[Lymphocytes and renal damage].
Explore the source record for details and available documents.
B-Lymphocytes↗
Biomedical subjects
A Amoroso
Publications and source records attributed to A Amoroso.
[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↗
Peptide-specific CTL in tumor infiltrating lymphocytes from metastatic melanomas expressing MART-1/Melan-A, gp100 and Tyrosinase genes: a study in an unselected group of HLA-A2.1-positive patients.
Peptide specificity of cultured tumor-infiltrating lymphocytes (TIL) was systematically investigated in a group of HLA-A2.1+ metastatic melanoma patients consecutively referred to our department for surgical treatment. Seven samples from 6 patients were studied. All surgical specimens showed evidence of gp 100, MART-1/Melan-A and Tyrosinase gene expression as detectable by reverse PCR (rPCR). Cultured TIL from 2 patients displayed cytotoxic activity against autologous or HLA-matched EBV-transformed cells previously pulsed with MART-1/Melan-A27-35 peptide. In contrast, no CTL activity against gp100(280-288) or tyrosinase1-9 peptides could be observed. TIL were then repeatedly stimulated in vitro with the same peptides. After 6 restimulation courses at weekly intervals, specific recognition of gp100(280-288) and MART-1/Melan-A peptides was detectable in 3 and 5 TIL populations, respectively. In one case Tyrosinase1-9-specific CTL could be demonstrated. Two TIL populations from metastases resected from a melanoma patient at 6 months' distance showed a different peptide specificity pattern, and no specific CTL could be generated from simultaneously sampled peripheral blood mononuclear cells (PBMC). All peptide-specific CTL populations also displayed significant cytotoxic activity against HLA-A2.1 matched melanoma cell lines expressing the antigens under investigation. Our data indicate that CTL specific for MART-Melan-A27-35, gp100(280-288) or Tyrosinase1-9 peptides could be expanded with varying frequency from TIL derived from 4 out of 6 HLA-A2.1+ patients whose tumors expressed the genes encoding these tumor-associated antigens (TAA).
Adult↗
Frequency of the new HLA-B*2709 allele in ankylosing spondylitis patients and healthy individuals.
Explore the source record for details and available documents.
Alleles↗
Evidence of linkage between susceptibility to multiple sclerosis and HLA-class II loci in Italian multiplex families.
To verify whether multiallelic polymorphisms belonging to HLA class II genes are linked to multiple sclerosis (MS) in the Italian population, we studied 28 multiplex MS families originating from different areas of Italy. Allelic characterization was carried out by analysis of RFLPs and oligonucleotide typing. Evidence supporting the existence of linkage between MS susceptibility and the HLA class II loci DRB1, DQA1 and DQB1 was provided using two non-parametric tests, affected sib-pair analysis, and affected-pedigree-member (APM) analysis. The APM analysis also suggested the existence of genetic heterogeneity for the HLA class II loci and MS susceptibility in our series. Linkage disequilibrium between MS susceptibility and the haplotype DRB1*1501,DQA1*0102,DQB1*0602 was demonstrated by applying the transmission linkage disequilibrium test to our families. Finally, lod score analysis suggests that in our Italian families, MS susceptibility is conferred by HLA class II alleles according to a low-penetrance autosomal recessive mode of inheritance.
Alleles↗
[Pheochromocytoma-gastric leiomyoblastoma association. A possible expression of Carney's triad. A case report].
The case of a 28 yrs old female patient affected by pheochromocytoma and gastric leiomyoblastoma was described. The simultaneous presence of these neoplasms in a young woman supported the diagnosis of the clinical syndrome known as "Carney's triad".
Adrenal Gland Neoplasms↗
HLA-haploidentical umbilical cord blood stem cell transplantation in a child with advanced leukemia: clinical outcome and analysis of hematopoietic recovery.
