Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036421 (PSS)
 10,989 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Scleroderma (progressive systemic sclerosis [PSS]) is known to be associated with abnormal T cell immunoregulation. In the present study, we evaluated lymphocyte phenotypes in patients with PSS and normal control subjects by flow cytometry and monoclonal antibodies for total T (CD3), T suppressor (CD8), T helper (CD4), T helper-inducer (CDw29), T suppressor-inducer (CD45R), human leukocyte antigen, DR+B (CD19), DR+T, and natural killer subsets, HNK-1 (CD57) and NKH-1 (CD56) cells. Patients with PSS compared to normal subjects had significantly lower percentages of CD3+ (p less than 0.005) and CD8+ (p less than 0.05) (similar to several patients with rheumatoid arthritis also evaluated), as well as CD45R (p less than 0.05), T+DR+ (p less than 0.05), and NKH-1 (CD56) (p less than 0.0005) cells. Patients with PSS with late-limited or generalized disease had lower percentages of CD8+, CD19, NKH-1+, and CDw29, but higher percentages of CD4+, HNK-1, and CD45R cells compared to patients with early stage disease, but these results were not statistically significant. These unique alterations in patients with PSS may prove to be useful in monitoring the stage of disease activity for therapy and further define immunologic defects.
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PMID:Altered T cell subpopulations and lymphocytes expressing natural killer cell phenotypes in patients with progressive systemic sclerosis. 201 71

In 47 cases of autoimmune diseases (25 SLE, 9 MCTD, 6 PSS, 7 RA), two B cell surface antigens, CD19 and CD20 were quantitatively measured with a flowcytometer. When compared with the results of healthy controls, CD19 antigens were observed to be ca. 10% decreased in SLE and ca. 20% increased in RA. CD20 antigens were observed to be ca. 25% increased in SLE and no changes in RA. No significant increase nor decrease was observed with MCTD and PSS patients. In SLE patients, the amount of CD19 antigen expression was positively related to serum C3 levels, and that of CD20 antigen was negatively related to it. It is not obvious in what mechanism the expression of these antigens are regulated, however, from the point that the expression relates to the amount of serum C3 level, the quantitative measurement of CD19 and CD20 antigens is possibly be a good marker to detect the state of autoimmune disease such as SLE.
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PMID:[Quantitative flowcytometric analysis of B cell surface antigens in patients with autoimmune diseases]. 753 32

The humoral immune response against elastin and collagen was studied in parallel with the delayed type hypersensitivity (DTH) reaction to elastin and the percentage of lymphocyte subpopulations in peripheral blood in 20 patients with systemic sclerosis (SSc). An increase of anti-elastin antibodies of all subclasses was found with a significant prevalence of IgE and IgA antibodies. The profile of anti-collagen type I and type IV antibodies showed an increase of IgE isotypes. In 25% of the patients (5 out of 20) positive DTH reactions to elastin were observed as compared to the negative skin reactions in all control individuals. At the same time a significant hyporeactivity to common bacterial and mould antigens was found in 40% of the patients (versus 16% in the control group) which could be an explanation for the low incidence of positive anti-elastin DTH reaction. The DTH hyporeactivity in SSc cases was in contrast with the increased percentage of CD4 T cells (58.4 vs. 42.0) and increased CD4/CD8 ratio (2.5 vs. 1.5) in the peripheral blood of the patients. This finding together with the increased IgE antibodies to elastin and collagen type I and type IV might suggest a possible shift of the immune balance towards the Th2 type of immune response. This is in line with the increased CD8+CD57+ cells which correlated with the highest number of other parameters studied - disease duration, total skin score, IgE anti-elastin antibodies, IgG anti-collagen type I antibodies, CD4/CD8 ratio and CD19 B cells. The results of this study demonstrated the existence of both humoral and cell-mediated immune response against elastin in SSc patients. However, we could not define whether this was an essential part of pathogenetic mechanisms or a secondary phenomenon reflecting the extent of the damage of connective tissue.
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PMID:Humoral and cellular immune response to elastin in patients with systemic sclerosis. 934 31

The aim of the present study was to examine the effects of academic examination stress on leukocyte subset distribution in university students. Thirty-eight university students had repeated blood collections for white blood cell differentiation and flow cytometric assay of lymphocytic subsets a few weeks before and after (i.e. two baseline conditions) as well as the day before a difficult academic examination (i.e. stress condition). Flow cytometry was used to determine the number of peripheral blood mononuclear cells (PBMC). In students, who were reactors to psychological stress (criterion based on changes in the Perceived Stress Scale, PSS), but not in stress non-reactors, a significant increase in the number of neutrophils, monocytes, CD8(+), CD2(+)CD26(+), and CD2(+)HLA-DR+ T cells and CD19(+) B cells, and significant reductions in the CD4(+)/CD8(+) T cell ratio were observed in the stress condition. There were significant and positive relationships between the stress-induced changes in perceived stress (PSS scale) and number of leukocytes, neutrophils, CD2(+), CD2(+)CD26(+) and CD2(+)HLADR+ T cells, and CD19(+) B cells. There were significant and negative relationships between the stress-induced changes in the CD4(+)/CD8(+) ratio and the stress-induced changes in the PSS scale. Female students taking oral contraceptives showed significantly higher stress-induced responses in number of leukocytes, neutrophils and CD19(+) B cells than male and female students without use of oral contraceptives. The results suggest that academic examination stress induces changes in the distribution of PBMC, which indicate immune activation and which are probably orchestrated by a stress-induced production of cytokines.
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PMID:The effects of psychological stress on leukocyte subset distribution in humans: evidence of immune activation. 989 53

