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Biomedical subjects

A Afeltra

Publications and source records attributed to A Afeltra.

At least 37 records · Page 2Linked to original sources

Systemic lupus erythematosus and multiple myeloma: a rare association.

OBJECTIVE: The association of systemic lupus erythematosus (SLE) and multiple myeloma (MM) is an uncommon event. We report the relapse of SLE in a patient with a previous history of MM, treated with chemotherapy and, subsequently, with alpha-2b interferon (alpha-2b IFN) as a maintenance therapy. The case is discussed in light of past relevant literature. METHODS: The history and clinical, laboratory and radiographic findings of the patient, as well as the subsequent therapeutic approach are discussed. In our review of the literature, journal articles are identified by Medline search. RESULTS: We describe the case of a woman who developed a multiple myeloma 14 years after a diagnosis of SLE. A careful literature review confirms that the association of these two diseases has been reported only in a few cases. When the plasma cell neoplasia occurred, SLE had been quiescent for several years; the patient was treated with prednisone-melphalan and, subsequently, with alpha-2b IFN as a maintenance therapy. On admission to our department, SLE was in a relapse phase, probably because of IFN treatment. The disease was poorly responsive to steroid therapy and required the use of cytotoxic drugs. CONCLUSIONS: The coexistence of SLE and MM is very rare and the possible pathogenetic mechanisms underlying this association remain unclear. The use of interferon in a patient with an autoimmune disease always invites caution.

Antineoplastic Agents↗

Expression of lactoferrin on human granulocytes: analysis with polyclonal and monoclonal antibodies.

Lactoferrin (LF), an iron-binding protein present in specific granules of neutrophils, is expressed on membrane after granulocyte activation. It may represent a target for anti-neutrophil cytoplasmic antibodies (ANCA) in patients affected by some immunomediated diseases. We recently produced two MoAbs, AGM 2.29 and AGM 10.14, that recognize two spatially distant epitopes of human LF. In this study we perform a cytometric analysis in order to evaluate the expression of LF on the surface of granulocytes obtained from freshly drawn blood or after purification, in both the presence and absence of stimuli. Our results demonstrate that LF is not constitutively expressed on membrane of circulating neutrophils. After priming with phorbol myristate acetate (PMA) or tumour necrosis factor-alpha (TNF-alpha), an increased mean fluorescence intensity (MFI) was obtained on neutrophils stained with polyclonal anti-LF antibodies and with AGM 2.29. The kinetics of LF expression during activation demonstrated a progressive increase in MFI within 45 min. No increase in MFI was documented when primed granulocytes were stained with MoAb AGM 10.14, thus indicating that the epitope recognized by AGM 10.14 is not exposed at the cell surface. Following membrane permeabilization, performed in order to analyse the binding of anti-LF MoAbs to cytoplasmic LF, a marked increase in MFI was obtained by staining granulocytes with both anti-LF MoAbs. Indirect immunofluorescence (IIF) analysis confirmed that AGM 2.29 and AGM 10.14 reacted with human granulocytes, showing a cytoplasmic pattern on formalin-acetone-fixed neutrophils and a perinuclear one on ethanol-fixed cells.

Animals↗

Coexpression of CD69 and HLADR activation markers on synovial fluid T lymphocytes of patients affected by rheumatoid arthritis: a three-colour cytometric analysis.

The aim of the present study was to evaluate the coexpression of very early (CD69), early (CD25) and late (HLADR) antigens and to analyse the mean fluorescence intensity (MFI) of such activation markers on synovial fluid (SF) and peripheral blood (PB) lymphocytes of patients affected by rheumatoid arthritis (RA) and other types of chronic synovitis (OCS). A three colour cytometric analysis was performed using a peridinin chlorophyll protein conjugated anti-CD3 antibody in combination with fluorescein isothiocyanate or phycoerythrin labelled anti-CD69, anti-HLADR, anti-CD25 monoclonal antibodies (mAbs). A T cell gating method was utilized, so that three sets of bivariant dot plot quadrant displays were obtained (CD69/HLADR, CD69/CD25, CD25/HLADR). A large percentage of SF T lymphocytes in RA showed the coexpression of very early and late activation antigens (CD3 + CD69 + HLADR +), whereas CD3 + CD69 + CD25 + bearing cells and CD3 + CD25 + HLADR + lymphocytes were only a small percentage. Similar results were obtained in patients with OCS, although to a lesser extent. No statistically significant differences in MFI of CD69 and HLADR positive SF T cells between RA and OCS were observed. The CD69 + CD25-HLADR + T cell subset is the most commonly represented in the synovial environment, among those we have evaluated; this phenotype may be characteristic of chronic inflammatory arthritis.

