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PubMed2003

Anti-c-Mpl (thrombopoietin receptor) autoantibody-induced amegakaryocytic thrombocytopenia in a patient with systemic sclerosis.

Amegakaryocytic thrombocytopenia (AMT) associated with systemic sclerosis (SSc) has been described in several case reports, but the underlying mechanisms have not been identified. Here we describe a rare case of SSc accompanied by thrombocytopenia and megakaryocytic hypoplasia, in which autoantibody against thrombopoietin receptor (c-Mpl) was detected. A 61-year-old woman with limited SSc was admitted to our hospital because of severe thrombocytopenia (platelet count 0.2 x 10(4)/mm(3)) with gingival bleeding. Her bone marrow was hypocellular with absent megakaryocytes, consistent with AMT. Treatment with corticosteroids and intravenous immunoglobulin infusions resulted in an increased platelet count, and she sustained a remission over a 1-year period, with a platelet count averaging 10.0 x 10(4)/mm(3). Her serum was strongly positive for anti-c-Mpl antibody, and IgG fraction purified from her serum inhibited thrombopoietin-dependent cell proliferation in vitro. Our case report suggests that AMT in patients with SSc could be mediated by the anti-c-Mpl antibody, which functionally blocks an interaction between thrombopoietin and c-Mpl.

Autoantibodies↗
PubMed1986

Cell-mediated immunity in rheumatic disease.

Rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis are the three most common systemic rheumatic diseases in which disordered immune function is thought to play a pathogenetic role. Each disease has different and characteristic abnormalities of the cellular immune system. In rheumatoid arthritis the identified abnormalities of immunoregulation are largely limited to specific antigens: Epstein-Barr virus and collagen. Systemic lupus erythematosus is characterized by exuberant B-cell activity with exaggerated humoral response, a diversity of autoantibodies, non-antigen-specific loss of suppressor cell function, and general suppression of cell-mediated immunity. In systemic sclerosis systemic defects of cellular and humoral immune function are mild, but the release of lymphokines and monokines at sites of inflammatory lesions is thought to be important in the pathogenesis of the disease. Similar immune cell-connetive tissue cell interactions are probably important in the propagation of rheumatoid synovitis. Thus, despite the many shared clinical and serologic features of these diseases as well as the presence of many patients who have clinically overlapping features of more than one of these entities, the immune defects and the immunopathogenesis of these disorders appear to be distinct.

Animals↗
PubMed2000

Limited cutaneous systemic sclerosis associated with MPO-ANCA positive renal small vessel vasculitis of the microscopic polyangiitis type.

Renal disease in systemic sclerosis may present in various patterns. A 66-year-old woman with a history of longstanding limited cutaneous systemic sclerosis of the CREST syndrome variant presented with a sudden left foot drop and rapidly progressive renal insufficiency associated with mild proteinuria, a nephritic urine sediment, and a urinary output of 900 mL/d. There was no history of intake of D-penicillamine, and there were no signs of malignant arterial hypertension or microangiopathic hemolytic anemia. Renal histology showed a small vessel vasculitis of the microscopic polyangiitis type. Serologic tests showed a marked increase of antineutrophil cytoplasmic antibodies with a perinuclear pattern and an elevated titer of antimyeloperoxidase antibodies. No clinical or laboratory signs of Sjögren's syndrome were present. This clinical report adds new information to the spectrum of renal disease in systemic sclerosis. It discusses the association between systemic sclerosis and small vessel vasculitis of the microscopic polyangiitis type as well as the possible meaning of serologic markers.

Acute Kidney Injury↗
PubMed1988

Decreased oesophageal blood flow in patients with Raynaud's phenomenon.