Growing attention has been focused on cord blood as a source of transplantable hematopoietic stem cells. However, clinical experience is rather limited. In this study we describe a child with advanced acute lymphoblastic leukemia who received an HLA-haploidentical cord blood transplant. The patient was transplanted in third complete remission after conditioning with fractionated total body irradiation, thiotepa and cyclophosphamide. Forty-one milliliters of cryopreserved umbilical cord blood, containing 0.15 x 10(8) nucleated cells/kg and 0.25 x 10(4) CFU-GM/kg, were infused. Cyclosporine and prednisone were administered for graft-versus-host disease (GVHD) prophylaxis. The patient received G-CSF from day +1 to day +35, but no improvement in granulocyte counts was observed. Therefore, administration of GM-CSF was started on day +36 to day +59, which resulted in a significant increase in white blood cells and granulocyte counts. Sustained myeloid engraftment was evidenced by a granulocyte count > 0.5 x 10(9)/l by day +41. The presence of donor-derived cells could be documented in the peripheral blood and bone marrow of the patient by cytogenetic analysis, HLA phenotyping and DNA studies. Forty-one days after transplant, clonogenic bone marrow assays showed the presence of low frequencies of primitive hematopoietic progenitor cells (BFU-E = 19/10(5) and CFU-GM = 8/10(5)). The chimerism was complete and no host-derived cells could be detected. However, the engraftment was restricted to the myeloid lineage whereas lymphoid and megakaryocytic engraftments were inadequate. The immunophenotype of the patient's peripheral blood showed the presence of T lymphocytes expressing an immature phenotype (CD2+ CD3-) at day +21.(ABSTRACT TRUNCATED AT 250 WORDS)
Child, Preschool↗
Usefulness of frequency analysis of cytotoxic T-lymphocytes precursors (CTL-p) for selection of HLA matched unrelated marrow donors.
A child with Sanfilippo syndrome and 5 potential unrelated marrow donors were typed serologically, tested in mixed lymphocyte reaction and typed by restriction fragment length polymorphism analysis in attempt to find a suitable donor. All donors were found to be identical with the recipient, however, these studies were not conclusive in identifying the best match donor. Therefore, recipient-donor pairs were examined by HLA-DR oligotyping. In addition we have studied the potential of cytotoxic T-lymphocytes precursors (CTL-p) analysis as a means of selection for matched unrelated donors. Low frequencies (1/10(5)) of pretransplant CTL-p correlated with oligotyping identity in all donor-recipient pairs evaluated. In one case oligotyping disclosed a previously unrecognized HLA-DRB1 disparity. This resulted in high frequencies of CTL-p (1/35,000). Based on this experience we can argue that CTL-p analysis may be used as an additional tool for selection of compatible unrelated marrow donors.
Bone Marrow Transplantation↗
Self class I molecules protect normal cells from lysis mediated by autologous natural killer cells.
The surface expression of given HLA class I alleles protects target cells from lysis mediated by natural killer (NK) clones specific for these (or related) alleles. We could define two groups of NK clones specifically recognizing either Cw4 and related C alleles ("group 1") or Cw3 and related C alleles ("group 2"), respectively. Monoclonal antibodies (mAb) to class I molecules should interfere with the interaction between NK receptors and class I molecules, thus resulting in lysis of protected target cells. However, none of the numerous available mAb to class I molecules had this effect. Therefore, we attempted to select new mAb on the basis of their ability to induce lysis of Cw4- or Cw3-protected lymphoblastoid cell lines by "group 1" or "group 2" NK clones, respectively. From mice immunized with phytohemagglutinin (PHA)-activated lymphocytes expressing either Cw3 or Cw4 alleles, two mAb were selected, the 6A4 (IgG1) and the A6-136 (IgM), on the basis of their ability to induce lysis of protected target cell. Both mAb immunoprecipitated molecules which, in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, gave two bands of 45 and 12 kDa, typical of the class I heavy chain and beta 2 microglobulin, respectively. It has been proposed (but not proven), that self major histocompatibility complex class I molecules protect normal cells from autologous NK cell lysis. Thus, we used the 6A4 and A6-136 mAb to assess this possibility directly. Cw4-specific ("group 1") and Cw3-specific ("group 2") NK clones were isolated from donors expressing the corresponding (or related) protective C alleles. None of these clones lysed autologous PHA-induced blasts, used as target cells. However, addition of the F(ab')2 of 6A4 mAb or the A6-136 mAb resulted in lysis of autologous target cells by "group 1" or "group 2" NK clones, respectively. These data provide direct evidence that the expression of class I molecules protects normal cells from lysis by autologous NK cells.
