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Results for “Systemic sclerosis”

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At least 19 recordsLinked to original sources

PubMed2024

Adeno-Associated Virus Type 5 Infection via PDGFRα Is Associated With Interstitial Lung Disease in Systemic Sclerosis and Generates Composite Peptides and Epitopes Recognized by the Agonistic Immunoglobulins Present in Patients With Systemic Sclerosis.

OBJECTIVE: The etiopathogenesis of systemic sclerosis (SSc) is unknown. Platelet-derived growth factor receptors (PDGFRs) are overexpressed in patients with SSc. Because PDGFRα is targeted by the adeno-associated virus type 5 (AAV5), we investigated whether AAV5 forms a complex with PDGFRα exposing epitopes that may induce the immune responses to the virus-PDGFRα complex. METHODS: The binding of monomeric human PDGFRα to the AAV5 capsid was analyzed by in silico molecular docking, surface plasmon resonance (SPR), and genome editing of the PDGFRα locus. AAV5 was detected in SSc lungs by in situ hybridization, immunohistochemistry, confocal microscopy, and molecular analysis of bronchoalveolar lavage (BAL) fluid. Immune responses to AAV5 and PDGFRα were evaluated by SPR using SSc monoclonal anti-PDGFRα antibodies and immunoaffinity-purified anti-PDGFRα antibodies from sera of patients with SSc. RESULTS: AAV5 was detected in the BAL fluid of 41 of 66 patients with SSc with interstitial lung disease (62.1%) and in 17 of 66 controls (25.75%) (P < 0.001). In SSc lungs, AAV5 localized in type II pneumocytes and in interstitial cells. A molecular complex formed of spatially contiguous epitopes of the AAV5 capsid and of PDGFRα was identified and characterized. In silico molecular docking analysis and binding to the agonistic anti-PDGFRα antibodies identified spatially contiguous epitopes derived from PDGFRα and AAV5 that interacted with SSc agonistic antibodies to PDGFRα. These peptides were also able to bind total IgG isolated from patients with SSc, not from healthy controls. CONCLUSION: These data link AVV5 with the immune reactivity to endogenous antigens in SSc and provide a novel element in the pathogenesis of SSc.

Humans↗

PubMed1979

Trigeminal neuropathy as the presenting symptom of systemic sclerosis.

Three cases of systemic sclerosis in which trigeminal neuropathy was the presenting symptom are described. All 3 patients had progressive diseases and 2 died from its complications. In each case extensive neurological investigation was undertaken before the disease was recognized and it is suggested that earlier recognition of the systemic sclerosis might obviate the need for this. Trigeminal neuropathy in systemic sclerosis was associated with a poor prognosis in 2 of the patients.

Adult↗

PubMedDate not supplied

Gastrointestinal systemic sclerosis in serologic mixed connective tissue disease.

Mixed connective tissue disease is a clinical entity defined by overlapping features of progressive systemic sclerosis, systemic lupus erythematosus, polymyositis, rheumatoid arthritis, and distinct serologic findings. Esophageal dilatation and dysmotility have been the only gastrointestinal manifestations reported. Three patients with serologic findings of mixed connective tissue disease and extensive gastrointestinal involvement compatible with the changes found in progressive systemic sclerosis are presented. Gastrointestinal manifestations of progressive systemic sclerosis are reviewed and were found to be indistinguishable from the findings in these patients.

Adult↗

PubMed1977

Penicillamine therapy in systemic sclerosis.

Twenty-two patients with progressive systemic sclerosis were treated with D-penicillamine in doses ranging up to 1250 mg/day for periods varying between a few months and four years. Side-effects occurred in 7 patients, necessitating drug withdrawal in 2. Cutaneous benefit occurred in 15 patients, but owing to side-effects from the drug, relapses, and development, persistence or advancement of visceral complications, an overall good result only occurred in 5. Seven patients showed improvements in joint function, but only 3 were regarded as having an overall good result. Peripheral vascular disease and visceral involvement seemed not to be influenced by D-penicillamine and sometimes appeared or advanced during treatment. Six patients died from visceral manifestations of systemic sclerosis and one from another cause. D-penicillamine is of limited value for the cutaneous features of progressive systemic sclerosis, but probably of no value for the vascular and visceral manifestations of the disease.

