%0 Journal Article %J J Cell Physiol %D 2019 %T Antibodies reacting to mimotopes of Simian virus 40 large T antigen, the viral oncoprotein, in sera from children. %A Mazzoni, Elisa %A Frontini, Francesca %A Rotondo, John Charles %A Zanotta, Nunzia %A Fioravanti, Arianna %A Minelli, Francesca %A Torreggiani, Elena %A Campisciano, Giuseppina %A Marcuzzi, Annalisa %A Guerra, Giovanni %A Tommasini, Alberto %A Touzé, Antoine %A Martini, Fernanda %A Tognon, Mauro %A Comar, Manola %X

Recent data indicate that the Simian virus 40 (SV40) infection appears to be transmitted in humans independently from early SV40-contaminated antipolio vaccines. Serum antibodies against SV40 large T antigen (Tag) were analyzed in children/adolescents and young adults. To investigate antibodies reacting to SV40 Tag antigens, serum samples ( n = 812) from children and young adults were analyzed by indirect ELISAs using specific SV40 Tag mimotopes. Mimotopes were synthetic peptides corresponding to SV40 Tag epitopes. In sera ( n = 412) from healthy children up to 17 years old, IgG antibodies against SV40 Tag mimotopes reached an overall prevalence of 15%. IgM antibodies against SV40 Tag were detected in sera of children 6-8 months old confirming and extending the knowledge that SV40 seroconversion occurs early in life. In children/adolescents affected by different diseases ( n = 180) SV40 Tag had a prevalence of 18%, being the difference no significant compared to healthy subjects ( n = 220; 16%) of the same age. Our immunological data indicate that SV40 circulates in children and young adults, both in healthy conditions and affected by distinct diseases. The IgM detection in sera from healthy children suggests that the SV40 infection/seroconversion occurs early in life (>6 months). Our immunological data support the hypothesis that SV40, or a closely related still unknown polyomavirus, infects humans. The SV40 seroprevalence is lower than common polyomaviruses, such as BKPyV and JCPyV, and other new human polyomaviruses. In addition, our immunological surveillance indicates a lack of association between different diseases, considered herein, and SV40.

%B J Cell Physiol %V 234 %P 3170-3179 %8 2019 Apr %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/30362540?dopt=Abstract %R 10.1002/jcp.27490 %0 Journal Article %J Ann Rheum Dis %D 2017 %T ADA2 deficiency (DADA2) as an unrecognised cause of early onset polyarteritis nodosa and stroke: a multicentre national study. %A Caorsi, Roberta %A Penco, Federica %A Grossi, Alice %A Insalaco, Antonella %A Omenetti, Alessia %A Alessio, Maria %A Conti, Giovanni %A Marchetti, Federico %A Picco, Paolo %A Tommasini, Alberto %A Martino, Silvana %A Malattia, Clara %A Gallizi, Romina %A Podda, Rosa Anna %A Salis, Annalisa %A Falcini, Fernanda %A Schena, Francesca %A Garbarino, Francesca %A Morreale, Alessia %A Pardeo, Manuela %A Ventrici, Claudia %A Passarelli, Chiara %A Zhou, Qing %A Severino, Mariasavina %A Gandolfo, Carlo %A Damonte, Gianluca %A Martini, Alberto %A Ravelli, Angelo %A Aksentijevich, Ivona %A Ceccherini, Isabella %A Gattorno, Marco %K Adenosine Deaminase %K Adolescent %K Age of Onset %K Case-Control Studies %K Child %K Child, Preschool %K DNA Mutational Analysis %K Female %K Heterozygote %K Homozygote %K Humans %K Immunoglobulins %K Immunosuppressive Agents %K Infant %K Intercellular Signaling Peptides and Proteins %K Italy %K Livedo Reticularis %K Male %K Pedigree %K Polyarteritis Nodosa %K Stroke %K Thalidomide %K Tumor Necrosis Factor-alpha %K Young Adult %X

OBJECTIVES: To analyse the prevalence of mutations in patients diagnosed with early onset livedo reticularis and/or haemorrhagic/ischaemic strokes in the context of inflammation or polyarteritis nodosa (PAN). Forty-eight patients from 43 families were included in the study.

METHODS: Direct sequencing of was performed by Sanger analysis. Adenosine deaminase 2 (ADA2) enzymatic activity was analysed in monocyte isolated from patients and healthy controls incubated with adenosine and with or without an ADA1 inhibitor.

RESULTS: Biallelic homozygous or compound heterozygous mutations were detected in 15/48 patients. A heterozygous disease-associated mutation (p.G47V) was observed in two affected brothers. The mean age of onset of the genetically positive patients was 24 months (6 months to 7 years). Ten patients displayed one or more cerebral strokes during their disease course. Low immunoglobulin levels were detected in six patients. Thalidomide and anti-TNF (tumour necrosis factor) blockers were the most effective drugs. Patients without mutations had a later age at disease onset, a lower prevalence of neurological and skin manifestations; one of these patients displayed all the clinical features of adenosine deaminase 2deficiency (DADA2) and a defective enzymatic activity suggesting the presence of a missed mutation or a synthesis defect.

CONCLUSIONS: DADA2 accounts for paediatric patients diagnosed with PAN-like disease and strokes and might explain an unrecognised condition in patients followed by adult rheumatologist. Timely diagnosis and treatment with anti-TNF agents are crucial for the prevention of severe complications of the disease. Functional assay to measure ADA2 activity should complement genetic testing in patients with non-confirming genotypes.