Animals↗
Anti-idiotypes against antiphospholipid antibodies are present in normal polyspecific immunoglobulins for therapeutic use.
In the present study we found that antiphospholipid activity in sera from patients with anticardiolipin antibodies was inhibited in vitro by therapeutic polyspecific normal immunoglobulins (IVIg). In fact, F(ab')2 fragments from IVIg (IVIg-F(ab')2) inhibited the binding of anticardiolipin antibodies to the corresponding antigen in a dose-dependent fashion, thus suggesting that the interaction between IVIg-F(ab')2 and anticardiolipin antibodies occurred within or near the antigen combining site. The maximal inhibition ranged from 35.25 +/- 5.56 to 64 +/- 5.48%. In addition, patients' IgG containing antiphospholipid activity specifically bound insolubilized IVIg-F(ab')2, as assessed by enzyme-linked immunosorbent assay (ELISA). These results indicate that IVIg obtained from a large pool of normal donors contain anti-idiotypic antibodies directed against idiotypes located on antiphospholipid antibodies. Moreover, our observations suggest that the reported favourable effect of high dose infusion of IVIg in patients with recurrent abortions due to antiphospholipid antibodies may depend, at least in part on inhibition of the binding of such autoantibodies to the corresponding antigens (s) and/or inactivation of idiotype bearing B cell clones.
Abortion, Habitual↗
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↗
Human leukocyte antigen class II polymorphisms and genetic susceptibility of IDDM in Egyptian children.
OBJECTIVE: To analyze the association between human leukocyte antigen (HLA) and insulin-dependent diabetes mellitus (IDDM) in the Egyptian population for the first time and, thus, to determine the frequency of risk-associated alleles identified by a genomic HLA class II typing. Egyptians are genetically classified as North Africans and considered to be between Caucasoids and Africans (closer to Caucasoids). RESEARCH DESIGN AND METHODS: HLA class II typing was performed for 50 IDDM patients and 50 healthy control subjects by a restriction fragment-length polymorphism (RFLP) technique. The analysis of position 57 of the DQB1 molecules was conducted by polymerase chain reaction and specific sequence oligonucleotide hybridization. RESULTS: The frequency of DRB1*0301-DRB3*0201-DQA1*0501-DQB1*0201 haplotype was 43.9% in the IDDM patients and 7.1% in the control subjects (P < 0.00001), reflecting the increased prevalence of DQA1*0501 susceptibility allele coding for arginine (Arg) in position 52 and DQB1*0201 susceptibility allele non-coding aspartic acid (Asp) at position 57. Alleles DQB1*0601 and 0603, both carrying Asp at position 57 of the beta-chain, and DQA1*0103, encoding a non-Arg 52 alpha-chain, were significantly decreased among the IDDM patients. The presence of four susceptibility residues (two DQA1 Arg 52+ and two DQB1 Asp 57-) conferred the highest relative risk at 20.2. On the other hand, homozygous genotypes for DQA1 non-Arg 52 and DQB1 Asp 57 were found only in the control group. CONCLUSIONS: IDDM susceptibility and resistance in the Egyptian population is strongly associated with the expressed DQ alpha- and beta-heterodimers in a dose-effective manner, as already defined in many different ethnic groups.
Alleles↗
Antimicrobial activity of 5,6-dihydrobenzo-[a]-carbazoles.
A new series of 5,6-dihydrobenzo[a]carbazoles was synthesized, some showing good antibacterial activity. The presence of a dialkylamino ethyl chain on the 2-, 3- or 4-O-substituent seems to be critical for such activity.
