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Biomedical subjects

P Annunziata

Publications and source records attributed to P Annunziata.

At least 19 recordsLinked to original sources
PubMed2005

Systemic lupus erythematosus in Europe at the change of the millennium: lessons from the "Euro-Lupus Project".

The "Euro-Lupus Cohort" is composed by 1000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium--the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors.

Age of Onset↗
PubMed2005

Long time interval between multiple sclerosis onset and occurrence of primary Sjögren's syndrome in a woman treated with interferon-beta.

Primary Sjören's syndrome with central nervous system involvement can clinically mimic multiple sclerosis (MS). However, SS and MS may coexist. We report here a case of a 48-year-old woman affected by relapsing-remitting MS, good responder to interferon (IFN)-beta 1a, developing sicca complex after 29 years from MS onset. At the age of 48, after 5 years successful treatment with i.m. IFN-beta 1a, xerophtalmia and xerostomia with dysphagia occurred. Autoantibody screening for connective tissue diseases, including anti-ENA, was negative. Schirmer's test showed reduced lacrimal gland function and a minor salivary gland biopsy showed chronic inflammatory infiltration with fibrosis, acinar atrophy and ductal ectasia. According to clinical and pathological findings a diagnosis of SS was made. Other cases of connective tissue diseases after IFN-beta treatment have been described. However, this is, to our knowledge, the first report on the development of primary SS after long time interval from MS onset in a woman treated with IFN-beta. Although there are no evidences about a possible role of IFN-beta in triggering SS yet, a screening for clinical and laboratory signs of SS should be assessed in MS patients during IFN-beta treatment.

Adjuvants, Immunologic↗
PubMed2003

High frequency of psoriasis in relatives is associated with early onset in an Italian multiple sclerosis cohort.

OBJECTIVES: An exploratory study has been carried out to assess the association of autoimmune diseases in multiple sclerosis (MS) families with clinical features and disability of MS patients. MATERIAL AND METHODS: Age at onset, symptoms and signs at onset, and disability were assessed in 177 patients with definite MS and 178 age- and sex-matched control patients with autoimmune diseases (78 with endocrine and 100 with rheumatological diseases) and correlated with the most frequent autoimmune diseases recorded in the families. RESULTS: Psoriasis was found in 30 relatives of 177 (16.9%) MS patients, thyroid disorders in 17 (9.6%) and allergies in 17 (9.6%). In the control group, psoriasis was found in 22 relatives of 178 (12%) patients, thyroid diseases in 19 (10.7%) and allergies in seven (3.9%). Of the 30 relatives with psoriasis in the MS group, 16 (53.3%) were fathers (P < 0.0001). There was a significant association of high frequency of family psoriasis with early age of MS onset (P = 0.025) but not with onset of symptoms or severe disability. CONCLUSION: In this Italian MS cohort, a subgroup of patients with a first- or second-degree relative with psoriasis had early onset of MS.

Adolescent↗
PubMed2002

Lessons from the "Euro-Lupus Cohort".

The "Euro-Lupus Cohort" is composed by 1,000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium - the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors.

Adolescent↗
PubMed2000

Anti-ganglioside antibodies in a large cohort of European patients with systemic lupus erythematosus: clinical, serological, and HLA class II gene associations. European Concerted Action on the Immunogenetics of SLE.

OBJECTIVE: To assay anti-ganglioside antibodies (aGM1) in sera of a large cohort of European patients with systemic lupus erythematosus (SLE) to define the prevalence of these autoantibodies in SLE; to evaluate the association of aGM1 with clinical manifestations and other autoantibodies found in SLE; and to search for aGM1 association with HLA class II alleles. METHODS: Four hundred forty-eight patients with SLE were consecutively enrolled in 8 centers from 6 European countries. All sera were tested for antinuclear antibodies by immunofluorescence on HEp-2 cells as substrate, anti-dsDNA, aGM1, aCL, abeta2-glycoprotein I (abeta2-GPI) antibodies by ELISA, and antineutrophil cytoplasmic antibodies (ANCA) by immunofluorescence and by ELISA. Genomic typing for HLA class II loci was performed by polymerase chain reaction-sequence specific oligonucleotide probe method. Clinical assessment was done at the time of enrolment. RESULTS: We found 41.9% of patients with clinical signs of neuropsychiatric involvement; 15.5% of patients were positive for aGM1, 8% of the IgG isotype and 8.6% of the IgM isotype; aGM1-IgG were associated with neuropsychiatric manifestations (NPM) (RR = 3.7), with migraine (RR = 2.4), with OBS (RR = 7.3), and with peripheral neuropathy (RR = 8.5). aGM1-IgM were associated with NPM (RR = 4) and with depression (RR = 3.4). Furthermore, the genetic study showed that aGM1-IgG were associated with HLA-DQB1*0404 (RR = 7.2) while aGM1-IgM were associated with HLA-DQB1*0605 (RR = 33.3). No associations were found between aGM1 and anti-dsDNA, aCL, abeta2GP1, or ANCA. CONCLUSION: Our results show aGM1 can be found in patients with SLE. aGM1 may play a pathogenetic role for some NPM in this condition.