Adult↗

Hashimoto's thyroiditis associated with urticaria and angio-oedema: disappearance of cutaneous and mucosal manifestations after thyroidectomy.

A 60 year old woman affected by Hashimoto's thyroiditis presented with a history of recurring episodes of urticaria and angio-oedema. Clinical and laboratory evaluation of the patient excluded allergy to external agents, hereditary angio-oedema, and occult infections. A pathogenic relation between Hashimoto's thyroiditis and chronic urticaria/angio-oedema was suspected. However, treatment with L-thyroxine had no influence on the frequency and severity of the cutaneous and mucosal manifestations, which occurred almost daily and required repeated administration of steroids. The patient therefore underwent total thyroidectomy. Cytometric analysis of intrathyroidal lymphocyte subsets showed unusual abnormalities. Urticaria and angio-oedema completely remitted after surgery; 18 months postoperatively the patient was still asymptomatic.

Angioedema↗

Two spatially distant epitopes of human lactoferrin.

Lactoferrin (LF) is an iron binding protein, which may represent a target for antineutrophil cytoplasmic antibodies (ANCA) in patients affected by rheumatoid arthritis, ulcerative colitis, and primary sclerosing cholangitis. Here we describe the production and characterization of two new monoclonal antibodies (MAbs) against human LF. These MAbs (AGM 10.14, an IgG1, and AGM 2.29, an IgG2b) recognize spatially distant epitopes of LF as assessed by cross-blocking experiments. We also demonstrated by indirect immunofluorescence that both MAbs react with ethanol-fixed neutrophil granulocytes showing a perinuclear staining pattern. AGM 2.29 and AGM 10.14 have been utilized as capture and labeled tracer antibody, respectively, in a double determinant immunoassay (DDIA) to measure soluble LF. The results obtained show that this DDIA allows us to quantify even low concentrations of LF, the maximal range of the assay sensitivity being between 12 and 780 ng/ml. Therefore, AGM 10.14 and AGM 2.29 may represent useful reagents for studying the role of autoantibodies to LF as well as for measuring soluble LF, which is a reliable secretory marker of neutrophil activation.

Animals↗

Antineutrophil cytoplasmic antibodies in synovial fluid and in serum of patients with rheumatoid arthritis and other types of synovitis.

OBJECTIVE: Antineutrophil cytoplasmic antibodies (ANCA) are present in several vasculitides and in other immunomediated diseases. The reported prevalence of ANCA in rheumatoid arthritis (RA) is variable. In addition, the presence of such autoantibodies has been poorly investigated in synovial fluid (SF). The objectives of this study were (1) to investigate the presence of ANCA both in the serum and in SF from patients with RA and other forms of synovitis (OS); (2) to analyze the reactivity of ANCA against isolated antigens proteinase 3 (PR3), myeloperoxidase (MPO) and lactoferrin (LF); and (3) to evaluate the clinical relevance of these autoantibodies. METHODS: Twenty-eight patients with RA, 13 with OS, and 17 with osteoarthritis (OA) of the knee joint were studied. No patient had clinical manifestations of vasculitis. SF and serum samples were investigated for the presence of ANCA by indirect immunofluorescence (IIF); the reactivity against PR3, MPO and LF was assessed by ELISA. RESULTS: ANCA were detected by IIF in SF of 39.3% patients with RA, 38.5% with OS, and 5.9% with OA. With 2 exceptions, patients who had ANCA in SF showed positivity also in serum. The presence of both anti-MPO and anti-LF antibodies was found in 3 patients with RA and 1 with OA; a patient with RA showed antibodies only against LF and another one with RA only against MPO. No reactivity was found against PR3. In patients with RA ANCA were not associated with disease activity. CONCLUSION: We found an increased incidence of ANCA both in SF and serum from patients with RA and OS. The pathogenic role and the clinical relevance of such autoantibodies in these diseases remain to be established.

Adult↗

[Cytokines and renal injury].

Cytokines play an important role in most physiological and pathological processes. In this note the authors review recent literature data about cytokines in mediating renal inflammatory diseases. These molecules are involved in every phase of inflammatory injury induce expression of MHC class II and adhesion molecules on renal cells, synthesis of chemoattractants; they are also involved in leukocyte localization and play a role in the induction of cell proliferation and the accumulation of extracellular matrix. The disturbances of the cytokine network may lead to inflammatory kidney disease that could be treated by novel therapeutic agents like anticytokine antibodies.