Cold-induced vasospasm seen in systemic sclerosis (SS) and Raynaud's phenomenon (RP) has previously been thought to be limited to peripheral skin sites. However, the oesophageal problems seen in SS cannot be sufficiently explained by connective tissue damage/abnormal motility alone. We wondered if temperature dependent ischaemia could occur in the oesophageal microcirculation. We have measured oesophageal temperature variation following oesophageal cold challenge: 50 ml of water at 7 degrees C and 17 degrees C, with 37 degrees C used as control, were introduced into the mid-oesophagus at a rate of 2 ml/s. Temperature was recorded using a thermocouple probe 5 cm above the gastro-oesophageal junction. The test was performed on 14 SS patients, eight patients with Raynaud's disease and 21 controls. The control's rewarming pattern followed a simple exponential curve. This did not vary with temperature or after repeated challenge. In the SS patients the time constant was significantly longer after cold challenge.

Adult↗
PubMed2005

Abnormal natural killer cell function in systemic sclerosis: altered cytokine production and defective killing activity.

Natural killer (NK) cells are innate immune effectors that produce various immunoregulatory cytokines. Recent studies have shown that NK cells are involved in the initiation of autoimmunity. In this study, we determined abnormalities of NK cells in systemic sclerosis (SSc), an autoimmune connective tissue disease, by assessing the frequency and absolute number, activation marker expression, cytokine production, and killing activity. The frequency and absolute number of NK cells increased in diffuse cutaneous SSc (dcSSc), whereas they were normal in limited cutaneous SSc (lcSSc). NK cells from both dcSSc and lcSSc patients exhibited activated phenotypes characterized by up-regulated CD16 and CD69 expression and downregulated CD62L expression. Interferon (IFN)-gamma production by non-stimulated NK cells from both dcSSc and lcSSc patients was increased compared to the normal control, whereas on stimulation, a reduced amount of IFN-gamma was produced. Interleukin (IL)-5 and IL-10 production by non-stimulated NK cells and IL-6 production by stimulated NK cells were augmented in dcSSc patients, but not in lcSSc patients. Despite the augmented cytokine production by non-stimulated NK cells, natural cytotoxicity activity and granzyme B secretion was reduced in NK cells from dcSSc and lcSSc patients. These results suggested that altered NK cell function contributes to immunological abnormalities in SSc.

Adult↗
PubMed2003

Correlation of serum collagen I carboxyterminal telopeptide concentrations with cutaneous and pulmonary involvement in systemic sclerosis.

OBJECTIVE: Systemic sclerosis (SSc) is characterized by fibrosis involving the skin and various internal organs. Type I collagen (Col I) is the most abundant extracellular matrix protein deposited in cutaneous involvement. We investigated Col I biochemical markers in patients with SSc. METHODS: All consecutive patients admitted for SSc over a 9 month period and a healthy control group were investigated. Serum concentrations of the C-terminal telopeptide of Col I (s-CTX-I), C-terminal type I procollagen propeptide (PICP), osteocalcin, and bone alkaline phosphatases (ALP), and urinary concentrations of deoxypyridinoline (u-DPD) and u-CTX-I were determined by ELISA. RESULTS: A total of 33 patients with SSc were included: mean age +/- SD was 54 +/- 12 yrs, with a mean disease duration of 5.4 +/- 3.9 years. Sixteen of 33 patients with SSc had s-CTX-I values exceeding the upper limit of normal values of the test and the mean +/- SEM was significantly higher (7388 +/- 1422 pmol/l) than in healthy controls (2800 +/- 1120 pmol/l; p < 0.001). s-CTX-I correlated with the Rodnan skin score (p = 0.003); it was higher in patients with diffuse disease (8459 +/- 3125; n = 14) than in patients with the limited form (6453 +/- 1235; n = 19; p < 0.02). This marker also correlated with acute phase reactants (C-reactive protein, p = 0.004; erythrocyte sedimentation rate, p = 0.02). s-CTX-I was high in patients with positive antitopoisomerase I autoantibodies (p = 0.04) and in patients with a decrease in forced vital capacity to less than 75% (p = 0.02). u-DPD concentration was high in patients with SSc (10.6 +/- 1.4 nmol/mmol creatinine vs 6.3 +/- 2.1 in controls; p < 0.01). No difference between patients and controls or correlations with the disease were found for PICP, u-CTX-I, osteocalcin, and bone ALP concentrations. CONCLUSION: s-CTX-I, a marker of Col I degradation, is correlated with cutaneous and pulmonary involvement and with acute phase reactants in patients with SSc. This marker is a good candidate for further evaluation for disease activity and treatment purposes.

