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Biomedical subjects

M Casadei Maldini

Publications and source records attributed to M Casadei Maldini.

17 recordsLinked to original sources

Anticardiolipin antibodies in children with atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a multifactorial etiology. Immunological abnormalities (cell-mediated immune hyperactivity, elevated IgE serum levels and eosinophil-derived mediators) have been observed. In a recent issue, Szakos et al. describe, in children with extrinsic type of AD, an association between the occurrence of anticardiolipin (ACL) IgM and specific IgE against mite, and also in relation to the severity of the disease. We studied 51 children (35 males and 16 females, mean age 44 months) with AD, whose diagnosis was made on the basis of Hanifin and Rajka's criteria. The evaluation of the severity of the disease was made using the SCORAD index. Eleven children had intrinsic type AD (group A); 40 children had extrinsic type AD, 14 of them had specific IgE only against food allergens (group B); 26 children had specific IgE also against inhalant allergens (group C). Twelve children without allergy were designated as the control group. Specific IgEs were determined using the CAP-System (Pharmacia, Uppsala, Sweden) for food and inhalant allergens. The measurement of ACL IgG and IgM was carried out by ELISA (Orgentec Diagnostika, Mainz, Germany). An increase in serum levels of ACL was observed in 13 children (25.5%): 1 child (9%) from group A, 7 children (50%) from group B and 5 children (19.2%) from group C with a statistically significant difference (P=0.038). Our study shows the presence of ACL-IgG above all in extrinsic AD, but no association was found between high levels of ACL and increased severity scoring of AD. Increased levels of ACL were observed in younger children (mean age 26.5 months; P=0.025) especially if sensitized against food allergens.

Allergens↗

Phenotyping of peripheral blood lymphocytes in adult coeliac disease.

In coeliac disease immunological abnormalities are not confined to the small bowel and it has been suggested that changes in peripheral blood lymphocytes may predispose to autoimmune or malignant complications. Using dual-colour immunofluorescence with labelled monoclonal antibodies, multiparameter flow cytometry was used to analyse peripheral blood lymphocytes in 32 untreated coeliacs, 29 treated coeliacs and 20 healthy volunteers. When the absolute numbers were considered, a decrease of CD3+, CD4+, CD8+ and CD19+ lymphocytes was found in untreated coeliacs compared with treated coeliacs and healthy volunteers. The proportion of CD3+ was significantly higher in untreated coeliacs (P<0.05) than in healthy volunteers. No differences were observed in CD4+, CD8+ and CD19+ subsets between the three groups studied. The proportion of CD3+ CD25+ and CD3+ HLA-DR+ cells were higher in untreated coeliacs (P<0. 001 and P>0.005) and in treated coeliacs (P<0.005 and P<0.05) than in healthy volunteers. On the contrary, natural killer cells and cytotoxic cells were lower in untreated and treated coeliacs than in healthy volunteers. As regards B-cell subsets, the only difference was the increase in FcepsilonR+ B cells in untreated coeliacs. The absolute reduction of peripheral lymphocytes in coeliac disease probably reflects their compartimentalization in intestinal mucosa. The decrease of natural killer cells and cytotoxic cells may be in keeping with the increased prevalence of malignancy in this condition. Finally, the phenotypic changes found in untreated coeliacs indicate T-cell activation.

Adult↗

Impaired lymphocyte proliferation in human acute pancreatitis.

