona, L. Mayer, S. Mechanic, N. Chiorazzi, L. Borche, G. Dighiero, A. Mannheimer-Lory, B. Diamond, F. Alt and C. Bona.
CD5 and immunoglobulin V gene expression in B cell lymphomas and chronic lymphocytic leukemia. Blood, 75:1518-1524 (1990).
56- L. Borche, A. Lim, J.-L. Binet and G. Dighiero.
Evidence that chronic lymphocytic leukemia B lymphocytes are frequently committed to production of natural autoantibodies. Blood, 76:562-569 (1990).
57- G. Dighiero, P. Lymberi, C. Monot and N. Abuaf.
Sera with high levels of anti-smooth muscle and anti-mitochondrial antibodies frequently bind to cytoskeleton proteins. Clinical and Experimental Immunology, 82:52-56 (1990).
58- A. Kaushik, R. Mayer, V. Fidanza, H. Zaghouani, A. Lim, C. Bona and G. Dighiero.
Ly1 and V-gene expression among hybridomas secreting natural autoantibody. Journal of Autoimmunity, 3:687-700 (1990).
59- French Cooperative Group on Chronic lymphocytic leukemia untreated patients Natural history of Stage
A chronic lymphocytic leukemia untreated patients. British Journal of Haematology, 76:45-57 (1990).
60- C. Magnac, J. de Saint Martin, D. Pidard, C. Legrand and G. Dighiero.
Platelet antibodies in serum of patients with human immunodeficiency-virus (HIV) infection. AIDS Research and Human Retroviruses, 6:1443-1449 (1990).
61- A. Cayota, F. Vuillier, D. Scott-Algara and G. Dighiero.
Preferential replication of HIV-1 virus in the CD45RA negative CD4+ subpopulation asymptomatic HIV-seropositive patients. The Lancet, 336:941 (1990).
62- D. Scott-Algara, F. Vuillier, M. Marasescu, J. de Saint Martin, and G. Dighiero.
Serum levels of IL-2, IL-1 , TNF and soluble receptor of IL-2 in HIV-1-infected patients. AIDS Research and Human Retroviruses, 7: 381-386 (1991).
63- F. Vuillier, D. Scott-Algara, P. Tortevoye, G. Pialoux and G. Dighiero.
Serial study of CD5-positive and CD5-negative B cell subpopulations in 335 HIV seropositive patients. Clinical and experimental Immunology, 85:476-480 (1991). 64- G. Dighiero, S. Hart, A. Lim, L. Borche, R. Levy and R.A. Miller. Autoantibody activity of immunoglobulins isolated from B-cell follicular lymphomas Blood, 78:581-586 (1991).
65-G. Dighiero, P. Travade, S. Chevret, P. Fenaux, C. Chastang, J.-L. Binet, and The French Cooperative Group on CLL.
B-Cell chronic lymphocytic leukemia. Present status and future directions. Blood, 78:1901-1914 (1991).
66- F. Vuillier, J.F. Claisse, C. VanDenVelde, Ph. Travade, C. Magnac, S. Chevret, J.L. Binet and G. Dighiero.
Evaluation of residual disease in B-cell chronic lymphocytic leukemia patients in clinical and bone-marrow remission using CD5-CD19 markers and PCR study of gene rearrangements. Leukemia and Lymphoma, 7:195-204 (1992).
67- A. Cayota, F. Vuillier, D. Scott-Algara, V. Feuillie and G. Dighiero.
Impaired proliferative capacity and abnormal cytokine profile of naive and memory CD4 T cells from HIV-seropositive patients Clinical and Experimental Immunology, 88:478-483 (1992).
68 - D. Scott-Algara, F. Vuillier, A. Cayota, and G. Dighiero.
NK cell activity during human immunodeficiency virus infection : a decrease in NK activity is observed at the clonal level and is not restored after in vitro long term culture of NK cells. Clinical and Experimental Immunology, 90:181-187, (1992).
69 - D. Scott-Algara, F. Vuillier, A. Cayota, V. Rame, D. Guétard, M. Marasescu, C. Dauguet, and G. Dighiero.
Non productive infection of purified NK cells by human immunodeficiency virus type 1 (HIV-1). Journal of General Virology, 74:725-731, (1993).
70 - A. Cayota, F. Vuillier, D. Scott-Algara, V. Feuillie and G. Dighiero.
