Absence of epicardial coronary stenosis in patients with systemic sclerosis with severe impairment of coronary flow reserve.
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Adult↗
Biomedical subjects
A Cauli
Publications and source records attributed to A Cauli.
Evaluation of cardiac functional abnormalities in systemic sclerosis by dobutamine stress echocardiography: a myocardial echostress scleroderma pattern.
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Adult↗
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↗
Increased level of HLA-B27 expression in ankylosing spondylitis patients compared with healthy HLA-B27-positive subjects: a possible further susceptibility factor for the development of disease.
OBJECTIVE: In B27 transgenic rats, susceptibility to the development of a spondyloarthropathy-like disease has been shown to correlate with the level of B27 transgene expression on lymphoid cells. The aim of this work was to study HLA-B27 molecule expression in peripheral blood mononuclear cells (PBMCs) from patients with ankylosing spondylitis (AS) and from normal controls (NC). METHODS: Twenty B27(+) AS patients and 16 B27(+) NC were studied. HLA-B27 whole molecules and free heavy chains (HCs) and total HLA class I molecules were evaluated at the surface of PBMCs by immunofluorescence and flow cytometry. B27 subtypes were defined with the PCR-SSP (polymerase chain reaction-sequence-specific primer) technique. Cellular activation was evaluated by the expression of CD69, CD25 molecules and interferon gamma (IFN-gamma) production. RESULTS: B27 expression was 55,536.3+/-18,961.0 MESF (molecules of equivalent soluble fluorochromes) units in AS and 25,936.0+/-12,117.5 MESF in NC (P=0.00009), total HLA class I expression was 448,840.2+/-136,293.8 MESF in AS and 533,494.4+/-232,931.1 MESF in NC (not significant), HC expression was 10,593.4+/-6,396.1 MESF in AS and 14,843.0+/-7,544.2 MESF in NC (not significant). The higher B27 expression in the SA group was not due to higher cell activation as it was not correlated with CD69 and CD25 expression in PBMCs or with the level of IFN-gamma. HLA-B27 expression did not correlate with indexes of disease status [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI)]. CONCLUSIONS: We found greater expression of HLA-B27 molecules in patients with AS than in healthy subjects. This phenomenon was not accompanied by general up-regulation of HLA class I molecules or by greater expression of classical T-cell activation markers. On this basis we propose that the higher expression of the HLA-B27 molecules is a further predisposing factor for the development of AS.
Acute Disease↗
Sustained normalization of cerebral blood-flow after iloprost therapy in a patient with neuropsychiatric systemic lupus erythematosus.
We report the case of a 30-year-old caucasian woman affected by SLE who developed neurological symptoms (prosopagnosia and visual-spatial agnosia) after nine years of disease. Brain MRI showed no abnormalities while a brain SPECT scan showed diffuse uptake defects and hypoperfusion areas in the right and left frontal-parietal regions. At that time the patient was on hydroxychloroquine (400 mg/day) and oral prednisolone (0.5 mg/kg/day) as maintenance therapy. One year later the patient showed worsening of Raynaud's phenomenon with digital dystrophic lesions and was therefore treated with an intravenous infusion of Iloprost (1.5 ng/kg/min per 6h/day for 10 days consecutively), while baseline treatment remained unchanged. One month later the patient showed a dramatic improvement in her cognitive function and subsequent SPECT scans showed the gradual disappearance of perfusion abnormalities. This first report of Iloprost treatment in CNS lupus suggests the potential therapeutic usefulness of this drug in patients with SLE and functional CNS involvement.
Adult↗
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↗
Raynaud's syndrome in systemic lupus erythematosus.
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Dominance, Cerebral↗
Increased pulmonary epithelial permeability in systemic sclerosis is associated with enhanced cutaneous nerve growth factor expression.
Background: Nerve growth factor (NGF), a neurotrophic factor that indirectly induces fibroblast proliferation and collagen production, has been found to be increased in the affected dermis of patients with systemic sclerosis (SSc). To investigate the possibility of a relationship between cutaneous NGF production and pulmonary damage in SSc, we studied seven non-smoking scleroderma patients. Methods: Abnormalities in lung structure were assessed by radiological lung examination, and pulmonary epithelial permeability (PEP) was determined by ventilation lung scintigraphy. All patients underwent skin punch biopsy with NGF immunohistological staining. Results: A statistically significant correlation was found between the PEP values and the cutaneous NGF staining scores, which were markedly increased in all of the patients examined, irrespective of the age, disease duration, or radiologically defined lung abnormalities. Conclusion: These results support the hypothesis that functional and anatomical changes in SSc target organs may be determined by a local tissue hyperproduction of NGF.