PURPOSE: We evaluated the proliferative response of lymphocytes to phytohemagglutinin P (PHA P), concanavalin A (Con A), and pokeweed mitogen (PWM) during the course of acute pancreatitis. PATIENTS AND METHODS: Sixty consecutive patients with acute pancreatitis were studied within 48 h of the onset of pain, and 16 of them were also studied 1 month after complete recovery. According to the Atlanta criteria, 21 patients had severe disease and 39 had mild disease. Fifteen healthy subjects and 11 patients with nonpancreatic acute abdomen were studied as controls. In 12 patients with acute pancreatitis the lymphocyte proliferation after stimulation with the three mitogens was also assessed in autologous and heterologous plasma. RESULTS: The lymphocyte proliferative response to optimal doses of PHA P, Con A, and PWM was significantly lower (p < 0.001) in acute pancreatitis patients (mean +/- SD; PHA P 74,310 +/- 22,960 cpm; Con A 64,669 +/- 20,188 cpm; PWM 26,714 +/- 6,436 cpm) than in healthy subjects (PHA P 111,316 +/- 12,044 cpm; Con A 96,276 +/- 12,327 cpm; PWM 33,957 +/- 3,601 cpm). Patients with nonpancreatic acute abdomen had a significantly higher lymphocyte proliferative response to PHA P and Con A than acute pancreatitis patients (PHA P p < 0.002; Con A p < 0.01; PHA P 91,116 +/- 22,995 cpm; Con A 77,879 +/- 19,083 cpm). In patients with acute pancreatitis, lymphocyte proliferation stimulated with PHA P and Con A was significantly lower (PHA P p < 0.005; Con A p < 0.001) in those with severe disease (PHA P 63,190 +/- 15,157 cpm; Con A 52,813 +/- 13,324 cpm) than in those with mild disease (PHA P 80,298 +/- 24,340 cpm; Con A 71,052 +/- 20,490 cpm). In the group of 16 patients studied during the initial phase of acute pancreatitis and 1 month after recovery, lymphocyte proliferation significantly improved after remission of the disease but remained impaired compared with that of healthy subjects. No difference was found in the lymphocyte proliferation of the 12 patients with acute pancreatitis assayed in autologous and heterologous plasma. CONCLUSIONS: The peripheral lymphocyte proliferative response to mitogen stimulation in patients with acute pancreatitis was decreased during the early phases of the disease.

Abdomen, Acute↗

CD8 lymphocyte subsets in active polymyalgia rheumatica: comparison with elderly-onset and adult rheumatoid arthritis and influence of prednisone therapy.

The aim of this study was to evaluate CD8 lymphocyte subsets in active polymyalgia rheumatica (PMR), to determine whether low percentages of CD8+ cells could be used to differentiate PMR from elderly-onset (EORA) and adult rheumatoid arthritis (RA), and to investigate the effects of prednisone on CD8 lymphocyte subsets. A significant reduction of percentages and absolute numbers of CD8bright+ cells was observed in patients with active PMR. Both CD8bright+, CD57- and CD8bright+, CD57+ subsets were significantly reduced. Reduced percentages of CD8+ cells were observed in 55% of patients with active PMR/giant cell arteritis (GCA), in 23% with EORA and in 44% with adult RA. Prednisone therapy in PMR patients, after only 1 week, increased the lymphocyte count and the absolute numbers of lymphocyte subsets significantly. However, the percentages of CD8bright+ cells remained persistently low for the 2 yr study period in 80% of the patients with low pre-treatment levels. Our results demonstrate that CD8 cell percentage is a poor epidemiological discriminator for PMR diagnosis. Notwithstanding the rise in absolute numbers of CD8 cell subsets induced by prednisone, the persistently low percentages of CD8+ cells in a group of PMR patients indicate an abnormality connected with the disease.

Age of Onset↗

Role of peripheral CD8 lymphocytes and soluble IL-2 receptor in predicting the duration of corticosteroid treatment in polymyalgia rheumatica and giant cell arteritis.

