Serum CXCL16 Concentrations Correlate with the Extent of Skin Sclerosis in Patients with Systemic Sclerosis

Objective.To determine serum concentrations of soluble CXCL16 and its clinical associations in patients with systemic sclerosis (SSc).Methods.Serum CXCL16 levels from 89 patients with SSc were examined by ELISA. In a retrospective longitudinal study, 68 sera from 28 patients with SSc were analyzed (followup 1.3 to 7.3 yrs).Results.Serum CXCL16 levels were elevated in patients with SSc compared with healthy controls (n = 42). Patients with diffuse cutaneous SSc (n = 52) had higher levels of CXCL16 than those with limited cutaneous SSc (n = 37). Serum CXCL16 levels correlated positively with the extent of skin sclerosis. In the longitudinal study, CXCL16 levels generally decreased on a parallel with the improvement in skin sclerosis.Conclusion.CXCL16 levels were increased in patients with SSc, and correlated with the extent of skin sclerosis, suggesting that CXCL16 may have a role in the development of skin fibrosis in SSc. Blockade of CXCL16 interaction might be a potential therapeutic target in patients with SSc.

Download Full-text

Novel disease-modifying drugs against skin fibrosis of systemic sclerosis

Trends in Immunotherapy ◽

10.24294/ti.v2.i3.1050 ◽

2019 ◽

Vol 2 (3) ◽

Author(s):

Mana Nishiguchi ◽

Yuki Yamamoto ◽

Masatoshi Jinnin

Keyword(s):

Systemic Sclerosis ◽

Early Stage ◽

Autoimmune Disorder ◽

Skin Fibrosis ◽

Type I ◽

Internal Organs ◽

Disease Modifying Drugs ◽

Skin Sclerosis ◽

Disease Modifying ◽

Late Stages

Systemic sclerosis (SSc) or scleroderma is an autoimmune disorder characterized by tissue fibrosis of the skin and internal organs. The etiology of the skin fibrosis is thought to be thickened dermis due to uncontrolled excessive deposition of various extracellular matrix, mainly type I collagen.Systemic treatments with anti-inflammatory and cytotoxic immunosuppressive properties, such as corticosteroids and immunosuppressants, are usually considered for skin sclerosis of patients with SSc. However, their approach must be initiated at the early stage, before the fibrosis is completed, and the effects of the corticosteroids and immunosuppressants are known to be reduced in the late stages of the sclerosis. Furthermore, various significant adverse effects of these treatments must be considered.This paper discusses the present day understanding of therapeutic options using disease-modifying drugs against skin sclerosis of SSc patients and the possible mechanisms.

Download Full-text

Is IL-4 a potential therapeutic target in systemic sclerosis-associated pulmonary fibrosis?

Clinical Immunology ◽

10.1016/j.clim.2011.09.010 ◽

2011 ◽

Vol 141 (3) ◽

pp. 240-241 ◽

Cited By ~ 2

Author(s):

Petros P. Sfikakis

Keyword(s):

Systemic Sclerosis ◽

Pulmonary Fibrosis ◽

Therapeutic Target ◽

Potential Therapeutic Target

Download Full-text

Elevated Circulating TWEAK Levels in Systemic Sclerosis: Association with Lower Frequency of Pulmonary Fibrosis

The Journal of Rheumatology ◽

10.3899/jrheum.081310 ◽

2009 ◽

Vol 36 (8) ◽

pp. 1657-1662 ◽

Cited By ~ 19

Author(s):

KOICHI YANABA ◽

AYUMI YOSHIZAKI ◽

EIJI MUROI ◽

TOSHIHIDE HARA ◽

FUMIHIDE OGAWA ◽

...