Adult↗

PubMed1975

Immunohistochemical findings in the renal vascular lesions of progressive systemic sclerosis.

Four selected patients with progressive systemic sclerosis showed deposition of immunoglobulins and complement in diseased renal arteries and arterioles. Although three patients had hypertension, in two of these malignant, the third patient did not have hypertension over a four year period. These findings suggest that immune complexes may be involved in the pathogenesis of some cases of progressive systemic sclerosis, the primary target being the vascular system.

Adult↗

PubMed2026

Imaging techniques for assessing the hand in systemic sclerosis: a systematic review.

BACKGROUND: Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease frequently associated with hand involvement, leading to significant functional impairment. Imaging techniques provide unique opportunities to visualize and quantify structural and functional abnormalities of the hand, supporting diagnosis, monitoring, and treatment evaluation. This systematic review summarizes the imaging techniques used in SSc. METHODS: A systematic search of PubMed and Embase was conducted. Eligible studies included original research articles in English that applied or evaluated imaging techniques of the hands in SSc, published after 2000. Ultrasound and nailfold capillaroscopy were excluded, given their established use. Screening was performed independently by two authors. Findings were synthesized by clinical manifestations, study quality was assessed using the QUADAS-2 tool. RESULTS: Sixty-one studies met the inclusion criteria. In total, 25 distinct imaging techniques were identified, enabling assessment of various hand structures, including vascular involvement, inflammation, fibrosis, calcifications, erosions, and bone marrow edema. Vascular imaging was most extensively studied, particularly in the context of Raynaud's phenomenon and digital ischemia, with multiple techniques demonstrating impaired perfusion and altered thermoregulatory responses. MRI consistently detected subclinical inflammatory and erosive changes of joints and soft tissues,. CT-based techniques provided detailed assessment of calcinosis cutis, while optical and photoacoustic methods showed promise for quantifying skin fibrosis. CONCLUSION: Imaging techniques provide valuable, complementary insights into hand involvement in SSc, often revealing subclinical disease. Despite promising results, limited standardization and longitudinal validation currently restrict clinical implementation. Future studies should focus on harmonizing protocols and validating against clinically meaningful outcomes.

Humans↗

PubMed2026

Vitamin D Supplementation Modulates Base Excision Repair (BER) Machinery in Systemic Sclerosis: A Prospective Longitudinal Study.

Systemic sclerosis (SSc) is a chronic, autoimmune, fibrotic disorder involving immune dysregulation, vascular abnormalities and progressive fibrosis. Although oxidative stress and defective DNA repair have been implicated in its pathogenesis, the impact of vitamin D on DNA repair pathways remains unclear. This study aimed to investigate the expression of DNA repair enzymes in SSc, explore their relationship with vitamin D status and assess the effects of vitamin D supplementation on the transcriptional expression of these enzymes. Peripheral blood samples were collected from 52 female patients with SSc and 31 age-matched healthy controls (HCs). Gene expression levels of base excision repair (BER) enzymes (APE1 and OGG1) and nucleotide excision repair (NER) enzymes (XPA and XPC) were analyzed. Serum vitamin D levels were measured and correlated with disease activity scores. In a prospective arm of the study, patients received six months of vitamin D supplementation and their DNA repair capacity was evaluated pre- and post-intervention. Baseline expression of APE1 and OGG1 was significantly lower in SSc patients than in HCs, whereas expression of the NER genes remained unchanged, indicating selective impairment of the BER pathway. Vitamin D deficiency was prevalent in SSc and inversely correlated with disease severity. Supplementation significantly increased serum vitamin D levels and up-regulated APE1 and OGG1 expression; while NER genes remained unaffected. These findings are consistent with evidence of elevated oxidative DNA lesions in SSc and support a mechanistic link between BER activity and the repair of oxidative DNA damage. SSc patients exhibit reduced transcription of BER-specific enzymes associated with vitamin D deficiency andrestoration of vitamin D levels partially rescues BER enzyme expression. These findingshighlight a potentially modifiable axis linking micronutrient status, genomic stability and disease activity and provide a rationale for investigating vitamin D optimization as an adjunctive strategy to enhance DNA repair and potentially attenuate inflammatory and fibrotic processes in SSc.

