Giuseppina Ruggiero
Giuseppina Ruggiero
affiliation: Università di Napoli Federico II
research area(s): Immunity And Infection, Cell Biology
Course: Molecular Pathology and Pathophysiology
University/Istitution: Università di Napoli Federico II
Academic Degrees:
1980 "Dottore in Medicina e Chirurgia" summa cum laude from the University of Naples "Federico II".
1983 Specialista in Oncologia from the Catholic University of Rome

Positions Held in the University and in other Research Institutions:
1984-1990 Research fellow, Chair of Immunology, Department of Cellular and Molecular Biology and Pathology University of Naples Federico II, Director Prof S. Zappacosta.
1990-1999 Tecnico laureato, Chair of Immunology, Department of Cellular and Molecular Biology and Pathology, University of Naples Federico II, Director Prof. S. Zappacosta.
from 2001 University Researcher, Chair of Immunology, Department of Cellular and Molecular Biology and Pathology, University of Naples Federico II.

Research Stays Abroad:
1993-1995 Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. Collaboration with H. Spits and A.M. Kruisbeek

Scientific Activity:
Main Research Lines Pursued:
- Study of the biology of HLA: HLA and disease association; Role of HLA class II antigens in the regulation of TCR dependent T cell activation
- Study of CD40-dependent co-stimulatory pathways in lymphocyte activation: Role of CD40/CD154 interaction in T cell development and selection processes and in eliciting NK distinct effector functions, like cytotoxicity and/or citokine production, in human models. Definition of the role of CD40 dependent pathways in the functional interactions between melanoma cells and the immune effectors.
- Study of immune-mediated mechanisms involved in the Selection/Expansion of Pathological precursors in Haematopoietic disorders.

Participation as responsible for Working Unit at the research projects:
1999-2001 Development of innovative strategies for diagnosis and prognostic evaluation of melanoma in humans (Italian Ministero Sanità grant 150.1/RF9.6)
2003-2005 Phenotypic and functional analysis of normal and defective T lymphocytes obtained from Paroxysmal Nocturnal Emoglobinuria affected patients (PRIN Project 2002)
2005-2007 Immune-mediated pathogenesis of Paroxysmal Nocturnal Haemoglobinuria and MyelodysplasticSyndromes: study of lymphoid compartment. (PRIN Project 2005)
2008-2010 Immune-mediated pathogenesis of Paroxysmal Nocturnal Hemoglobinuria and Myelodylpastic Syndromes: an analysis of the tolerance control mechanisms. (PRIN Project 2007)

Membership in Scientific Societies:
Since 1987 Gruppo di Cooperazione in Immunologia (GCI), now Italian Society of Immunology, Clinical Immunology and Allergology (SIICA)
Since 1992 European Foundation of Immunogenetics (EFI)
Since 1992 Scuola Superiore di Immunologia Ruggero Ceppellini (from 1997-2001 in the Director's Board, as Scientific Secretary)
Since 2004 Gruppo Italiano di Citometria (GIC; Cytometry Italian Association)
Paroxysmal Nocturnal Haemoglobinuria (PNH) and Myelodysplastic Syndromes (MDS) represent haematopoietic disorders characterised by the clonal expansion and dominance of pathological haematopopietic progenitors.
In PNH the occurrence in a stem progenitor of a somatic mutation of the PIG-A gene, involved in the first steps of the biosynthesis of the Glycosyl-Phosphatidyl-Inositol (GPI) anchor has been observed to be insufficient to account for the clonal dominance of the mutated clone. In this regard, we and others suggested the involvement of immune-mediated mechanisms for the GPI-defective clonal emergence and dominance.
MDS are clonal disorders characterised by an ineffective haematopoiesis followed by frequent development of leukemia, whose aetiology is still unclear. Notably, the onset of idiopathic MDS depends on a complex sequence of events including immune-mediated suppression of progenitor cells growth. A number of data have been indicating that a common pathogenetic background could underlie haemopoietic disorders characterised by clonal expansions/dominance, as PNH and MDS. In this context the occurrence of an immune-mediated attack against autologous haemopoietic progenitors and/or mesenchimal elements has been hypothesised.
Our recent data proposed that functional persistence of CD154 (CD40 ligand), whose involvement in the pathogenesis of auto-immune disorders has been described, is relevant for the expansion and dominance of GPI-defective clones in PNH patients. In addition, the possibility that additional tolerance control mechanisms might be involved in the selection of GPI-defective clones is currently investigated.
A complex network of peripheral mechanisms usually accounts for the control of immune response. Regulatory systems include mechanisms intrinsic to the antigen activation and to T cell differentiation as well as those mediated by regulatory CD4+CD25+Fox-p3+ (Treg) and Valpha24Vbeta11 NKTi populations. Notably, the availability of Treg subset is strictly dependent on the cytokine milieu, as represented by TGF-beta/IL-6 production ratio.
Our data showed that an NK-dependent mechanism might be relevant for the selection, expansion and progression of a dysplastic progenitor in one MDS patients. In addition, we consistently found that a low level of BM Treg in the presence of increased BM recruitment of CD8 lymphocytes and/or the presence of high CD54 expression on BM CD8 in patients characterise a subgroup of MDS patients in the first stage of the disease. Such data suggest that this immune profiles could provide useful criteria for a more homogeneous grouping of MDS patients in which the immune-pathogenesis might be inferred. Thus, we are addressing the hypothesis that grouping criteria based on above described immunological profiles might provide an useful tool to validate the occurrence of immune-pathogenesis in a subgroup of MDS patients and predict their response to immune-modulating therapeutic approaches.
1. Ulianich L, Terrazzano G, Annunziatella M, Ruggiero G, Beguinot F, Di Jeso B. (2011), ER stress impairs MHC Class I surface expression and increases susceptibility of thyroid cells to NK-mediated cytotoxicity. Biochem Biophys Acta. 1812:431-438

