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Biomedical subjects

A Doria

Publications and source records attributed to A Doria.

142 records · Page 8Linked to original sources
PubMedDate not supplied

Role of soluble and cell surface molecules in the pathogenesis of autoimmune skin diseases.

The skin is one of the most commonly involved tissue in rheumatic autoimmune diseases. Different mechanisms are thought to be implicated in the pathogenesis of skin lesions. In genetically predisposed individuals, ultraviolet (UV) light can contribute to the induction of skin lesions via an inflammatory process. UV light promotes the release of cytokines by keratinocytes and the induction of adhesion molecules on the surface of epidermal cells initiating a cascade of inflammatory events and recruiting immunoinflammatory cells into the skin. In this review data regarding the expression of TNF-alpha in lesional skin tissue from subacute cutaneous lupus erythematosus patients and the role of interferons in the pathogenesis of skin manifestations of rheumatic autoimmune diseases are reported. In addition, an overview on the expression of cellular adhesion molecules in these diseases is provided.UV light can also induce apoptosis in keratinocytes. During this cell death several enzymes became activated. Among them, desoxyribonuclease (DNase) is an enzyme involved in degrading DNA during apoptosis. Data regarding the activity of DNAse in patients with cutaneous lupus erythematosus as a possible risk factor for the development of systemic disease are here reported.

Apoptosis↗
PubMedDate not supplied

Psoriasis and psoriatic arthritis: immunological aspects and therapeutic guidelines.

Psoriasis is an inflammatory skin disease that affects 1-3% of the European population. Chronic plaque psoriasis, the commonest form of the condition - affecting the majority of patients - usually manifests as red, heavily scaled plaques on elbows, knees, scalp and lower back, but any skin surface may be affected. Psoriasis is associated with an inflammatory sero-negative arthritis, namely "psoriatic arthritis", in approximately 15%of patients with psoriasis and occurs more commonly in people with inflammatory bowel disease such as patients with Crohn's disease. Several studies have demonstrated the role of genetic predisposition, innate and adaptive immunity in the pathogenesis of psoriasis. There is considerable evidence that innate immunity and specifically a dysregulation of the innate immune response is central to the development of psoriasis. The role of TNFalpha is particularly intriguing. The evidence includes further observations that a variety of anti-TNF approaches such as monoclonal antibodies and fusion proteins of soluble TNF receptors are effective therapies both in psoriasis and psoriatic arthritis. In this review, in addition to pathogenetic aspects, some preliminary guidelines for the use of anti-TNFalpha therapy in patients with psoriasis and psoriatic arthritis will be discussed.

Arthritis, Psoriatic↗
PubMedDate not supplied

Autoinflammatory syndromes.

The autoinflammatory disorders are a new and expanding classification of inflammatory diseases characterized by recurrent episodes of systemic inflammation in the absence of pathogens, autoantibodies or antigen specific T cells. These disorders are caused by primary dysfunction of the innate immune system, without evidence of adaptive immune dysregulation. Innate immune abnormalities include aberrant responses to pathogen associated molecular patterns (PAMPs) like lipopolysaccharide and peptidoglycan, prominent neutrophilia in blood and tissues, and dysregulation of inflammatory cytokines (IL-1beta, TNF-alpha) or their receptors. The autoinflammatory diseases comprise both hereditary (Familial Mediterranean Fever, FMF; Mevalonate Kinase Deficiency, MKD; TNF Receptor Associated Periodic Syndrome, TRAPS; Cryopyrin Associated Periodic Syndrome, CAPS; Blau syndrome; Pyogenic sterile Arthritis, Pyoderma gangrenosum and Acne syndrome, PAPA; Chronic Recurrent Multifocal Osteomyelitis, CRMO) and multifactorial (Crohn's and Behçet's diseases) disorders. Mutations responsible for FMF, TRAPS, CAPS, PAPA are in proteins involved in modulation of inflammation and apoptosis.

Autoimmune Diseases↗
PubMedDate not supplied

Increased titres of IgM anti-heparan sulfate antibody in Behçet's disease.

