Giusi Prencipe

Giusi Prencipe
Ospedale Pediatrico Bambino Gesù | Bambino Gesù · Laboratory of Immuno-Rheumatology

PhD

About

67
Publications
7,680
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1,460
Citations
Additional affiliations
January 2006 - May 2015
Ospedale Pediatrico Bambino Gesù
Position
  • PostDoc Position

Publications

Publications (67)
Article
CD8+ T-cell activation has been demonstrated to distinguish patients with primary and infection-associated hemophagocytic lymphohistiocytosis (pHLH and iaHLH) from patients with early sepsis. We evaluated the activation profile of CD8+ T cells in patients with various forms of secondary HLH (sHLH), including macrophage activation syndrome (MAS). Fl...
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Haploinsufficiency of A20 (HA20) is an inflammatory disease caused by mutations in the TNFAIP3 gene classically presenting with Behcet’s-like disease. A20 acts as an inhibitor of inflammation through its effect on NF-kB pathway. Here we describe four consanguineous patients (three sisters and their mother) with a predominantly autoimmune phenotype,...
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The activation of several inflammatory pathways has recently been documented in patients and different cellular and animal models of nephropathic cystinosis. Upregulated inflamma-tory signals interact with many pathogenic aspects of the disease, such as enhanced oxidative stress, abnormal autophagy, inflammatory cell recruitment, enhanced cell deat...
Article
Interferon-γ (IFNγ) is a pleiotropic cytokine with multiple effects on the inflammatory response and on innate and adaptive immunity. Overproduction of IFNγ underlies several, potentially fatal, hyperinflammatory or immune-mediated diseases. Several data from animal models and/or from translational research in patients point to a role of IFNγ in hy...
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Objective To investigate the activation of the IFNγ signaling pathway in monocytes of patients with secondary hemophagocytic lymphohistiocytosis (sHLH)/macrophage activation syndrome (MAS) and to evaluate whether levels of phosphorylated STAT1 represent a biomarker for the identification of patients at early stages of the disease. Methods Fresh wh...
Article
Objective To evaluate the impact of early treatment and IL1RN genetic variants on the response to anakinra in systemic juvenile idiopathic arthritis (sJIA). Methods Response to anakinra was defined as clinically inactive disease (CID) at 6 months, without glucocorticoids treatment. Demographic, clinical and laboratory characteristics of 56 patient...
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We describe a 2 year old boy with two previously undescribed frameshift mutations in the interferon (IFN)α/β receptor 2 (IFNAR2) gene presenting with hemophagocytic lymphohistiocytosis (HLH) following measles-mumps-rubella vaccination. Functional analyses show the absence of response to type I IFN in the patient’s cells, as revealed by the lack of...
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Perinatal asphyxia triggers an acute inflammatory response in the injured brain. Complement activation and neuroinflammation worsen brain damage after a systemic ischemia/reperfusion insult. The increase of mannose binding lectin (MBL) during asphyxia may contribute to the brain damage, via activation of the complement lectin pathway. The possible...
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Background and objective Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease (AID) worldwide. The disease is caused by mutations in the MEFV gene encoding the inflammasome sensor Pyrin. Clinical diagnosis of FMF is complicated by overlap in symptoms with other diseases, and interpretation of genetic testing is c...
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Background: Nephropathic cystinosis, a hereditary lysosomal storage disorder caused by dysfunction of the lysosomal cotransporter cystinosin, leads to cystine accumulation and cellular damage in various organs, particularly in the kidney. Close therapeutic monitoring of cysteamine, the only available disease-modifying treatment, is recommended. Wh...
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Background: Fibrodysplasia ossificans progressiva (FOP) is the most catastrophic form of heterotopic ossification, due to ongoing intracellular signaling through the bone morphogenic protein pathway. The paroxysmal appearance of inflammatory lumps and elevated inflammatory markers during flares, suggest that FOP is an auto-inflammatory disease. Ba...
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Aim of this study was to investigate the activation of the IFNγ pathway in the affected liver and in the blood of patients with secondary hemophagocytic lymphohistiocytosis (sHLH). To this purpose, the mRNA expression levels of IFNG and IFNγ-inducible genes as well as Tyrosine (701)-phosphorylated signal transducer and activator of transcription 1...
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Hemophagocytic lymphohistiocytosis (HLH) is characterized by immune dysregulation due to inadequate restraint of overactivated immune cells and is associated with a variable clinical spectrum having overlap with more common pathophysiologies. HLH is difficult to diagnose and can be part of inflammatory syndromes. Here, we identify a novel hematolog...