Adolescent↗
PubMed1999

Evidence of blood-brain barrier alteration and activation in HIV-1 gp120 transgenic mice.

OBJECTIVE: To verify whether HIV envelope protein gp120 changes the blood-brain barrier in vivo, as a fundamental mechanism of early central nervous system damage by HIV-1. DESIGN: Analysis of the functional integrity and immune activation of the blood-brain barrier in brains of HIV-1 gp120 transgenic mice secreting circulating gp120 at levels similar to those detected in AIDS patients. METHODS: Number of vessels/mm2 section area with perivascular albumin and percentage of vessels expressing adhesion molecules (ICAM-1 and VCAM-1) were determined by immunohistochemistry in frozen brains from autopsied transgenic and non-transgenic mice. The percentage of vessels showing substance P immunoreactivity was also calculated, as this neuropeptide is known to mediate the increase in permeability of the rat brain endothelium in vitro caused by HIV-1 gp120. RESULTS: The number of vessels with albumin extravasation was significantly higher in transgenic than non-transgenic mice brains (P = 0.0003). A greater percentage of ICAM-1- and VCAM-1-positive brain vessels in transgenic than non-transgenic mice was shown (P = 0.0017 and P = 0.0008 respectively). Significant immunoreactivity for substance P was detected in brain vessels in transgenic mice and a significant correlation was found between the percentage of substance P-positive and ICAM-1-positive brain vessels (P < 0.0001) in transgenic mice. CONCLUSIONS: These findings demonstrate that HIV-1 gp120 is capable of changing and activating in vivo the vascular component of the blood-brain barrier.

Animals↗
PubMed1999

Early synthesis and correlation of serum anti-thyroid antibodies with clinical parameters in multiple sclerosis.

A high frequency of anti-thyroid antibodies has been demonstrated in multiple sclerosis (MS), but there is a lack of data on the possible association of thyroid autoimmunity with disease activity. To assess whether anti-thyroid antibodies are synthesized early in MS or are induced over the course of the disease and whether or not they are correlated with clinical findings, we assayed serum anti-peroxidase and anti-thyroglobulin antibodies in 129 relapsing-remitting MS patients at the time of diagnosis and prior to any immunosuppressive or immunomodulatory treatment. Anti-peroxidase antibodies were detected in 28/129 (21.7%) MS patients, compared to 12/130 (9.2%) neurological controls (P=0.006) and 8/152 (5.3%) normal healthy subjects (P<0.0001). High titres of anti-thyroglobulin antibodies were detected in 11/129 (8.5%) MS patients compared to 6/130 (4.6%) patients with other neurological diseases (P=0.22) and 5/152 (3.3%) normal healthy subjects (P=0.07). Anti-peroxidase antibodies were associated with initial relapse in 14 of 28 (50%) of the patients compared to 18/101 (18%) without antibodies (P=0.001). Similarly, anti-thyroglobulin antibodies were associated with first relapse in 8/11 (73%) of the patients compared to 11/118 (9.3%) of those without (P<0.0001). However, there was no correlation between anti-thyroid antibody titres and disease duration or CSF IgG index values. By contrast, a significant inverse correlation was found between anti-thyroglobulin antibody titres and EDSS score (r(s)=-0. 75; P=0.008). Our findings demonstrate that anti-peroxidase and anti-thyroglobulin antibodies are synthesized early in relapsing-remitting MS and are associated with early clinical disease activity. Furthermore, high titres of anti-thyroglobulin antibodies are associated with low disability scores, suggesting a possible protective role of these antibodies that deserves further investigation.

Adolescent↗
PubMed1998

HIV-1 gp120 increases the permeability of rat brain endothelium cultures by a mechanism involving substance P.

