Elevated levels of soluble CD40 ligand (sCD40L) in serum of patients with systemic autoimmune diseases

Goules, Andreas V.; Tzioufas, Athanasios G.; Manousakis, M.; Kirou, Kyriakos A.; Crow, Mary K.; Routsias, John G.

doi:10.1016/j.jaut.2006.02.002

Cited by 127 publications

(88 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, CD40 ligation on dendritic cells leads these cells to maturation to express an antigen-presenting phenotype. CD40L has also been found to be expressed on a variety of other cell types such as platelets, B cells, mast cells, basophils and natural killer cells in many diseases [1], and CD40-CD40L interaction is involved in many autoimmune diseases, such as systemic lupus erythematosus [8], rheumatoid arthritis [9], systemic sclerosis [10], primary Sjögren’s syndrome [11], multiple sclerosis [12], inflammatory bowel diseases [13], chronic urticaria [14], and in allograft rejection [15]. Collectively, the disruption of the CD40-CD40L pathway is critically related to the manifestation of autoimmune diseases and has been considered as a promising therapeutic target.…”

Section: Introductionmentioning

confidence: 99%

Increased Serum Levels of Circulating CD40 Ligand in Patients with Bullous Pemphigoid: Preliminary Results

Watanabe

Ishiura²,

Nakashima³

et al. 2007

Dermatology

View full text Add to dashboard Cite

Background: Autoimmune bullous diseases are characterized by autoantibodies against specific adhesion molecules of the skin and/or mucous membrane. While these autoantibodies are known to play a primary role in the disease manifestation, it remains unknown how disease-specific autoreactive B cells and autoantibodies are induced. Recent studies have indicated the importance of the CD40 and CD40 ligand (CD40L) receptor-ligand pair in the immunopathogenesis of autoimmune diseases. CD40L circulates in soluble form, and some reports suggest that serum soluble CD40L (sCD40L) levels are increased in various autoimmune diseases. Objectives: To determine serum sCD40L levels in patients with pemphigus vulgaris (PV) and bullous pemphigoid (BP), and to determine their correlation with clinical findings and laboratory findings. Patients and Methods: Sera from 10 PV patients, 35 BP patients and 12 normal controls were subjected to ELISA assays to measure serum levels of sCD40L, anti-desmoglein-3 antibody and anti-BP180 antibody. Results and Conclusions: Circulating sCD40L levels were significantly elevated in BP patients, but not in PV patients. Serum sCD40L levels increased in the early stage of disease onset and recurrence in BP patients. In conclusion, circulating sCD40L levels may be a useful marker for early activation of autoimmune diathesis and, furthermore, an effective therapeutic target in patients with BP.

show abstract

Section: Introductionmentioning

confidence: 99%

Increased Serum Levels of Circulating CD40 Ligand in Patients with Bullous Pemphigoid: Preliminary Results

Watanabe

Ishiura²,

Nakashima³

et al. 2007

Dermatology

View full text Add to dashboard Cite

show abstract

“…Soluble plasma CD40 ligand is elevated in diseases with strong female prevalence: Hashimoto thyroiditis (95% female),40 systemic lupus erythematosus (88% female),41 and Sjögren syndrome (92% female) 41. ITGB1BP2 (melusin) is also an X‐linked gene and a known protective factor in cardiac injury 42.…”

Section: Discussionmentioning

confidence: 99%

Thymosin Beta‐4 Is Elevated in Women With Heart Failure With Preserved Ejection Fraction

