PubMed Health⌕ Search

Biomedical subjects

Diego Franciotta

Publications and source records attributed to Diego Franciotta.

14 recordsLinked to original sources
PubMed2006

Cytokines and chemokines in cerebrospinal fluid and serum of adult patients with acute disseminated encephalomyelitis.

Cytokines and chemokines contribute to the pathogenesis of acute disseminated encephalomyelitis (ADEM). Using a multiplex immunochemiluminescence ELISA, we measured 8 Th1/Th2 cytokines and 18 chemokines in the cerebrospinal fluid (CSF) and serum of 17 ADEM patients, 14 multiple sclerosis (MS) patients, and 7 healthy controls (HCs). Relative to HCs, ADEM patients had significantly high mean CSF concentrations of chemokines with attractant/activating properties towards neutrophils (CXCL1 and CXCL7), monocytes/T cells (CCL3 and CCL5), Th1 cells (CXCL10), and Th2 cells (CCL1, CCL22, and CCL17). Mean CSF concentrations of CXCL7, CCL1, CCL22, and CCL17 were higher in ADEM than in MS, whereas those of CCL11 were lower in MS than in ADEM and HCs. CSF pleocytosis correlated with CSF concentrations of CXCL1, CXCL10, CCL1, CCL17, and CCL22. Most of the functionally homologous chemokines correlated with each other. CSF Th1/Th2 cytokines were not detectable in most samples. Their mean concentrations did not differ in the three groups, and the same held for serum cytokines and chemokines. Our data suggest that the upregulation of chemokines active on neutrophils and Th2 cells differentiates ADEM from MS inflammation, and that both Th1 and Th2 chemokines might be produced in ADEM. Chemokines upregulated in ADEM could become CSF biomarkers after a posteriori evaluations in unselected case series.

Adult↗
PubMed2005

Interferon-gamma- and interleukin-4-producing T cells in Down's syndrome.

Down's syndrome (DS) associates with genetic-dependent dysregulation of the interferon (IFN) system. We used intracellular cytokine staining to analyse the percentages of IFN-gamma- and interleukin (IL)-4-producing T cells in the peripheral blood of patients with DS, individuals with mental retardation (MR), and healthy controls (HCs). The percentages of IFN-gamma-producing CD4(+) and CD8(+) T cells (IFGCs), namely Th1 (mean, 21.4+/-S.D. 1.3) and Tc1 (12.6+/-1.1), and the Th1/Th2 ratio (6.1+/-0.2) in DS were significantly higher than in MR (15.9+/-1.3, 7.9+/-0.6, 4.8+/-0.3) and in HCs (15.6+/-1.9, 7.2+/-1.1, 4.6+/-0.6). Most of the DS patients with high IFGC percentages were seropositive for anti-transglutaminase IgA. We found no correlation between sex, age, APOE genotypes, coexisting autoimmune diseases, susceptibility to infections, or degree of cognitive impairment and high IFGC percentages. This abnormality might thus contribute to immune dysfunction in DS without manifest clinical correlates.

Adult↗
PubMed2005

Consensus recommendations of the Italian Association for Neuroimmunology for immunochemical cerebrospinal fluid examination.

In 2002-2003, the Italian Association for Neuroimmunology (AINI) ran a program for procedure and method standardization in neuroimmunology. The main purposes of the program were: a) to improve the overall quality of analytical performance and, simultaneously, to reduce costs by resource optimization; b) to establish the bases for clinical guidelines in neurology; c) to promote the formation of laboratory networks and of joint research projects; d) to facilitate the procedures for certification required by governmental/non-governmental agencies. This report summarizes the consensus recommendations of a panel of AINI neuroimmunologists/biochemists involved in the field of cerebrospinal fluid examination. The collection process for said recommendations was guided by "impact-factored" literature and the knowledge of the experts involved. Communication was by email and face-to-face at two dedicated AINI workshops.

Animals↗
PubMed2005

Immunological patterns identifying disease course and evolution in multiple sclerosis patients.

Reliable, and easy to measure, immunological markers able to denote disease characteristics in multiple sclerosis (MS) patients are still lacking. We applied a multivariate statistical analysis on results obtained by measuring-by real-time RT-PCR-mRNA levels of 25 immunological relevant molecules in PBMCs from 198 MS patients. The combined measurement of mRNA levels of IL-1beta, TNF-alpha, TGF-beta, CCL20 and CCR3 was able to distinguish MS patients from healthy individuals. CXCR5, CCL5, and CCR3 combined mRNA levels identify primary progressive MS patients while TNF-alpha, IL-10, CXCL10 and CCR3 differentiate relapsing MS patients. Our results indicate that multi-parametric analysis of mRNA levels of immunological relevant molecules in PBMCs may represent a successful strategy for the identification of putative peripheral markers of disease state and disease activity in MS patients.

Adult↗
PubMed2004

Congenital adrenal hyperplasia and multiple sclerosis: is there an increased risk of multiple sclerosis in individuals with congenital adrenal hyperplasia?