Keyword(s):

Longitudinal Study ◽

Systemic Sclerosis ◽

Pulmonary Fibrosis ◽

Lupus Erythematosus ◽

Tumor Necrosis ◽

Vital Capacity ◽

Protective Factor ◽

Serum Levels ◽

Clinical Associations ◽

Necrosis Factor

Objective.To determine serum levels of tumor necrosis factor-related weak inducer of apoptosis (TWEAK) and its clinical associations in patients with systemic sclerosis (SSc).Methods.Serum TWEAK levels from 70 patients with SSc were examined by ELISA. In a retrospective longitudinal study, sera from 23 patients with SSc were analyzed (followup 0.8–7.2 yrs).Results.Serum TWEAK levels were elevated in patients with SSc (n = 70) compared with healthy controls (n = 31) and patients with systemic lupus erythematosus (n = 22). Among patients with SSc, there were no differences in serum TWEAK levels between limited cutaneous SSc and diffuse cutaneous SSc. Patients with SSc who had elevated TWEAK levels less often had pulmonary fibrosis and decreased vital capacity than those with normal TWEAK levels. In the longitudinal study, SSc patients with inactive pulmonary fibrosis or without pulmonary fibrosis consistently exhibited increased TWEAK levels, while those with active pulmonary fibrosis showed decreased TWEAK levels during the followup period.Conclusion.TWEAK levels were increased in patients with SSc, and associated with a lower frequency of pulmonary fibrosis in patients with SSc. TWEAK could be a protective factor against the development of pulmonary fibrosis in this disease and as such would be a possible therapeutic target.

Download Full-text

Peroxisome proliferator-activated receptor γ: innate protection from excessive fibrogenesis and potential therapeutic target in systemic sclerosis

Current Opinion in Rheumatology ◽

10.1097/bor.0b013e32833de1a7 ◽

2010 ◽

Vol 22 (6) ◽

pp. 671-676 ◽

Cited By ~ 52

Author(s):

Jun Wei ◽

Swati Bhattacharyya ◽

John Varga

Keyword(s):

Systemic Sclerosis ◽

Therapeutic Target ◽

Peroxisome Proliferator ◽

Potential Therapeutic Target ◽

Peroxisome Proliferator Activated Receptor

Download Full-text

Serum Calponin 3 Levels in Patients with Systemic Sclerosis: Possible Association with Skin Sclerosis and Arthralgia

Journal of Clinical Medicine ◽

10.3390/jcm10020280 ◽

2021 ◽

Vol 10 (2) ◽

pp. 280

Author(s):

Hirohito Kotani ◽

Ayumi Yoshizaki ◽

Kazuki M. Matsuda ◽

Yuta Norimatsu ◽

Ai Kuzumi ◽

...

Keyword(s):

Systemic Sclerosis ◽

Confidence Interval ◽

Elevated Serum ◽

Clinical Manifestations ◽

Joint Involvement ◽

Enzyme Linked Immunosorbent Assay ◽

Skin Thickness ◽

Healthy Controls ◽

Skin Sclerosis ◽

Level Group

Systemic sclerosis (SSc) is a connective tissue disease characterized by tissue fibrosis and vasculopathy in various organs with a background of inflammation initiated by autoimmune abnormalities. Calponin 3 plays a role in the cell motility and contractibility of fibroblasts during wound healing in the skin. We aimed to evaluate serum calponin 3 levels in SSc patients and their association with clinical manifestations of SSc. Serum samples were collected from 68 patients with SSc and 20 healthy controls. Serum calponin 3 levels were examined using enzyme-linked immunosorbent assay kits, and their association with clinical features of SSc was statistically analyzed. The upper limit of the 95% confidence interval of serum calponin 3 levels in healthy controls was utilized as the cut-off value when dividing SSc patients into the elevated and normal groups. Serum calponin 3 levels were significantly higher in SSc patients than in healthy controls (mean (95% confidence interval), 15.38 (14.66–16.11) vs. 13.56 (12.75–14.38) ng/mL, p < 0.05). The modified Rodnan total skin thickness score was significantly higher in the elevated serum calponin 3 level group than in the normal level group (median (25–75th percentiles), 10.0 (2.0–16.0) vs. 6.5 (3.25–8.75), p < 0.05). Moreover, SSc patients with increased serum calponin 3 levels also had a higher frequency of arthralgia (40% vs. 9%, p < 0.05). Elevated serum calponin 3 levels were associated with skin sclerosis and arthralgia in SSc patients. Serum calponin 3 levels might be a biomarker that reflects the severity of skin sclerosis and joint involvement in SSc.