Animals↗

Comparative effects of arginine and other amino acid deprivation on in vitro expression of lymphocyte activation markers.

Enteral or parenteral arginine supplementation enhances lymphocyte activation after mitogenic stimulation, in rats and humans. Arginine deprivation in culture media is associated with a reduction of lymphocyte activation; this effect, however, has not yet been proven to be specific for arginine. This study was designed to evaluate the specificity of arginine deprivation from culture media on the reduction of in vitro lymphocyte activation. Peripheral blood mononuclear cells, obtained from 11 healthy volunteers, were cultured in RPMI 1640, selectively deprived of single amino acids (i.e. arginine, phenylalanine, leucine, methionine, and threonine) and supplemented with phytohemagglutinin (PHA). The expression of interleukin-2 receptor and transferrin receptor was evaluated by cytometric analysis; the levels of soluble IL-2 receptor were determined by immuno-enzymatic assay. Results were compared with those obtained by culturing cells in non-deprived, RPMI 1640 medium. The expression of transferrin and IL-2 receptor, as well as the levels of IL-2 soluble receptor, were significantly reduced in all deprived media irrespective of the lacking amino acid. These results suggest that the reduction of in vitro lymphocyte activation is not an arginine specific effect. Therefore, the known enhancement of immune response, following arginine supplementation in vivo, is likely to involve a more complex series of events.

Journal Article↗

Anti-cardiolipin antibodies in autoimmune thyroid diseases.

OBJECTIVE: In recent years anti-phospholipid antibodies have gained much attention since they are frequently associated with thrombosis, recurrent abortion, and thrombocytopenia. Besides disease-specific autoantibodies, other autoantibodies reactive with both organ and non-organ specific autoantigens have been found in patients with autoimmune thyroid diseases. Therefore the objective of this study was to evaluate the presence and significance of anti-phospholipid antibodies in untreated patients with different forms of autoimmune thyroid diseases. PATIENTS AND METHODS: Thirty-one patients (26 females, five males; mean age 42.5 years) affected by different autoimmune thyroid diseases were studied. Fourteen patients were affected by Graves' disease, eight by silent thyroiditis, five by Hashimoto's thyroiditis. Four patients with Graves' disease in remission were also evaluated. Anti-cardiolipin antibodies were detected by enzyme linked immunosorbent assay. In five Graves' disease patients anti-cardiolipin antibodies were evaluated before and after 3 months of therapy with methimazole. RESULTS: Seventeen out of 31 patients were positive for IgG and/or IgM anti-cardiolipin antibodies, the highest levels occurring in three Graves' disease patients with severe thyrotoxicosis. In four of five Graves' patients evaluated before and after methimazole therapy, anticardiolipin antibodies decreased following treatment. None of the patients with increased IgG and/or IgM anticardiolipin antibodies showed clinical manifestations of the anti-phospholipid syndrome during our observation which ranged from 1 to 5 years. CONCLUSIONS: Our results showed an increased incidence of anti-cardiolipin antibodies in patients affected by autoimmune thyroid diseases. However, these autoantibodies seem merely to represent a non-specific marker of immune dysregulation.

Adult↗

CD5+ B lymphocytes and CD4+ CD45RA+ T cells in Graves' disease.

Fifteen patients affected by new-onset Graves' disease with ophthalmopathy have been examined for lymphocyte subset phenotypes by two-colour cytometric analysis. CD5+ B cells were significantly increased in comparison to the normal population (43.2 +/- 20.6% versus 19.5 +/- 6.9%; p < 0.0009); total T cells showed a normal amount (70.4 +/- 9.6%), but the levels of THLADR+ cells were significantly increased in comparison to the control group (13.7 +/- 10.5% versus 4.7 +/- 3.2%; p < 0.007). The characterization of the subset suppressor-inducer CD4+ CD45RA+, evaluated as percentage of the total CD4+ T cells, showed a significant decrease in comparison with the control group (43.8 +/- 13.5% versus 52.3 +/- 6.5%; p < 0.03). Serum immunoglobulin evaluation showed a statistically significant increase of IgM (p < 0.05) and a significant decrease of IgA (p < 0.02). A statistical correlation between IgM levels and percentage of CD5+ B cells has been found (p < 0.04). The defect of suppressor-inducer T cell subset, along with the increase of CD5+ B cells may contribute to the pathogenetic mechanism of the disease in patients with a genetically-induced aberrant immune response.

Adult↗

Expression of CD69 antigen on synovial fluid T cells in patients with rheumatoid arthritis and other chronic synovitis.