Aged↗
PubMed2006

Differential expression of stromal cell-derived factor 1 and its receptor CXCR4 in the skin and endothelial cells of systemic sclerosis patients: Pathogenetic implications.

OBJECTIVE: Systemic sclerosis (SSc) is characterized by early endothelial damage evolving to vascular desertification. Stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4 regulate specific steps in new vessel formation. We undertook this study to determine whether an alteration of the SDF-1/CXCR4 axis might be involved in the pathogenetic mechanisms following ischemic damage during SSc. METHODS: We enrolled 36 SSc patients and 15 controls. Skin biopsy samples were obtained from each subject, and the expression of SDF-1 and CXCR4 was assessed by immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR), and Western blot analyses. Furthermore, isolated microvascular endothelial cells (MVECs) from 4 patients with diffuse cutaneous SSc (dcSSc) and 3 controls were analyzed for SDF-1 and CXCR4 by confocal laser scanning microscopy, RT-PCR, and Western blotting. RESULTS: SDF-1 and CXCR4 were up-regulated in the skin of patients with early (edematous) SSc, both in the diffuse and limited cutaneous forms, and progressively decreased, with the lowest expression in the latest phases of both SSc subsets. MVECs from patients with dcSSc expressed significantly higher amounts of both isoforms of SDF-1 in the early stage of disease, with a progressive reduction of SDF-1 and CXCR4 in later stages. On the surface of cultured MVECs from patients with dcSSc, SDF-1 and CXCR4 colocalized in polarized areas, suggesting that they are activated in vivo and that they are under strict genetic control to retain capping function. CONCLUSION: Due to its transient expression, SDF-1 could be considered a future therapeutic target to induce new vessel formation in SSc.

Adult↗
PubMed2006

[Pulmonary arterial hypertension in collagenoses: clinical features, epidemiology, pathogenesis, diagnosis and treatment].

Pulmonary arterial hypertension (PAH) is a severe vasculopathy, which is characterised by progressive narrowing and obliteration of the pulmonary arterioles and increased endothelin-1 levels. The increase of vascular resistance in the lung vessels leads to chronic pressure overload and to right heart failure, if untreated. PAH often occurs in association with rheumatic-inflammatory diseases (e.g., in 15% of patients with systemic sclerosis (SSc), especially in the limited form or in CREST patients) and determines their prognosis: in advanced stages, untreated patients die within a short period. Therefore all SSc patients, particularly the newly diagnosed ones, should be screened for PAH with echocardiography. If PAH is suspected, a right heart catheter should be performed, and if PAH is confirmed, adequate treatment should be initiated. While few years ago lung transplantation was the only option for patients with severe PAH, in recent years enormous progress was seen in drug treatment. Today prostanoids (Ventavis) and the endothelin receptor antagonist bosentan (Tracleer) are available for patients with PAH in WHO/NYHA stage III: they have substantially improved the prognosis of PAH in the last years. Since few months, also the phosphodiesterase inhibitor sildenafil (Revatio) is available. The combination of drugs with different mode of action will likely further improve the prognosis of PAH patients.

Algorithms↗
PubMed2005

Systemic sclerosis and gastric MALT lymphoma.

