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Journal of pediatric gastroenterology and nutrition 08/2012; · 2.18 Impact Factor
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Gastrointestinal endoscopy 05/2012; 75(5):1123-4. · 6.71 Impact Factor
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Laura Passerini,
Sven Olek,
Sara Di Nunzio,
Federica Barzaghi,
Sophie Hambleton,
Mario Abinun,
Alberto Tommasini, Silvia Vignola,
Marco Cipolli,
Mario Amendola,
Luigi Naldini,
Luisa Guidi,
Massimiliano Cecconi,
Maria G Roncarolo,
Rosa Bacchetta
The Journal of allergy and clinical immunology 12/2011; 128(6):1376-1379.e1. · 9.17 Impact Factor
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ABSTRACT: Inflammatory bowel disease (IBD) is often associated with extraintestinal manifestations (EIMs) such as optic neuritis (ON), although this has been described in only a few adult patients so far, all of whom were affected with Crohn's disease (CD). Furthermore, ON and demyelinating diseases have been demonstrated to be more frequent in IBD patients than in control populations. In our current case report, we describe a child with active CD who developed sudden blindness due to bilateral ON that was not related to any known cause, and that promptly responded to a high dose of steroids. Investigations and a clinical follow-up have so far ruled out the development of demyelinating diseases in this patient. To our knowledge, this is the first report of ON in a pediatric patient with CD. Possible explanations for this case include an episodic EIM of an active bowel disease, an associated autoimmune disorder such as a recurrent isolated ON, the first manifestation of multiple sclerosis, or another demyelinating disease that could appear in a later follow-up.
World Journal of Gastroenterology 10/2011; 17(38):4344-6. · 2.47 Impact Factor
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Gastrointestinal endoscopy 02/2011; 73(2):401-3. · 6.71 Impact Factor
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Laura Passerini,
Sara Di Nunzio,
Silvia Gregori,
Eleonora Gambineri,
Massimiliano Cecconi,
Markus G Seidel,
Giantonio Cazzola,
Lucia Perroni,
Alberto Tommasini, Silvia Vignola,
Luisa Guidi,
Maria G Roncarolo,
Rosa Bacchetta
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ABSTRACT: Mutations of forkhead box p3 (FOXP3), the master gene for naturally occurring regulatory T cells (nTregs), are responsible for the impaired function of nTregs, resulting in an autoimmune disease known as the immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. The relevance of other peripheral tolerance mechanisms, such as the presence and function of type 1 regulatory T (Tr1) cells, the major adaptive IL-10-producing Treg subset, in patients with IPEX syndrome remains to be clarified. FOXP3(mutated) Tr1-polarized cells, differentiated in vitro from CD4(+) T cells of four IPEX patients, were enriched in IL-10(+) IL-4(-) IFN-γ(+) T cells, a cytokine production profile specific for Tr1 cells, and expressed low levels of FOXP3 and high levels of Granzyme-B. IPEX Tr1 cells were hypoproliferative and suppressive, thus indicating that FOXP3 mutations did not impair their function. Furthermore, we isolated Tr1 cell clones from the peripheral blood of one FOXP3(null) patient, demonstrating that Tr1 cells are present in vivo and they can be expanded in vitro in the absence of WT FOXP3. Overall, our results (i) show that functional Tr1 cells differentiate independently of FOXP3, (ii) confirm that human Tr1 and nTregs are distinct T-cell lineages, and (iii) suggest that under favorable conditions Tr1 cells could exert regulatory functions in IPEX patients.
European Journal of Immunology 01/2011; 41(4):1120-31. · 5.10 Impact Factor
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ABSTRACT: Chronic intestinal failure is a condition causing severe impairment of intestinal functions; long-term total parenteral nutrition is required to provide adequate nutritional support.
This is a 15-year follow-up study of paediatric patients with intestinal failure receiving long-term home parenteral nutrition.
Thirty-six patients were included in the study, all aged <16 years. Total parenteral nutrition and home parenteral nutrition were administered respectively to 100.97 and 85.20 patients-year. Today, 12 out of 36 patients are still on parenteral nutrition. A total of 99 central venous catheters were inserted, for mean 2.75 catheters/patient. The overall incidence rates of catheter-related complications was 1.79 per 1000 days-catheter for sepsis and 3.37 per 1000 days-catheter for mechanical complications. Two multivariate Cox-models have been used to examine the role of some predictors for septic or mechanical complications. The only risk factor for septic complications was the indication for parenteral nutrition, and the only predictor of mechanical complications was the insertion period.
Our experience in the treatment of paediatric patients with gastrointestinal diseases confirms that long-term parenteral nutrition has become a safe and appropriate method in the treatment of severe chronic intestinal failure.