OBJECTIVE: To analyse whether an HIV-1 envelope protein might play a role in damaging the blood-brain barrier as a fundamental step in the early invasion of the central nervous system by HIV-1. DESIGN: Analysis of permeability of rat brain endothelium cultures to albumin, to assess the functional integrity of the vascular component of the blood-brain barrier. METHODS: Rat brain endothelium cultures prepared by cerebral microvessels were exposed to recombinant gp120IIIB on microporous membranes and passage of biotin-labelled albumin was analysed. Scanning electron microscopy was used to analyse cell culture morphology. Some cultures were preincubated with N-nitro-L-arginine methyl ester (L-NAME), a selective inhibitor of nitric oxide synthase, or with spantide, a selective substance P antagonist. RESULTS: HIV-1 gp120 increased the permeability of rat brain endothelial cells to albumin in a dose-dependent manner. Scanning electron microscopy revealed profound gp120-induced alterations in cell morphology accounting for the increased permeability to macromolecules. These alterations were neutralized by anti-gp120 monoclonal antibody but not by isotype control antibody or L-NAME. By contrast, spantide and anti-substance P polyclonal antibody completely blocked the gp120-induced increase in albumin permeability. Control cultures exposed to measles virus nucleoprotein showed an increase in permeability that was not blocked by spantide. Brain endothelial cells, exposed to gp120, displayed cell surface immunoreactivity for substance P, suggesting that substance P is secreted by brain endothelium in response to gp120 stimulation and binds to brain endothelial cells through a receptor-mediated mechanism. CONCLUSIONS: These findings suggest a role for substance P in the gp120-induced increase in permeability of brain endothelium.

Animals↗
PubMed1998

Enhanced secretion of substance P by cytokine-stimulated rat brain endothelium cultures.

Substance P (SP) was analyzed in rat brain endothelium cultures after cytokine stimulation. SP secretion was found after stimulation with high doses of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha). High doses of interferon-gamma (INF-gamma) had no effect on this secretion. Elevated SP release was found to be associated with mRNA expression of beta-preprotachykinin (beta-PPT), precursor of SP, in the cells. Under cytokine stimulation, part of SP was bound to brain endothelial cell surface, suggesting the existence of an autocrine network for this neuropeptide. These findings suggest that SP may have an immunomodulatory action at the blood-brain barrier during inflammatory and autoimmune processes in the central nervous system.

Animals↗
PubMed1997

IL-6 detection in multiple sclerosis brain.

By using a double-label immunohistochemistry technique, we demonstrated the presence of interleukin-6 (IL-6) in acute and chronic active plaques from the brain of six patients with multiple sclerosis (MS). IL-6 was mainly associated with astrocytes and rarely with macrophages or mononuclear infiltrating cells. The pattern of distribution for IL-6 immunoreactivity was similar to that of HLA-DR expression, but the two molecules almost never colocalized on the same cell. Our data indicate that in MS central nervous system IL-6 is predominantly located within resident glial cells which are concentrated at the sites of ongoing demyelination and immune activation. Although IL-6 exhibits several proinflammatory activities, indirect evidence suggests that the cytokine may also play an immunomodulatory role in inflammatory demyelinating disorders.

Adolescent↗
PubMed1997

Detection of Borrelia burgdorferi DNA and complement membrane attack complex deposits in the sural nerve of a patient with chronic polyneuropathy and tertiary Lyme disease.

We report a patient who developed a chronic sensory-motor polyneuropathy and a progressive myelopathy 4 years after a tick bite. An increased serum antibody titer to Borrelia burgdorferi suggested a diagnosis of Lyme neuroborreliosis, although a concomitant cervical spondylosis probably contributed to spinal cord damage. Treatment with ceftriaxone resulted in a marked improvement of neuropathic symptoms, providing indirect evidence of spirochetal infection. Search for B. burgdorferi DNA by polymerase chain reaction amplification on sural nerve confirmed the diagnosis, demonstrating that the spirochete localized in the peripheral nervous system. The presence of complement membrane attack complex deposits and macrophage infiltrates around epineurial vessels and within the endoneurium suggests that the neuropathy in our patient was immune-mediated.

Aged↗
PubMed1997

High levels of cerebrospinal fluid IgM binding to myelin basic protein are associated with early benign course in multiple sclerosis.

We assessed human myelin basic protein (MBP) binding IgM levels in CSF. MBP is the most studied putative antigen in multiple sclerosis (MS) and immune responses against it may be involved in the demyelination process. We also correlated these levels with EDSS score and other parameters of disease progression and prognosis, both at the time of CSF analysis and during follow-up. CSF IgM anti-MBP levels were assayed by measuring total IgM levels with solid-phase ELISA in CSF samples from 66 patients with relapsing-remitting MS, 11 subjects without neurological diseases, 20 patients with non-inflammatory neurological diseases and 7 patients with lymphocytic meningitis, before and after immunoabsorption with human MBP. Confirmation of IgM binding specificity was performed by immunoblotting of positive CSF samples onto MBP coated-nitrocellulose sheets. Clinical evaluation (disability score, number and time of attacks) was performed during a mean follow-up of 2.7 +/- 1.1 years. 23 of the 66 relapsing-remitting MS patients (33.8%) had elevated IgM anti-MBP levels. In this patient subgroup, IgM anti-MBP levels correlated with the IgM index (r = 0.71; P = 0.0001), but not with CSF/serum albumin (r = 0.08; P = 0.72). In the first year of follow-up, patients with low IgM anti-MBP suffered from more numerous attacks than those with elevated levels (0.86 +/- 0.63 versus 0.43 +/- 0.58; P = 0.017). Patients with high IgM binding to MBP had a first attack during follow-up in a significantly higher time than those with low binding (28.87 +/- 4.7 versus 17 +/- 2.6 months, respectively; P = 0.005) and reached a decrease of 0.5 EDSS point significantly faster than those with low IgM (16.17 +/- 1.2 versus 29.7 +/- 2.6 months, respectively; P = 0.0002). A similar significant finding was observed when the time to reach low disability score (EDSS < or = 2.0) was analyzed (10.7 +/- 2.57 +/- 3.3 months, respectively; P = 0.014). These findings demonstrate that in a subgroup of MS patients, elevated CSF levels of IgM anti-MBP are associated with early favorable course and therefore suggest that IgM binding to MBP could be a possible prognostic marker in relapsing-remitting MS to select early MS patients for future trials.

