Fiorella Petronzelli - Academia.edu (original) (raw)

Papers by Fiorella Petronzelli

Disease Markers, 1996

Celiac disease HLA typing Accumulating evidence shows that susceptibility to celiac disease (CD) ... more Celiac disease HLA typing Accumulating evidence shows that susceptibility to celiac disease (CD) is conferred by the HLA-DQ2 heterodimer encoded by the DQA 1 *0501 and DQB 1 *020 1 alleles usually inherited in cis with the DRB 1 *03 haplotype or in trans with the DRB 1 *05 and DRB I *07 haplotypes (

Tissue Antigens, 1992

Abstract: Oligotyping for HLA-DRB1, DQA1 and DQB1 specificities has been performed on PCR-amplifi... more Abstract: Oligotyping for HLA-DRB1, DQA1 and DQB1 specificities has been performed on PCR-amplified DKA from 55 Italian celiac children, living in Rome. and 50 blood donors. 52.6% of CD patients were DR3;DQ A1 *0501; DQB 1 *0201 -positive versus 14% of controls (RR = 6.85) and 34.5% were DR5,7;DQA1*0501;DQB1*0201-positive versus 2% of controls (RR = 25.86). 7 patients (12.7%) were negative for the DQA1 *0501/B1 *0201 dimer: 3 of them were DR4 (5.4%) and the others typed as DR1,5; 1,7: 5,7 and w6,7. No patient was negative for both DQA1*0501 and DQB1*0201 alleles.

Human Immunology, 1993

We here describe the case of a serological HLA-A blank found to segregale from a female ~o her ch... more We here describe the case of a serological HLA-A blank found to segregale from a female ~o her child and the subsequent molecular analysis of the corresponding HLA-A allele The mother was serologP tally typed A2 = 338 -Cw4 -. and the child A3 -r 835. 851. CW4 --mUS leading to the feature of reverse HLA-A homozygosltv We iso-

Human Heredity, 2000

The involvement of HLA genes in the susceptibility to coeliac disease (CD) has been well document... more The involvement of HLA genes in the susceptibility to coeliac disease (CD) has been well documented and represents the only consistently observed genetic feature of this multifactorial disease. In the present study, the search for new susceptibility genes has been devoted to a candidate region suggested by the association of CD with Williams syndrome (WS). This genetic disorder is due to a deletion in the 7q11.23 region that includes the elastin (ELN) gene. An increased prevalence of CD in WS patients has been previously reported and a case of CD-WS is also described in the present study. We used the ELN17 microsatellite marker mapped within the ELN gene to look for a possible contribution of this region to the susceptibility to CD. The analysis of 74 Italian CD families provided no evidence of association with the ELN17 marker.

Annals of Human Genetics, 1997

In order to assess the effect of the HLA region on familiality of coeliac disease (CD), we carrie... more In order to assess the effect of the HLA region on familiality of coeliac disease (CD), we carried out a study on 121 CD index cases and 325 first degree relatives. The transmission disequilibrium test confirmed the importance of the HLA-DR3 haplotype in CD susceptibility. However, the different distortion found in affected children inheriting maternal or paternal DR3 alleles suggested that the sex of the parent might influence the risk conferred by this haplotype. The increase in risk to siblings of affected individuals relative to the risk in the general population (λ s ) and the contribution of the HLA genes to this clustering (λ sHLA ) have also been estimated. Non-overlapping data from the literature have been collected and combined with our sample to extend such analysis. Then, the percentage contribution of the HLA region to the development of CD among siblings was 36n2%. This result confirms that the HLA genotypes are an important genetic background to CD development but shows that additional susceptibility factors remain to be identified.

Acta Paediatrica, 1994

The presence of dental enamel defects in coeliac disease and their relation to hypocalcaemia or a... more The presence of dental enamel defects in coeliac disease and their relation to hypocalcaemia or a particular HLA class in 82 Italian children with coeliac disease was studied. Demarcated opacities or hypoplasia were detected in 23 subjects (group 1) while minimal or no dental lesions were found in the remaining 59 patients (group 2); in 189 normal controls, enamel lesions were significantly less frequent than in patients with coeliac disease (14.8% versus 28.0%; p < 0.005). No statistically significant differences were found for age at diagnosis and calcium concentrations between groups 1 and 2. Regression analysis showed a correlation between age at diagnosis and number of teeth with enamel defects. In our patients, the presence of HLA DR3 antigen significantly increased the risk of dental lesions, while genotype DR5,7 seemed to protect against enamel defects. A logistic regression analysis of the variables age, serum calcium concentrations, number of affected teeth, type of enamel defect and DR antigens showed that only DR antigens discriminated coeliac disease patients with from those without enamel defects.

Human Immunology, 1992

Celiac disease (CD) has been recently reported to be primarily associated with the DQ(c~I*0501, /... more Celiac disease (CD) has been recently reported to be primarily associated with the DQ(c~I*0501, /31"0201) heterodimer encoded in cis on DR3 haplotype and in trans in DR5,7 heterozygous individuals. The high incidence of DR5,7 heterozygotes, reflecting the high frequency of the DR5 allele in Italy, makes the analysis of the Italian CD patients critical.