OBJECTIVES: To determine if the presence of low percentages of CD8 positive cells or high levels of soluble interleukin-2 receptors (sIL-2R) define a subgroup of patients with more severe polymyalgia rheumatica and giant cell arteritis (PMR/GCA). METHODS: 38 PMR/GCA patients were followed up prospectively. Serum levels of sIL-2R and peripheral blood CD8 lymphocytes were measured before the start of corticosteroid treatment, after six months of treatment and at the last visit. Phenotypical analysis of lymphocyte subpopulations was performed with a two colour technique, and assay of sIL-2R was performed using an enzyme-linked immunosorbent kit. Forty four healthy people matched for age and gender comprised a healthy control group. RESULTS: The median duration of follow up was 28 months (range 7-65). Corticosteroid treatment lasted a median of 23.5 months (7-65). Eleven patients (29%) were in remission at the end of follow up; 45% of the patients had at least one relapse or recurrence. Compared with controls, patients with active disease had a significantly lower percentage of CD8 cells and significantly increased sIL-2R levels. Erythrocyte sedimentation rate, C reactive protein, and sIL-2R values were significantly less after six months of steroid treatment compared with before treatment. The percentage of CD8 cells remained significantly lower at six months and the end of follow up compared with controls, while sIL-2R levels remained significantly greater. Patients in whom the percentage of CD8 cells at six months was lower than one SD of the mean of normal controls (26%) had a significantly longer duration of corticosteroid treatment, a greater cumulative dose of prednisone and more relapses or recurrences compared with patients in whom the percentage was in the normal range. The duration of treatment and the cumulative dose of prednisone were not influenced by the percentage of CD8 cells before treatment therapy or by the levels of sIL-2R after six months of treatment. CONCLUSIONS: A reduced percentage of CD8 cells after six months of treatment may be a useful outcome parameter which would identify a group of PMR/GCA patients likely to experience more severe disease, defined as longer duration of corticosteroid treatment, higher cumulative dose of prednisone, and relapse or recurrence of disease.

Aged↗

Serum soluble CD4 and CD8 levels in polymyalgia rheumatica.

OBJECTIVE: Soluble CD4 (sCD4) and sCD8 were measured in the sera of 19 patients with active polymyalgia rheumatica (PMR). METHODS: We correlated the results obtained with lymphocyte subpopulations, soluble interleukin 2 receptors (sIL-2R), and clinical and laboratory variables at diagnosis. In addition 15 patients were prospectively studied during a 6 month period of prednisone therapy. Assays of the sCD4 and sCD8 molecules and of the sIL-2R were performed using an enzyme-linked immunosorbent kit. RESULTS: Serum sCD8 and sIL-2R levels were significantly elevated in patients with active disease compared to normal controls, while serum sCD4 and the relative percentage of CD8+ T cell levels decreased. In the 15 patients prospectively studied sCD8 levels fell significantly after 1 week of therapy along with the remission of clinical disease and normalization of erythrocyte sedimentation rate. At the end of the study period, sCD8 values did not differ from normal controls and they were significantly reduced compared to baseline values. CD8+ lymphopenia persisted at the end of the study. sCD4 levels remained significantly lower during the study period. sIL-2R levels fell significantly at the end of the study period. However, the 6-month levels of sIL-2R remained significantly higher compared to controls. CONCLUSION: The rise of serum sCD8 levels observed in patients with PMR with active disease suggests an early activation of CD8 T cells. The therapeutic effect of steroid in PMR may be partially mediated by its effect on CD8 activated cells.

Aged↗

Immunologic effects in patients with psoriatic arthritis treated with cyclosporine A.

Twelve patients with psoriatic arthritis (PsA) and very active articular disease resistant to conventional second line therapy entered into a 6-month open study of cyclosporine A (CsA) at a starting dosage of 3 mg/kg/day. Comparisons of phenotypic characteristics of lymphocytes and response to mitogens of peripheral blood mononuclear cells (PBMC) were made between these patients with PsA before CsA therapy, 7 patients without prior 2nd line therapy, 14 untreated patients with psoriasis alone, and 61 healthy controls. We confirmed a significant reduction of the basal percentage of CD8+ cells and an increase in the CD4/CD8 ratio in patients with PsA before CsA therapy compared to controls. These abnormalities were not present in patients with PsA without prior 2nd line therapy and in patients with psoriasis alone. Peripheral blood activated T cells (CD3+, HLA-DR+), natural killer (NK) (CD3-, CD16+ and/or CD56+), total B and CD5+ B cells were decreased only in patients with PsA before CsA therapy. The reduction of non-MHC restricted cytotoxicity T (CD3+, CD16+ and/or CD56+) was observed in all the 3 groups of patients compared to controls. After the 6 months of CsA therapy we observed a significant increase of CD3+, HLA-DR+, CD3+, CD16+ and/or CD56+, total B, and CD20+, CD5+ cells in the 11 patients with PsA compared to pretreatment values. Contrary to azathioprine, CsA does not impair the NK cell population which has a protective role against cancer and viral infections.

Antigens, CD↗

Soluble interleukin 2 receptors in polymyalgia rheumatica/giant cell arteritis. Clinical and laboratory correlations.