OBJECTIVE: Endothelial dysfunction is crucial in Behçet's disease (BD) pathogenesis, and measures of endothelial damage are potential markers of BD activity. Heparan sulfate (HS) is the most abundant proteoglycan in the endothelial cells, and anti-HS antibodies have been reported in subjects with vascular damage, due to vasculitis/vasculopathy. The aim of our study was to measure serum anti-HS antibodies in patients with BD and to determine whether their presence correlates with disease activity or clinical manifestations. METHODS: Thirty-two patients with BD (21 men, 11 women) (median age 36.81+/-12.0 years) were considered. Of these, 13 had clinically active disease at the time of study. The mean disease duration was 7.31+/- 8.2 years (median 6 years). Anti-HS antibodies were measured by ELISA. As controls, sera from 40 sex- and age-matched healthy subjects, and 78 age-matched patients with systemic lupus erythematosus (SLE) were studied. RESULTS: Anti-HS IgM antibody titres were significantly higher in BD patients compared to healthy subjects (p=0.016) and SLE controls (p=0.0008). No differences in anti-HS IgG antibody titres were observed among the 3 groups. Using categorical data, increased titres of IgM anti-HS antibodies were significantly more frequent in patients with BD vs patients with SLE (p=0.02). The presence of the antibodies, of either isotype, did not correlate with disease duration, disease activity or clinical manifestations. CONCLUSIONS: BD patients have increased IgM anti-HS antibody titres compared to healthy and SLE controls. These antibodies did not correlate with disease activity or discrete clinical features, but might be relevant for pathogenic mechanisms of the disease.

Adult↗
PubMedDate not supplied

Clinical value of a peculiar nuclear fluorescence staining in systemic sclerosis.

Using unfixed rat liver sections as substrate for the detection of antinuclear antibodies, distinct nuclear staining was observed in the sera of patients with systemic sclerosis. Its reaction differed from previously described fluorescence patterns and was characterized by numerous fine speckles throughout the nucleus associated with one or more coarse lines. These lines were more evident in diluted sera, when fine speckled fluorescence faded. This picture "fine speckles with lines" (FLS) was defined. The FLS pattern was present in 35% of 91 patients with systemic sclerosis, while it was absent in 517 patients with rheumatic and non-rheumatic disorders and in 100 matched healthy subjects. Moreover, the FSL pattern was significantly associated with the diffuse subset of systemic sclerosis (50% of cases) and was related to the presence of anti-Scl-70 antibody. These results indicate that this fluorescent pattern of antinuclear antibodies may be considered a simple and very useful aid in the diagnosis and prognosis of systemic sclerosis.

Adult↗
PubMedDate not supplied

Effect of D-penicillamine on the T cell phenotype in scleroderma. Comparison between treated and untreated patients.

To investigate the possible immunomodulatory mechanism of D-penicillamine in Scleroderma (Scl), we analysed the surface phenotype of circulating T lymphocytes in 17 Scl patients, 6 of these studied before and after D-penicillamine treatment, 8 only before and 3 only after treatment. The drug was administered for 6 to 24 consecutive months with a median daily dose of 500 mg. The study of peripheral blood purified T cells was carried out using single-colour immunofluorescence and flow cytometry analysis (Ortho Diagnostic System) with monoclonal antibodies such as OKT4 (CD4, helper/inducer), OKT8 (CD8, cytotoxic/suppressor), OKDR and MLR4 (activated T cells), and Tec-5/9 (CD26, activated T cells with specific helper function for B cell differentiation). All of the patients showed lower CD8+ and higher MLR4+ and DR+ T cells than the controls, while CD26+ and CD4+ circulating T lymphocytes were lower in all of the treated in comparison with all of the untreated patients. A decrease in CD26+, CD4+ and total T cells was also observed after treatment in the 6 patients studied pre- and post-therapy. These results support the hypothesis that D-penicillamine selectively impairs the helper T cell subset in Scl patients.

Adult↗
PubMedDate not supplied

International survey on the management of patients with SLE. I. General data on the participating centers and the results of a questionnaire regarding mucocutaneous involvement.