CASE-REPORT: A 76-year-old woman was admitted for evaluation of esophagitis complicating limited cutaneous systemic sclerosis. Endoscopy showed persistent grade III esophagitis and an erythematous antral lesion found upon biopsy to be a lymphoma of mucosa-associated lymphoid tissue (MALT). Tests were positive for Helicobacter pylori. Moderate mucosal infiltration by endoscopic ultrasonography was the only finding from staging investigations. Six months after treatment to eradicate H. pylori, a repeat endoscopy showed no evidence of the lesion. DISCUSSION: MALT lymphomas are usually confined to the gastric wall. Gastric MALT lymphomas have a well-established association with H. pylori infection. The clinical manifestations are nonspecific. Endoscopy usually shows a focus of erythema or, less often, erosion. The diagnosis rests on histological examination of a biopsy, which shows infiltration by monoclonal cells whose immunophenotype is characteristic of marginal-zone B cells. Eradication of H. pylori is the mainstay of treatment.

Aged↗
PubMed2002

High prevalence of polymorphisms of angiotensin-converting enzyme (I/D) and endothelial nitric oxide synthase (Glu298Asp) in patients with systemic sclerosis.

PURPOSE: Systemic sclerosis is characterized by progressive microvascular occlusion and fibrosis and by an imbalance in the fibrinolytic system. In vivo and in vitro studies suggest that the renin-angiotensin system partly regulates vascular fibrinolytic balance. Angiotensin II increases the production and secretion of plasminogen activator inhibitor-1, while angiotensin-converting enzyme (ACE) contributes to reduced production of tissue plasminogen activator and endothelial nitric oxide synthesis by bradykinin degradation. The aim of our study was to investigate the effects of ACE insertion/deletion (I/D) and endothelial nitric oxide synthase (eNOS) Glu298Asp (G894-->T) and T-786-->C polymorphisms in patients with systemic sclerosis. SUBJECTS AND METHODS: We studied 73 consecutive patients (47 with limited and 26 with diffuse cutaneous systemic sclerosis) and 112 control subjects. ACE I/D and eNOS polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The ACE I/D and the eNOS G894-->T polymorphisms were more common in patients than in controls (for the ACE D allele: odds ratio [OR] = 3.4; 95% confidence interval [CI]: 1.5 to 7.9; P = 0.003; for the eNOS T allele: OR = 1.9; 95% CI: 1.0 to 3.4; P = 0.04). There was no association between the eNOS T-786-->C polymorphism and systemic sclerosis. CONCLUSIONS: Our findings of an increased risk of systemic sclerosis in ACE D and eNOS 894T allele carriers suggest that these polymorphisms may contribute to the pathogenesis of the disease.

Adult↗
PubMed2001

Gastro-intestinal permeability is increased in patients with limited systemic sclerosis.

OBJECTIVE: to evaluate gastro-intestinal (GI) permeability in patients with limited systemic sclerosis (LSS) at baseline and after oral acetylsalicylic acid (ASA). METHODS: 13 patients with LSS and 10 controls were studied. Baseline GI permeability was assessed with orally administered sucrose, mannitol, and lactulose. Gastric lesions and Helicobacter status were investigated by endoscopy. In 5 patients and 6 controls (with normal baseline permeability) the GI permeability response was assessed after oral ASA. RESULTS: compared with controls, gastric (p<0.05) and intestinal (p<0.02) permeability was higher in LSS patients, at baseline. After oral ASA gastric permeability (sucrose) increased in both groups (controls: 186%, LSS: 265%), whereas the lactulose/mannitol ratio raised significantly only in LSS (+31% and +148%; p<0.05 vs controls). CONCLUSIONS: baseline permeability is altered in LSS; the exaggerated response of the small intestine to ASA may represent a genetically determined or a disease-related dysfunction of the mucosal barrier.

Adult↗
PubMed2001

Analysis of leukemia inhibitory factor, type 1 and type 2 cytokine production in patients with eosinophilic fasciitis.