Adolescent↗
PubMed1997

The potential role of hepatitis C virus in the pathogenesis of the neurological syndrome in chronic hepatitis C.

A 72-year-old man developed chronic sensory neuropathy (CSN) during chronic hepatitis C (HCV) infection. Neurological symptoms began one year after acute HCV hepatitis and slowly worsened over three years. No conventional cause for CSN was found. Circulating antinervous tissue antibodies (including anti-Hu) and inflammatory infiltrates in sural nerve biopsy specimens were absent. However, the presence of anti-HCV antibody and HCV-RNA in cerebrospinal fluid indicated that HCV had reached the intrathecal compartment, suggesting the direct viral involvement in the pathogenesis of CSN.

Aged↗
PubMed1995

Serum anti-brain endothelium antibodies and cognitive assessment in patients with Binswanger's encephalopathy.

The pathogenic mechanism underlying the vascular changes in Binswanger's encephalopathy (BE) is unknown. To test whether alterations of the humoral immunity may lead to endothelium damage, we analyzed serum levels of anti-brain endothelium antibodies (ABEA) (IgG and IgM) in 16 BE patients, 19 subjects with ischemic vascular disease without mental deterioration and 18 normal healthy subjects. ABEA IgM were found elevated in 1/16 (6%) BE patients and in 4/19 (21%) patients with cerebrovascular diseases; an increase in ABEA IgG was found in 6/16 (38%) BE patients and in 7/19 (37%) cerebrovascular patients. Association with anti-cardiolipin antibodies (IgG and/or IgM) was found in 50% of BE patients with elevated ABEA and only 10% of those with no increase, whereas high titres of anti-neurofilament antibodies (1:10,000) were detected in 40% and 71% respectively. In BE, ABEA IgG but not IgM showed a trend, although not significant, towards a correlation with the duration of the disease (rs = 0.47; p = 0.07) and significantly correlated with the cognitive function as assessed by the Mini mental state (MMS) score (rs = 0.56; p = 0.02). Higher mean values of the MMS score were found in BE patients with elevated ABEA than in those without (p = 0.04). This difference was not due to language disorders neither to an association with stroke risk factors or anti-neurofilament antibodies. However, there were no significant differences in MMS scores between cerebrovascular patients with ABEA and those without. A "neuro-protective" role is hypothesized for the ABEA in the development of dementia in BE.

Aged↗
PubMed1995

Association of polyclonal anti-GM1 IgM and anti-neurofilament antibodies with CSF oligoclonal bands in a young with amyotrophic lateral sclerosis.

INTRODUCTION: The significance of the association of motor neuron syndromes with anti-GM1 antibodies remains unclear. We report the immunological study of a juvenile case of amyotrophic lateral sclerosis (ALS). MATERIALS AND METHODS: Serum anti-Gm1 and anti-neurofilament antibodies were assayed by ELISA and western blotting and cerebrospinal fluid (CSF) isoelectrofocusing was performed. Immunocytochemical studies were carried out with the patient's serum and CSF on human brain and spinal cord sections. RESULTS: Serum polyclonal IgM anti-GM1, anti-neurofilament antibodies and CSF oligoclonal bands were detected. Furthermore, an in vitro production of anti-GM1 IgM was demonstrated. Immunocytochemical studies showed cytoplasm motor neuron immunostaining, due to both IgG and IgM, that substantially decreased after immunoabsorption of the serum with bovine neurofilament proteins but not with GM1-containing liposomes. No immunostaining was obtained with CSF. Immunosuppressive treatment with cyclophosphamide and two cycles of plasma exchanges lowered anti-GM1 antibody levels, but did not determine any clinical improvement. CONCLUSION: To our knowledge, this is the first report of ALS, associated with circulating levels and in vitro production of polyclonal IgM anti-GM1, anti-neurofilament antibodies and CSF oligoclonal bands. These findings suggest the occurrence in our patients of an autoimmune process that could be involved in the pathogenesis of ALS.

Adult↗