OBJECTIVE: The diagnosis and treatment of the mucocutaneous (MC), neuropsychiatric (NP), and renal (RN) manifestations of systemic lupus erythematosus (SLE) remain unsolved issues. To shed light on these issues, a questionnaire was prepared and sent to 153 lupus centres around the world, in order to determine the level of agreement between experts in their approach to these complex aspects of the disease. METHODS: The first section of the questionnaire was designed to collect information on the characteristics of the responding lupus centres. The second section was dedicated to MC manifestations, with questions focusing on: (i) the frequency of MC manifestations as a whole and of the single clinical MC entities; (ii) clinical features, outcome and therapy of subacute cutaneous lupus erythematosus (SCLE); (iii) the utility of the lupus band test (LBT); and (iv) the use of various therapeutic protocols to treat MC manifestations. RESULTS: Sixty-one questionnaires from 19 countries were analysed. Out of these, 37 were completed by Departments of Rheumatology, 21 by Departments of Internal Medicine or Clinical Immunology, and 3 by Departments of Nephrology. About 66% of these centres stated that they were currently following more than 100 lupus cases, 95% had an in-patient ward and 82% had their own laboratory. The American College of Rheumatology classification criteria and various scales for disease activity assessment were regularly used by 87% and 57% of centres respectively. The overall prevalence of MC manifestations was judged to be over 30% by 82% of the respondents (Rs), and over 60% by 36% of the Rs. Among the different MC manifestations, malar rash was reported to be the most frequent (40%), followed by alopecia (24.1%) and oral ulcers (18.6%). In reporting the prevalence of each MC manifestation, the Rs showed a low level of agreement, the coefficient of variation (CV) being > 0.75 for all of the manifestations listed with the exception of malar rash (CV = 0.54). Poor agreement among centers was also found for the reported association of various MC manifestations with SCLE (15 different answers), and on the prognostic factors for SCLE (17 different answers). There was agreement on the best procedure (up to 70% of the Rs preferred a non-UV exposed skin area) and on the utility of the LBT (83% using it only for diagnostic purpose). Hydroxychloroquine was the most popular therapeutic protocol, being used by 85% of the Rs for a wide variety of MC manifestations. Among other therapies, azathioprine was used by 59%, dapsone by 41%, and thalidomide by 35% of the Rs, all to treat a wide spectrum of MC manifestations. Pulse steroid, cyclosporin A and pulse cyclophosphamide were less commonly employed (by 27%, 22% and 13% of the Rs, respectively), and were reserved for the most severe MC manifestations, particularly vasculitis. CONCLUSION: The present survey indicates that, although most of the participating centres had extensive experience in the management of SLE, their approach to the MC manifestations was not homogeneous, and collaborative studies are clearly needed, particularly to optimise the therapeutic protocols.

Alopecia↗
PubMedDate not supplied

International survey on the management of patients with SLE. II. The results of a questionnaire regarding neuropsychiatric manifestations.