Journal Article↗
Do B cells influence disease progression in chronic synovitis? Lessons from primary hypogammaglobulinaemia.
We describe a 62-yr-old male patient with primary hypogammaglobulinaemia (PH) who fulfilled the 1987 American Rheumatism Association/American College of Rheumatology revised diagnostic criteria for rheumatoid arthritis (RA) but, despite persistent symmetrical synovitis, did not develop erosions. Virology studies and blood and synovial fluid (SF) cultures were consistently negative; a search for crystals in the SF was unrevealing. Peripheral blood (PB) B cells were absent, whilst the PB CD3(+) cell count was normal. The ratio of naive (CD45RA(+)) to memory (CD45R0(+)) cells was also normal (1:1) but the CD4:CD8 ratio was reversed. To our knowledge, this is the first report which combines the immunophenotypic analysis of the PB with that of the SF and synovial membrane (SM). This confirmed the absence of B cells and the reversed CD4:CD8 ratio. However, as in other chronic arthropathies, the SF and SM cellular infiltrate consisted almost exclusively of memory T cells, consistent with the preferential localization of this subset to inflamed tissues. This case indicates that synovitis can proceed persistently in the absence of B cells and that the migratory mechanisms of T cells are not altered. However, the case suggests that the absence of B cells and negativity for rheumatoid factor, combined with an increased presence of CD8(+) (suppresser/cytotoxic) T cells in the joint, might contribute to the non-erosive nature of the synovitis.
Agammaglobulinemia↗
CD1 expression in psoriatic and rheumatoid arthritis.
OBJECTIVE: CD1 is a novel class of molecules which present non-protein antigens to T cells. The objective of this study was to evaluate the expression of CD1 in the skin and synovium of patients with psoriatic arthritis (PsA) in comparison with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Paired lesional skin (SK) and synovial membrane (SM) from four PsA patients, paired SK and SM from four RA patients, SM from eight RA and eight OA patients, and normal SK from four volunteers were studied using standard immunohistochemistry. RESULTS: In all PsA and RA skin samples CD1-positive cells were abundantly detected both in the dermis and in the epidermis. However, in the 24 SM examined CD1-positive cells were rarely found. In one patient only with RA, a few CD1a-positive cells were found in the SM. CD1b was scarcely expressed in the lining layer (LL) of five SM and in very few cells in the sublining layer (SL) of 11 SM. CD1c was rarely expressed in the LL of six SM and in very few cells in the SL of 13 SM. CONCLUSION: The paucity of CD1 in the PsA and RA synovium suggests that different subsets of antigen-presenting cells are involved in the pathogenesis of dermatitis and synovitis, respectively.
Adult↗
Central nervous system involvement in systemic lupus erythematosus: cerebral imaging and serological profile in patients with and without overt neuropsychiatric manifestations.
The aim of this study was to evaluate morphological and functional abnormalities by cerebral imaging in a series of systemic lupus erythematosus (SLE) patients with and without overt central nervous system (CNS) manifestations, and to detect possible relationships with clinical parameters and a large panel of autoantibodies, including those reactive against neurotypic and gliotypic antigens. 68 patients with SLE were investigated in a cross-sectional study which included clinical evaluation of symptoms, cerebral magnetic resonance imaging (MRI) and brain single photon emission tomography (SPECT) analysis, electroencephalography (EEG), and serological tests for antibodies directed against nuclear, cytoplasmic neuronal and glial cell-related antigens. The results of this study showed: (1) a significant positive association of (a) anti-glial fibrillary acidic protein (GFAP) serum antibodies with neuropsychiatric (NP) manifestations and (b) anti-serin proteinase 3 (anti-PR3/c-ANCA) serum antibodies with pathological cerebral SPECT; (2) the presence of significantly higher values of (a) SLICC organ damage index in patients with abnormal MRI and (b) SLAM activity index in patients with abnormal SPECT; and (3) the association of (a) abnormal MRI with nonactive NP manifestations and (b) combined abnormality of brain SPECT and MRI with the occurrence of overall overt NP manifestations and with those of the organic/major type. Neuropsychiatric manifestations, namely those of the organic/major type, appeared to be significantly associated to the presence of a serum antibody against GFAP, a gliotypic antigen. There was also evidence of an association between SPECT abnormality and the presence of anti-PR3 (c-ANCA). Furthermore, brain imaging by MRI and SPECT applied to SLE patients appears to express CNS involvement significantly related to specific categories of NP manifestations. The abnormalities detected by the two tests seem to be preferentially associated with different activity phases of the NP disorder or of the lupus disease.