Differential requirements for HIV-1 replication in naive and memory CD4 T-cells from asymptomatic HIV-1 seropositive carriers and AIDS patients Clinical and Experimental Immunology, 91:241-248, (1993).
71- M. Houdayer, J.-P. Bouvet, A. Wolff, C. Magnac, J.-C. Guillemot, L. Borche and G. Dighiero.
Simultaneous presence, in one serum, of four monoclonal antibodies which may correspond to different steps in the clonal evolution from polyreactive to monoreactive antibodies Journal of Immunology, 150:311-319, (1993).
72 - O. Pritsch, C. Magnac, G. Dumas, C. Egile and G. Dighiero.
V gene usage by seven hybrids displaying autoantibody activity, derived from CD5+ B-chronic lymphocytic leukemia (CLL) lymphocytes and displaying autoantibody activity. Blood, 151:3103-3112, (1993)
73 - The French Cooperative Group on Chronic Lymphocytic Leukemia.
Is the CHOP regimen a good treatment in advanced CLL (Stages B and C). Results from two randomized trials Leukemia and Lymphoma, 13 (5):449-456 (1994).
74- M.A. De La Fuente, E. Coumaran, A. Pereira, M. Juan, F. Vivanco, D. Roelcke, G. Dighiero and T. Galart.
Molecular characterization of a monoclonal IgMk (GAS) cold agglutinin (CA) of anti-Sia-Ib specificity that co-existed with a clonally related monoclonal IgG3k (GAS) lacking CA activity. Blood, 83:1310-1322 (1994).
75- A. Cayota, F. Vuillier, J. Siciliano and G. Dighiero.
Defective protein tyrosine phosphorylation and altered levels of p59fyn and p56lck in CD4 cells from HIV-1 infected patients. International Immunology, 6:611-621 (1994).
76 - H.W. Schroeder Jr. and G. Dighiero.
The pathogenesis of chronic lymphocytic leukemia: analysis of the antibody repertoire. Immunology Today, 15:288-294 (1994).
77 - R.P. Gale, F. Caligaris-Cappio, G. Dighiero, M. Keating, E. Montserrat, K. Rai.
Recent progress in Chronic Lymphotyic Leukemia. Leukemia, 8 (9):1610-1614 (1994).
78 -D. Scott-Algara, M. Lafon, F. Vuillier, G. Pialoux, Ch. Dauguet and G. Dighiero.
Viral superantigen-induced anergy of T cell and polyclonal B-cell activation in HIV-1 infection. European Journal of Immunology, 24:595-2601 (1994).
79 - K. Maloum, F. Davi, C. Magnac, O. Pritsch, E. McIntyre, F. Valensi, J.L. Binet, H. Merle-Beral, G. Dighiero.
Analysis of VH gene expression in CD5+ and CD5- B-CLL. Blood , 86:3883-389 (1995).
80 - K. Maloum, C. Magnac, O. Pritsch, J.L. Binet, H. Merle-Béral, G. Dighiero.
Skewed rearrangement of the VH4-21 gene during pre-B acute lymphoblastic leukemia. Leukemia and Lymphoma, 17:435-441 (1995).
81 - F. Vuillier, D. Scott-Algara, A. Cayota, J. Siciliano, MP.-T. Nugeyre, G. Dighiero.
Flow cytometric analysis of protein-tyrosine phosphorylation in peripheral T-cell subsets: application to healthy and HIV-seropositive subjects. Journal of Immunologicall Methods, 185:43-56, (1995).
82 - A. Cardona, O. Pritsch, G. Dumas, J.-F. Bach, G. Dighiero.
Evidence for an antigen driven selection process in human autoantibodies against acethylcholine receptor. Molecular Immunology, 32:1215-1223, (1995).
83 - V. Eclache, C. Magnac, H.J. Delecluse, F. Davi, M. Raphael, G. Dighiero.
Complete Nucleotide Sequence of Ig B Genes in Three Cases of Burkitt Lymphoma Associated with AIDS. Leukemia and Lymphoma, 20:281-290, (1996).
84 - L. Diaw, C. Lefebvre d'Hellencourt, P. Cornillet, F. Vuillier, M. Guenounou, G. Dighiero.
Expression and production of cytokines by heterohybrids and their parental B cells in CLL., Leukemia and Lymphoma, 21:281-291, (1996).
85 - A. Cayota, F. Vuillier, G. Gonzalez, and G. Dighiero.