OBJECTIVE: To determine the diagnostic and therapeutic approach used in clinical practice for the management of systemic lupus erythematosus (SLE) patients with primary SLE-mediated neuropsychiatric (NP) manifestations. METHODS: A questionnaire was drawn up to assess how clinicians manage various clinical manifestations of SLE. A portion of this questionnaire was designed to assess how clinicians diagnose and treat primary NP-SLE. Most of the questions in the NP-SLE section consisted of lists of different clinical manifestations and laboratory or radiological studies that participants were asked to rate on a scale of importance [from 1 (extremely important) to 5 (not important)] to the diagnosis of primary NP-SLE. The questionnaire also assessed how different NP manifestations are treated in clinical practice. The relative importance of each clinical manifestation was determined through its mean score, and the agreement among participants on each issue was determined using the coefficient of variation (CV). Fifty-nine lupus centers participated in the NP-SLE portion of the survey. RESULTS: The clinical manifestations which were considered to be of extreme or major importance for the diagnosis of primary NP-SLE were seizures, psychosis, transverse myelitis, stroke, transient ischemic attack (TIA) and aseptic meningitis. Among the radiological and laboratory studies, only brain magnetic resonance imaging (MRI) and antiphospholipid antibodies (aPL) achieved "extremely important" mean scores (between 1 and 2). aPL testing was used routinely in the majority of patients (mean 96.8%; CV = 0.1), while brain MRI was used less frequently (mean 56.5%; CV = 0.61). Only brain MRI and cerebral angiography were considered to be helpful in differentiating cerebral vasculopathy from multi-infarct (mean score = 1.6 and 1.9, respectively), whereas a prompt response to treatment with increased doses of steroids was considered helpful in differentiating SLE-related psychosis from steroid-induced psychosis (mean score = 1.58). The results of aPL testing, coagulation tests for the lupus anticoagulant, an brain MRI were considered to be of extreme or major importance in decisions involving treatment with anticoagulant or anti-platelet therapy. Symptomatic therapies, such as heparin, or anti-convulsant, anti-platelet, oral anticoagulant, and antipsychotic therapy were the most widely used. Corticosteroids were the most frequently used immunosuppressive therapy. The administration of other immunosuppressive agents as specific treatment for NP-SLE was uncommon. CONCLUSIONS: Our survey found that in clinical practice, the NP manifestations currently considered to be diagnostic of primary SLE-mediated CNS involvement are not limited to those included in the American Rheumatism Association (ARA) criteria, e.g. seizures and psychosis. Antiphospholipid antibodies appeared to be the laboratory parameter most frequently relied upon in the diagnosis of NP-SLE, and in decisions regarding treatment. Apart from that, only brain MRI and, in selected cases, cerebral angiography seemed to be of real help in diagnosis. The lack of consensus regarding the treatment of primary NP-SLE manifestations most probably reflects both the complex nature of neurological illness in SLE patients and the lack of clear diagnostic criteria.

Adrenal Cortex Hormones↗
PubMedDate not supplied

International survey on the management of patients with SLE. III. The results of a questionnaire regarding renal involvement.

OBJECTIVE: To assess the practice patterns in the management of lupus nephritis (LN) of physicians dealing with systemic lupus erythematosus. METHODS: A multiple choice questionnaire was sent to 135 lupus centers, mainly in Europe. It was divided into 4 sections, one of which regarded LN. Sixty-one centers (40%) sent the questionnaire back before the meeting; however two of them did not fill out the LN section. Therefore, 59 valid LN questionnaires were collected and analyzed. Statistical evaluation was performed using frequency analysis and the chi-square test. RESULTS: In 50 centers (85%), renal biopsy is performed in all patients with clinically evident renal involvement, and in most of them it is repeated in cases of relapse and/or ineffectiveness of treatment. Oral steroid alone is the therapy preferred by 67% of responding physicians in patients with WHO class II LN. Multi-drug therapy is favoured by 57% in patients with class III LN, by 79% for mild-to-moderate forms of class IV LN (IVm), by 84% for moderate-to-severe forms of class IV LN (IVs), by 47% for mild-to-moderate forms of class V LN (Vm), and by 65% for moderate-to-severe forms of class V LN (Vs). Steroids plus cyclophosphamide (CYPH) is the association most commonly used for class III, IVm and IVs LN, having been indicated by 70%, 80% and 88% of the centers, respectively. Furthermore, pulse CYPH is largely preferred to oral CYPH by the majority of centers. It is worth noting that 41 centers (70%, p < 0.01) utilise the same drugs in the treatment of both WHO class IVm and IVs LN. No clear trends in the use of multi-drug associations were identifiable in the treatment of class V LN. Moreover, most of the centers (64%) said that they rely on histologic parameters in order to define renal prognosis and that they consider the chronicity index to be the best predictor of poor renal outcome (74% of the centers). CONCLUSIONS: It was possible to identify some clear trends in the behaviour of physicians who are "expert" in lupus patients: (i) they perform a renal biopsy in order to charaterize the LN and repeat it when they are faced with relapse or ineffective therapy; (ii) they treat WHO class II LN with oral steroids alone and class III and IV LN with steroids associated with CYPH (CYPH, generally in a pulse regimen); and (iii) they define renal prognosis by means of histologic predictors, especially the chronicity index. However, no trend seemed to exist for the treatment of class V LN, particularly Vm.

Biopsy↗