OBJECTIVES: The expression of the CD69 antigen on synovial fluid and peripheral blood lymphocytes was studied in 12 patients with rheumatoid arthritis (RA), five subjects with other forms of chronic synovitis, and on the peripheral blood lymphocytes of 15 patients with systemic lupus erythematosus (SLE) and immune vasculitis. METHODS: The CD69 antigen and other activation markers (HLA-DR, interleukin 2 receptor (IL-2R), transferrin receptor) were measured by cytometric analysis. In patients with RA soluble IL-2R was determined by enzyme linked immunosorbent assay (ELISA). RESULTS: The percentage of T cells bearing CD69 was significantly increased in synovial fluid from patients with RA (30.3 (13)%) and other chronic synovitis (18 (9)%). The expression of CD69 on peripheral blood lymphocytes of patients with RA, other chronic synovitis, and SLE and immune vasculitis was within the normal range 2.1 (1.2)%. According to previously published work, a high proportion of synovial fluid T cells are HLA-DR positive (64.2 (12.4)% in synovial fluid from patients with RA and 61 (1.2)% in synovial fluid from patients with other chronic synovitis). Transferrin receptor expression on synovial fluid was up-regulated compared with that on peripheral blood. The increase of IL-2R expression on synovial fluid lymphocytes v peripheral blood was not significant; the quantitative determination of soluble IL-2R levels gave a mean value of 921 (351) U/ml in synovial fluid of patients with RA, 672 (229) U/ml in the serum of the same patients, and 273 (100) U/ml in serum from normal subjects. CONCLUSIONS: Synovial fluid lymphocytes are in a different functional state than peripheral blood lymphocytes. CD69 antigen is an interesting cellular marker which should be studied in patients with chronic synovitis. The unusual expression of the activation antigens and the sequence of their appearance require further study.

Antigens, CD↗

[The parenteral administration of essential amino acids in patients on periodic hemodialysis treatment. A pilot study].

In an attempt to improve the nutritional status of seven hemodialysed patients, 500 ml of a 5.5% nephrological essential amino acid solution (EAA) were administered during each dialysis session for 2 months. At the end of this treatment, a significant increase in albuminemia was found (p < 0.05). These results are an encouragement to continue this therapy, especially if it is kept in mind that the half-life of albumin is much shorter than the period of EAA administration.

Adolescent↗

Peripheral blood cell repopulation following high-dose cyclophosphamide.

High-dose cyclophosphamide can be used to obtain haematological stem cells from the peripheral blood. In this paper we analyse the dynamics of appearance of cells with these characteristics, together with the impact of this drug on the immunological system. Cyclophosphamide seems to possess immunomodulating effects even at high doses.

Antineoplastic Combined Chemotherapy Protocols↗

Restoration of immune functions after chemotherapy.

A paradigmatic case in which anticancer chemotherapy could paradoxically lead to immune restoration is reported. A patient with hairy cell leukemia was unsuccessfully treated with alpha-interferon. Treatment had to be withdrawn because of unusual toxicity and therapy with cytotoxic drugs had to be administered. Not only did the anticancer agents produce a complete remission of the disease, but the immunological profile of the patient improved. This case report raises the problem of the interference of chemotherapy with the immune system in cancer patients.

Antineoplastic Agents↗

[A clinico-epidemiological study on the efficacy of thymopentin therapy in patients with chronic bronchitis and cellular immunity deficiency].

The immunological in vivo effects of thymopentin (TP5) treatment in eleven hypo-anergic patients affected with chronic bronchitis are reported. Significant improvement of cellular immunity, evaluated by skin tests, and an increase of percentage of CD4+ cells and natural killer activity are demonstrated. The clinical evaluation showed an evident reduction of infectious episodes of acute bronchitis after TP5 treatment.

Aged↗

[Recurrent infections of the urogenital tract: preliminary results of a study on the clinical and immunological effects of thymopentin treatment].

We are carrying on a trial with subcutaneous injections of thymopentin in a group of patients that presented more than 2 infectious episodes of uro-genital tract in the latest 18 months. Microbiological investigations were performed with microscopic and cultural examinations before and after six weeks of treatment with thymopentin (TP5) associated with antibiotic therapy chosen on the basis of cultural response. The follow-up was prolonged to 6 months. The immunological studies were performed at the same moments, by a panel of monoclonal antibodies and by the evaluation of the NK activity and granulocytic phagocytosis. The cellular immunity was studied by skin tests. In our patients, during the follow-up period, we observed a significant reduction of infectious episodes, an increase of NK activity, and a restoration of cellular immunity in hypoergic subjects.

Adolescent↗