47 results on '"autoimmunità"'
Search Results
2. Tiroide e nutrizione: non solo iodio
- Author
-
Ruggeri, Rosaria M., Migliaccio, Silvia, Cerutti, Matteo, Rotondi, Mario, and Croce, Laura
- Published
- 2024
- Full Text
- View/download PDF
3. La Sindrome Insulinica Autoimmune (Sindrome di Hirata): dalla clinica al trattamento
- Author
-
Verrienti, Martina, Daniele, Andrea, Lupo, Sabrina, Franceschetti, Paola, Zatelli, Maria Chiara, and Ambrosio, Maria Rosaria
- Published
- 2024
- Full Text
- View/download PDF
4. Clinical, immunological and genenetic profile of chronic neutropenia: beyond primary autoimmune and idiopathic forms
- Author
-
Beccaria, Andrea
- Subjects
Neutropenie pediatriche ,PIRD ,autoimmunità ,profilo linfocitario ,Settore MED/38 - Pediatria Generale e Specialistica ,pediatric neutropenia ,autoimmunity ,lymphocytes impairment ,Settore MED/15 - Malattie del Sangue - Published
- 2023
5. DISSECTING THE GENETIC ARCHITECTURE OF AUTOIMMUNITY: A SPOTLIGHT ON PRIMARY BILIARY CHOLANGITIS
- Author
-
30955, DIPARTIMENTO DI MEDICINA E CHIRURGIA (SCHOOL OF MEDICINE AND SURGERY), AREA MIN. 06 - SCIENZE MEDICHE, 30955, DIPARTIMENTO DI MEDICINA E CHIRURGIA (SCHOOL OF MEDICINE AND SURGERY), and AREA MIN. 06 - SCIENZE MEDICHE
- Abstract
ASSELTA, ROSANNA, open, The main goal of this PhD project was to leverage the great body of genetic knowledge generated by high-throughput DNA sequencing to better characterize the genetic architecture of immune diseases, with a main focus on Primary Biliary Cholangitis (PBC). Our work has employed established statistical methods such as meta-analysis as well as novel data mining tools, such as packages dedicated to the study of chromosome X (chrX) and Machine Learning (ML) softwares. In addition, we have also applied established computational methods and ML tools to shed light on the evolutionary history of variants associated with immune-mediated traits. More specifically, the meta-analysis of previous Genome-Wide Association Studies (GWAS) in PBC has identified additional risk loci and, by means of functional annotation of credible causal variants and multi-omic analysis, has produced a list of candidate genes together with several drugs that are potentially suitable for re-purposing to PBC. The extensive analysis of chrX has identified several suggestive new loci associated with PBC located on this chromosome. The major finding of the X-Wide Association Study (XWAS) approach has been the identification of a genome-wide significantly associated locus characterized by the presence of different genes and of a superenhancer possibly involved in their co-regulation, as well as in the regulation of FOXP3 (which is located in the same TAD). Based on the new set of variants identified in the international meta-analysis, we have generated a novel Polygenic Risk Score (PRS) that has been incorporated in a new integrative risk model. This model, that has included 22 non-HLA variants, one HLA variant and sex, is accurate (Area Under the Curve (AUC) 0.83 and 0.81 in the two cohorts under study) and well calibrated. The PRS has pinpointed a subgroup of subjects at strikingly higher risk (OR ~ 14) of developing the disease that should be the target of tailored follow-up strategies. Prospective studie, Lo scopo principale di questo lavoro di tesi di dottorato è stato l'utilizzo dell'ampio materiale genetico disponibile a seguito del sequenziamento del DNA per migliorare la caratterizzazione dell'architettura genetica delle malattie autoimmuni, con un focus specifico sulla Colangite Biliare Primitiva. Il nostro lavoro ha utilizzato metodi statistici "classici" come la meta-analisi e metodi di analisi dati nuovi, come pacchetti dedicati allo studio del cromosoma X e software di Machine Learning. Inoltre abbiamo applicate tecniche di biologia evoluzionistica computazionale per studiare la storia evolutiva delle varianti associate alla immunità., 0, open, Gerussi, A
- Published
- 2022
6. DISSECTING THE GENETIC ARCHITECTURE OF AUTOIMMUNITY: A SPOTLIGHT ON PRIMARY BILIARY CHOLANGITIS
- Author
-
ASSELTA, ROSANNA, Gerussi, A, INVERNIZZI, PIETRO, GERUSSI, ALESSIO, ASSELTA, ROSANNA, Gerussi, A, INVERNIZZI, PIETRO, and GERUSSI, ALESSIO
- Abstract
Lo scopo principale di questo lavoro di tesi di dottorato è stato l'utilizzo dell'ampio materiale genetico disponibile a seguito del sequenziamento del DNA per migliorare la caratterizzazione dell'architettura genetica delle malattie autoimmuni, con un focus specifico sulla Colangite Biliare Primitiva. Il nostro lavoro ha utilizzato metodi statistici "classici" come la meta-analisi e metodi di analisi dati nuovi, come pacchetti dedicati allo studio del cromosoma X e software di Machine Learning. Inoltre abbiamo applicate tecniche di biologia evoluzionistica computazionale per studiare la storia evolutiva delle varianti associate alla immunità., The main goal of this PhD project was to leverage the great body of genetic knowledge generated by high-throughput DNA sequencing to better characterize the genetic architecture of immune diseases, with a main focus on Primary Biliary Cholangitis (PBC). Our work has employed established statistical methods such as meta-analysis as well as novel data mining tools, such as packages dedicated to the study of chromosome X (chrX) and Machine Learning (ML) softwares. In addition, we have also applied established computational methods and ML tools to shed light on the evolutionary history of variants associated with immune-mediated traits. More specifically, the meta-analysis of previous Genome-Wide Association Studies (GWAS) in PBC has identified additional risk loci and, by means of functional annotation of credible causal variants and multi-omic analysis, has produced a list of candidate genes together with several drugs that are potentially suitable for re-purposing to PBC. The extensive analysis of chrX has identified several suggestive new loci associated with PBC located on this chromosome. The major finding of the X-Wide Association Study (XWAS) approach has been the identification of a genome-wide significantly associated locus characterized by the presence of different genes and of a superenhancer possibly involved in their co-regulation, as well as in the regulation of FOXP3 (which is located in the same TAD). Based on the new set of variants identified in the international meta-analysis, we have generated a novel Polygenic Risk Score (PRS) that has been incorporated in a new integrative risk model. This model, that has included 22 non-HLA variants, one HLA variant and sex, is accurate (Area Under the Curve (AUC) 0.83 and 0.81 in the two cohorts under study) and well calibrated. The PRS has pinpointed a subgroup of subjects at strikingly higher risk (OR ~ 14) of developing the disease that should be the target of tailored follow-up strategies. Prospective studie
- Published
- 2022
7. Evaluation of a large cohort of adult patients with Ménière’s disease: bedside and clinical history
- Author
-
Mario Bussi, Rosa Alessia Battista, Federica Di Berardino, Omar Gatti, Iacopo Cangiano, Roberto Teggi, and Marco Familiari
- Subjects
Adult ,Pediatrics ,medicine.medical_specialty ,Ménière’s disease ,vestibular function tests ,familiarità ,esame vestibolare ,autoimmunità ,Nystagmus ,Vestibology ,sindrome di Ménière ,03 medical and health sciences ,0302 clinical medicine ,Vertigo ,medicine ,Humans ,migraine ,Family history ,030223 otorhinolaryngology ,Head Impulse Test ,Meniere Disease ,Retrospective Studies ,Anamnesis ,family history ,biology ,business.industry ,autoimmunity ,Head impulse test ,emicrania ,biology.organism_classification ,medicine.disease ,General Energy ,Otorhinolaryngology ,Migraine ,030220 oncology & carcinogenesis ,Cohort ,medicine.symptom ,business ,Meniere's disease - Abstract
The purpose of this study was to assess vestibular findings and clinical history in a large cohort of patients affected by Ménière's disease.We retrospectively analysed 511 adult patients fulfilling criteria for definite unilateral Ménière's disease according to Barany Society. Thorough clinical history, audiometric exam, central nervous system MRI, quantification of serum autoantibodies and complete vestibular function test were performed.Mean age at clinical record was 55.4 years, while age at onset of the first vertigo attack was 47.4 ± 14.3 years. Ménière's disease overlapped with migraine in 43.4% of patients. In 31.7% of cases, positivity was found for at least one autoantibody. Forty-nine patients (9.6%) had family history for Ménière's disease. Bedside examination resulted in 14.7% positivity for video head impulse test, 58.9% for skull vibration-induced nystagmus, 38.7% for the positional test and 23.1% for the post head shaking test. Complete negative examination was reported in 115 cases.Ménière's disease was seen to present a characteristic phenotypic pattern in our cohort, confirming the crucial role of thorough anamnesis and bedside examination in diagnosis.Sindrome di Ménière: valutazione dell’esame vestibolare e della storia clinica in un’ampia popolazione.Analizzare un’ampia casistica di pazienti affetti da sindrome di Ménière con particolare attenzione al dato anamnestico ed ai test di funzione vestibolare.Sono stati raccolti retrospettivamente i dati di 511 pazienti affetti da sindrome di Ménière monolaterale definita, che soddisfacevano i criteri della Barany Society. Ogni paziente è stato sottoposto a raccolta anamnestica, esame audiometrico tonale, RM encefalo, test di autoimmunità ed esame otovestibolare.L’età media alla presentazione clinica è stata di 55,4 anni mentre l’età del primo episodio di vertigine è risultata essere 47,4 ± 14,3. Il 43,4% della popolazione soffre contestualmente di emicrania. Nel 31,7% dei casi è stata quantificata una positività di almeno un autoanticorpo. Quarantanove pazienti hanno riferito un familiare affetto da possibile sindrome di Ménière. La video head impulse è risultata positiva nel 14,7%, il test vibratorio nel 58,9%, 38,6% il test posizionale nel 38,7% e la HST nel 23,1%; una completa negatività ai test vestibolari è stata rilevata in 115 casi.La sindrome di Ménière è spesso associata ad un fenotipo clinico e strumentale suggestivo che conferma il ruolo cruciale di una attentata raccolta anamnestica e dell’esame vestibolare nella diagnosi.