Annals of Human Genetics, 1997

Human Immunology, 1993

To compare the quantitative effect of the DQc~/3 heterodimers DQa52Arg+,357Asp-and DQa 1 *0501,31... more To compare the quantitative effect of the DQc~/3 heterodimers DQa52Arg+,357Asp-and DQa 1 *0501,31"0201 on susceptibility to IDDM and CD, we characterized, at the genomic level, the DQce 52 and DQ3 57 residues of 50 IDDM Italian patients observed in Rome. The results were compared with those of a previous study concerning the oligotyping of DQ dimers in a group of CD children belonging to the same population. Our data confirm that both diseases are primarily associated with HLA-DQoq3 heterodimers, but the distributions of the respective susceptible DQA 1 and DQB 1 alleles in the two diseases were different. In fact, the highest risk of IDDM is for subjects ceSS,/3SS that could express, by either cis-or trans-association, four susceptible heterodimers and decreases in proportion to the number of these; in regard to CD, the highest risk was found for individuals who carried only one predisposing heretodimer. Human Immunology 36. 156-162 ¢1993~

Tissue Antigens, 1991

Abstract: Using PCR and SSO probes from the 11th International Histocompatibility Workshop, we ol... more Abstract: Using PCR and SSO probes from the 11th International Histocompatibility Workshop, we oligotyped for HLA-DRB1 gene and DQA1*0501, DQB1*0201 alleles 10 celiac families each with 2 affected children. All families belong to the Italian population except for one, whose mother is originaly from Cape Verde island. 8/10 sibling pairs share the DQA1*0501/B1*0201 heterodimer, inherited in cis or in trans arrangement. All the dimer-negative patients were DR4-positive.

Tissue Antigens, 1995

Abstract: Polymorphism in the 5′-upstream regulatory region of the DQA1 gene has been recently de... more Abstract: Polymorphism in the 5′-upstream regulatory region of the DQA1 gene has been recently described. Using PCR-SSO method and SSCP analysis we have investigated this polymorphism in a group of 111 Italian blood donors which had been oligotyped for DRB1, DQA1 and DQB1 genes. Eight allelic variants were detected. Looking at the relationships among QAP sequences and DQA1 and DRB1 genes, three alternative situations were found: 1. a one-to-one relation between QAP and DQA1 alleles, independently of the other class II genes; 2. the same QAP allele in association with different DQA1-DRB1 haplotypes; 3. the same DQA1 allele with different QAP sequences according to the DRB1 specificity. No unexpected associations with DQB1 gene were found. These results must be interpreted considering that DQA1 and DRB1 genes are transcribed in opposite directions so that the promoter region of DQA1 gene lies between DQA1 and DRB1, close to the former but several hundreds kb away from the latter.

Human Immunology, 1998

Polymorphism in the HLA-DQA1 promoter (QAP) sequences could influence the gene expression through... more Polymorphism in the HLA-DQA1 promoter (QAP) sequences could influence the gene expression through a differential binding of transcriptional factors. Considering the main role played by the Y-box in the transcription, we focused on the QAP4 variants differing for a G vs A transition from the QAP Y-box consensus sequence. Electrophoretic Mobility Shift Assay using the two Y-box sequences was performed to determine whether this mutation could be reflected in an allele-specific binding of transcriptional factors. Indeed, the NF-Y specific band, recognised by supershift experiments, was clearly observed using the Y-box consensus probe but it was barely detectable with the QAP4 one. On the contrary, two other complexes were found to more strongly interact with QAP4 Y-box in comparison to the consensus sequence.

Journal of Biological Chemistry, 2000

performance liquid chromatography; BisTris, bis(2-hydroxyethyl)iminotris(hydroxymethyl)methane.

Journal of Biomedicine and Biotechnology, 2009

Avidin is a glycoprotein from hen egg white that binds biotin with very high affinity. Here we de... more Avidin is a glycoprotein from hen egg white that binds biotin with very high affinity. Here we describe OXavidin, a product containing aldehyde groups, obtained by ligand-assisted sugar oxidation of avidin by sodium periodate. OXavidin chemically reacts with cellular and tissue proteins through Schiff 's base formation thus residing in tissues for weeks while preserving the biotin binding capacity. The long tissue residence of OXavidin as well as that of OXavidin/biotinylated agent complex occurs in normal and neoplastic tissues and immunohistochemistry shows a strong and homogenous stromal localization. Once localized in tissue/tumor, OXavidin becomes an "artificial receptor" for intravenous injected biotin allowing tumor targeting with biotinylated therapeutics like radioisotopes or toxins. Moreover, present data also suggest that OXavidin might be useful for the homing of biotinylated cells. Overall, OXavidin exhibits a remarkable potential for many different therapeutic applications.