CD4+ lymphocytes from HIV-infected patients display impaired CD45-associated tyrosine phosphatase activity which is enhanced by anti-oxidants. Clinical and Experimental Immunology, 104:11-17, (1996).
86 - A. Cayota, F. Vuillier, G. Gonzalez, and G. Dighiero.
In vitro antioxidant treatment recovers proliferative response of anergic CD4+ lymphocytes from human immunodeficiency virus-infected individuals. Blood, 87:4746-4753, (1996).
87 - O. Pritsch, G. Hudry-Clergeon, M. Buckle, Y. Pétillot, J.P. Bouvet, J. Gagnon, and G. Dighiero.
Can immunoglobulin CH1 constant region domain modulate antigen binding affinity of antibodies. Journal of Clinical Investigation, 98 (10):2235-2243, (1996).
88 - F. Davi, K. Maloum, A. Michel, O. Pritsch, C. Magnac, E. Macintyre, F. Salomon-Nguyen, J.L. Binet, G. Dighiero, and H. Merle-Béral.
High frequency of somatic mutations in the VH genes expressed in prolymphocytic leukemia. Blood, 88:3953-3961, (1996).
89 - L. Diaw, C. Magnac, O. Pritsch, M. Buckle, P.M. Alzari, and G. Dighiero.
Structural and affinity studies of IgM polyreactive natural autoantibodies. Journal of Immunology, 158:968-976, (1997).
90 - K. Maloum, O. Pritsch, C. Magnac, F. Davi, J.L. Binet, H. Merle-Béral, and G. Dighiero.
VH gene expression in CD5 positive and CD5 negative B cell chronic lymphoid malignancies. Leukemia and Lymphoma, 24 (5-6):437-448, (1997).
91 - M. Brugiatelli, J.F. Claisse, B. Lenormand, F. Morabito, V. Callea, K. Maloum, S Chevret, J.L. Binet, G. Dighiero, P. Travade.
Long-term clinical outcome of B-cell lymphocytic leukaemia patients in clinical remission phase evaluated at phenotypic level. British Journal of Haematology, 97:113-118, (1997).
92 - G. Dumas, O. Pritsch, A. Pereira, T. Gallart, and G. Dighiero.
A murine model of human cold agglutinin disease. British Journal of Haematol ogy, 98:589-596, (1997).
93- K. Maloum, C. Magnac, Z. Azgui, C. Cau, F. Charlotte, J.L. Binet, H. Merle-Béral, and G. Dighiero.
VH gene expression in hairy cell leukemia. British Journal of Haematology, 101 (1):171-178, (1998).
94- G. Dighiero, K. Maloum, B. Desablens, B. Cazin, M. Navarro, R. Leblay, M. Leporrier, J. Jaubert, G. Lepeu, B. Dreyfus, J.L. Binet, P. Travade for the French Cooperative Group in CLL.
Chlorambucil in indolent chronic lymphocytic leukemia New England Journal of Medicine, 338:1506-1514, (1998).
95- J.P. Bouvet, G. Dighiero.
From natural polyreactive autoantibodies to A La Carte monoreactive antibodies to infectious agents: is it a small world after all? Infection and Immunity, 66 (1):1-4, (1998).
96- F. Fais, F. Ghiotto, S Hashimoto, B Sellars, S.L. Allen, P. Schulman, V.P. Vinciguerra, K Rai, L.Z. Rassenti, T.J. Kipps, G. Dighiero, H.W. Schroeder Jr, M. Ferrarini, N. Chiorazzi.
Ig heavy chain variable region gene sequence analyses of IgM+ and non-IgM+ chronic lymphocytic leukemia B cells suggest selection for distinct surface membrane receptors. Journal of Clinical Investigation, 102: 1515-1525, (1998).
97- H. Gonzalez, V. Leblond, Z. Azgui, C. Cau, F. Charlotte, J.L. Binet, H. Merle-Beral, and G. Dighiero.
Severe autoimmune hemolytic anemia in eight patients treated with fludarabine. Hematology and Cell Therapy, 40: 113-118, (1998).
98- C. Brito, N. Naviliat, A. Tiscornia, F. Vuillier, G. Gualco, G. Dighiero, R. Radi, and A. Cayota.
Peroxynitrite inhibits T-lymphocyte activation and proliferation by promoting impairment of tyrosine phosphorylation and activation-induced apoptotic death. Journal of Immunology, 162(6):3356-3366, (1999).
99- B. Payelle-Brogard, C. Magnac, F. Mauro, F. Mandelli and G. Dighiero.