- Published
- 2021
8. DISSECTING THE GENETIC ARCHITECTURE OF AUTOIMMUNITY: A SPOTLIGHT ON PRIMARY BILIARY CHOLANGITIS
- Author
-
GERUSSI, ALESSIO, Gerussi, A, and INVERNIZZI, PIETRO
- Subjects
immunology ,X chromosome ,immunologia ,MED/12 - GASTROENTEROLOGIA ,autoimmunity ,fegato ,cromosoma X ,genetica ,genetic ,autoimmunita - Abstract
Lo scopo principale di questo lavoro di tesi di dottorato è stato l'utilizzo dell'ampio materiale genetico disponibile a seguito del sequenziamento del DNA per migliorare la caratterizzazione dell'architettura genetica delle malattie autoimmuni, con un focus specifico sulla Colangite Biliare Primitiva. Il nostro lavoro ha utilizzato metodi statistici "classici" come la meta-analisi e metodi di analisi dati nuovi, come pacchetti dedicati allo studio del cromosoma X e software di Machine Learning. Inoltre abbiamo applicate tecniche di biologia evoluzionistica computazionale per studiare la storia evolutiva delle varianti associate alla immunità. The main goal of this PhD project was to leverage the great body of genetic knowledge generated by high-throughput DNA sequencing to better characterize the genetic architecture of immune diseases, with a main focus on Primary Biliary Cholangitis (PBC). Our work has employed established statistical methods such as meta-analysis as well as novel data mining tools, such as packages dedicated to the study of chromosome X (chrX) and Machine Learning (ML) softwares. In addition, we have also applied established computational methods and ML tools to shed light on the evolutionary history of variants associated with immune-mediated traits. More specifically, the meta-analysis of previous Genome-Wide Association Studies (GWAS) in PBC has identified additional risk loci and, by means of functional annotation of credible causal variants and multi-omic analysis, has produced a list of candidate genes together with several drugs that are potentially suitable for re-purposing to PBC. The extensive analysis of chrX has identified several suggestive new loci associated with PBC located on this chromosome. The major finding of the X-Wide Association Study (XWAS) approach has been the identification of a genome-wide significantly associated locus characterized by the presence of different genes and of a superenhancer possibly involved in their co-regulation, as well as in the regulation of FOXP3 (which is located in the same TAD). Based on the new set of variants identified in the international meta-analysis, we have generated a novel Polygenic Risk Score (PRS) that has been incorporated in a new integrative risk model. This model, that has included 22 non-HLA variants, one HLA variant and sex, is accurate (Area Under the Curve (AUC) 0.83 and 0.81 in the two cohorts under study) and well calibrated. The PRS has pinpointed a subgroup of subjects at strikingly higher risk (OR ~ 14) of developing the disease that should be the target of tailored follow-up strategies. Prospective studies are needed to evaluate the potential role of PRS in first-degree relatives of patients with PBC. We have also presented the first example of a successful, proof-of-concept analysis of GWAS data with ML to study genetic liability of PBC. ML is computationally feasible and generates accurate information that can be leveraged for disease prediction (AUC 0.73). Our ML-based model predicts genetic susceptibility to PBC through a methodologically innovative and explainable method. The innovation relies on the explainability of the rules for disease prediction, predicting genetic liability at the individual level; in addition, rules have considered groups of variants instead of single variants alone, paving the way for integrating gene-gene interactions in genetic predictive models. Finally, to study the evolutionary determinants of variants related to immune-mediated complex traits, we have leveraged information about genetic variants of archaic hominins and genomic estimates of deleteriousness at nucleotide-resolution to estimate the mutational load in Neanderthals along the genome. We have shown that the allele frequency in high coverage Neanderthal genomes is informative of the fate of alleles in the human population. While the common identified pattern is that Neandertal fragments bringing more deleterious variants have been purged away, several fragments involved in immunity are observed nowadays at high frequencies in human populations. After confirming the enrichment of Neanderthal ancestry in immune-related traits and genes, we also observed that regions of the human genome carrying putatively deleterious variants and involved in immunity do not show traces of purifying selection but rather the opposite, reinforcing the notion that immune-related genes are under balancing selection.
- Published
- 2022
9. HLA class II genes in precision-based care of childhood diseases: what we can learn from celiac disease
- Author
-
Giovanna Del Pozzo, Carmen Gianfrani, Federica Farina, Stefania Picascia, Serena Vitale, and Mariavittoria Laezza
- Subjects
Glutens ,T-Lymphocytes ,Clinical Decision-Making ,Genes, MHC Class II ,autoimmunità ,Disease ,Human leukocyte antigen ,medicine.disease_cause ,Natural history of disease ,Risk Assessment ,Autoimmunity ,03 medical and health sciences ,Negative selection ,Therapy compliance ,Diet, Gluten-Free ,0302 clinical medicine ,Predictive Value of Tests ,Risk Factors ,030225 pediatrics ,HLA-DQ Antigens ,medicine ,Humans ,Enteropathy ,Genetic Predisposition to Disease ,Genetic Testing ,Precision Medicine ,celiachia ,business.industry ,fungi ,nutritional and metabolic diseases ,medicine.disease ,Prognosis ,Celiac Disease ,Early Diagnosis ,Phenotype ,Pediatrics, Perinatology and Child Health ,Immunology ,Risk assessment ,business ,030217 neurology & neurosurgery - Abstract
Celiac disease (CeD) is a chronic immuno-mediated enteropathy caused by dietary gluten with marked autoimmunity traits. The human leukocyte antigen (HLA) class II heterodimers represent the main predisposing factor, although environmental agents, as viral infection, gut microbiota, and dietary regimen, also contribute to CeD risk. These molecules are involved in autoimmunity as they present self-antigens to autoreactive T cells that have escaped the thymic negative selection. In CeD, the HLA class II risk alleles, DQA1*05-DQB1*02 and DQA1*03-DQB1*03, encode for DQ2.5 and DQ8 heterodimers, and, furthermore, disease susceptibility was found strictly dependent on the dose of these genes. This finding questioned how the expression of HLA-DQ risk genes, and of relative surface protein on antigen-presenting cells, might be relevant for the magnitude of anti-gluten inflammatory response in CeD patients, and impact the natural history of disease, its pathomechanisms, and compliance to dietary treatment. In this scenario, new personalized medical approaches will be desirable to support an early, accurate, and non-invasive diagnosis, and to define genotype-guided preventive and therapeutic strategies for CeD. To reach this goal, a stratification of genetic risk, disease outcome, and therapy compliance based on HLA genotypes, DQ2.5/DQ8 expression measurement and magnitude of T cell response to gluten is mandatory. Impact: This article revises the current knowledge on how different HLA haplotypes, carrying the DQ2.5/DQ8 risk alleles, impact the onset of CeD.This review discusses how the expression of susceptibility HLA-DQ genes can determine the risk assessment, outcome, and prevention of CeD.The recent insights on the environmental factors contributing to CeD in childhood are reviewed.This review discusses the use of HLA risk gene expression as a tool to support medical precision approaches for an early and non-invasive diagnosis of CeD, and to define genotype-guided preventive and therapeutic strategies.
