Morphoea lesions are associated with aberrant expression of membrane cofactor protein and decay accelerating factor in vascular endothelium

Venneker, G.T.; Das, Pranab K.; Naafs, Bernard; Tigges, A. J.; Bos, Jan D.; Asghar, Syed S.

doi:10.1111/j.1365-2133.1994.tb08498.x

Cited by 16 publications

(3 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In patients with systemic sclerosis (Scleroderma or SSc), DAF was found to be decreased or undetectable in endothelium of both lesional skin and nonlesional skin compared to controls [37]. Interestingly this result was later reproduced in morphea lesions, suggesting a link between systemic autoimmune disease skin lesions and low DAF levels, although low DAF levels are also seen in psoriatic skin lesions [38, 39]. These studies, however, are limited by their power and lack of supporting follow-up studies.…”

Section: Daf In Human Autoimmune Diseasesmentioning

confidence: 99%

The Role of Decay Accelerating Factor in Environmentally Induced and Idiopathic Systemic Autoimmune Disease

Toomey

Cauvi

Pollard

2014

Autoimmune Diseases

View full text Add to dashboard Cite

Decay accelerating factor (DAF) plays a complex role in the immune system through complement-dependent and -independent regulation of innate and adaptive immunity. Over the past five years there has been accumulating evidence for a significant role of DAF in negatively regulating adaptive T-cell responses and autoimmunity in both humans and experimental models. This review discusses the relationship between DAF and the complement system and highlights major advances in our understanding of the biology of DAF in human disease, particularly systemic lupus erythematosus. The role of DAF in regulation of idiopathic and environmentally induced systemic autoimmunity is discussed including studies showing that reduction or absence of DAF is associated with autoimmunity. In contrast, DAF-mediated T cell activation leads to cytokine expression consistent with T regulatory cells. This is supported by studies showing that interaction between DAF and its molecular partner, CD97, modifies expression of autoimmunity promoting cytokines. These observations are used to develop a hypothetical model to explain how DAF expression may impact T cell differentiation via interaction with CD97 leading to T regulatory cells, increased production of IL-10, and immune tolerance.

show abstract

Section: Daf In Human Autoimmune Diseasesmentioning

confidence: 99%

The Role of Decay Accelerating Factor in Environmentally Induced and Idiopathic Systemic Autoimmune Disease

Toomey

Cauvi

Pollard

2014

Autoimmune Diseases

View full text Add to dashboard Cite

show abstract

“…Moreover, they compared these samples with samples of HC and patients with other autoimmune diseases. MCP and DAF expression were altered only in SSc patients, suggesting defective endothelial protection, due to a reduced expression of complement regulatory proteins [29,30]. These results were confirmed by Scambi et al which detected the abnormal deposition of the membrane attack complex (MAC) on the endothelium in skin biopsies of SSc patients and reduced MCP expression on the vascular endothelial surface of patients.…”

Section: Discussionmentioning

confidence: 76%

Increased Complement Activation in Systemic Sclerosis Patients with Skin and Lung Fibrosis