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Nod-like Receptor Pyrin domain containing proteins (NLRPs) expressed by resident renal cells may contribute to the pathogenesis of multiple renal diseases. Cystinosis is a genetic disorder that affects kidney and particularly proximal tubular epithelial cells (PTEC). Here, we investigated the expression of NLRP family members in human control and c...
Conference Paper
Background Use of NGS in patients with unclassifiable disease lies a possible approach to the identification of novel disease causing genes. Objectives We report a patient with an early onset inflammatory bowel disease with granulomatous lesions and recurrent HLH episodes carrying a missense mutation in the WNT6 gene. Methods A trio based Whole E...
Conference Paper
Background Systemic juvenile idiopathic arthritis (sJIA) is a polygenic autoinflammatory disease. Innate immune mechanisms appear to play a central role in the pathogenesis of the disease. Nevertheless, a better understanding of the pathophysiology of sJIA is still needed to identify patients responsive to IL-1 or IL-6 targeted therapies. Objectiv...
Conference Paper
Background The NLRC4 inflammasome activation is essential in host defence, particularly against enteric pathogens. Gain-of-function mutations in NLRC4 are associated with a distinct autoinflammatory syndrome characterized by enterocolitis and recurrent HLH. Objectives To report safety and efficacy of faecal microbiota transplantation (FMT) in a pa...
Conference Paper
Background Despite continuous advances in the identification of novel causative genes, several patients with a clinical autoinflammatory phenotype remain unclassifiable Objectives: to describe a novel hematological and autoinflammatory disorder in three unrelated patients caused by a de novo missense mutation of CDC42 Methods Whole exome sequencin...
Article
Purpose of review: IL-18 is a pleiotropic cytokine involved in the regulation of innate and adaptive immune responses. IL-18 pro-inflammatory activities are finely regulated in vivo by the inhibitory effects of the soluble IL-18-binding protein (IL-18BP). The elevation of circulating levels of IL-18 has been described in children with systemic juv...
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Background Systemic juvenile idiopathic arthritis (sJIA) is an inflammatory condition that presents with fever, rash and arthritis. At onset systemic features are predominant and the diagnosis may be a challenge. Secondary hemophagocytic lymphohistiocytosis (sHLH) forms may be associated with different disorders, including rheumatic diseases, and t...
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Objective To identify the role of mature nerve growth factor (mNGF), its immature form proNGF and their receptors in arthritis inflammation. Methods Real-time PCR, western blot and ELISA were performed to evaluate NGF, proNGF, their receptor and cytokine expression in synovial tissue and cells of patients with juvenile idiopathic arthritis (JIA) a...
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Background: The pathogenesis of macrophage activation syndrome (MAS) is not clearly understood: a large body of evidence supports the involvement of mechanisms similar to those implicated in primary hemophagocytic lymphohistiocytosis. Objective: To investigate the pathogenic role of interferon-γ (IFNγ) and the therapeutic efficacy of IFNγ neutra...
Article
Background: An increasing number of infants are diagnosed with food protein induced enterocolitis syndrome (FPIES), a non-IgE-mediated food allergy. Until now, T-cell, food-specific mechanisms have been hypothesized. Methods: 16 children (11M, 5F), affected by FPIES from cow's milk, wheat, fruit, rice and others, experienced 25 acute episodes ma...
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The mannose-binding lectin (MBL) is a member of the collectin family, belonging to the innate immunity system. Genetic, biologic, and clinical properties of MBL have been widely investigated throughout the last decades, although some interesting aspects of its potential clinical relevance are still poorly understood. Low circulating concentrations...
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Background Macrophage activation syndrome (MAS) is a severe complication of rheumatic disease in childhood, particularly in systemic Juvenile Idiopathic Arthritis (sJIA). It is characterize by an uncontrolled activation and proliferation of T lymphocytes and macrophages. Main contentMAS is currently classified among the secondary or acquired forms...
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Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease worldwide. It is caused by mutations in the inflammasome adaptor Pyrin, but how FMF mutations alter signaling in FMF patients is unknown. Herein, we establish Clostridium difficile and its enterotoxin A (TcdA) as Pyrin-activating agents and show that wild-type...