Analysis of the B-Cell Receptor B29 (CD79b) gene in Familial Chronic Lymphocytic Leukemia Blood, 94:3516-3522, (1999).
100- L. Diaw, D. Siwarski, A. Coleman, J. Kim, G. Jones, G. Dighiero, and K. Huppi.
Restricted Ig-V gene expression accompanies secondary rearrangements of Ig-VL genes in mouse plasmacytomas. Journal of Experimental Medicine, 190 (10):1405-1416, (1999).
101- G. Dighiero, and N.R. Rose.
Natural autoantibodies, B-cell, Tolerance and Autoimmunity - The discrepancy between Ehrlich's views and those of Metchnikoff on autoimmunity. Immunology Today, 20(9):423-427, (1999).
102- O. Pritsch, X. Troussard, C. Magnac, F.R. Mauro, F. Davi, B. Payelle-Brogard, G. Dumas, M. Pulik, F. Clerget, F. Mandelli, N. Chiorazzi, H.W. Schroeder Jr, M. Leporrier, and G. Dighiero.
VH gene usage by family members affected with chronic lymphocytic leukaemia. British Journal of Haematology, 107(3):616-624, (1999).
103- C. Magnac, L. Sutton, B. Cazin, C. Laurent, J.-L. Binet, H. Merle-Béral, G. Dighiero and K. Maloum.
Detection of minimal residual disease in B Chronic Lymphocytic Leukemia (CLL). Hematology and Cell Therapy, 40:13-18 (1999).
104- M. Levy, L. Edelman, G. Dighiero.
Sequence Homologies between a Monoclonal Murine Anti-Blood Group A and Antibodies Recognizing Carbohydrate Antigens of Red Blood Cells. Vox Sanguinis, 79(4), 251 (2000).
105- S. Havouis, S., Dumas, G., Ave, P., Pritsch, O., Huerre, M., Dighiero, G. & Pourcel, C.
Negative regulation of autoreactive B cells in transgenic mice expressing a human pathogenic cold agglutinin. European Journal of Immunology, 30:2290-2299, (2000).
106- K. Maloum, O. Pritsch, C. Magnac, F. Vuillier, F. Davi, X. Troussard, F. F. Mauro, J. Bénichou, H. Merle-Béral, G. Dighiero.
Expression of unmutated VH genes is a detrimental prognostic factor in Chronic Lymphocytic Leukemia. Blood, 96:377-379, (2000)
107- J.P. Bouvet & G. Dighiero.
Cross-reactivity and polyreactivity: the two sides of a coin [letter]. Immunology Today, 21:411-241, (2000).
108- G. Dighiero & J.L. Binet.
When and how to treat Chronic Lymphocytic Leukemia Editorial. New England Journal of Medicine, 343 (24):1799-1801, (2000).
109- O. Pritsch, C. Magnac, G. Dumas, J.P. Bouvet, P. Alzari and G. Dighiero.
Can Isotype Switch Modulate Antigen Binding Affinity And Influence Clonal Selection? European Journal of Immunology, 30(12):3387-3395, (2000).
110- M. Levy, L. Edelman, and G. Dighiero.
Molecular characterization of a monoclonal murine anti-blood group A antibody. Immunology Letters, 76:15-23, (2001).
111- J.P. Bouvet, C.P. Quan, and G. Dighiero.
Polyreactivity is not an artefact. (Originally published in J. Immunol. Methods 254 (2001) 199-201). Journal of Immunological Methods, 257:221-223, (2001).
112- M. Leporrier, S. Chevret, B. Cazin, N. Boudjerra, P. Feugier, B. Desablens, M.J. Rapp, J. Jaubert, C. Autrand, M. Divine, B. Dreyfus, K. Maloum, P. Travade, G. Dighiero, J.L. Binet, and C. Chastang for the French Cooperative Group on CLL.
Randomized comparison of fludarabine, CAP, and ChOP in 938 previously untreated stage B and C chronic lymphocytic leukemia patients. Blood, 98:2319-2325, (2001).
113- J.P. Bouvet, C.P. Quan, and G. Dighiero.
Polyreactivity is not an artefact. Journal of Immunological Methods, 254:199-201, (2001).
114- M. Leporrier, S. Chevret, B. Cazin, N. Boudjerra, P. Feugier, B. Desablens, M.J. Rapp, J. Jaubert, C. Autrand, M. Divine, B. Dreyfus, K. Maloum, P. Travade, G. Dighiero, J.L. Binet, and C. Chastang for the French Cooperative Group on CLL.