OBJECTIVE: Eosinophilic fasciitis (EF) is a scleroderma-like disease of unknown etiology characterized by skin induration, elevated immune globulins, and peripheral eosinophilia. The hallmarks of the chronic cutaneous involvement in this syndrome are inflammation and fibrosis of the fascia. To determine how the inflammatory process in EF may be regulated, we investigated the spontaneous and mitogen induced [lipopolysaccharide (LPS), phytohemagglutinin (PHA) or both LPS+PHA] syntheses of interleukins (IL)-2, 5 and 10, interferon-gamma (IFN-gamma), and leukemia inhibitory factor (LIF) cytokines by peripheral blood mononuclear cells (PBMC) from 4 patients with active EF and compared them to those of 10 healthy individuals. METHODS: We used a short term whole blood assay and culture supernatants were collected after 24 h to measure the IL-2 and IFN-gamma contents and after 48 h to evaluate IL-5, IL-10, and LIF. Supernatant cytokine concentrations were determined by ELISA. RESULTS: All 4 patients had similar patterns of cytokine secretion. Cytokine production did not differ between patients and controls under basal conditions or when LPS was added to the cultures. In contrast, under PHA or LPS+PHA stimulation, significantly higher amounts of all 5 cytokines were detected in samples from patients compared to those from controls. CONCLUSION: Overall, our data suggest that EF is characterized by an increased capacity of PBMC to produce IL-5 and IL-10, possibly leading to eosinophilia and immune globulin overexpression. In this context, the simultaneous elevations of type 1 cytokines (IL-2 and IFN-gamma) and LIF production by the same cells may be an attempt by the immune system to limit the exacerbation of a type 2 dominant response.

Adult↗
PubMed2006

Impact of pain in health related quality of life of patients with systemic sclerosis.

OBJECTIVES: Systemic sclerosis (SSc) has an heterogenous clinical pattern, with variable organ involvement and degrees of severity. Like in other rheumatic diseases, the self-questionnaires have been used to evaluate SSc globally. The aim of the study is as to evaluate the quality of life (QoL) in patients with either diffuse or limited SSc, and to examine the impact of pain on the QoL scores. METHODS: Patients with SSc, either diffuse or limited SSc, were included in a cross-sectional study. The QoL was evaluated with the short-form 36 (SF-36) and the functional repercussion with the SSc-modified Health Assessment Questionnaire (S-HAQ). RESULTS: A total of 89 patients (67 with diffuse and 22 with limited SSc) were included. The SF-36 score values were lower in SSc patients than those reported in the general population. The physical component scores (PCS) of the SF-36 was significantly worse in diffuse compared with limited SSc (P < 0.05). The PCS was significantly negatively related to the number of clinical manifestations (ANOVA, P < 0.0001). The mental component score (MCS) was not influenced by the type of SSc or the number of clinical manifestations presented by the patient. The QoL of SSc patients was highly correlated with pain (R = 0.69) and disability (R = 0.70). Interestingly, the QoL of SSc patients was only slightly correlated with cutaneous (R = 0.42) and pulmonary involvement (R = 0.57). CONCLUSION: The QoL of patients with SSc is strongly influenced by the type of SSc, the burden of clinical manifestations, the functional disability and by the pain, whatever its cause. The treatment of pain should be considered as priority to improve the QoL of SSc patients.

Adolescent↗
PubMed2002

Increased microchimeric CD4+ T lymphocytes in peripheral blood from women with systemic sclerosis.

Recent studies have demonstrated the presence of microchimeric cells in peripheral blood and skin lesions from patients with systemic sclerosis (SSc). In a previous study we found that some peripheral blood CD3+ cells from female patients with SSc contained male DNA. Here, peripheral blood samples from 47 patients with SSc (30 with diffuse cutaneous SSc and 17 with limited cutaneous SSc) and 22 healthy controls were sorted for CD4+ and CD8+ T cells. Both positively and negatively selected populations were analyzed for male DNA by quantitative PCR. Analysis of Y chromosome sequences in the sorted cells demonstrated the presence of microchimerism in 82.9% of SSc patients compared to 63.6% of controls. The numbers of CD4+ and CD8+ T cells were found to be significantly higher in the SSc patients than in controls. Furthermore, patients with dcSSc were observed to have significantly more CD4+ microchimeric T cells than the controls. In the CD8+ T-cell population, there was a trend toward more microchimeric cells in the patients but this did not reach significance. These results support the hypothesis that microchimeric CD4+ T cells may be involved in the pathogenesis of SSc.