Humans↗

PubMed1979

Rapid onset of lung involvement in progressive systemic sclerosis.

Lung involvement in progressive systemic sclerosis (PSS) is common but usually is of chronic onset late in the course. Skin changes usually antedate pulmonary findings. Presentation of PSS with rapid development of pulmonary interstitial fibrosis, without skin changes, has not previously been described. Such a case is discussed here and the radiologic and pathologic findings and course of pulmonary PSS are reviewed.

Humans↗

PubMed1977

Immunochemical study on serum proteins in systemic sclerosis.

Forty one patients with systemic sclerosis were studied after separation into three groups according to Barnett's classification. A multi-dimensional statistical analysis eight serum proteins revealed a difference between control patients and patients with type I and type II scleroderma. Type I scleroderma was characterised by a rise in alpha 2 macroglobulin and in the C4 fraction of complement, whilst in type II scleroderma all the proteins studied were raised, with the exception of CO complement, which was normal, and transferrin which was markedly decreased.

Blood Proteins↗

PubMed1979

Idiopathic calcific pancreatitis, CRST syndrome and progressive systemic sclerosis.

A 43-year old man with CRST syndrome (calcinosis, Raynaud's phenomenon, sclerodactyly and telangiectasia) and progressive systemic sclerosis presented with a four-year history of relapsing abdominal pain, the result of chronic pancreatitis, not associated with alcoholism, biliary disease, or any of the known causes of pancreatitis. He had a good response to retrograde pancreatic duct drainage but exhibited management problems and complications that may be peculiar to the systemic sclerosis patient with pancreatitis. A cause and effect relationship between progressive systemic sclerosis and pancreatic disease is not proven but we believe there is evidence to suggest such a relationship.

Adult↗

PubMed1979

Osteolysis of the ribs in progressive systemic sclerosis.

In a patient with progressive systemic sclerosis (PSS), osteolysis of the posterior portion of the rib cage developed in an insidious fashion, without symptoms or preceding trauma. Six previous examples of rib resorption in PSS are reviewed. The destructive mechanism is unknown but may be related to endarteritis and ischemia.

Bone Resorption↗

PubMed1978

The association of HLA-B8 with visceral disease in systemic sclerosis.

Seventy-one patients with systemic sclerosis (SS) were typed for twenty-seven HLA alleles of the A and B loci, and the findings were related to both the extent of visceral disease and tests of cellular immune competence in a subgroup of fifty-two of these patients. Nineteen pa;ients with widespread visceral involvement and more rapidly progressive disease had an increased frequency of HLA-B8 (relative risk = 4.14; P less than 0.05) when compared to thirty-three less severely affected patients and 3000 controls. Patients with severe and progressive disease also had defective cell-mediated immunity with reductions in both the numbers of circulating thymus-dependent (T) lymphocytes and in the lymphocyte transformation response to phytohaemagglutinin. These findings suggest that a genetic factor, such as an abnormal immune response gene, may be involved in the progression of the disease.

Adult↗

PubMed2026

Transpulmonary proteomic gradient analysis in women with pulmonary arterial hypertension associated with systemic sclerosis.