Download Full-text

Novel Disease-Modifying Drugs against Skin Fibrosis of Systemic Sclerosis

Trends in Immunotherapy ◽

10.24294/ti.v4.i2.1050 ◽

2020 ◽

Vol 4 (2) ◽

pp. 59

Author(s):

Mana Nishiguchi ◽

Yuki Yamamoto ◽

Masatoshi Jinnin

Keyword(s):

Systemic Sclerosis ◽

Early Stage ◽

Autoimmune Disorder ◽

Skin Fibrosis ◽

Type I ◽

Internal Organs ◽

Disease Modifying Drugs ◽

Skin Sclerosis ◽

Disease Modifying ◽

Late Stages

Download Full-text

The ubiquitin proteasome system as a potential therapeutic target for systemic sclerosis

Translational Research ◽

10.1016/j.trsl.2018.03.003 ◽

2018 ◽

Vol 198 ◽

pp. 17-28 ◽

Cited By ~ 4

Author(s):

Silke Meiners ◽

John Evankovich ◽

Rama K. Mallampalli

Keyword(s):

Systemic Sclerosis ◽

Therapeutic Target ◽

Ubiquitin Proteasome System ◽

Potential Therapeutic Target ◽

Ubiquitin Proteasome

Download Full-text

Use of Serum Clara Cell 16-kDa (CC16) Levels as a Potential Indicator of Active Pulmonary Fibrosis in Systemic Sclerosis

The Journal of Rheumatology ◽

10.3899/jrheum.100591 ◽

2011 ◽

Vol 38 (5) ◽

pp. 877-884 ◽

Cited By ~ 32

Author(s):

MINORU HASEGAWA ◽

MANABU FUJIMOTO ◽

YASUHITO HAMAGUCHI ◽

TAKASHI MATSUSHITA ◽

KATSUMI INOUE ◽

...

Keyword(s):

Longitudinal Study ◽

Systemic Sclerosis ◽

Pulmonary Fibrosis ◽

Lupus Erythematosus ◽

Characteristic Curve ◽

Serum Levels ◽

Clara Cell ◽

Inactive Disease ◽

Surfactant Protein D ◽

Healthy Controls

Objective.To clarify the clinical significance of concentrations of serum Clara cell 16-kDa protein (CC16; previously denoted CC10) in the diagnosis and monitoring of pulmonary fibrosis (PF) in patients with systemic sclerosis (SSc); and to compare CC16 levels with levels of the current most reliable serum markers for PF, such as Krebs von den Lungen-6 (KL-6) antigen and surfactant protein-D (SP-D).Methods.Serum levels of CC16, KL-6, and SP-D were determined by ELISA in 92 patients with SSc, 20 patients with systemic lupus erythematosus (SLE), and 20 healthy controls. In a retrospective longitudinal study, correlation of serum CC16 levels with the activity of PF was assessed in 16 SSc patients with PF.Results.Although CC16 levels were higher in patients with SSc than in SLE patients or healthy controls, the difference was not significant. Increased serum CC16 levels were associated with involvement of PF, especially active PF, as well as KL-6 and SP-D. Receiver operating characteristic curve analysis revealed that the utility of CC16 is slightly inferior to KL-6, but was comparable with that of SP-D for detecting PF in patients with SSc. In the longitudinal study, serum levels of CC16, KL-6, and SP-D were significantly decreased in the inactive disease phase compared to the active disease phase.Conclusion.CC16 levels can be used as a potential serum biomarker for PF in addition to KL-6 and SP-D in patients with SSc.

Download Full-text