Drum

Tan

Chan

et al. 2017

JAHA

View full text Add to dashboard Cite

BackgroundThymosin beta‐4 (TB4) is an X‐linked gene product with cardioprotective properties. Little is known about plasma concentration of TB4 in heart failure (HF), and its relationship with other cardiovascular biomarkers. We sought to evaluate circulating TB4 in HF patients with preserved (HFpEF) or reduced (HFrEF) ejection fraction compared to non‐HF controls.Methods and Results TB4 was measured using a liquid chromatography and mass spectrometry assay in age‐ and sex‐matched HFpEF (n=219), HFrEF (n=219) patients, and controls (n=219) from a prospective nationwide study. Additionally, a 92‐marker multiplex proximity extension assay was measured to identify biomarker covariates. Compared with controls, plasma TB4 was elevated in HFpEF (985 [421–1723] ng/mL versus 1401 [720–2379] ng/mL, P<0.001), but not in HFrEF (1106 [556–1955] ng/mL, P=0.642). Stratifying by sex, only women (1623 [1040–2625] ng/mL versus 942 [386–1891] ng/mL, P<0.001), but not men (1238.5 [586–1967] ng/mL versus 1004 [451–1538] ng/mL, P=1.0), had significantly elevated TB4 in the setting of HFpEF. Adjusted for New York Heart Association class, N‐terminal pro B‐type natriuretic peptide, age, and myocardial infarction, hazard ratio to all‐cause mortality is significantly higher in women with elevated TB4 (1.668, P=0.036), but not in men (0.791, P=0.456) with HF. TB4 is strongly correlated with a cluster of 7 markers from the proximity extension assay panel, which are either X‐linked, regulated by sex hormones, or involved with NF‐κB signaling.ConclusionsWe show that plasma TB4 is elevated in women with HFpEF and has prognostic information. Because TB4 can preserve EF in animal studies of cardiac injury, the relation of endogenous, circulating TB4 to X chromosome biology and differential outcomes in female heart disease warrants further study.

show abstract

“…The method of CD40L gene therapy appears to provide an opportunity to muster different anticancer approaches in one therapy and offers an attractive option for further clinical trials. However, cleaved product from membrane-bound CD40L, soluble CD40L, has been observed to enter into systemic circulation and cause inflammatory diseases (11). Platelet-derived sCD40L is a proatherogenic cytokine and consistently related to obesity, diabetes and increased cardiovascular risk (12).…”

Section: Discussionmentioning

confidence: 99%

Anti-tumor activity of gene transfer of the membrane-stable CD40L mutant into lung cancer cells

Li²,

Wang³

et al. 2010

Int J Oncol

View full text Add to dashboard Cite

Abstract. Gene transfer of CD40 ligand (CD40L) holds promise as a novel therapy for lymphoid malignancies and a number of solid carcinomas because of its multiple antitumor activities. However, membrane-bound CD40L can be cleaved into a soluble form, sCD40L, which contributes to systemic inflammatory and cardiovascular diseases, and induces survival signals in the absence of protein synthesis block, suggesting a deleterious side effect of CD40L gene therapy. We generated a plasmid encoding non-cleavable human CD40L mutant (pcDNA3.1 + -CD40L-M) to determine the direct anti-proliferative and pro-apoptotic effects in CD40-positive lung adenocarcinoma cell line A549, to verify activation of immature dentritic cells (DCs) by co-cultivation with the transfected A549 cells and to evaluate the lower expression of sCD40L relative to that of wild-type CD40L (CD40L-WT) transfectant in cell-free supernatants. These studies suggest that gene transfer of the membrane-stable CD40L mutant into CD40-positive cells may provide an efficient and safe method to treat non-small cell lung cancer.

show abstract

Elevated levels of soluble CD40 ligand (sCD40L) in serum of patients with systemic autoimmune diseases

Cited by 127 publications

References 47 publications

Increased Serum Levels of Circulating CD40 Ligand in Patients with Bullous Pemphigoid: Preliminary Results

Increased Serum Levels of Circulating CD40 Ligand in Patients with Bullous Pemphigoid: Preliminary Results

Thymosin Beta‐4 Is Elevated in Women With Heart Failure With Preserved Ejection Fraction

Anti-tumor activity of gene transfer of the membrane-stable CD40L mutant into lung cancer cells

Contact Info

Product

Resources

About