%B Ann Rheum Dis %V 76 %P 1648-1656 %8 2017 Oct %G eng %N 10 %1 http://www.ncbi.nlm.nih.gov/pubmed/28522451?dopt=Abstract %R 10.1136/annrheumdis-2016-210802 %0 Journal Article %J Mol Med Rep %D 2016 %T Action of methotrexate and tofacitinib on directly stimulated and bystander-activated lymphocytes. %A Piscianz, Elisa %A Candilera, Vanessa %A Valencic, Erica %A Loganes, Claudia %A Paron, Greta %A De Iudicibus, Sara %A Decorti, Giuliana %A Tommasini, Alberto %X

Chronic inflammation associated with autoimmune activation is characteristic of rheumatic diseases from childhood to adulthood. In recent decades, significant improvements in the treatment of these types of disease have been achieved using disease modifying anti-rheumatic drugs (DMARDs), such as methotrexate (MTX) and, more recently, using biologic inhibitors. The recent introduction of kinase inhibitors (for example, tofacitinib; Tofa) further increases the available ARDs. However, there are patients that do not respond to any treatment strategies, for whom combination therapies are proposed. The data regarding the combined action of different drugs is lacking and the knowledge of the mechanisms of ARDs and their actions upon pathogenic lymphocytes, which are hypothesized to sustain disease, is poor. An in vitro model of inflammation was developed in the current study, in which stimulated and unstimulated lymphocytes were cultured together, but tracked separately, to investigate the action of MTX and Tofa on the two populations. By analysing lymphocyte proliferation and activation, and cytokine secretion in the culture supernatants, it was established that, due to the presence of activated cells, unstimulated cells underwent a bystander activation that was modulated by the ARDs. Additionally, varying administration schedules were demonstrated to affect lymphocytes differently in vitro, either directly or via bystander activation. Furthermore, MTX and Tofa exerted different effects; while MTX showed an antiproliferative effect, Tofa marginally effected activation, although only a slight antiproliferative action, which could be potentiated by sequential treatment with MTX. Thus, it was hypothesized that these differences may be exploited in sequential therapeutic strategies, to maximize the anti‑rheumatic effect. These findings are notable and must be accounted for, as bystander‑activated cells in vivo could contribute to the spread of autoimmune activation and disease progression.

%B Mol Med Rep %V 14 %P 574-82 %8 2016 Jul %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/27175898?dopt=Abstract %R 10.3892/mmr.2016.5263 %0 Journal Article %J Clin Immunol %D 2015 %T Altered germinal center reaction and abnormal B cell peripheral maturation in PI3KR1-mutated patients presenting with HIGM-like phenotype. %A Lougaris, Vassilios %A Faletra, Flavio %A Lanzi, Gaetana %A Vozzi, Diego %A Marcuzzi, Annalisa %A Valencic, Erica %A Piscianz, Elisa %A Bianco, AnnaMonica %A Girardelli, Martina %A Baronio, Manuela %A Loganes, Claudia %A Fasth, Anders %A Salvini, Filippo %A Trizzino, Antonino %A Moratto, Daniele %A Facchetti, Fabio %A Giliani, Silvia %A Plebani, Alessandro %A Tommasini, Alberto %K B-Lymphocytes %K Child, Preschool %K Female %K Germinal Center %K Humans %K Hyper-IgM Immunodeficiency Syndrome %K Infant %K Male %K Mutation %K Phenotype %K Phosphatidylinositol 3-Kinases %K RNA Splice Sites %K Sequence Analysis, DNA %B Clin Immunol %V 159 %P 33-6 %8 2015 Jul %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/25939554?dopt=Abstract %R 10.1016/j.clim.2015.04.014 %0 Journal Article %J World J Gastroenterol %D 2011 %T Ages of celiac disease: from changing environment to improved diagnostics. %A Tommasini, Alberto %A Not, Tarcisio %A Ventura, Alessandro %K Autoantibodies %K Celiac Disease %K Diet, Gluten-Free %K Gliadin %K Glutens %K History, 19th Century %K History, 20th Century %K History, 21st Century %K History, Ancient %K History, Medieval %K Humans %K Transglutaminases %X

From the time of Gee's landmark writings, the recent history of celiac disease (CD) can be divided into many ages, each driven by a diagnostic advance and a deeper knowledge of disease pathogenesis. At the same time, these advances were paralleled by the identification of new clinical patterns associated with CD and by a continuous redefinition of the prevalence of the disease in population. In the beginning, CD was considered a chronic indigestion, even if the causative food was not known; later, the disease was proven to depend on an intolerance to wheat gliadin, leading to typical mucosal changes in the gut and to a malabsorption syndrome. This knowledge led to curing the disease with a gluten-free diet. After the identification of antibodies to gluten (AGA) in the serum of patients and the identification of gluten-specific lymphocytes in the mucosa, CD was described as an immune disorder, resembling a chronic "gluten infection". The use of serological testing for AGA allowed identification of the higher prevalence of this disorder, revealing atypical patterns of presentation. More recently, the characterization of autoantibodies to endomysium and to transglutaminase shifted the attention to a complex autoimmune pathogenesis and to the increased risk of developing autoimmune disorders in untreated CD. New diagnostic assays, based on molecular technologies, will introduce new changes, with the promise of better defining the spectrum of gluten reactivity and the real burden of gluten related-disorders in the population. Herein, we describe the different periods of CD experience, and further developments for the next celiac age will be proposed.

%B World J Gastroenterol %V 17 %P 3665-71 %8 2011 Aug 28 %G eng %N 32 %1 http://www.ncbi.nlm.nih.gov/pubmed/21990947?dopt=Abstract %R 10.3748/wjg.v17.i32.3665