BMC Biotechnology, 2007

Background There is much evidence that tumor cells elicit a humoral immune response in patients. ... more Background There is much evidence that tumor cells elicit a humoral immune response in patients. In most cases, the presence of antibodies in peripheral blood is detected only in small proportion of patients with tumors overexpressing the corresponding antigen. In the present study, we analyzed the significance of local humoral response provided by tumor-infiltrating lymphocytes in breast cancer patients. Methods The ability of a patient's immune system to produce specific antibodies inside tumor tissue, capable of recognizing tumor cells, was explored through analysis of the oligoclonality of antibodies derived from tumor-infiltrating lymphocytes and construction of a series of recombinant antibody libraries in scFv format, derived from breast tumor-infiltrating B lymphocytes. These libraries and one from peripheral blood lymphocytes of a single breast cancer patient were panned against three purified surface tumor antigens, such as CEA, MUC1 and ED-B domain, and against intact MCF7 breast carcinoma cells. Results Application of novel display vector, pKM19, allowed isolation of a large panel of breast cancer-specific antibodies against known tumor antigens, as well as against breast carcinoma cells. Reactivity of novel scFvs was confirmed by ELISA, immunohistochemistry, fluorescence staining and flow cytometry. We demonstrated that seven of ten primary breast tumor specimens, obtained using discarded surgical material, could be exploited as an appropriate source for generation of phage display libraries, giving highly specific antitumor antibodies which recognize heterologous tumor cells. Conclusion Local humoral immune response within tumor tissue in breast cancer patients frequently has an oligoclonal character. Efficient selection of specific antitumor antibodies from recombinant antibody libraries, derived from such oligoclonal tumor-infiltrated B lymphocytes, indicates the presence of natural immune response against tumor antigens in these patients. The described method is very promising for development of antitumor antibodies, potentially useful for diagnostic and therapeutic approaches.

PLOS One, 2011

We recently reported that the oxidized avidin, named AvidinOXH, resides for weeks within injected... more We recently reported that the oxidized avidin, named AvidinOXH, resides for weeks within injected tissues as a consequence of the formation of Schiff's bases between its aldehyde groups and tissue protein amino groups. We also showed, in a mouse pre-clinical model, the usefulness of AvidinOX for the delivery of radiolabeled biotin to inoperable tumors. Taking into account that AvidinOX is the first oxidized glycoprotein known to chemically link to injected tissues, we tested in the mouse a panel of additional oxidized glycoproteins, with the aim of investigating the phenomenon. We produced oxidized ovalbumin and mannosylated streptavidin which share with avidin glycosylation pattern and tetrameric structure, respectively and found that neither of them linked significantly to cells in vitro nor to injected tissues in vivo, despite the presence of functional aldehyde groups. The study, extended to additional oxidized glycoproteins, showed that the in vivo chemical conjugation is a distinctive property of the oxidized avidin. Relevance of the high cationic charge of avidin into the stable linkage of AvidinOX to tissues is demonstrated as the oxidized acetylated avidin lost the property. Plasmon resonance on matrix proteins and cellular impedance analyses showed in vitro that avidin exhibits a peculiar interaction with proteins and cells that allows the formation of highly stable Schiff's bases, after oxidation.

British Journal of Cancer, 2003

The Pretargeted Antibody-Guided RadioImmunoTherapy (PAGRIT) method is based on intravenous, seque... more The Pretargeted Antibody-Guided RadioImmunoTherapy (PAGRIT) method is based on intravenous, sequential administration of a biotinylated antibody, avidin/streptavidin and (90)Y-labelled biotin. The hybridoma clone producing the monoclonal antitenascin antibody BC4, previously used for clinical applications, was found not suitable for further development because of the production of an additional, nonfunctional light chain. In order to solve this problem, the new cST2146 hybridoma clone was generated. The monoclonal antibody ST2146, produced by this hybridoma, having the same specificity as BC4 but lacking the nonfunctional light chain, was characterised. ST2146 was found able to bind human tenascin at an epitope strictly related, if not identical, to the antigenic epitope of BC4. It showed, compared to BC4, higher affinity and immunoreactivity and similar selectivity by immunohistochemistry. Biodistribution studies of biotinylated ST2146 and three other monoclonal antitenascin antibodies showed for ST2146 the highest and more specific tumour localisation in HT29-grafted nude mice. On the overall, ST2146 appears to be a good alternative to BC4 for further clinical development of PAGRIT.

SUMMARY Here we present our experience in the clinical and pre-clinical use of avidin and avidin ... more SUMMARY Here we present our experience in the clinical and pre-clinical use of avidin and avidin chemical derivatives for clearing or targeting biotinylated therapeutics. Our data show that, despite immunogenicity, the avidin-biotin system can be exploited for safe, selective and efficient therapeutic approaches.

Disease Markers, 1996

Tissue Antigens, 1992

Human Immunology, 1993

Human Heredity, 2000

Annals of Human Genetics, 1997

Acta Paediatrica, 1994

Human Immunology, 1992

Annals of Human Genetics, 1997

Human Immunology, 1993

Tissue Antigens, 1991

Tissue Antigens, 1995

Human Immunology, 1998

Journal of Biological Chemistry, 2000

performance liquid chromatography; BisTris, bis(2-hydroxyethyl)iminotris(hydroxymethyl)methane.

Journal of Biomedicine and Biotechnology, 2009

BMC Biotechnology, 2007

PLOS One, 2011

British Journal of Cancer, 2003