- Published
- 2020
10. Differential expression of predisposing HLA-DQ2.5 alleles in DR5/DR7 celiac disease patients affects the pathological immune response to gluten
- Author
-
Stefania Picascia, Federica Farina, Giovanna Del Pozzo, Pasquale Barba, Carmen Gianfrani, and Laura Pisapia
- Subjects
CD4-Positive T-Lymphocytes ,0301 basic medicine ,Glutens ,T cell ,Immunology ,Cell ,lcsh:Medicine ,Antigen-Presenting Cells ,Gene Expression ,autoimmunità ,Biology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,HLA-DQ Antigens ,Genotype ,Gene expression ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Allele ,lcsh:Science ,Receptor ,Alleles ,B-Lymphocytes ,Multidisciplinary ,celiachia ,lcsh:R ,HLA-DQ2 ,nutritional and metabolic diseases ,HLA-DR Antigens ,HLA ,Celiac Disease ,Receptors, TNF-Related Apoptosis-Inducing Ligand ,030104 developmental biology ,medicine.anatomical_structure ,lcsh:Q ,030217 neurology & neurosurgery - Abstract
The DR5-DQ7/DR7-DQ2 genotype is very frequent among patients affected by celiac disease (CD), in Europe. This genotype, associated to high risk of CD, carries the HLA-DQA1*05 and HLA-DQB1*02 predisposing alleles, in trans configuration. The alleles encode the DQ2.5 heterodimer responsible of gluten peptide presentation on the surface of antigen-presenting cells (APCs), and consequent pathogenic CD4+ T cell activation. We demonstrated that DR5/DR7 APCs induce an anti-gluten CD4+ T cell response, of comparable intensity to that observed with APCs carrying DR1/DR3 genotype, which risk alleles are in cis configuration. In addition, we showed that DR5/DR7 APCs from celiac patients stimulated an effector CD4+ T cell response higher with respect to that induced by DR5/DR7 APCs from healthy subjects. To explain these findings, we assessed the DQ2.5 RNA and protein quantity. We showed that the expression of DQA1*05 and DQB1*02 risk alleles is much higher than the expression of non-CD-associated alleles, in agreement with the previous results obtained with DR1/DR3 genotype. The differential expression of transcripts influences the quantity of DQα1*05 and DQβ1*02 chains and, as consequence, the cell surface density of DQ2.5 heterodimers. Moreover, both RNA and proteins, are more abundant in APCs from celiac patients than controls. Finally, to unravel the mechanism regulating the expression of predisposing DQA1*05 and DQB1*02 alleles, we quantified the new synthetized RNA and found that the differential expression is explained by their transcription rate. Our results confirmed that the strength of antigen-specific CD4+ T cell response is mainly determined by the amount of gluten in the diet and provided a new possible approach for a personalized diagnosis and for risk stratification.
- Published
- 2020
11. Il sistema immunitario
- Author
-
Gentile, Fabrizio and Formisano, Silvestro
- Subjects
reazioni di ipersensibilità ,risposte immunitarie ,immunodeficienze ,autoimmunità ,Immunologia ,Immunologia, risposte immunitarie, reazioni di ipersensibilità, autoimmunità, immunodeficienze - Published
- 2018
12. Prefazione
- Author
-
Fabio Polidori, Arianna Marchente, and Polidori, Fabio
- Subjects
Vivente ,Vita ,Derrida ,Autoimmunità ,Morte - Abstract
«Autoimmunità» non è una specie di passe-partout per aprirsi la strada attraverso ambiti tra loro eterogenei e ridurli a una sorta di estrinseca omologazione; è bensì l’indicatore di ciò che non cessa di affermarsi in quanto vivente: una vulnerabilità al cuore di ogni istanza vitale, sociale, politica, una vulnerabilità che non costituisce un tratto negativo opposto al vivente ma che è – secondo il paradosso di fronte a cui un pensiero logicamente articolato non può non arrestarsi – proprio la sua più intima e positiva risorsa.
- Published
- 2018
13. Prefazione
- Author
-
Polidori, Fabio
- Subjects
Vivente ,Vita ,Derrida ,Autoimmunità ,Morte - Published
- 2018
14. Difetti della tolleranza immunologica, autoimmunità e rigetto dei trapianti
- Author
-
Gentile, Fabrizio
- Subjects
rigetto dei trapianti ,Tolleranza immunologica ,Tolleranza immunologica, difetti della tolleranza, modified self, mimesi epitopica, autoimmunità, rigetto dei trapianti ,autoimmunità ,modified self ,difetti della tolleranza ,mimesi epitopica - Published
- 2018
15. Verso una biologia politica: 'vita morte' e autoimmunità nel pensiero di Jacques Derrida
- Author
-
Marchente, Arianna, Marchente, Arianna, and POLIDORI, FABIO
- Subjects
Biologia ,Vita ,Derrida ,Morte ,Autoimmunità ,Settore M-FIL/01 - Filosofia Teoretica - Abstract
L'odierna biopolitica ha spesso accusato la decostruzione derridiana di essersi mantenuta lontana dal tema della vita, anche e soprattutto nelle sue implicazioni politiche. Il presente lavoro intende dimostrare come invece la vita rappresenti la matrice stessa della decostruzione. Non semplicemente la vita, ma la vita nel suo intrinseco e costituivo rapporto con la morte. Dall'interesse per la biologia mostrato da Derrida nelle sue primissime opere, passando attraverso la lettura di un ciclo di seminari parzialmente inedito del '75-'76, intitolati appunto "La vie la mort", fino ad arrivare alla formalizzazione della paradossale legge autoimmunitaria, si dimostrerà che la decostruzione ha sempre parlato di vita e si metterà in luce la rilevanza e l'urgenza politica di questo discorso. Today's bio-politics has often accused Derrida's deconstruction to be kept away from the theme of life and its political implications. Not just life, but life in its intrinsic and constitutive relationship with death. Starting from an interest on biology shown by Derrida in his earliest works, passing through the reading of a series of seminars partially unreleased in '75-'76, entitled "La vie la mort", up to the formalization of the paradoxical autoimmune law, we will prove that deconstruction has always talked about life and we will show the importance and urgency of this political discourse.
- Published
- 2016
16. Nuovi metodi per lo studio dell'azione di farmaci anti-reumatici sui linfociti regolatori
- Author
-
CANDILERA, VANESSA, Candilera, Vanessa, and TOMMASINI, ALBERTO
- Subjects
Settore MED/38 - Pediatria Generale e Specialistica ,Tofacitinib ,FOXP3 ,autoimmunità ,Tregs ,AR - Abstract
L'artrite reumatoide è una malattia autoimmune per la quale non si è ancora trovata una cura che ne blocchi il decorso invalidante. il tofacitinib è un DMARD's di nuova generazione di cui si sa ancora molto poco. in questo lavoro di tesi abbiamo studiato gli effetti di questo farmaco nei confronti di una popolazione linfocitaria specifica ( i linfociti regolatori).
- Published
- 2016
17. Patologie autoimmuni della tiroide
- Author
-
Minciullo, Paola Lucia, Ruggeri, Rosaria Maddalena, and Gangemi, Sebastiano
- Subjects
Morbo di Basedow-Grave ,Tiroidite di Hashimoto ,autoimmunità ,Tiroiditi autoimmuni, Tiroidite di Hashimoto, Morbo di Basedow-Grave, autoimmunità ,Tiroiditi autoimmuni - Published
- 2016
18. VIRAL DIABETES: VIRUS DIABETOGENICITY AND HOST SUSCEPTIBILITY
- Author
-
Seiho Nagafuchi and Antonio Toniolo
- Subjects
Type 1 diabetes ,Virus, autoimmunità, diabete, isole di Langerhans, pancreas, infezione, eziologia ,viruses ,autoimmunità ,infezione ,Biology ,medicine.disease ,Virology ,Virus ,Serology ,diabete ,Tyrosine kinase 2 ,Polymorphism (computer science) ,Diabetes mellitus ,Immunology ,medicine ,eziologia ,pancreas ,Pathogen ,Gene ,isole di Langerhans - Abstract
Diabetes mellitus (DM) is on the rise worldwide, and is associated with improvement in socioeconomic conditions, increasing wealth, high caloric and fat intake, and reduced physical activity. Accumulating evidence also suggests a causal/triggering link with environmental factors, such as toxins and viruses. A variety of viral infections have been associated with the development of diabetes. There might be no ‘diabetes virus’, but there might be a variety of ‘diabetogenic viruses’ that contribute to diabetes in people who are particularly susceptible due to genetic or physiologic conditions. Increasing evidence is showing that human enteroviruses (EVs) are prominent among possible causal candidates for type 1 diabetes mellitus (T1D). However, evidence for diabetogenicity of viruses is still missing. For a pathogen, causality should fulfill the etiologic criteria known as ‘modified Koch’s postulates’. Recently, we presented evidence that mutations of Tyk2 gene are responsible for diabetes susceptibility of mice infected with the diabetogenic D strain of encephalomyocarditis virus (EMC-D). Observations have been extended to identify the human polymorphism of TYK2 gene associated with increased risk for virus-induced diabetes in humans. An update is given on the possible diabetogenic role of EVs with reference to experimental work in animals and to human studies (viral serology, pancreas histopathology, virus detection in blood and in tissues of diabetic patients). For the identification of a diabetogenic virus, the development of a sensitive experimental model is imperative. In vivo assay systems should include an animal model appropriately simulating a susceptible human and carrying susceptibility genes or factors. This work summarizes current knowledge on virus-induced diabetes together with evidence from experimental models, susceptibility genes in mice, candidate diabetogenic viruses and susceptibility genes in humans. Perspectives on the identification of diabetogenic viruses - which may possibly lead to innovative strategies for the cure or prevention of diabetes – are also presented.