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Objectives Interferon-γ (IFNγ) is the pivotal mediator in murine models of primary haemophagocytic lymphohistiocytosis (pHLH). Given the similarities between primary and secondary HLH (sec-HLH), including macrophage activation syndrome (MAS), we investigate the involvement of the IFNγ pathway in MAS by evaluating levels of IFNγ and of the induced c...
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Frequently fatal, primary hemophagocytic lymphohistiocytosis (HLH) occurs in infancy resulting from homozygous mutations in NK and CD8 T cell cytolytic pathway genes. Secondary HLH presents after infancy and may be associated with heterozygous mutations in HLH genes. We report two unrelated teenagers with HLH and an identical heterozygous RAB27A mu...
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Macrophage activation syndrome is a term used to identify hemophagocytic lymphohistiocytosis secondary to rheumatic diseases (rheuHLH). It is a severe, potentially fatal condition that occurs in the context of rheumatic diseases, particularly systemic juvenile idiopathic arthritis. It is part of secondary HLH forms, that are clinically and biochemi...
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The NLRP12 related autoinflammatory disorder (NLRP12-RD) is a rare autosomal dominant disease, caused by mutations in the NLRP12 gene, a member of NLRs family involved in negative regulation of NF-kB pro-inflammatory pathways. At present, few cases have been reported, although novel NLRP12 variants have recently been described.
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Objective. Systemic juvenile idiopathic arthritis (s-JIA) is associated with high levels of Interleukin-6 (IL-6) in serum and in synovial fluid. Also, impairment of natural killer (NK) cell function is often observed. Our aim was to evaluate a possible link between these two biological findings, as well as with the development of macrophage activat...
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The identification of early noninvasive biochemical markers of disease is a crucial issue of the current scientific research, particularly during the first period of life, since it could provide useful and precocious diagnostic information when clinical and radiological signs are still silent. The ideal biomarker should be practical and sensitive i...
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The role of Interleukin(IL)-6 in the pathogenesis of joint and systemic inflammation in rheumatoid arthritis (RA) and systemic juvenile idiopathic arthritis (s-JIA) has been clearly demonstrated. However, the mechanisms by which IL-6 contributes to the pathogenesis are not completely understood. This study investigates whether IL-6 affects, alone o...
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Full-text available
Systemic juvenile idiopathic arthritis (s-JIA) is associated with high levels of Interleukin-6 (IL-6) in serum and in synovial fluid. Also, impairment of natural killer (NK) cell function is often observed. Our aim was to evaluate a possible link between these two biological findings, as well as with the development of macrophage activation syndrom...
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Background: As described in animal models, the lectin-complement pathway is central to the propagation of ischemia-reperfusion injuries in many tissues, including the brain. Similarly, it might affect the genesis of brain damage in preterm infants. MBL2 gene single-nucleotide polymorphisms (SNPs), regulating mannose-binding lectin (MBL) serum leve...
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Background This study aims to investigate the inflammasome response in peripheral blood mononuclear cells (PBMCs) and the expression of inflammasome components in bone biopsies from patients with chronic recurrent multifocal osteomyelitis (CRMO). Methods The expression of inflammasome components mRNAs was evaluated in PBMCs isolated from 15 CRMO p...
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Nerve growth factor (NGF) levels are highly increased in inflamed tissues, but their role is unclear. We show that NGF is part of a regulatory loop in monocytes: inflammatory stimuli, while activating a proinflammatory response through TLRs, upregulate the expression of the NGF receptor TrkA. In turn, NGF, by binding to TrkA, interferes with TLR re...
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Intralysosomal cystine crystal accumulation, due to mutations in the CTNS gene, is a hallmark of nephropathic cystinosis, but the role of these crystals in disease pathogenesis remains unclear. We hypothesized that, similar to other host-derived crystalline moieties, cystine crystals can induce IL-1β production through inflammasome activation. Thus...
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Cryopyrin-associated periodic syndrome (CAPS) is an autoinflammatory syndrome caused by heterozygous mutations of CIAS1/NLRP3 gene. Affected patients may present three different phenotypes: familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome and CINCA syndrome. Common symptoms include sporadic or cold-induced non pruritic urticari...