BACKGROUND: Congenital adrenal hyperplasia (CAH) is an inherited recessive disorder of adrenal steroidogenesis, generally caused by a total or partial deficiency in 21-hydroxylase, due to a deletion of or mutations in the CYP21 gene (the gene that codes for 21-hydroxylase). Impaired cortisol biosynthesis results in corticotropin hypersecretion, which leads to overproduction of intermediate metabolites and androgens. OBJECTIVE: To describe for the first time, to our knowledge, a patient with CAH and multiple sclerosis (MS). DESIGN: Case report. PATIENT: A 22-year-old woman, diagnosed at birth as having a salt-losing 21-hydroxylase deficiency, had sudden visual loss in the right eye and pyramidal, sensory, and cerebellar signs. Repeated brain magnetic resonance images showed focal white matter lesions in periventricular areas, the corpus callosum, the cerebellum, and the brainstem. A cerebrospinal fluid examination revealed several oligoclonal bands. Thereafter, she had 2 relapses, characterized by ataxia and diplopia, and recovered after corticosteroid treatment. RESULTS: The reported case fulfills the diagnostic criteria for CAH and MS. CONCLUSIONS: Some clues suggest that the association between CAH and MS could be nonincidental: a possible MS susceptibility locus is on chromosome 6p21, on which the CYP21 gene is located; the CYP21 gene and the CYP21P pseudogene alternate in tandem with the C4 genes (the genes that code for the homonym complement protein) (C4AQ0 is particularly frequent in patients with relapsing-remitting MS); and, in previous studies, brain magnetic resonance imaging showed T2-hyperintense focal areas in the white matter of CAH patients. Our observation should alert neurologists to the presence of signs and symptoms suggestive of late-onset CAH in MS patients and, in turn, endocrinologists to the appearance of neurological signs and symptoms in CAH patients.

Adrenal Hyperplasia, Congenital↗
PubMed2002

IL-1 genes in myasthenia gravis: IL-1A -889 polymorphism associated with sex and age of disease onset.

Myasthenia gravis (MG) is a multifactorial autoimmune disease of the neuromuscular junction. We investigated the relation between four polymorphisms of the interleukin (IL)-1 gene cluster on 2q12-22, and MG susceptibility and clinical features in a large cohort of individuals. No polymorphism was associated with MG susceptibility. However, the IL-1A -889 CC genotype was associated with early disease onset (p=0.0044) in the whole MG group and the subgroup of CC males developed MG about 18 years earlier than males carrying other IL-1A -889 genotypes (p=0.022). This finding suggests that IL-1A is a disease modifier in MG, or is in linkage disequilibrium with an unknown locus on chromosome 2.

Adolescent↗
PubMedDate not supplied

Caspase-1 levels in biological fluids from patients with multiple sclerosis and from patients with other neurological and non-neurological diseases.

In multiple sclerosis (MS), pathological white matter damage in the central nervous system is sustained by immune-inflammatory response. Caspase-1 plays a pivotal role in immune-mediated inflammation, as it regulates the cellular export of IL-1beta and IL-18. We carried out a preliminary in vitro study of the kinetics of extracellular caspase-1 release. We then measured caspase-1 levels in paired serum and cerebrospinal fluid (CSF) samples of 75 MS patients, 15 healthy subjects, and patients with other neurological diseases. Paired synovial fluid and serum samples of patients with juvenile idiopathic arthritis, and paired sputum and serum samples of asthma patients were also studied. Mean serum caspase-1 concentrations did not differ between groups. Caspase-1 was detected in the CSF of patients with acute, but not stable, MS [7.5 +/- (SEM) 0.9 pg/ml; test's sensitivity, 56% and specificity, 100%]. Its levels correlated with pleocytosis. The highest mean caspase-1 levels were found in the arthritic synovial fluids (945.5 +/- 126.6 pg/ml, which correlated with erythrocyte sedimentation rate), and in the sputum samples (370.1 +/- 71.0 pg/ml, which correlated with the number of macrophages in the sputum). On condition that caspase-1 is determined in the fluids pertaining to the disease-specific inflammatory sites, its level is a reliable marker of ongoing immune-inflammatory response. The enzyme measurement in CSF can also help define state-trait in MS.

Arthritis, Juvenile↗
PubMedDate not supplied

Serial immunoprecipitation assays for interferon--(IFN)-beta antibodies in multiple sclerosis patients.

We devised a sensitive, radioimmunoprecipitation assay (RIPA) for anti-interferon (IFN)-beta-binding antibody (BAB) detection. Our RIPA showed good agreement with a reference RIPA (mean difference, -3.2 +/- 10.6 AU), and detected BAB to both IFN-beta-1a and IFN-beta-1b. Neutralizing antibodies to IFN-b (NAB) were also determined with a standard method. BAB and NAB were measured in 393 serum samples from 77 multiple sclerosis (MS) patients treated with IFN-beta-1a or -1b, who were studied over two years, and subsequently classified as responders and non-responders. BAB were found at higher concentrations, and more frequently detected, in IFN-beta-1b- than in IFN-beta-1a-treated patients, and, at highest titres, preferentially in patients who were positive for NAB. However, in our series of MS patients, both titres and frequency of detection of BAB or NAB did not differ between IFN-b responders and non-responders.

Autoantibodies↗
PubMedDate not supplied

Antibodies to cerebellar nerve fibres in two patients with paraneoplastic cerebellar ataxia.

The aim of this study was to characterize two new atypical anti-neuronal antibodies using an immunohistochemical method on rat cerebellum and Western blot techniques with primate cerebellar tissue and with recombinant neuronal proteins. Atypical sera from two patients with paraneoplastic neurological syndromes associated with different tumours were detected. Case number 1 presented cerebellar degeneration and Merkel cell carcinoma and case number 2 paraneoplastic brainstem encephalitis and malignant fibrous histiocytoma. By immunohistochemistry, the two new atypical antibodies showed a similar fibrillar positivity in the molecular and granular layers and around the Purkinje cells. The dot blot with recombinant neuronal proteins (HuD, NOVA-1, CDR62/Yo, Amphiphysin) was negative, whereas the Western blot with neuronal antigens of primate cerebellum identified two different proteins with molecular weights (64 kD in case number 1, and 70 kD in case number 2). In conclusion, the two new antibody reactivities against nerve fibres should be integrated into the diagnostic paraneoplastic neurological syndromes guidelines.

Animals↗