- Published
- 2015
19. CTLA-4 as a genetic determinant in autoimmune Addison's disease
- Author
-
Dag E. Undlien, Alberto Falorni, Olle Kämpe, Heather J. Cordell, Simon H. S. Pearce, Beate Skinningsrud, William E R Ollier, Andrea D. Short, Klaus Badenhoop, Anette S. B. Wolff, Eystein S. Husebye, Anna L. Mitchell, and Gesine Meyer
- Subjects
Adult ,Male ,Immunology ,Single-nucleotide polymorphism ,Locus (genetics) ,autoimmunità ,Human leukocyte antigen ,Biology ,Polymorphism, Single Nucleotide ,Genetic determinism ,Genetic Determinism ,Malattia di Addison ,Addison Disease ,Genetics ,Humans ,SNP ,CTLA-4 Antigen ,Genetic Predisposition to Disease ,Malattia di Addison, associazione genica, complesso maggiore di istocompatbilità, autoimmunità ,ddc:610 ,Allele ,Genetic Association Studies ,Genetics (clinical) ,Haplotype ,Genetic Variation ,complesso maggiore di istocompatbilità ,Odds ratio ,Middle Aged ,3. Good health ,associazione genica ,Original Article ,Female - Abstract
In common with several other autoimmune diseases, autoimmune Addison’s disease (AAD) is thought to be caused by a combination of deleterious susceptibility polymorphisms in several genes, together with undefined environmental factors and stochastic events. To date, the strongest genomic association with AAD has been with alleles at the HLA locus, DR3–DQ2 and DR4. The contribution of other genetic variants has been inconsistent. We have studied the association of 16 single-nucleotide polymorphisms (SNPs) within the CD28–CTLA-4–ICOS genomic locus, in a cohort comprising 691 AAD patients of Norwegian and UK origin with matched controls. We have also performed a meta-analysis including 1002 patients from European countries. The G-allele of SNP rs231775 in CTLA-4 is associated with AAD in Norwegian patients (odds ratio (OR)=1.35 (confidence interval (CI) 1.10–1.66), P=0.004), but not in UK patients. The same allele is associated with AAD in the total European population (OR=1.37 (CI 1.13–1.66), P=0.002). A three-marker haplotype, comprising PROMOTER_1661, rs231726 and rs1896286 was found to be associated with AAD in the Norwegian cohort only (OR 2.43 (CI 1.68–3.51), P=0.00013). This study points to the CTLA-4 gene as a susceptibility locus for the development of AAD, and refines its mapping within the wider genomic locus. publishedVersion
- Published
- 2015
20. Expression and enzymatic activity of small intestinal tissue transglutaminase in celiac disease
- Author
-
Ivana Caputo, Salvatore Auricchio, Raffaele Porta, Riccardo Troncone, V.M. Salvati, Francesco Paparo, Giuseppe Mazzarella, Carla Esposito, Esposito, C, Paparo, Francesco, Caputo, Ivana, Porta, Raffaele, Salvati, Vm, Mazzarella, G, Auricchio, Salvatore, Troncone, Riccardo, Paparo, F, Caputo, I, Salvati, V. M., and Troncone, R.
- Subjects
Adolescent ,Duodenum ,Tissue transglutaminase ,autoimmunità ,Disease ,Humans ,RNA, Messenger ,Intestinal Mucosa ,Child ,chemistry.chemical_classification ,celiachia ,Transglutaminases ,Hepatology ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,Gastroenterology ,Infant ,nutritional and metabolic diseases ,RNA ,transglutaminasi ,Molecular biology ,digestive system diseases ,Celiac Disease ,Enzyme ,Biochemistry ,chemistry ,Child, Preschool ,biology.protein ,lesione intestinale - Abstract
OBJECTIVES: The molecular and functional properties of small intestinal tissue transglutaminase are largely unknown despite growing interest because of its role in celiac disease (CD). In this study, we aimed to evaluate tissue transglutaminase expression and enzymatic activity in bioptic fragments obtained from the duodenum of untreated individuals with CD and from control subjects. METHODS: Analysis of tissue transglutaminase mRNA expression was performed by reverse transcription-polymerase chain reaction (RT-PCR). The presence of the enzyme in bioptic fragments as well as in homogenates from CD patients and controls was revealed by immunohistochemistry and Western blot, respectively, using the antitissue transglutaminase CUB 7402 clone. To evaluate in situ transglutaminase activity, sections of bioptic fragments were incubated in the presence of 5 mmol/L CaCl(2) with 5-(biotinamido)pentylamine or, alternatively, with a biotinylated glutamine-containing hexapeptide (TVQQEL) and the biotinylated 31-43 A-gliadin-derived peptide. RESULTS: Tissue transglutaminase mRNA levels were 1.0-fold higher (p < 0.05) in CD patients than in controls. Immunohistochemistry and in situ demonstration of enzymatic activity in celiac mucosa clearly showed an increased expression of active tissue transglutaminase in the extracellular matrix of the subepithelial region and in the enterocytes. Staining of the biotinylated 31-43 A-gliadin peptide in the same area of tissue transglutaminase suggested the presence of lysine-donor substrates in intestinal mucosa. CONCLUSIONS: Tissue transglutaminase is more expressed and active in defined areas of the small intestinal mucosa from patients with CD. The presence in the celiac mucosa of proteins able to act as amine-donor substrates suggests that tissue transglutaminase-mediated post-translational modification of proteins cross-linked with gliadin peptides may represent a pathogenic mechanism of CD.
- Published
- 2003
21. Comparative analysis of different biofactories for the production of a major diabetes autoantigen
- Author
-
Annalisa Brozzetti, Mario Pezzotti, Matilde Merlin, Elisa Gecchele, Stefano Capaldi, Linda Avesani, and Alberto Falorni
- Subjects
Baculoviridae ,diabete mellito ,Transgene ,Genetic Vectors ,Glutamate decarboxylase ,hGAD65mut ,Nicotiana benthamiana ,medicine.disease_cause ,Autoantigens ,Polymerase Chain Reaction ,Inclusion bodies ,law.invention ,Autoimmune diabetes ,Bioreactors ,law ,autoimmunità ,autoantigene ,piante transgeniche ,Tobacco ,Escherichia coli ,medicine ,Genetics ,Humans ,hGAD65 ,Crosses, Genetic ,DNA Primers ,Original Paper ,biology ,Glutamate Decarboxylase ,Plants, Genetically Modified ,biology.organism_classification ,Molecular biology ,Recombinant protein production ,Recombinant Proteins ,Molecular farming ,Genetically modified organism ,Diabetes Mellitus, Type 1 ,Biochemistry ,Recombinant DNA ,Animal Science and Zoology ,Agronomy and Crop Science ,Biotechnology - Abstract
The 65-kDa isoform of human glutamic acid decarboxylase (hGAD65) is a major diabetes autoantigen that can be used for the diagnosis and (more recently) the treatment of autoimmune diabetes. We previously reported that a catalytically-inactive version (hGAD65mut) accumulated to tenfold higher levels than its active counterpart in transgenic tobacco plants, providing a safe and less expensive source of the protein compared to mammalian production platforms. Here we show that hGAD65mut is also produced at higher levels than hGAD65 by transient expression in Nicotiana benthamiana (using either the pK7WG2 or MagnICON vectors), in insect cells using baculovirus vectors, and in bacterial cells using an inducible-expression system, although the latter system is unsuitable because hGAD65mut accumulates within inclusion bodies. The most productive of these platforms was the MagnICON system, which achieved yields of 78.8 μg/g fresh leaf weight (FLW) but this was substantially less than the best-performing elite transgenic tobacco plants, which reached 114.3 μg/g FLW after six generations of self-crossing. The transgenic system was found to be the most productive and cost-effective although the breeding process took 3 years to complete. The MagnICON system was less productive overall, but generated large amounts of protein in a few days. Both plant-based systems were therefore advantageous over the baculovirus-based production platform in our hands. Electronic supplementary material The online version of this article (doi:10.1007/s11248-013-9749-9) contains supplementary material, which is available to authorized users.