CD4-Positive T-Lymphocytes↗
PubMed1991

Bilateral bronchoalveolar lavage in progressive systemic sclerosis: interlobar variability, lymphocyte subpopulations, and functional correlations.

Bilateral bronchoalveolar lavage (BAL) was carried out in right middle and left upper lobes of 22 nonsmoking females suffering from progressive systemic sclerosis in order to assess interlobar differences and functional correlation of the BAL composition. The patients' age ranged from 20 to 66 years, and the mean disease duration was 10.4 years. The most frequent finding was a mild BAL lymphocytosis (right in 11 of 22 patients; left in 8 of 22), but eosinophilic (right in 11 of 22; left in 5 of 22 patients) and neutrophilic (right in 9 of 22 patients; left in 1 of 22) alveolitis was recognized as well. Differential counts suggestive of alveolitis limited to one of the lavaged lobes were demonstrated in about one fourth of the cases. Including increased cellularity among the criteria of pathological BAL fluid composition, 14% of the subjects showed bilateral BAL results within the normal range. OKT8-positive lymphocytes were significantly increased in 3 patients, but the mean values were not. Total lung capacity, vital capacity, and forced expiratory volume in 1 s correlated inversely with BAL neutrophil (p less than 0.05) and granulocytic (p less than 0.01) differential counts; the strongest, positive correlation was demonstrated regarding the lymphocyte/granulocyte ratios (p less than 0.0005). In conclusion, several patterns of alveolitis as well as a bilaterally normal BAL composition were found in our series; moreover, even if inhomogeneous alveolitis did occur, a single lavage performed in the right middle lobe correctly detected or excluded the presence of an alveolitis in 95% of our patients.

Adult↗
PubMed2001

Treatment of Raynaud's phenomenon with intravenous prostaglandin E1alpha-cyclodextrin improves endothelial cell injury in systemic sclerosis.

OBJECTIVE: To evaluate the efficacy and safety of prostaglandin (PG) E1alpha-cyclodextrin for Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc) and its effect on variables of immune activation and endothelial injury in SSc such as tumor necrosis factor-alpha (TNF-alpha), soluble interleukin 2 receptor (sIL-2R), circulating intercellular adhesion molecule-1 (cICAM-1), von Willebrand factor (vWF), and tissue-type plasminogen activator (t-PA). METHODS: We studied 36 women with SSc, 24 of them given three 60 microg intravenous PGE1alpha-cyclodextrin infusions on 5 consecutive days at 6 week intervals during the winter. RP symptoms and healing of digital lesions were evaluated. Twenty age matched healthy women were the controls. TNF-alpha, sIL-2R, cICAM-1, vWF, and t-PA were measured after the first and last infusion of PGEE1alpha-cyclodextrin and correlated with clinical features. RESULTS: RP symptoms improved in 87% of the patients. The benefit of each 5 day cycle lasted 4 or more weeks in 75%. PGE1alpha-cyclodextrin reduced the daily frequency of RP symptoms by 20% (p < 0.05), 41% (p < 0.005), and 53% (p < 0.0005) from baseline after the 1st, 2nd, and 3rd infusions, respectively. The severity of the attacks was reduced to a limited degree. In 12 of the 14 patients with digital lesions, these healed completely. Ten patients had mild side effects during treatment (headache, increased intestinal motility, flushing). TNF-alpha, sIL-2R, cICAM-1, vWF, and t-PA plasma concentrations were significantly higher in patients with SSc than controls (p < 0.05, p < 0.001). TNF-alpha, sIL-2R, and cICAM-1 were higher in diffuse SSc and patients with lung involvement. The plasma levels of cICAM-1 and t-PA were significantly reduced after the 1st infusion of PGE1alpha-cyclodextrin (both p < 0.005) and further reduced after the last (p < 0.0005 and p < 0.005). CONCLUSION: PGE1alpha-cyclodextrin reduces RP symptoms and plasma levels of the markers of endothelial injury in SSc, suggesting that an improvement of endothelial dysfunction contributes to its prolonged therapeutic effect.