Fetal CD34(+) CD38(+) cells have recently been found to persist in maternal peripheral blood for many years after pregnancy. CD34(+) CD38(+) cells are progenitor cells that can differentiate into mature immune-competent cells. We asked whether long-term fetal microchimerism occurs in T lymphocyte, B lymphocyte, monocyte, and natural-killer cell populations of previously pregnant women. We targeted women with sons and used polymerase chain reaction for a Y-chromosome-specific sequence to test DNA extracted from peripheral blood mononuclear cells (PBMC) and from CD3, CD19, CD14, and CD56/16 sorted subsets. We also asked whether persistent microchimerism might contribute to subsequent autoimmune disease in the mother and included women with the autoimmune disease scleroderma. Scleroderma has a peak incidence in women after childbearing years and has clinical similarities to chronic graft-versus-host disease that occurs after allogeneic hematopoietic stem-cell transplantation, known to involve chimerism. Sixty-eight parous women were studied for male DNA in PBMC and 20 for PBMC subsets. Microchimerism was found in PBMC from 33% (16 of 48) of healthy women and 60% (12 of 20) women with scleroderma, P =.046. Microchimerism was found in some women in CD3, CD19, CD14, and CD56/16 subsets including up to 38 years after pregnancy. Microchimerism in PBMC subsets was not appreciably more frequent in scleroderma patients than in healthy controls. Overall, microchimerism was found in CD3, CD19, and CD14 subsets in approximately one third of women and in CD56/16 in one half of women. HLA typing of mothers and sons indicated that HLA compatibility was not a requirement for persistent microchimerism in PBMC subsets. Fetal microchimerism in the face of HLA disparity implies that specific maternal immunoregulatory pathways exist that permit persistence but prevent effector function of these cells in normal women. Although microchimerism in PBMC was more frequent in women with scleroderma than healthy controls additional studies will be necessary to determine whether microchimerism plays a role in the pathogenesis of this or other autoimmune diseases.
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PMID:Long-term fetal microchimerism in peripheral blood mononuclear cell subsets in healthy women and women with scleroderma. 1006 76

The fate of B lymphocytes is dependent on intrinsic and B cell antigen receptor (BCR)-induced signals. These signals are modified and interpreted by other cell-surface molecules such as CD19 and CD22 that govern mature B cell activation. This review assesses our current understanding of how CD19 and CD22 regulate B lymphocyte signaling and how alterations in these response-regulators contribute to autoimmunity in mice and humans. We propose that CD19 functions as a specialized adapter protein that regulates B lymphocyte signaling and autoantibody production. Overexpression of CD19 by B cells in systemic sclerosis patients correlates with autoantibody production and transgenic mice that overexpress CD19 produce similar autoantibodies. CD19 establishes a novel Src-family kinase activation loop that regulates basal signal transduction thresholds in resting B cells and amplifies Src-family kinase activation following BCR ligation. Reciprocally, CD22 is a potent regulator of CD19 function. These observations provide insight into how CD19 and CD22 govern the molecular ordering and intensity of signals transduced in B cells that may contribute to autoimmunity.
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PMID:CD19 and CD22 regulate a B lymphocyte signal transduction pathway that contributes to autoimmunity. 1075 Mar 75

The aim of this study was to estimate if alterations of lymphocyte subsets obtained by broncholaveolar lavage (BAL) were related to clinical data observed in nonsmoking patients with systemic sclerosis (SSc). Clinical examination included chest X-rays, spirometry and arterial blood gasometry. Patients were divided into group A (pulmonary changes present, n = 15) and B (without any changes, n = 7). Healthy subjects constituted the control group (n = 10). BAL lymphocytes were phenotyped using monoclonal antibodies coupling CD4, CD8 (both in coexpression with CD25), CD19 and HLA-DR human antigens and flow cytometer FACStar (Becton-Dickinson). Parallel staining was performed in peripheral blood. BAL lymphocyte typing was completed by BAL routine cytology. In SSc patients we found increased BAL total cell number, percentage of neutrophils, eosinophils and macrophage giant cells, as well as high percent of CD25+ and HLA-DR+ lymphocytes. In the group A neutrophilic alveolitis was observed in nearly half of cases: total lymphocyte number (per 1 ml of BAL fluid) and significantly reduced CD4/CD8 ratio were found. In the group B, as compared with controls, we found significantly elevated lymphocyte total cell number per 1 ml of BAL fluid (including particular subsets: CD3+, CD4+, CD8+). Also significantly high CD4+25+ lymphocyte percent was observed. Summing up, cytological and/or immunological alterations were observed in all examined SSc patients. The intensity of these alterations seems to be related to the clinical data. A decreased value of CD4/CD8 ratio may play a role in the local appearance of pulmonary changes in the course of systemic sclerosis.
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PMID:[Changes in lymphocyte subsets in bronchoalveolar lavage fluid in patients with systemic sclerosis]. 1076 46