- Published
- 2014
22. Il deficit di vitamina D può rappresentare un fattore di rischio per la poliabortività attivando i meccanismi dell’immunità cellulare e dell’autoimmunità
- Author
-
Miriam Cellini and Marco Centanni
- Subjects
business.industry ,poliabortività ,Medicine ,autoimmunità ,vitamina D ,business ,Humanities - Published
- 2014
23. Enteroviruses in Blood Diabetes and Viruses
- Author
-
Toniolo, Antonio, Maccari, Giuseppe, Salvatoni, Alessandro, and Baj, Andreina
- Subjects
diabete ,virus ,infezioni ,autoimmunità ,eziologia ,patogenesi - Published
- 2013
24. The Shc family protein adaptor, Rai, acts as a negative regulator of Th17 cell development
- Author
-
Ulivieri, Cristina, Savino, MARIA TERESA, Ortensi, B, Pelicci, G, Emmi, L, D’Elios, Mm, and Baldari, Cosima
- Subjects
linfociti T ,Adattatori molecolari ,autoimmunità ,Adattatori molecolari, linfociti T, autoimmunità - Published
- 2012
25. Capitolo 23 - IMMUNOPATOLOGIA
- Author
-
Gentile, Fabrizio and Formisano, S.
- Subjects
Rigetto dei trapianti ,Immunodeficienze ,Immunopatologia ,Reazioni di ipersensibilità ,Autoimmunità - Published
- 2011
26. 'SINDROME DI BECHET, CELIACHIA E DIABETE MELLITO DI I TIPO': ....RARO CASO A TIPIZZAZIONE ANOMALA
- Author
-
MARCHESE, Donatella, MARTINES, Enrico, SPECIALE, Riccardo, MARTINES, Francesco, Marchese, D, Martines, E, Speciale, R, and Martines, F
- Subjects
Celiachia ,Settore MED/31 - Otorinolaringoiatria ,Bechet ,Afte orali ,Autoimmunità ,Settore MED/32 - Audiologia - Abstract
La malattia di Behcet è una malattia rara, a genesi autoimmune, multifattoriale ad esordio tra la seconda e la terza decade di vita, a più elevata incidenza nei cosiddetti territori della via della seta (Medio Oriente) oltre che, nel Bacino del Mediterraneo. In Europa la prevalenza è 1:500.000 con maggiore incidenza nel sesso femminile. Clinicamente è caratterizzata da lesioni ulcerose ricorrenti del cavo orale che si accompagnano a ulcere genitali o lesioni cutanee, oculari o Pathergy Test positivo . Il "Behcet's Disease International Study Group" ha identificato nella presenza di ulcere del cavo orale associate a due delle lesioni sovracitate la diagnosi clinica di malattia di Behcet. Nel 60-70% dei casi è descritta un’associazione con il fenotipo HLA-B51. Nonostante si tratti di patologia su base autoimmunitaria, difficilmente si associa ad altre manifestazioni cliniche quali Morbo celiaco, Diabete, Crohn et al. Gli autori descrivono un caso clinico di una ragazza di 24 anni già affetta da diabete mellito e celiachia, giunta alla nostra osservazione per lesioni ulcero-necrotiche a carico della tonsilla palatina di sinistra, da circa 20 giorni. L’ipotesi diagnostica iniziale di malattia di Behcet era stata scartata per l'assenza di sintomi o segni associati, nonchè per la tipizzazione del sistema HLA risultata positiva per l’MHC-II B-63. La consulenza reumatologica confermava una diagnosi di morbo celiaco poiché le manifestazioni orali risultavano compatibili con una fase evolutiva dello stesso (positività nel 25% dei pazienti con morbo celiaco). La progressione dei fenomeni ulcerotici a carico della tonsilla omolaterale e la comparsa di manifestazioni analoghe a carico della tonsilla controlaterale, in una fase di apparente quiescenza di celiachia, ha indotto gli autori ad ipotizzare la presenza di una Malattia di Behcet, sebbene questa si associ ad altre malattie autoimmuni solamente nel 2-4% dei casi. Esclusivamente la biopsia escissionale e la comparsa a distanza di mesi, di lesioni genitali, ha permesso di porre diagnosi di certezza di una rara associazione, la quarta ad oggi descritta in letteratura, di Diabete Mellito di I tipo, Malattia Celiaca e Morbo di Behcet a tipizzazione atipica.
- Published
- 2011
27. Le malattie autoimmuni del pancreas
- Author
-
Frulloni, Luca, Scattolini, Chiara, Amodio, Antonio, Katsotourchi, Anna Maria, and Vantini, Italo
- Subjects
pancreatite cronica ,autoimmunità ,terapia - Published
- 2009
28. Human interleukin 17-producing cells originate from a CD161+CD4+ T cell precursor
- Author
-
Veronica Santarlasci, Paola Parronchi, Sergio Romagnani, Laura Maggi, Enrico Maggi, Massimiliano Fambrini, Francesca Frosali, Elena Lazzeri, Lorenzo Cosmi, Gianfranco Abbate, Gabriella Rodolico, Manuela Capone, Marzia Caproni, Francesco Annunziato, Valentina Querci, Raffaele De Palma, Francesco Liotta, Liberato Berrino, Francesco Tonelli, Roberta Angeli, Cosmi, L., DE PALMA, Raffaele, Santarlasci, V., Maggi, L., Capone, M., Frosali, F., Rodolico, G., Querci, V., Abbate, G., Angeli, R., Berrino, Liberato, Fambrini, M., Caproni, M., Tonelli, F., Lazzeri, E., Parronchi, P., Liotta, F., Maggi, E., Romagnani, S., and Annunziato, F.
- Subjects
Th17 ,malattie infiammatorie croniche ,autoimmunità ,Adult ,CD4-Positive T-Lymphocytes ,Receptors, Retinoic Acid ,T cell ,Immunology ,Thymus Gland ,Biology ,Article ,Interleukin 21 ,Th2 Cells ,Crohn Disease ,T-Lymphocyte Subsets ,medicine ,Immunology and Allergy ,Cytotoxic T cell ,Humans ,Psoriasis ,Th17, malattie infiammatorie croniche, autoimmunità ,Lectins, C-Type ,RNA, Messenger ,Antigen-presenting cell ,Interleukin 3 ,Inflammation ,Receptors, Thyroid Hormone ,Interleukin-17 ,Infant, Newborn ,Cell Differentiation ,T helper cell ,Receptors, Interleukin ,Articles ,Nuclear Receptor Subfamily 1, Group F, Member 3 ,Th1 Cells ,Natural killer T cell ,Fetal Blood ,Hematopoietic Stem Cells ,Molecular biology ,Up-Regulation ,medicine.anatomical_structure ,Case-Control Studies ,Antigens, Surface ,Interleukin 12 ,NK Cell Lectin-Like Receptor Subfamily B - Abstract
We demonstrate that CD161 is a highly up-regulated gene in human interleukin (IL) 17 T helper cell (Th17) clones and that all IL-17–producing cells are contained in the CD161+ fraction of CD4+ T cells present in the circulation or in inflamed tissues, although they are not CD1-restricted natural killer T cells. More importantly, we show that all IL-17–producing cells originate from CD161+ naive CD4+ T cells of umbilical cord blood, as well as of the postnatal thymus, in response to the combined activity of IL-1β and IL-23. These findings implicate CD161 as a novel surface marker for human Th17 cells and demonstrate the exclusive origin of these cells from a CD161+CD4+ T cell progenitor.