This study investigated proteomic alterations in the pulmonary circulation of patients with pulmonary arterial hypertension associated with systemic sclerosis (PAH-SSc) by analyzing the transpulmonary protein gradient and comparing the proteomic profiles with systemic sclerosis (SSc) without PAH. Twenty women were included (10 PAH-SSc, 64.6 ± 10.8 years; 10 SSc, 62.8 ± 11.5 years). The transpulmonary gradient was defined as the difference in biomarker concentrations between wedge-position and pulmonary artery blood samples. Peptides were analysed using liquid chromatography-mass spectrometry, and differentially abundant proteins were identified with Proteome Discoverer. Protein-protein interaction networks were generated with STRING and visualized in Cytoscape. A total of 270 proteins were detected, with no significant transpulmonary gradient alterations. However, patients with PAH-SSc showed distinct proteomic profiles compared to SSc. Multivariate analysis identified 48 differentially abundant proteins in pulmonary artery plasma, with 15 overrepresented and 33 downregulated in PAH-SSc. Among these, the downregulation of transforming growth factor-beta-induced protein ig-h3 (TGFβI/ig-h3) points to a potential involvement of the TGF-β-related extracellular matrix remodelling pathway in PAH-SSc. However, further validation in larger and independent cohorts is required before its relevance as a biomarker or therapeutic target can be established. In conclusion, while no transpulmonary proteomic gradient was observed, the proteomic profiles of PAH-SSc and SSc were different. The profile in PAH-SSc was characterized by differences in immune response, lipid metabolism, and hemostatic proteins. SIGNIFICANCE: This study offers the first proteomic characterization of the transpulmonary gradient in PAH-SSc and SSc. Although no differences in the gradient were found, the pulmonary artery plasma proteome of PAH-SSc patients showed a distinct pattern compared to SSc. Several proteins associated with immune function, haemostasis, and cellular processes were altered, which may indicate specific pathophysiological features of PAH-SSc or suggest how lung dysfunction develops in SSc. Targeting dysregulated proteins like TGFβI/ig-h3 or addressing immune-coagulation imbalances may support future research studies. Overall, these findings refine the molecular profile of PAH-SSc and provide a basis for future large-scale studies aimed at clarifying disease mechanisms and identifying clinically relevant molecular signatures.

Humans↗

PubMed1978

Total osteolysis of the mandibular condyle in progressive systemic sclerosis.

This report calls attention to the complete resorption of the mandibular condyle in progressive systemic sclerosis (scleroderma), a previously unreported finding. This was associated with osteolysis of the ipsilateral coronoid process, both mandibular angles, and autoamputation of the fingertips. The Panorex provides a simple, effective method for studying the mandible in systemic sclerosis. Similar mandibular osteolysis with vinyl chloride exposure is noted.

Bone Diseases↗

PubMed1979

Systemic sclerosis with subcutaneous nodules.

A case of systemic sclerosis with subcutaneous nodules is described. The nodules consisted of fibrinoid degeneration with surrounding fibrosis, but lacked the typical histiocytic palisade of the rheumatoid nodule. The patient had neither coexistent rheumatoid arthritis nor circulating rheumatoid factor.

Female↗

PubMed1979

Joint involvement in systemic sclerosis.

Eleven out of 24 patients with systemic sclerosis had radiological features of inflammatory polyarthritis. Juxta-articular osteoporosis was present in 9 patients, erosions in 5 and loss of joint space in 6 patients. Only one patient had a positive rheumatoid factor. Titres of rheumatoid factor, anti-nuclear factor, and plasma viscosity were comparable in patients with and without radiological abnormalities. Measurements of grip strength and finger-palm flexion also were similar in the two groups. However, in individual cases joint or tendon sheath disease was associated with loss of function.

Adult↗

PubMed1979

Cardiac involvement in progressive systemic sclerosis.

The case of a patient with progressive systemic sclerosis (PSS) who developed electro- and vectorcardiographic patterns of myocardial necrosis without clinical picture of myocardial infarction is reported. The coronarography showed no obstruction of coronary arteries and cineventriculography a hypodynamic enlarged left ventricle. The analysis of electrocardiograms from 43 other patients affected with PSS revealed myocardial necrosis in 5 of them. The clinical syndrome of myocardial infarction was absent in all these cases. Moreover, the hemodynamic investigation in 13 cases allowed to record a dip-plateau figure on the right ventricle pressure curve in 3 of them. In PSS, the electrocardiographic aspects of "necrosis" as well as hemodynamic restrictive findings or ventricular enlargement at ventriculography could indicate myocardial disease.

Adult↗

PubMed1979

A syndrome resembling progressive systemic sclerosis after bone marrow transplantation. A model for scleroderma?

Six long term survivors of bone marrow transplants developed a syndrome similar to progressive systemic sclerosis (PSS). Cutaneous involvement (6/6), pulmonary disease (6/6), musculoskeletal involvement (4/6), keratoconjunctivitis/positive Schirmer's test (4/6), Raynaud's phenomenon (2/6), and renal and cardiac disease (1/6) were similar to findings in PSS patients. T and B lymphocyte counts and functions were also similar. This PSS-like syndrome, including visceral involvement, after bone marrow transplantation lends support to an immunologic hypothesis of the pathogenesis of progressive systemic sclerosis.

Antigen-Antibody Complex↗