Pellicano

Miglionico

Romaggioli

et al. 2022

JPM

View full text Add to dashboard Cite

Introduction: The involvement of complement system in the phenotypic expression of systemic sclerosis (SSc) is a debated topic. We aimed to assay complement fractions in SSc patients and to correlate their levels with the clinical course of disease. Key points: 1. CH50 is increased in SSc patients compared to HC; 2. Serum C2 levels are increased in SSc patients compared to HC; 3. CH50 may represent a biomarker of skin and lung fibrosis severity in SSc patients. Method: Complement hemolysis 50% (CH50), C2, C3 and C4 levels have been assessed in 85 SSc patients and 47 healthy controls (HC). Results: SSc patients displayed a statistically significant higher value of CH50 [76.3 U/mL (IQR 65.8–89.4 U/mL) vs. 29.6 U/mL (IQR 24.7–34 U/mL); p < 0.0001] and of C2 [26.1 mg/L (IQR 24.1–32.1 mg/L) vs. 22.7 mg/L (IQR 20.6–24.4 mg/L); p < 0.0001] if compared to HC. Patients with diffuse cutaneous SSc (dcSSc) had higher levels of CH50 than patients with limited cutaneous SSc (lcSSc) [83.6 U/mL (IQR 72.3–102.7 U/mL) vs. 71.3 U/mL (IQR 63.7–83.6 U/mL); p = 0.003]. SSc patients with interstitial lung disease (ILD) had higher CH50 levels if compared to SSc patients without ILD [79.6 U/mL (IQR 68.3–97.4 U/mL) vs. 69.7 U/mL (54.6–85.7 U/mL); p = 0.042]. A positive linear correlation existed between CH50 and the modified Rodnan Skin Score (mRSS) (r = 0.285, p = 0.008) and disease severity scale (DSS) (r = 0.285, p = 0.005); a negative linear correlation was demonstrated between CH50 and the diffusing capacity of carbon monoxide (DLco) (r = −0.252, p = 0.012). In multiple linear regression analysis, only DSS was significant (p = 0.01, beta coefficient 2.446). Conclusions: Our results show an increment of CH50 and serum C2 levels in SSc patients in comparison to HC; we retain that CH50 may represent a biomarker of disease severity and of skin and lung fibrosis in these patients.

show abstract

“…The group of membrane-bound complement regulators include the membrane cofactor protein (MCP or CD46), which is a cofactor of FI in the proteolytic inactivation of C3b and C4b, and the decay accelerating factor (DAF or CD55), which accelerates the breakdown of C3- and C5-convertases [ 24 – 26 ]. Recently, Venneker et al demonstrated an impaired expression of MCP and DAF in endothelium of the lesional and non-lesional skin of SSc patients and in the skin of patients with morphea, in comparison to healthy controls and subjects affected by other autoimmune diseases, suggesting that a defective endothelial protection might be mediated by reduced expression of the complement regulatory proteins [ 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

The Local Complement Activation on Vascular Bed of Patients with Systemic Sclerosis: A Hypothesis-Generating Study

et al. 2015

View full text Add to dashboard Cite

ObjectiveThe role of complement system in the pathogenesis of systemic sclerosis (SSc) has been debated during the last decade but an evident implication in this disease has never been found. We carried out an explorative study on SSc patients to evaluate the expression of soluble and local C5b-9 complement complex and its relation with a complement regulator, the Membrane Cofactor Protein (MCP, CD46) on skin vascular bed as target distinctive of SSc disease. We also analyzed two polymorphic variants in the complement activation gene cluster involving the MCP region.MethodsC5b-9 plasma levels of SSc patients and healthy subjects were analyzed by ELISA assay. Archival skin biopsies of SSc patients and controls were subjected to immunofluorescence analysis to detect C5b-9 and MCP on vascular endothelial cells. The expression of MCP was validated by immunoblot analysis with specific antibody. Polymorphic variants in the MCP gene promoter were tested by a quantitative PCR technique-based allelic discrimination method.ResultsEven though circulating levels of C5b-9 did not differ between SSc and controls, C5b-9 deposition was detected in skin biopsies of SSc patients but not in healthy subjects. MCP was significantly lower in skin vessels of SSc patients than in healthy controls and was associated with the over-expression of two polymorphic variants in the MCP gene promoter, which has been related to more aggressive phenotypes in other immune-mediated diseases.ConclusionsOur results firsty document the local complement activation with an abnormal expression of MCP in skin vessels of SSc patients, suggesting that a subset of SSc patients might be exposed to more severe organ complications and clinical evolution due to abnormal local complement activation.

show abstract

Morphoea lesions are associated with aberrant expression of membrane cofactor protein and decay accelerating factor in vascular endothelium

Cited by 16 publications

References 25 publications

The Role of Decay Accelerating Factor in Environmentally Induced and Idiopathic Systemic Autoimmune Disease

The Role of Decay Accelerating Factor in Environmentally Induced and Idiopathic Systemic Autoimmune Disease

Increased Complement Activation in Systemic Sclerosis Patients with Skin and Lung Fibrosis

The Local Complement Activation on Vascular Bed of Patients with Systemic Sclerosis: A Hypothesis-Generating Study

Contact Info

Product

Resources

About