- Published
- 2008
29. Autoantibodies against type I Interferons as an additional diagnostic criteria for Autoimmune Polyendocrine Syndrome type I
- Author
-
Maria Dominguez, Antonella Meloni, Andrew J. Cant, Vivienne McConnell, Desa Lilic, Colm Costigan, Andrew R. Gennery, Maria Furcas, Filomena Cetani, David W. Denning, Alberto Falorni, Anthony Meager, Kelli R. Ryan, Roberto Perniola, Mikulas Pura, Peter D. Arkwright, Anette S. B. Wolff, Nick Willcox, Gavin P. Spickett, Mario Abinun, Eystein S. Husebye, and Claudio Marcocci
- Subjects
medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,T-Lymphocytes ,Clinical Biochemistry ,autoanticorpi ,Thyroid Gland ,Chronic Candidiasis ,medicine.disease_cause ,Biochemistry ,Sensitivity and Specificity ,Autoimmune Polyendocrinopathy Syndrome ,Autoimmunity ,Autoimmune Diseases ,sindrome poliendocrina autoimmune ,Diagnosis, Differential ,Endocrinology ,Internal medicine ,Myasthenia Gravis ,medicine ,Humans ,Point Mutation ,Chronic mucocutaneous candidiasis ,Polyendocrinopathies, Autoimmune ,Autoantibodies ,business.industry ,Biochemistry (medical) ,Autoimmunità ,Autoantibody ,Interferon-alpha ,Autoimmune polyendocrinopathy ,Syndrome ,interferon ,medicine.disease ,Autoimmune polyendocrine syndrome type 1 ,Autoimmune polyendocrine syndrome ,Immunology ,Interferon Type I ,business - Abstract
Context: In autoimmune polyendocrinopathy syndrome type I (APS-I), mutations in the autoimmune regulator gene (AIRE) impair thymic self-tolerance induction in developing T cells. The ensuing autoimmunity particularly targets ectodermal and endocrine tissues, but chronic candidiasis usually comes first. We recently reported apparently APS-I-specific high-titer neutralizing autoantibodies against type I interferons in 100% of Finnish and Norwegian patients, mainly with two prevalent AIRE truncations. Objectives: Because variability in clinical features and age at onset in APS-I frequently results in unusual presentations, we prospectively checked the diagnostic potential of anti-interferon antibodies in additional APS-I panels with other truncations or rare missense mutations and in disease controls with chronic mucocutaneous candidiasis (CMC) but without either common AIRE mutation. Design: The study was designed to detect autoantibodies against interferon-α2 and interferon-ω in antiviral neutralization assays. Setting and Patients: Patients included 14 British/Irish, 15 Sardinian, and 10 Southern Italian AIRE-mutant patients with APS-I; also 19 other patients with CMC, including four families with cosegregating thyroid autoimmunity. Outcome: The diagnostic value of anti-interferon autoantibodies was assessed. Results: We found antibodies against interferon-α2 and/or interferon-ω in all 39 APS-I patients vs. zero of 48 unaffected relatives and zero of 19 British/Irish CMC patients. Especially against interferon-ω, titers were nearly always high, regardless of the exact APS-I phenotype/duration or AIRE genotype, including 12 different AIRE length variants or 10 point substitutions overall (n = 174 total). Strikingly, in one family with few typical APS-I features, these antibodies cosegregated over three generations with autoimmune hypothyroidism plus a dominant-negative G228W AIRE substitution. Conclusions: Otherwise restricted to patients with thymoma and/or myasthenia gravis, these precocious persistent antibodies show 98% or higher sensitivity and APS-I specificity and are thus a simpler diagnostic option than detecting AIRE mutations.
- Published
- 2008
30. Interessamento dell'Apparato Respiratorio in corso di varie patologie
- Author
-
BARIFFI, FRANCESCO, PONTICIELLO, ANTONIO, SANDUZZI ZAMPARELLI, ALESSANDRO, R. Zuin, Bariffi, Francesco, Ponticiello, Antonio, and SANDUZZI ZAMPARELLI, Alessandro
- Subjects
interstiziale ,autoimmunità ,malattie del connettivo - Published
- 2008
31. Screening of a kidney cDNA library for the identification of autoimmune proteins from serum of membranous nephropathy patients
- Author
-
Cavazzini, Fabrizio, Magistroni, R, Furci, L, Leonelli, M, Ligabue, Giulia, Lupo, Valentina, and Albertazzi, Alberto
- Subjects
Libreria di fagi ,Glomerulo Nefrite Membranosa ,Autoimmunità ,cDNA library ,membranouis nephropathy - Published
- 2008
32. The association of genetic polymorphisms and autoimmune Addison’s disease
- Author
-
Annalisa Brozzetti, Giovanni Gambelunghe, Daria La Torre, Cristina Tortoioli, and Alberto Falorni
- Subjects
musculoskeletal diseases ,Genetics ,morbo di addison ,biology ,Immunology ,Autoantibody ,insufficienza surrenalica ,Human leukocyte antigen ,genetica ,Major histocompatibility complex ,medicine.disease ,PTPN22 ,hla ,CTLA-4 ,Autoimmune polyendocrine syndrome ,MHC class I ,biology.protein ,medicine ,autoimmunità ,Immunology and Allergy ,Allele ,skin and connective tissue diseases - Abstract
Autoimmune Addison's disease (AAD) is a complex genetic disease that results from the interaction of a predisposing genetic background with as yet unknown environmental factors. The disease is marked by the appearance of circulating autoantibodies against steroid 21-hydroxylase. Mutations of the autoimmune regulator gene are responsible for the so-called autoimmune polyendocrine syndrome type I (APS I), of which AAD is a major disease component. Among genetic factors for isolated AAD and APS II, a major role is played by HLA class II genes: HLA-DRB1 0301-DQA1 0501-DQB1 0201 and DRB1 04-DQA1 0301-DQB1 0302 are positively, and RB1 0403 is negatively, associated with a genetic risk for AAD. The MHC class I chain-related gene A allele 5.1 is strongly and positively associated with AAD. Other gene polymorphisms contributing to genetic risk for AAD are MHC2TA, the gene coding for class II transactivator, the master regulator of class II expression, cytotoxic T lymphocyte antigen-4, PTPN22 and the vitamin D receptor.
- Published
- 2008
33. Vaccinazione genica: prospettive nel trattamento delle malattie autoimmuni
- Author
-
Filaci, Gilberto, Ferrera, Francesca, and Indiveri, F.
- Subjects
vaccinazione tollerogenica ,lupus sistemico eritematoso ,autoimmunità - Published
- 2007
34. La sclerosi sitemica progressiva
- Author
-
Gerli, Roberto, Bassetti, D., and BARTOLONI BOCCI, Elena
- Subjects
sclerosi sistemica ,autoimmunità - Published
- 2007
35. Retrovirus-like long-terminal repeat DQ-LTR13 and genetic susceptibility to type 1 diabetes and autoimmune Addison's disease
- Author
-
Giovanni Gambelunghe, Vittorio Bini, Rossella Libé, Roberta Giordano, Giovanni De Giorgi, Ingrid Kockum, F Celi, Corrado Betterle, and Alberto Falorni
- Subjects
musculoskeletal diseases ,Adult ,Risk ,Linkage disequilibrium ,Adolescent ,Endocrinology, Diabetes and Metabolism ,autoimmunità ,morbo di Addison ,medicine.disease_cause ,insufficienza corticosurrenalica primitiva ,Autoimmunity ,Addison Disease ,Diabete di tipo 1 ,retrovirus ,long-tandem repeat ,polimorfismo genico ,HLA ,immune system diseases ,HLA-DQ Antigens ,Internal Medicine ,medicine ,Genetic predisposition ,Adrenal insufficiency ,Humans ,Genetic Predisposition to Disease ,skin and connective tissue diseases ,Child ,Alleles ,Genetic association ,Autoimmune disease ,Type 1 diabetes ,sistema maggiore di istocompatibilità ,business.industry ,Terminal Repeat Sequences ,Infant ,Odds ratio ,Middle Aged ,medicine.disease ,Diabetes Mellitus, Type 1 ,Phenotype ,Haplotypes ,Italy ,Retrovirus ,diabete di tipo 1 ,associazione genetica ,Child, Preschool ,Immunology ,business - Abstract
Controversial data are available on the association between the retrovirus-like long-terminal repeat (LTR) DQ-LTR13 and genetic susceptibility to type 1 diabetes and other autoimmune diseases. We analyzed DNA samples from 315 type 1 diabetic patients, 166 autoimmune Addison’s disease (AAD) patients, 1,054 healthy subjects, and 144 families of type 1 diabetic offspring. DQ-LTR13 was more frequent among patients than healthy subjects (Pc < 0.0006), and a preferential transmission of DQB1*0302-LTR13+ from parents to type 1 diabetic offspring was observed. DQ-LTR13 was in linkage disequilibrium (LD) with DQB1*0302 but not DQB1*0201. The presence of DQ-LTR13 increased the odds ratio of DQB1*0302 2.9- to 3.2-fold for type 1 diabetes and AAD. DRB1*0403 was absent in all of the 169 DRB1*04-positive patients but present in 27% (34 of 127) DRB1*04-positive healthy subjects (Pc < 0.001). DQ-LTR13 was detected in 1 of 34 (3%) DRB1*0403-positive healthy subjects and 36 of 93 (39%) individuals carrying another DRB1*04 allele (Pc = 0.002). Multivariate logistic regression analysis revealed that DQ-LTR13 is not independently associated with type 1 diabetes and AAD after correction for DQB1*0302 and DRB1*0403. Conversely, DQB1*0201, DQB1*0302, DRB1*0401, and DRB1*0403 were all significantly associated with disease risk also after correction for DQ-LTR13. We provide conclusive evidence that the genetic association of DQ-LTR13 with type 1 diabetes and AAD is primarily due to a LD with DQB1*0302 and DRB1*0403.