Anti-Infective Agents↗
Reversible adrenal insufficiency after adrenal hemorrhage.
Explore the source record for details and available documents.
Abortion, Habitual↗
The set of naturally processed peptides displayed by DR molecules is tuned by polymorphism of residue 86.
The response to tetanus toxoid (TT) was studied in immune donors that carry two alleles of DR5 that differ only at DR beta residue 86: DRB1*1101 (G86, abbreviated 1101) and DRB1*1104 (V86, abbreviated 1104). A large number of TT-specific T cell clones was isolated and the epitopes recognized in association with 1101 and 1104 were mapped. We found that two epitopes (p2 and p32) can be recognized in association with both 1101 and 1104 while three epitopes (p23, p27 and p30) are recognized in association with 1101, but never in association with 1104. The sets of naturally processed self peptides displayed by 1101 and 1104 were characterized using alloreactive T cell clones. We found that all 1104 alloreactive clones recognize both 1104 and 1101, while approximately 30% of the alloreactive 1101 clones fail to recognize 1104. Thus it is apparent that both naturally processed TT and self peptides displayed on 1104 molecules represent a fraction of those displayed on 1101 molecules. The mechanism responsible for this differential presentation was investigated by comparing the capacity of 1101 and 1104 antigen-presenting cells to present TT or synthetic peptides to specific T cells and by measuring the binding of these peptides to DR molecules. Three sets of results suggest that V86 acts as a constraint to the binding of naturally processed peptides: (i) all 1104-restricted or alloreactive T cell clones recognize TT- or allo-epitopes presented by 1101 as well, thus ruling out a major effect of V86 as a residue determining T cell restriction specificity; (ii) presentation of naturally processed peptides correlates in general with the capacity of long synthetic peptides to bind to 1101 or 1104 and (iii) while the naturally processed p30 epitope discriminates between 1101 and 1104, a short synthetic peptide binds equally well to and is comparably recognized in association with both 1101 and 1104. Taken together these results suggest that the natural polymorphism at residue 86 might be a molecular switch that finely tunes the complexity of the peptide collection presented on DR molecules.
Alleles↗
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↗
Identification of unrelated HLA-identical bone marrow donors: RFLP, oligotyping and PCR fingerprinting for HLA class II compared to MLC responses.
22 patients awaiting bone marrow transplantation (BMT) and 65 unrelated healthy HLA-A, B and DR serologically identical donors were studied. 21 patients were non reactive on mixed lymphocyte culture (MLC) towards at least one BMT donor, resulting in 32 pairs MLC-negative. 33 other HLA-matched donors gave proliferative responses on MLC. The phenotype DR3/DR7 was significantly higher in patients (P) and donors (D) studied (p < 0.00001). P and D pairs were DNA typed by RFLP analysis for DRB, DQA and DQB genes, and DNA matched by PCR Fingerprinting (PCRF) for DRB, DQA, DQB and DPB. Six patients and 18 donors were also oligotyped for the subtypes of DR1, DR3, DR4 and DR5. Patients and donors were divided according to identity on RFLP, PCRF and responsiveness on MLC, represented by RRI. In the group of MLC non responder pairs, 11% had differences on DRB PCRF compared to 57% in the group of MLC responders (p = 0.0002). The mean RRI value of PCRF DRB incompatible pairs was significantly higher compared to RRI of compatible pairs (p = 0.012). With respect to PCRF for DPB, 75% of MLC-ve pairs were different. Also the mean RRI value was significantly lower in DPB identical pairs compared to non identical ones (p = 0.048). The compatibility between P/D pairs assessed by oligotyping was in accordance with DRB PCRF. PCRF for DQB, but not for DQA, corresponded to MLC responses. Our findings confirm that PCRF offers a precise and fast alternative in DNA matching for DRB. We also suggest that PCRF for DQB and DPB, together with DRB, could eventually substitute MLC.
Bone Marrow Transplantation↗