2. Cortese L., Terrazzano G., Piantedosi D, Sica M., Prisco M., Ruggiero G., Ciaramella P. (2011), Prevalence of anti-platelet antibodies in dogs naturally co-infected by Leishmania infantum and Ehrlichia canis. Vet. J.188:118-21

3. Alfinito F, Sica M, Luciano L, Della Pepa R, Palladino C, Ferrara I, Giani U, Ruggiero G, Terrazzano G. (2010) Immune dysregulation and dyserythropoiesis in MDS. Br. J. Haematol. 148:90-8

4. Cortese L., Sica M., Piantedosi D, Ruggiero G, Pero ME, Terrazzano G, Mastellone V, P. Ciaramella P. (2009) Secondary immune-mediated thrombocytopenia in dogs naturally infected by Leishmania infantum. Vet. Rec. 164:778-782

5. Ruggiero G, Sica M, Luciano L, Savoia F, Cosentini E, Alfinito F, Terrazzano G. (2009) A Case of Myelodysplastic syndrome associated with CD14+CD56+ monocytosis, expansion of NK lymphocytes and defect of HLA-E expression. Leuk Res 33:181-5.

6. Lombardi ML, Terrazzano G, Cosentini E, Gargiulo L, Risitano A, Camerlengo R, Sica M, Aufiero D, Poggi A, Pirozzi G, Rotoli B, Luzzatto L, Notaro R, Alfinito F, Ruggiero G. (2008) Paroxysmal Nocturnal Hemoglobinuria: significant association with specific HLA-A, B, C and DR alleles in Italian patients. Hum Immunol 69:202-6

7. Cacciapuoti C., Terrazzano G., Barone L., Becchimanzi C., Sica M.,Rotoli B., Ruggiero G., Alfinito F. (2007) GPI-defective PNH granulocytes show enhanced bacterial ingestion in the presence of decreased respiratory burst induction. American J Hematol. 82: 98-107.

8. Terrazzano G., Cortese L., Piantedosi D., Zappacosta S., Di Loria A., Santoro D., Ruggiero G., Ciaramella P. (2006) Presence of anti-platelet IgM and IgG antibodies in dogs naturally infected by Leishmania infantum. Vet. Immunol. Immunopathol. 110:331-7

9. Terrazzano G., Sica M., Becchimanzi C., Costantini S., Rotoli B., Zappacosta S., Alfinito F., Ruggiero G. (2005) T cells from Paroxysmal Nocturnal Hemoglobinuria (PNH) patients show an altered CD40-dependent pathway. J Leukoc Biol. 78:27-36.
Project Title:
Analysis of immune-mediated mechanisms involved in the selection, dominance and progression of dysplastic progenitors in Myelodysplastic Syndromes.

Project Title:
Analysis of immune-mediated mechanisms involved in the selection, expansion and dominance of GPI-defective progenitors in PNH.