- Published
- 2005
36. Italian addison network study: update of diagnostic criteria for the etiological classification of primary adrenal insufficiency
- Author
-
Francesco Dotta, Antonio Bizzarro, Giorgio Arnaldi, Corrado Betterle, Annamaria De Bellis, Renato Zanchetta, Alberto Falorni, Vittorio Bini, Paolo Beck-Peccoz, Claudio Tiberti, Antonio Bellastella, Stefano Laureti, Franco Mantero, Fausto Santeusanio, Falorni, A, Laureti, S, DE BELLIS, Annamaria, Zanchetta, R, Tiberti, C, Arnaldi, G, Bini, V, BECK PECCOZ, P, Bizzarro, Antonio, Dotta, F, Mantero, F, Bellastella, A, Betterle, C, and Santeusanio, F.
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,insufficienza corticosurrenalica ,autoimmunità ,Disease ,Immunologic Tests ,medicine.disease_cause ,Biochemistry ,Primary Adrenal Insufficiency ,Autoimmunity ,Endocrinology ,Addison Disease ,Internal medicine ,Adrenal insufficiency ,Humans ,Medicine ,Child ,Aged ,Autoantibodies ,Aged, 80 and over ,business.industry ,classificazione eziologica ,Biochemistry (medical) ,Autoantibody ,Middle Aged ,medicine.disease ,Logistic Models ,Addison's disease ,Autoimmune polyendocrine syndrome ,Adrenal Cortex ,Etiology ,Female ,Steroid 21-Hydroxylase ,flow-chart ,business - Abstract
Primary adrenal insufficiency (PAI) is clinically evident in one in 8000 individuals. A correct etiological classification is critical for correct disease management. To update the diagnostic criteria for the etiological classification of PAI, a multicentric network was established in Italy, and 222 patients with PAI were studied. Both 21-hydroxylase and adrenal cortex autoantibodies (21OHAb and ACA, respectively) were tested in two independent laboratories on coded samples and found in 65-66% and 58-61% of cases, respectively. Autoimmune polyendocrine syndrome I was diagnosed in 11 of the 222 patients. Of the remaining 211 patients, 38 (18%) had a nonautoimmune form of PAI. In 145 subjects (65%), the presence of adrenal autoantibodies, without signs of other forms of PAI, led to a diagnosis of autoimmune Addison's disease. In six cases (3%), PAI remained idiopathic. Logistic regression analysis showed a 92.2-92.7% probability of correct reclassification for the two 21OHAb assays and 84.5-85.9% for the ACA assays. We conclude that the simultaneous presence of both 21OHAb and ACA permits unambiguous diagnosis of autoimmune Addison's, whereas subjects with low antibody titers should undergo both instrumental and biochemical tests to exclude other causes of PAI. Lastly, we developed a comprehensive flowchart for the classification of PAI for use in routine clinical practice.
- Published
- 2004
37. Aspetti immunologici e genetici del diabete autoimmune latente dell’adulto (LADA)
- Author
-
Falorni, Alberto
- Subjects
diabete mellito ,autoimmunità ,genetica - Published
- 2003
38. Gli esami utili per la diagnosi ed il controllo del LES
- Author
-
Gerli, Roberto
- Subjects
lupus eritematoso sistemico ,autoimmunità - Published
- 2002
39. Sindrome da insufficienza corticosurrenalica primitiva: nuovi concetti eziopatogenetici e diagnostici
- Author
-
Fausto Santeusanio, Stefano Laureti, and Alberto Falorni
- Subjects
Philosophy ,insufficienza corticosurrenalica ,terapia ,genetica ,autoimmunità ,Humanities - Abstract
Lo spettro clinico dell’insufficienza cortico-surrenalica primitiva (ICSP) e cambiato in maniera sostanziale nel corso delle ultime decadi per l’identificazione di nuove entita nosologiche, la migliore comprensione delle varie manifestazioni cliniche e i notevoli sviluppi della genetica e della biologia molecolare. In questo articolo descriveremo i progressi ottenuti negli ultimi anni nelle conoscenze della fisiopatologia dell’adrenalite autoimmune, attualmente la causa piu frequente di ICSP; discuteremo inoltre su altre patologie, meno frequenti, che possono essere causa di ICSP. La conoscenza di tali condizioni patologiche e delle metodologie che ne consentono l’individuazione e utile per il clinico endocrinologo al fine di garantire quella precisa e rapida classificazione eziologica che e il cardine di un’efficace gestione clinica del paziente.
- Published
- 2001
40. Seven-year follow-up of 138 Italian patients with indifferentiated connective tissue diseases
- Author
-
Danieli, G., Cappelli, M., Franceschini, F., Cattaneo, R., Gerli, Roberto, and Et, A.
- Subjects
malattie del tessuto connettivo ,autoimmunità - Published
- 2001
41. c) Sindrome di Sjogren
- Author
-
BARIFFI, FRANCESCO, PONTICIELLO, ANTONIO, D. Olivieri, Bariffi, Francesco, and Ponticiello, Antonio
- Subjects
interstiziale ,Sjogren ,autoimmunità - Published
- 2000
42. Timo ed autoimmunità: implicazioni immunologiche e cliniche della timectomia nell’uomo. Atti 37° Congresso Nazionale Società Italiana di Reumatologia
- Author
-
Tomassini, C., Bistoni, O., Cesarotti, M., Allegrucci, R., Biagini, P., and Gerli, Roberto
- Subjects
timo ,autoimmunità ,timectomia - Published
- 2000
43. Target di autoimmunità endocrina in corso di terapia con IFN-alfa in pazienti con epatite cronica da HCV. 30°congr.naz. SISMIP, Ferrara 6-9 ottobre 1999
- Author
-
Francisci, Daniela and Stagni, G.
- Subjects
epatite cronica ,hcv ,autoimmunità ,ifn-alfa - Published
- 1999
44. Endocrinopatie autoimmuni
- Author
-
Ulisse, Salvatore, Cozzi, M. R., Jannini, E. A., and D'Armiento, Massimino
- Subjects
Autoimmunità, Ghiandole endocrine, Patogenesi ,Ghiandole endocrine ,Autoimmunità ,Patogenesi - Published
- 1992
45. L'ipotesi autoimmunitaria della schizofrenia. Recettore solubile dell'Interleuchina 2 e Tumor Necrosis Factor
- Author
-
DI MICHELE V, PELLEGRINI P, BERGHELLA AM, DEL BEATO T, PIANCATELLI D, CASACCHIA M, ADORNO D, and CASCIANI CU
- Subjects
schizofrenia. Recettore solubile IL2 ,autoimmunità - Abstract
non disponibile
- Published
- 1991
46. Accuratezza e correlazione istologica degli anticorpi anti actina nella diagnosi di malattia celiaca
- Author
-
Fabbro, Elisa and Not, Tarcisio
- Subjects
MED/38 PEDIATRIA GENERALE E SPECIALISTICA ,celiachia ,anticorpi anti actina ,autoimmunità ,MED.MAT.INFANT.PED.SVIL.EDUCAZ.PERINAT - Abstract
2006/2007 La celiachia (CD) è un’enteropatia immuno-mediata scatenata dall’ingestione di glutine in soggetti geneticamente predisposti. La prevalenza di questa patologia varia tra 1/100 e 1/300; nella sua forma tipica si manifesta con diarrea, malassorbimento, e deficit di crescita, ma è ora noto che esistono molte forme atipiche, con eterogeneità di manifestazioni spesso extraintestinali, o addirittura forme asintomatiche che sfuggono alla diagnosi. Per la diagnosi abbiamo oggi a disposizione markers sierologici molto sensibili e specifici, ma in ogni caso la conferma di celiachia prevede l’esecuzione di una biopsia intestinale che dimostri le tipiche alterazioni istologiche. Recenti lavori hanno evidenziato che in una buona percentuale di soggetti con celiachia vengono prodotti, oltre agli anticorpi anti-Endomisio e anti-Tranglutaminasi, presenti nella quasi totalità dei pazienti, gli anticorpi anti-Actina (AAA) e dal momento che questi sembrano correlare strettamente con la severità della lesione intestinale sono stati proposti come markers sierologici di danno istologico La messa a punto di una metodica standardizzata in grado di dosarli potrebbe quindi risultare molto utile e potrebbe già nell’immediato futuro rivoluzionare la diagnostica della malattia celiaca in quanto una semplice indagine sierologica, non invasiva e di basso costo, che preveda il dosaggio degli anticorpi anti-Transglutaminasi (noto test ad elevata sensibilità e specificità) unitamente a quello degli anticorpi ani-Actina, potrebbe rappresentare una valida alternativa alla biopsia intestinale. In questo contesto si inserisce il progetto relativo al mio Dottorato di Ricerca. Lo studio si propone infatti di confermare i risultati precedentemente ottenuti e di mettere a punto un procedimento operativo semplice e ripetibile. In una prima fase il dosaggio degli anticorpi anti-Actina è stato eseguito mediante un test di immunofluorescenza indiretta su sieri opportunamente trattati.;si è notato, infatti, che un pretrattamento fisico (riscaldamento a 56°C per 45 minuti) o chimico (aggiunta di EDTA a una concentrazione 0,1mM) dei sieri inibisce una proteina, la Gelsolina, che, se presente, maschera il legame Actina-anticorpo rendendo il test poco sensibile. Da questo studio è emerso che la presenza degli anticorpi anti-Actina correlava con la severità della lesione intestinale. E’ stata poi valutata la validità del test mediante il calcolo statistico di sensibilità e specificità e tramite la misurazione della discordanza tra la lettura di più operatori.diversi . Il lavoro svolto ha purtroppo dimostrato una bassa sensibilità e specificità di questo test in particolare se