Signaling thresholds influence the balance between humoral immunity and autoimmunity. Cell surface CD19 regulates intrinsic and Ag receptor-induced B lymphocyte signaling thresholds, and transgenic mice that overexpress CD19 by 3-fold generate spontaneous autoantibodies in a genetic background not associated with autoimmunity. To quantify the extent that genetically determined differences in expression of a single cell surface molecule can influence autoantibody production, we have assessed autoimmunity in a C57BL/6-transgenic mouse line with subtle 15-29% increases in CD19 cell surface expression (CD19 transgenic). Antinuclear Abs, especially anti-spindle pole Abs, rheumatoid factor, and autoantibodies for ssDNA, dsDNA, and histone were produced in these transgenic mice, but not littermate controls. This demonstrates that small changes in CD19 expression can induce autoantibody production. Remarkably, similar changes in CD19 expression were found on B cells from patients with systemic sclerosis, a multisystem disorder of connective tissue with autoantibody production. CD19 density on blood B cells from systemic sclerosis patients was significantly ( approximately 20%) higher compared with normal individuals, whereas CD20, CD22, and CD40 expression were normal. These results suggest that modest changes in the expression or function of regulatory molecules such as CD19 may shift the balance between tolerance and immunity to autoimmunity. Thereby autoimmune disease may result from a collection of subtle multigenic alterations that could include incremental density changes in cell surface signaling molecules.
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PMID:Quantitative genetic variation in CD19 expression correlates with autoimmunity. 1108 9

Our objective was to investigate the phenotype of helper T cells in the peripheral blood of patients with systemic sclerosis (SSc). PBMC from 15 patients with SSc and 15 sex- and age-matched controls were investigated for lymphocyte subpopulations (CD3, CD4, CD8, CD19, CD16/CD56, CD3-DR); IL-2, IL-4, and IFN-gamma mRNAs; and the relative cytokines in their cytoplasm. The last assay was carried out both in unstimulated and in PMA-activated PBMC. SSc patients presented a higher percentage of activated T cells, CD3+ DR+ (19.7 +/- 9.9 vs 5.1 +/- 2.5%; P < 0.0001); 12 of them presented IFN-gamma mRNA-positive cells; and none IL-2 or IL-4 mRNAs. Under basal conditions, PBMC from six SSc patients contained IL-2, IL-4, and IFN-gamma (i.e., they showed both Th1 and Th2 activation), and 1 IFN-gamma only. PMA-stimulated PBMC of patients differed from those of controls only in the increased percentage of IFN-gamma positive cells (52 +/- 12 vs 37 +/- 11%; P < 0.01). Our study demonstrates that Thl activation occurs in the peripheral blood of SSc patients. This evidence must be faced with from both a pathogenetic and a therapeutical point of view.
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PMID:Peripheral blood T lymphocytes from systemic sclerosis patients show both Th1 and Th2 activation. 1140 28

The tight-skin (TSK/+) mouse, a genetic model for human systemic sclerosis (SSc), develops cutaneous fibrosis and autoantibodies against SSc-specific target autoantigens. Although molecular mechanisms explaining the development of fibrosis and autoimmunity in SSc patients or TSK/+ mice remain unknown, we recently demonstrated that SSc patients overexpress CD19, an important regulatory molecule expressed by B lymphocytes. B cells from CD19-deficient mice are hyporesponsive to transmembrane signals, while B cells overexpressing CD19 are hyperresponsive and generate autoantibodies. In this study, TSK/+ B cells also exhibited a hyperresponsive phenotype with decreased surface IgM expression, enhanced serum Ig production, and spontaneous autoantibody production. Moreover, CD19 tyrosine phosphorylation was constitutively augmented in TSK/+ B cells. CD19-mediated [Ca(2+)](i) responses, Vav phosphorylation, and Lyn kinase activity were similarly enhanced. Studies of TSK/+ mice deficient in CD19 expression demonstrated that CD19 deficiency significantly decreased skin fibrosis in TSK/+ mice. Additionally, CD19 loss in TSK/+ mice upregulated surface IgM expression and completely abrogated hyper-gamma-globulinemia and autoantibody production. CD19 deficiency also inhibited IL-6 production by TSK/+ B cells. Thus, chronic B cell activation resulting from augmented CD19 signaling in TSK/+ mice leads to skin sclerosis possibly through IL-6 overproduction as well as autoimmunity.
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PMID:CD19-dependent B lymphocyte signaling thresholds influence skin fibrosis and autoimmunity in the tight-skin mouse. 1204 59


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