Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024141 (systemic lupus erythematosus)
44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have found evidence for a human alloantigenic system on the very late activation protein -2 (VLA-2) heterodimer (platelet GPIa/IIa). Sera from two patients with systemic lupus erythematosus (SLE) contained antibodies that immunoprecipitated surface molecules from platelets and fibroblasts that comigrated on SDS-PAGE and two-dimensional O'Farrell gels with platelet GPIa (VLA-alpha2 chain) and platelet GPIIa (VLA-beta chain). These SLE antibodies were alloreactive as they precipitated VLA molecules from only 5 of 22 normal donors' platelets and did not react with the lupus patients' own platelets, despite the expression of apparently normal amounts of VLA on the donors' cells. Two-dimensional O'Farrell analysis demonstrated no differences in the molecular weight or isoelectric point of GPIa and GPIIa obtained from platelets of alloantibody reactive or unreactive donors. Sequential immunoprecipitation experiments with VLA chain-specific monoclonal antibodies, and the pattern of immunoprecipitation of several different VLA heterodimers demonstrated that the alloantibody-reactive determinant was present on the VLA-2 heterodimer, and not other VLA molecules. Thus, these SLE sera demonstrate a previously unrecognized antigenic polymorphism of the VLA-2 (platelet GPIa/IIa) heterodimer, platelet alloantigen Hca.
...
PMID:Antigenic polymorphism of human very late activation protein-2 (platelet glycoprotein Ia-IIa). Platelet alloantigen Hca. 264 23

Several adhesion molecules and CD45RO have been reported to be upregulated on the cell surface of 'memory' T cells. Using triple-color flow cytometry, we compared the levels of typical 'memory' cell markers on peripheral blood T-cell subpopulations in a number of kidney transplant recipients, patients with systemic lupus erythematosus, newborn infants and healthy donors. CD45RO, VLA-beta 1 (CD29), VLA-5 alpha (CD49e), LFA-1 (CD11a/18), and CD2 were found to be closely coregulated on CD4+ T cells, while regulation of VLA-2 alpha (Cd49b), VLA-4 alpha (CD49d) and CD44 was quite discordant. In CD8+ T cells, by contrast, multiple subsets of 'memory'-type cells were distinguished. Unlike TCR alpha/beta T cells, which expressed either high or low levels of LFA-1, TCR gamma/delta cells all expressed high levels of LFA-1 (CD11a/CD18). Examination of T cells from kidney graft fine-needle aspiration biopsies during rejection revealed intragraft accumulation of 'memory'-type T cells expressing high levels of CD2 and LFA-1 (CD11a/CD18). Regarding peripheral blood T-cell subsets, differences between patients and healthy controls were only of a quantitative nature.
...
PMID:Discordant expression of LFA-1, VLA-4alpha, VLA-beta 1, CD45RO and CD28 on T-cell subsets: evidence for multiple subsets of 'memory' T cells. 752 37

In the peripheral blood (PB) we detected so-called early plasma cells that might already be committed to entering the bone marrow (BM). By two-colour staining with FITC-anti-CD38 antibody, their intensity (CD38++) of expression of CD38 antigen was between that of germinal centre (GC) B cells (low expression (CD38+)) and that of BM plasma cells (high expression (CD38++)), and their phenotype was CD38++ CD19+ CD10- CD20- CD21+ CD24- CD39+ CD5- VLA-4+ VLA-5- MPC-1- without expression of surface membrane IgM (SmIgM). Morphological and immunological examination of the sorted cells confirmed that they were plasmacytoid cells with expression of cytoplasmic IgG (cIgG). Variations of these early plasma cells were examined in various diseases. In active systemic lupus erythematosus, bacterial septicaemia and liver cirrhosis, early plasma cell levels were significantly increased in PB, and after subsidence of such inflammation (inactive states) these cells returned to normal levels. In contrast, normal early plasma cells were significantly suppressed in myelomas, whilst normal or slightly increased numbers of early plasma cells was found in benign monoclonal gammopathy (BMG). In addition, the number of normal early plasma cells returned to a normal level in myeloma cases with complete responses. Therefore, early plasma cells were identified phenotypically, and an increase and decrease in these cells in PB may reflect mobilization and suppression, respectively, of activated B cells into BM plasma cells.
...
PMID:Identification of early plasma cells in peripheral blood and their clinical significance. 856 94

Adhesion molecules are critical in the cellular interactions involved in specific immune responses. They are used for homing, cell migration, cell-cell contact and, in some cases, for the delivery of costimulatory signals. Since the host-versus-graft (HVG) reaction represents a particular form of T-B-cell interaction, we have explored whether the inhibition of lymphocyte function-associated antigen-1/intracellular adhesion molecule-1 (LFA-1/ICAM-1) interactions and the signalling through very late activation antigen-4 (VLA-4) have any effect on the development of a lupus-like disease in BALB/c mice injected at birth with (BALB/cxC57BL/6)F1 spleen cells. In close association with the development of tolerance to donor allografts, these mice show a polyclonal activation of F1 donor B cells by alloreactive host CD4+ T cells, manifested by the production of autoantibodies (autoAbs) and the development of a mild glomerulonephritis. The dose of the monoclonal antibody (mAb) employed has been adjusted to block completely the molecule on the surface of peripheral lymphocytes without interfering with the induction of neonatal tolerance. Injection of saturating doses (100 microg/2 days) of either anti-LFA-1alpha or anti-ICAM-1 mAbs, but not anti-VLA-4alpha or anti-LFA-1beta mAbs, blocks the production of anti-ssDNA autoAbs and the thrombocytopenia characteristic of this HVG disease (HVGD). However, anti-VLA-4alpha treatment is only able to delay the production of autoAbs and the anti-LFA-1beta treatment, not to modify the evolution of the HVGD. These results point to the relevance of LFA-1/ICAM-1 interactions, but not of the VLA-4-mediated signal, in the polyclonal B-cell activation occurring during the allogeneic interactions between host T helper type 2 cells and donor B cells in HVGD.
...
PMID:Different roles for LFA-1 and VLA-4 integrins in T-B-cell interactions in vivo. 1044 65