confrontato con la metodica ELISA classica utilizzata per la ricerca degli anticorpi anti Transglutaminasi tessutale nei sieri dei pazienti celiaci. Lo screening di una libreria totale di paziente celiaco ha permesso di identificare alcuni cloni anti Actina positivi che producono un pattern d’immunofluorescenza del tutto identico a quello dei sieri AAA positivi trattati .Questo dimostra che gli anticorpi selezionati da librerie totali sono gli stessi di quelli presenti nel siero dei pazienti celiaci e che il trattamento chimico e fisico non altera il sito di legame antigenico ma va a inibire esclusivamente la proteina sierica che mascherando il sito di legame dell’antigene all’anticorpo rende il test poco sensibile. La disponibilità di questi cloni di anticorpi anti Actina selezionati da una libreria totale di mucosa intestinale di celiaco potrà far comprendere meglio il ruolo di questi autoanticorpi nella patogenesi del danno intestinale della malattia celiaca. Nella seconda parte di questo Dottorato è stata valuta la prevalenza degli anticorpi anti Actina anche in pazienti con Cardiomiopatia Dilatativi Idiopatica (CMPD) e nei loro famigliari di primo grado. Questa malattia ha un’eziopatogenesi per lo più sconosciuta. Probabilmente si tratta di una condizione a patogenesi eterogenea tuttavia almeno in una certa parte dei pazienti la Cardiomiopatia Dilatativa Idiopatica potrebbe essere un malattia autoimmune organo specifica in cui il processo distruttivo è ristretto all’ organo bersaglio e gli autoanticorpi riconoscono e reagiscono con lo specifico antigene Il dato interessante che emerge da questa tesi è che la positività agli AAA non è casuale ma è presente in gruppi di famiglie. Si può quindi ipotizzare che gli anticorpi anti-Actina siano un potenziale fattore patogenetico e non un’ epifenomeno dell’ infiammazione tessutale di fase acuta. Nel prossimo futuro saranno necessari studi prospettici per l’ identificazione dei meccanismi patogenetici alla base di questa associazione e per comprendere se una precoce identificazione degli anticorpi anti Actina tra i famigliari di soggetti con CMPD possa modificare la storia naturale di questa patologia gravata da una severa prognosi (Fabbro E et al,“Uselessness of anti-actin antibody in celiac disease screening” Clinica Chimica Acta 390; 2008 134–137) XX Ciclo
- Published
- 1977
47. Multidirectional dysfunction of the immune response in patients with systemic lupus erythematosus
- Author
-
Giuseppe Alvise Ramirez, Ramirez, GIUSEPPE ALVISE, and MANFREDI, ANGELO ANDREA M. A.
- Subjects
linfociti T ,immunodeficienza ,lupu ,autoimmunity ,T cell ,autoimmunità ,allergy ,allergia - Abstract
Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease characterised by protean clinical manifestations and multifaceted pathogenic background. Allergic reactions and infectious events complicate the course of SLE but their reciprocal correlations are poorly understood. Availability of accurate tools to stratify patients with homogeneous endo/phenotypes and guide personalised treatments is still an unmet need. Despite the potential pathogenic role of T cells in SLE, little is known about the quantitative and qualitative features of antigen-specific T cell responses. Based on clinical data demonstrating a tripartite association between disease flares, allergic and infectious events, a multi-step experimental plan was designed to seek and characterise antigen-specific T cells recognising histone-, Epstein-Barr virus (EBV)- and penicilloylated albumin-derived peptides in patients with SLE in comparison to patients with Takayasu’s arteritis and healthy controls. Genetic studies confirmed that human leukocyte antigen (HLA)-DRB1*03:01 is a risk factor for SLE and revealed novel associations among DRB1*11:01, allergic and infectious events, and between DRB1*07:01 and infection protection. Stem-cell memory T cells (TSCM) were expanded in patients with SLE possibly accounting for persisting inflammation. Using direct ex vivo visualisation of antigen-specific T cells stained with class II HLA tetramers through flow cytometry, histone-specific CD4+ T cells were selectively detected in patients with SLE and their accumulation in the peripheral blood associated with the presence of anti-DNA antibodies. Penicilloylated albumin-specific T cells identified patients with beta-lactam allergy. EBV-specific cells were detected as expected in patients and controls. Variations in the size of the three types of antigen-specific T cell populations were reciprocally correlated and cytokine responses to isolated epitopes revealed activation of multiple inflammatory pathways suggesting cross-contamination between antimicrobial, allergic and autoreactive responses. Histone-specific and EBV-specific effector memory T cells and T regulatory cells decreased during SLE flares, possibly reflecting peripheralization into target tissues and defective anti-inflammatory responses. EBV-specific TSCM also decreased and EBV-induced cytokine responses were impaired during active phases of the disease possibly indicating mis-differentiation of precursors, and ineffective antiviral responses. These data support the existence of a multidirectional dysfunction of the immune response, possibly traceable and targetable through T cell responses, as a pathophysiological and clinical hallmark of SLE. Il lupus eritematoso sistemico (LES) è una malattia autoimmune multiorgano caratterizzata da manifestazioni cliniche multiformi e da un quadro patogenetico dalle molteplici sfaccettature. Lo sviluppo di reazioni allergiche ed eventi infettivi può complicare il decorso del LES ma le relazioni intercorrenti tra la malattia e queste due tipologie di eventi immuno-mediati sono scarsamente conosciute. La disponibilità di strumenti accurati per stratificare i pazienti in endo/fenotipi omogenei e per guidare trattamenti personalizzati è ancora un bisogno insoddisfatto. Nonostante il potenziale ruolo patogenetico delle cellule T nel LES, esistono poche conoscenze riguardo alle caratteristiche delle risposte T antigene-specifiche, sia dal punto di vista quantitativo che qualitativo. A partire da una serie di dati clinici che mostravano un'associazione tripartita tra riacutizzazioni di malattia, eventi infettivi e allergici, è stato disegnato uno studio finalizzato a identificare e caratterizzare le risposte T cellulari dirette contro peptidi derivati da istoni, virus di Epstein-Barr (EBV) e albumina penicilloilata in pazienti con LES, confrontati con pazienti con arterite di Takayasu e controlli sani. I dati genetici hanno confermato che l'allele DRB1*03:01 del complesso maggiore di istocompatibilità (MHC) di classe II è un fattore di rischio per il LES e ha rivelato nuove associazioni tra l'allele DRB1*11:01 e lo sviluppo di manifestazioni allergiche ed infettive e tra DRB1*07:01 e un minor tasso di infezioni. Le cellule T staminali della memoria (TSCM) erano espanse in pazienti con LES, fornendo un possibile correlato biologico per lo stato di infiammazione cronica caratteristico della malattia. Grazie alla visualizzazione diretta ex vivo in citometria a flusso delle cellule T antigene specifiche grazie a tetrameri di MHC, è stato possibile rilevare che i pazienti con LES e in particolare i soggetti con anticorpi antiDNA sono portatori di cellule T specifiche per istoni. Le cellule T specifiche per albumina penicilloilata hanno identificato soggetti con allergia a beta-lattamici. Le cellule specifiche per EBV sono state rilevate (come atteso) in pazienti e controlli. Le tre popolazioni di cellule antigene specifiche hanno mostrato pattern paralleli di variazione dimensionale e le risposte citochiniche ad un singolo epitopo di interesse hanno mostrato l'attivazione di multiple vie di segnale infiammatorio, suggerendo la presenza di interferenze reciproche tra risposte antimicrobiche, allergiche e autoreattive. Le cellule T effettrici della memoria e regolatrici specifiche per istoni ed EBV diminuivano in corso di attività di LES, forse come riflesso di una loro delocalizzazione periferica nel contesto dei tessuti bersaglio e di un'insufficiente risposta antinfiammatoria. In fase di attività di malattia le TSCM anti EBV risultavano analogamente diminuite, al pari delle risposte citochiniche all'EBV, indicando potenzialmente fenomeni di differenziazione incongrua dei precursori degli effettori e la presenza di risposte antivirali non efficaci. Questi dati suggeriscono l'esistenza di una disfunzione multidirezionale della risposta infiammatoria, potenzialmente tracciabile e identificabile come obbiettivo di trattamento attraverso lo studio delle risposte T cellulari, come caratteristica clinica e fisiopatologica del LES.
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.