Randomized comparison of fludarabine, CAP, and ChOP in 938 previously untreated stage B and C chronic lymphocytic leukemia patients. Blood, 98:2319-2325, (2001).
115- F. Vuillier, K. Maloum, E.K. Thomas, C. Jouanne, G. Dighiero and D. Scott-Algara.
Functional monocyte-derived dendritic cells can be generated in Chronic Lymphocytic Leukemia. British Journal of Haematology, 115(4):831-844, (2001).
116 - S. Havouis, G. Dumas, I. Chambaud, P. Ave, M. Huerre, A. Blanchard, G. Dighiero, and C. Pourcel.
Transgenic B lymphocytes expressing a human cold agglutinin escape tolerance following experimental infection of mice by Mycoplasma pulmonis. European Journal of Immunology, 32 :1147-1156, (2002).
117 - B. Payelle-Brogard, C. Magnac, A. Alcover, P. Roux, and G. Dighiero.
Defective assembly of the B-cell receptor chains accounts for its low expression in B-chronic lymphocytic leukaemia. British Journal of Haematology, 118(4):976-985, (2002).
118 - P. Oppezzo, C. Magnac, S. Bianchi, F. Vuillier, A. Tiscornia, G. Dumas, B. Payelle-Brogard, F. Ajchembaum-Cymbalista, G. Dighiero, and O. Pritsch.
Do CLL B cells correspond to naive or memory B-lymphocytes ? Evidences for an active Ig switch unrelated to phenotypic expression and Ig mutational pattern in B-CLL cells. Leukemia, 16(12):2438-46, (2002).
119 - I. Theodorou, L. Abel, F. Mauro, B. Duprey, C. Magnac, B. Payelle-Brogard, F. Davi and G. Dighiero.
High occurence of DRB1 11 in chronic lymphocytic leukaemia families British Journal of Haematology, 119 :713-715, (2002).
120 - F. Vuillier, K. Maloum, E.K. Thomas, C. Magnac, G. Dumas, B. Payelle-Brogard, P. Oppezzo, G. Dighiero and D. Scott-Algara.
Idiotype-pulsed dendritic cells are able to induce anti-tumoral cytotoxic CD8 cells in chronic lymphocytic leukaemia. British Journal of Haematology, 120(2) :243, (2003).
121- C. Magnac, R. Porcher, F. Davi, J. Nataf, B. Payelle-Brogard, R.P. Tang, P. Oppezzo, V. Lévy, G. Dighiero, F. Ajchenbaum-Cymbalista.
Serum thymidine kinase level is a good predictor for Ig-V mutational status in B-CLL. Leukemia, sous presse, (2002).
122- P. Oppezzo, F. Vuillier, Y. Vasconcelos, G. Dumas, C. Magnac, B. Payelle-Brogard, O. Pritsch, G. Dighiero.
CLL B-cells expressing AID display a dissociation between class switch recombination and somatic hypermutation. Blood, 101 (10) :4029-4032, (2003).
123- B. Payelle-Brogard, C. Magnac, P. Oppezzo, G. Dumas, G. Dighiero, and F. Vuillier.
Retention and defective assembly of the B-cell receptor in the endoplasmic reticulum of Chronic Lymphocytic Leukemia B cells cannot be reverted upon CD40 ligand stimulation. Leukemia, , (2003).
124- Y. Vasconcelos, F. Davi, V. Levy, P. Oppezzo, C. Magnac, A. Michel, M. Yamamoto, O. Pritsch, H. Merle-Béral, K. Maloum, F. Ajchembaum-Cymbalista, and G. Dighiero.
Binet's staging system and VH genes are independent but complementary prognostic indicators in CLL. Journal of Clinical Oncology, (2003).
125- G. Dighiero.
Unsolved issues in CLL biology and management. Leukemia, (2003).
126- A.C. Tiscornia, A. Cayota, A.I. Landoni, C. Brito, P. Oppezzo, F. Vuillier, C. Robello, G. Dighiero, R. Gabus, O. Pritsch.
Post-transcriptional regulation of inducibl nitric oxide synthase in chronic lymphocytic leukemia B cells in pro-apoptotic and anti-apoptotic culture conditions. Leukemia, (2003).
Fundación "Lolita Rubial"
Minas, noviembre de 2004.