Serum levels of soluble interleukin 2 receptors (sIL-2R) were measured in 21 patients with polymyalgia rheumatica (PMR)/giant cell arteritis (GCA) prior to steroid treatment. These levels were significantly elevated in patients with PMR/GCA compared with healthy controls (p = 0.002). A significantly longer duration of morning stiffness (p = 0.005) was observed in patients with a high concentration of sIL-2R. A significant correlation was observed at diagnosis between sIL-2R and erythrocyte sedimentation rate (ESR) (p = 0.01) and between ESR and C-reactive protein (CRP) (p = 0.005). We investigated prospectively a group of 10 patients over a period of 6 months of prednisone therapy. At the end of the study sIL-2R levels fell significantly compared to pretreatment values (p = 0.02), but remained significantly higher compared to controls (p = 0.02). ESR and CRP values also fell significantly compared to pretreatment levels (p = 0.0001 in both cases). We observed a significant correlation between the decrease in ESR values and the decrease in sIL-2R and CRP levels after 6 weeks (p = 0.01 in both cases) and after 6 months of therapy (p = 0.002 and p = 0.05). sIL-2R may be considered a useful serologic marker for monitoring response to steroid therapy in patients with PMR/GCA. This laboratory variable correlated more closely with ESR than with CRP. The presence of elevated levels of sIL-2R is likely to reflect T cell activation occurring in PMR/GCA. T lymphocyte activation persisted after 6 months of steroid therapy, despite rapid and continuous control of disease manifestations.

Aged↗

Low dose cyclosporine A in psoriatic arthritis: relation between soluble interleukin 2 receptors and response to therapy.

Twelve patients with psoriatic arthritis (PsA) were treated with low doses of cyclosporine A (CsA) (the initial dose was 3 mg/kg daily) and were entered into an open 6-month study. At the end of the study arthritis was improved in 7 patients (number of patients achieving a 50% or more reduction in the number of swollen or tender joints) and unchanged in 4 patients. Cutaneous psoriasis also improved significantly as shown by psoriasis area and severity index score. Only one patient withdrew from the study after one month because of severe nephrotoxicity. Serum creatinine fell to baseline value 6 weeks after the discontinuation of CsA. Three patients had minor side effects. CsA maintained articular improvement also in the 9 patients who are still taking this drug (mean duration of therapy of 12 +/- 0.8 months). There was no significant reduction of erythrocyte sedimentation rate during the study period. We assayed levels of soluble interleukin 2 receptors (sIL-2R) in serial serum samples obtained from 10 patients during the study period. Concentrations of sIL-2R were significantly increased in patients with PsA compared to controls. In 6 responder patients we observed a parallel decrease in joint pain/tenderness score and serum sIL-2R values. This finding was not observed in 4 nonresponders. Our results suggest that low dose CsA is a short term effective and safe therapy in patients with PsA and that serial sIL-2R levels are a useful means of measuring changes in disease activity.

Arthritis, Psoriatic↗

[Simultaneous analysis of lymphocyte markers using triple color markers].

The introduction in flow cytometry of the new reagent Streptavidin Duochrome allows the simultaneous three color analysis of biological samples. Streptavidin Duochrome is a phycoerythrin-Texas red fluorochrome complex conjugated to the protein streptavidin. This novel complex exploits the principle fluorescence energy transfer when this reagent is used with FITC, PE and biotin-conjugated monoclonal antibodies; three different emissions of fluorescence are possible simultaneously using an argon laser at 488 nm (FACScan Becton Dickinson). Using Paint-a-gate software which analyses samples and displays the three colors on a screen, antigen distribution on multiple cell populations is obtained. Single, double and triple labeled cells (up to seven combinations) are visualized and quantified quickly and easily. Using a panel of normal donors we have evaluated the following combinations: CD3/CD4/CD8 to visualize T lymphocytes and their subsets; CD3/CD19/CD16 to quantify quickly the T, B, NK populations; CD4/Leu8/Leu18 to analyse the helper subset and CD3/CD8/Leu7. Our purpose is to evaluate the importance of this new kind of analysis to study the heterogeneity of several lymphocytic populations.

Antigens, Differentiation↗