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Systemic juvenile idiopathic arthritis (sJIA) accounts for 10-20% of all patients with JIA. The clinical features include fever, evanescent rash, arthralgia and arthritis, myalgia, lymphadenopathy, hepatomegaly, splenomegaly and serositis. Interleukin 1 (IL-1) has been shown to be a major mediator of the inflammatory cascade that underlies sJIA (1)...
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Nephropathic cystinosis is a rare autosomal recessive disorder caused by a mutation in the CTNS gene, which encodes for cystinosin. It is characterized by the lysosomal accumulation of cystine, which leads to the formation of cystine crystals within various organs, including kidneys, brain, cornea, intestine and bone marrow. The exact role of intra...
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Cryopyrin-associated periodic syndromes (CAPS) comprise a spectrum of distinct, rare, autosomal dominant autoinflammatory disorders of increasing severity caused by NLRP3 gene mutations. We describe a 13-year-old female who presented, in the initial phase of the disease, recurrent episodes of high fever, pericarditis, arthralgia, arthritis of the k...
Article
Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality among premature infants. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that has been implicated in the pathophysiology of inflammatory bowel diseases. The MIF promoter contains a functionally relevant single nucleotide polymorphism (SNP) G→C...
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Objectives – To investigate the dose of enoxaparin required in neo-nates to achieve target therapeutic ranges of anti factor Xa 48 hours after starting therapy, and compare this dose to recommended guideline dosages for neonates. Methods – We retrospectively reviewed 19 records of newborns who received enoxaparin at different doses for the treatmen...
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To investigate the accuracy of procalcitonin (PCT) as a diagnostic marker of nosocomial sepsis (NS) and define the most accurate cut-off to distinguish infected from uninfected neonates. Six neonatal intensive care units (NICUs). 762 neonates admitted to six NICUs during a 28-month observational study for whom at least one serum sample was taken on...
Article
The aim of the present study was to evaluate whether polymorphisms of the mannose-binding lectin (MBL-2) gene and MBL serum levels on admission to neonatal intensive care unit are associated with necrotizing enterocolitis (NEC) in preterm infants and to verify MBL expression in NEC bowels. In this retrospective cohort study, 107 neonates (41 with N...
Article
Background: Necrotizing Enterocolitis (NEC) is a leading cause of morbidity and mortality among preterm neonates. To identify subsets of neonates at high risk of NEC is a challenge. Local pro-inflammatory response of the host could be of relevance in the still unclear pathogenesis of NEC. Macrophage migration inhibitory factor (MIF) is a pro-inflam...
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Full-text available
Background: Necrotizing Enterocolitis (NEC) is a leading cause of morbidity and mortality among preterm neonates. To identify subsets of neonates at high risk of NEC is a challenge. Local pro-inflammatory response of the host could be of relevance in the still unclear pathogenesis of NEC. Macrophage migration inhibitory factor (MIF) is a pro-inflam...
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Full-text available
High levels of Nerve Growth Factor (NGF) are found in chronic inflammatory diseases, including synovial fluids (SF) of juvenile idiopathic arthritis (JIA) patients. The effects of high NGF levels on immune cell activity and inflammatory process are unknown. Objective To evaluate the effects of NGF and the role of its receptor TrkA on cytokine produ...
Article
OBJECTIVE: To investigate the accuracy of procalcitonin (PCT) as a diagnostic marker of nosocomial sepsis (NS) and define the most accurate cut-off to distinguish infected from uninfected neonates. SETTING: Six neonatal intensive care units (NICUs). PATIENTS: 762 neonates admitted to six NICUs during a 28-month observational study for whom at least...
Article
Background: MBL initiates complement activation and could have a role in the pathogenesis of ischemia-reperfusion pathologies, such as NEC. We investigated the association between MBL2 genotype, the development of NEC and the MBL expression on specimens of bowel tissue in a cohort of preterm neonates in NICU.
Article
We investigated the association of mannose-binding lectin (MBL) serum levels with nosocomial sepsis (NS), their changes overtime during infection, their relation with pathogens, with the MBL2 genotype and their relationship with mortality. In a prospective observational study, we included 365 critically ill neonates: 261 had no infection and 104 ha...
Article
Bronchopulmonary dysplasia (BPD) is a common adverse outcome of prematurity, causing severe morbidity and mortality. The cytokine macrophage migration inhibitory factor (MIF) has been recently shown to favor murine fetal lung development. In this prospective study, we evaluate the expression of MIF in the lung and in the serum of preterm infants (n...

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