Digestive and Liver Disease 01/2011; 43(1):28-33. · 3.05 Impact Factor
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Sara Di Nunzio,
Massimiliano Cecconi,
Laura Passerini,
Alicia N McMurchy,
Udo Baron,
Ivana Turbachova, Silvia Vignola,
Erica Valencic,
Alberto Tommasini,
Anne Junker,
Giantonio Cazzola,
Sven Olek,
Megan K Levings,
Lucia Perroni,
Maria Grazia Roncarolo,
Rosa Bacchetta
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ABSTRACT: Forkhead box P3 (FOXP3) is constitutively expressed by CD4(+)CD25(hi) regulatory T cells (nTregs). Mutations of FOXP3 cause a severe autoimmune syndrome known as immune dysregulation polyendocrinopathy enteropathy X-linked, in which nTregs are absent or dysfunctional. Whether FOXP3 is essential for both differentiation and function of human nTreg cells remains to be demonstrated. Because FOXP3 is an X-linked gene subject to X-chromosome inactivation (XCI), we studied 9 healthy female carriers of FOXP3 mutations to investigate the role of wild-type (WT) versus mutated FOXP3 in different cell subsets. Analysis of active WT versus mutated (mut)-FOXP3 allele distribution revealed a random pattern of XCI in peripheral blood lymphocytes and in naive and memory CD4(+)T cells, whereas nTregs expressed only the active WT-FOXP3. These data demonstrate that expression of WT-FOXP3 is indispensable for the presence of a normal nTreg compartment and suggest that FOXP3 is not necessary for effector T-cell differentiation in humans.
Blood 10/2009; 114(19):4138-41. · 9.90 Impact Factor
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Eleonora Gambineri,
Lucia Perroni,
Laura Passerini,
Lucia Bianchi,
Claudio Doglioni,
Franco Meschi,
Riccardo Bonfanti,
Yves Sznajer,
Alberto Tommasini,
Anita Lawitschka, [......],
Wilhelm Friedrich,
Dragana Janic,
Nadira Azzi,
Erick Richmond, Silvia Vignola,
Arrigo Barabino,
Giuseppe Chiumello,
Chiara Azzari,
Maria-Grazia Roncarolo,
Rosa Bacchetta
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ABSTRACT: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is an autoimmune genetic disorder caused by mutation of the forkhead box protein 3 gene (FOXP3), a key regulator of immune tolerance.
We sought to provide clinical and molecular indicators that facilitate the understanding and diagnosis of IPEX syndrome.
In 14 unrelated affected male subjects who were given diagnoses of IPEX syndrome based on FOXP3 gene sequencing, we determined whether particular FOXP3 mutations affected FOXP3 protein expression and correlated the molecular and clinical data.
Molecular analysis of FOXP3 in the 14 subjects revealed 13 missense and splice-site mutations, including 7 novel mutations. Enteropathy, generally associated with endocrinopathy and eczema, was reported in all patients, particularly in those carrying mutations within FOXP3 functional domains or mutations that altered protein expression. However, similar genotypes did not always result in similar phenotypes in terms of disease presentation and severity. In addition, FOXP3 protein expression did not correlate with disease severity.
Severe autoimmune enteropathy, which is often associated with increased IgE levels and eosinophilia, is the most prominent early manifestation of IPEX syndrome. Nevertheless, the disease course is variable and somewhat unpredictable. Therefore genetic analysis of FOXP3 should always be performed to ensure an accurate diagnosis, and FOXP3 protein expression analysis should not be the only diagnostic tool for IPEX syndrome.
The Journal of allergy and clinical immunology 11/2008; 122(6):1105-1112.e1. · 9.17 Impact Factor
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ABSTRACT: Matrix metalloproteinases (MMP) are a large family of proteolytic enzymes involved in the remodeling of extracellular matrix during tissue resorption in idiopathic arthritides. We investigated serum and synovial fluid (SF) concentrations of MMP-3 and its tissue inhibitor (TIMP-1) in juvenile idiopathic arthritides (JIA).
Sera from 45 patients with active, 15 patients with inactive JIA, and 15 healthy controls were evaluated by ELISA for MMP-3 (stromelysin-1), TIMP-1, and soluble p75 tumor necrosis factor receptor (sTNFR). Paired SF concentrations were evaluated in 19 patients with JIA.
MMP-3 serum concentrations were significantly higher in patients with active poly- and oligoarticular JIA versus inactive patients (p = 0.04 and p = 0.02, respectively) and healthy controls (p < 0.001 for both). Serum MMP-3, but not TIMP-1, concentration displayed a variable degree of correlation with clinical and laboratory variables of disease activity and with p75 sTNFR concentrations (r = 0.37, p = 0.005). SF MMP-3 concentrations were 30-300 times higher than those found in paired sera (p < 0.001, Wilcoxon rank test). A clear inversion of MMP-3/TIMP-1 ratio was observed when sera (median 0.31. range 0.02-1.5) were compared with the corresponding SF samples (5.3, range 4.9-5.5; p < 0.001).
MMP-3 (stromelysin-1) is clearly overexpressed in SF of patients with JIA. An inadequate counter-expression of TIMP-1 may represent a crucial event for the development and perpetuation of tissue damage.
The Journal of Rheumatology 04/2002; 29(4):826-31. · 3.69 Impact Factor