Adult↗
PubMed2004

Serum concentrations of soluble P-selectin glycoprotein ligand-1 are increased in patients with systemic sclerosis: association with lower frequency of pulmonary fibrosis.

OBJECTIVE: To determine serum concentrations of soluble P-selectin glycoprotein ligand-1 (sPSGL-1) and its clinical associations in patients with systemic sclerosis. METHODS: Serum sPSGL-1 concentrations from 65 patients with systemic sclerosis were examined by enzyme linked immunosorbent assay. In a retrospective longitudinal study, 177 sera from 35 patients with systemic sclerosis were analysed (follow up 0.3 to 6.3 years) RESULTS: Serum sPSGL-1 was raised in patients with limited cutaneous systemic sclerosis (lSSc) (n = 34) and diffuse cutaneous systemic sclerosis (dSSc) (n = 31) compared with healthy controls (n = 22) and patients with systemic lupus erythematosus (n = 20) or dermatomyositis (n = 20). Patients with systemic sclerosis who had raised sPSGL-1 concentrations less often had pulmonary fibrosis and decreased vital capacity (%VC) than those with normal sPSGL-1 levels. sPSGL-1 concentrations were positively correlated with %VC in patients with systemic sclerosis. In the longitudinal study, patients with systemic sclerosis but without pulmonary fibrosis had consistently increased sPSGL-1 concentrations in the early phase, while those with pulmonary fibrosis had decreased sPSGL-1 throughout the follow up period. CONCLUSIONS: A raised serum sPSGL-1 is associated with a lower frequency and severity of pulmonary fibrosis in systemic sclerosis. sPSGL-1 could be a protective factor against the development of pulmonary fibrosis in this disease and as such would be a possible therapeutic target.

Adolescent↗
PubMed1995

T cell proliferative response induced by DNA topoisomerase I in patients with systemic sclerosis and healthy donors.

The in vitro T cell proliferative response to DNA topoisomerase I (topo I) was examined in 26 systemic sclerosis (SSc) patients with anti-topo I antibody, 10 SSc patients without anti-topo I antibody, and 21 healthy donors. Using recombinant fusion proteins encompassing the entire human topo I amino acid sequence, a topo I-specific proliferative response was detected in PBMC cultures from 25 (96%) anti-topo I-positive SSc patients, 4 (40%) anti-topo I-negative SSc patients, and 13 (62%) healthy donors. Molecular typing at MHC class II loci revealed that all SSc patients and healthy donors having either DRB1*1501,2 (DR15), DRB1*1101,3,4 (DR11), or DRB1*07 (DR7) were responders. Characterization of the topo I-induced T cell proliferative response showed that (a) the responding cells were CD4+ T cells; (b) antigen-presenting cells were necessary for the response; (c) the response was restricted by HLA-DR, and to a lesser extent by HLA-DQ; and (d) the estimated frequency of the responding T cells determined by limiting dilution analysis was 1/9,277-1/24,853. PBMC cultures from anti-topo I-positive SSc patients showed a high T cell proliferative response after only 3 d of culture with topo I. Anti-topo I-negative SSc patients and healthy donors had no proliferative response after 3 d, but did respond after 7 d of culture. T cell proliferative responses to six truncated topo I fragments tested individually showed different patterns of T cell proliferation that were dependent upon the responder's HLA-DR alleles. These results indicate that T cells reactive with topo I are components of the normal T cell repertoire, and that the topo I-specific T cell proliferative response is not associated with the presence or absence of SSc or anti-topo I antibody, but is restricted by MHC class II alleles.

Adult↗