Adolescent↗
Bleomycin-induced scleroderma: report of a case with a chronic course rather than the typical acute/subacute self-limiting form.
We report a case of bleomycin-induced scleroderma in a 35-year-old woman treated with chemotherapy for Hodgkin's disease. Approximately 6 months after the first chemotherapy cycle, the patient developed skin sclerosis in both arms. The lesion showed no signs of spontaneous clinical amelioration and treatment with steroids was unsuccessful. A partial remission of the skin sclerosis was instead obtained by the administration of D-penicillamine. A family history revealed other cases of autoimmune diseases and HLA typing showed the presence of antigens associated with scleroderma. The association between bleomycin therapy and scleroderma is discussed.
Adult↗
HLA-DRB1*01 and DRB1*04 alleles in Sardinian rheumatoid arthritis patients.
In Sardinia, like in other Caucasoid populations, rheumatoid arthritis (RA) is significantly associated with HLA-DR4 and DR1 antigens. To discover which DR4 and DR1 alleles were associated with the disease we selected 22 Sardinian patients affected by RA. Fifty DR4+ and 28 DR1+ healthy individuals coming from the same geographical area were used as controls. In the Sardinian patients only two DRB1*04 alleles were observed: DRB1*0405 in 11 and DRB1*0403 in three patients. The DRB1*0102 allele was observed in two patients and DRB1*0101 in six patients. Hereditary predisposition to RA in Sardinia therefore seems to be almost exclusively associated with the DRB1*0405 and DRB1*0101 alleles which share the 67LLEQRRAA74-85VG86 epitope in the peptide binding groove.
Alleles↗
Interleukin-1, interleukin-1 receptor antagonist and macrophage populations in rheumatoid arthritis synovial membrane.
To determine whether interleukin-1 (IL-1) and interleukin-1 receptor antagonist (IL-1ra) are produced by different macrophage subsets, we applied immunoperoxidase and double-labelling immunofluorescence techniques to 10 rheumatoid arthritis (RA) and 10 osteoarthritis (OA) synovial membranes. In RA, greater numbers of early 27E10+ macrophages were found in the sublining layer while mature 25F9+ macrophages were more abundant in the lining layers. The majority of IL-1alpha+ cells were also IL-1ra+ (79 +/- 12% sublining layer, 98 +/- 2% lining layer). In OA sublining layer, a higher percentage of cells double stained for 25F9 and IL-1ra was detected compared to those double stained for 25F9 and IL-1alpha (P < 0.004). In OA, 25F9+ macrophages demonstrated a lower percentage of IL-1alpha+ in the lining and sublining layers compared to RA (P < 0.02 and P < 0.004, respectively). It may be concluded that once monocytes have migrated into the RA joint, they undergo phenotypic and functional changes from an early profile (27E10+, CD14+, low percentage of IL-1+ and IL-1ra+ cells) to a mature profile (CD14+/-, 25F9+, RM3/1+, high percentage of IL-1+ and IL-1ra+ cells).
Adult↗
Percentage of anti-CD4 monoclonal antibody-coated lymphocytes in the rheumatoid joint is associated with clinical improvement. Implications for the development of immunotherapeutic dosing regimens.
OBJECTIVE: We assessed the effect of a daily dosing schedule of the chimeric anti-CD4 monoclonal antibody (MAb), cM-T412, in rheumatoid arthritis (RA) patients, and compared lymphocyte changes in the peripheral blood (PB) and synovial fluid (SF) of these patients. METHODS: Twelve patients received 50 mg/day of cM-T412 for 5 days, followed by a maintenance treatment of 50 mg/week for 5 weeks (6 patients), or a retreatment course of 50 mg/day for 5 days after 5 weeks (6 patients). Paired PB and SF samples were obtained during treatment for analysis. RESULTS: Changes in lymphocyte count and coating with the MAb in PB did not reflect changes in the SF. After 5 daily treatments, the percentage of cM-T412-coated CD4+ lymphocytes in SF correlated with the degree of clinical improvement seen in patients at 2 weeks after the initiation of therapy (r = 0.75, P < 0.05). CONCLUSION: These results demonstrate the importance of antibody dosage and treatment regimen in determining clinical benefit. Our findings suggest that the percentage of cM-T412-coated CD4+ lymphocytes in SF may be a predictor of clinical outcome.
Adult↗
Cutaneous lymphocyte antigen-positive T lymphocytes preferentially migrate to the skin but not to the joint in psoriatic arthritis.
OBJECTIVE: To investigate whether T cell migration into different sites of inflammation (skin and synovium) within the same individual is principally regulated by tissue-specific homing or by more general mechanisms related to inflammation. METHODS: Expression of cutaneous lymphocyte antigen (CLA) and its ligand, E-selectin, was analyzed by immunohistochemistry and immunofluorescence using paired skin and synovial membrane (SM) samples from patients with psoriatic arthritis (PsA). To investigate disease specificity, delayed-type hypersensitivity (DTH) skin lesions, induced by tuberculin purified protein derivative, and SM from patients with rheumatoid arthritis (RA), were studied as controls. To directly examine cell migration in in vivo, the proportion of CLA+ T lymphocytes migrating into suction-induced skin blisters was assessed by flow cytometry. Using the same technique, levels of paired peripheral blood and synovial fluid (SF) T cells were also analyzed. RESULTS: CLA+ T cells preferentially accumulated in the skin, but not in the joint, of patients with PsA. Similarly, CLA+ T lymphocytes predominated in the DTH skin lesions of RA patients, but were very rare in the SM of RA patients, and were scarcely represented in the SF of patients with several chronic inflammatory arthropathies. In addition, CLA+ T lymphocytes preferentially migrated into epidermal skin blisters. This preferential pattern of CLA+ T cell accumulation was not related to the selective expression of E-selectin, since this was similar in the skin and SM of both PsA and RA patients. CONCLUSION: The distinct pattern of T cell infiltration into sites of inflammation within the skin and synovium is regulated by both organ-specific homing and general inflammation-related mechanisms.
Adult↗
T-lymphocyte immunophenotyping in polymyositis and dermatomyositis.
The objective was to elucidate the immunological abnormalities underlying polymyositis (PM) and dermatomyositis (DM). The phenotype of peripheral blood mononuclear cell (PBMNC) subsets and cell surface expression of activation (CD25 and HLA-DR) and adhesion (LFA-1) molecules was studied in 12 patients with PM and in 10 patients with DM. PBMNC subsets and expression of T-cell activation molecules were evaluated by cytofluorography. Double immunofluorescence and indirect immunoperoxidase techniques were applied to muscle biopsies to define T-cell phenotype and LFA-1/ICAM-1 expression. In PM, the absolute number of circulating cytotoxic (CD8+CD28+) T cells was selectively reduced. T cells showed increased expression of activation molecules, CD25 and HLA-DR, and increased adhesion capacity as the absolute numbers of CD3+CD25+, CD8+HLA-DR+, CD3+LFA-1+('bright') and CD8+ CD8+LFA-1+('bright') cells were higher than in healthy donors and DM patients. In PM muscle biopsies, T cells were mainly CD3+CD8+ and LFA-1+; additionally, endothelial cells and myofibres surrounded by T cells showed positive staining for ICAM-1. In DM, there was a general lymphopenia that led to a decreased absolute number of all T-lymphocyte subsets. It is proposed that in PM, in contrast to DM, LFA-1/ICAM-1 interactions enable activated CD8+ T cells to migrate selectively into the inflamed muscle and to adhere to myofibres, leading to tissue injury.
Adult↗
Reduction of synovial inflammation after anti-CD4 monoclonal antibody treatment in early rheumatoid arthritis.
OBJECTIVE: To study the effect of chimeric anti-CD4 monoclonal antibody (MAb) therapy on synovial inflammation, in order to interpret the clinical experience with anti-CD4 treatment. METHODS: The immunohistologic features of synovial biopsy specimens before and 4 weeks after anti-CD4 MAb (cM-T412) therapy were studied in patients with rheumatoid arthritis. The patients received intravenous doses of either placebo (n = 1) or 10 mg (n = 4), 25 mg (n = 2), or 50 mg (n = 1) of cM-T412 daily for 5 consecutive days. RESULTS: Although the patients did not experience clinical improvement, significant decreases in the number of circulating CD4+ cells, the degree of synovial inflammatory infiltration, and the mean scores for expression of adhesion molecules were found in the 7 patients 4 weeks after receiving cM-T412. The scores for infiltration with CD4+ and other inflammatory cells were particularly reduced following treatment with either 25 mg or 50 mg cM-T412. Cytokines, such as interleukin-1 beta and tumor necrosis factor alpha, could still be detected in the synovial tissue after treatment. CONCLUSION: The decline in the numbers of inflammatory cells and adhesion molecules in synovial tissue after CD4+ cell depletion supports the view that CD4+ T cells orchestrate local cellular infiltration. The lack of clinical effect of anti-CD4 therapy might be explained by an insufficient decrease in the number of synovial CD4+ cells and by the persistence of cytokines. Determination of whether more adequate dosing would lead to a clinical improvement must await further study.
Adult↗