Contribution of Soluble Forms of Programmed Death 1 and Programmed Death Ligand 2 to Disease Severity and Progression in Systemic Sclerosis

Fukasawa, Takemichi; Yoshizaki, Ayumi; Ebata, Satoshi; Nakamura, Kouki; Saigusa, Ryosuke; Miura, Shunsuke; Yamashita, Takashi; Hirabayashi, Megumi; Ichimura, Yohei; Taniguchi, Takashi; Asano, Yoshihide; Shimizu, Hisashi; Kazoe, Yutaka; Mawatari, Kazuma; Kitamori, Takehiko; Sato, Shinichi

doi:10.1002/art.40164

Cited by 60 publications

(64 citation statements)

References 44 publications

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“…1C). In addition, serum levels of soluble forms of PD-1 and its ligand PD-L2 were recently shown to be elevated in SSc (14). Li et al describe increased TIM-3 on CD4 + and CD8 + T cells in peripheral blood from rheumatoid arthritis patients (39), while our data show no changes in TIM-3 in SSc T cell subsets, but an increase in NK cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…In support of this, an exhaustion-like phenotype marked by an increase in co-IR expression correlated with less flares in lupus patients (10), while the presence of TIM-3 + T cells was associated with milder forms of multiple sclerosis (13). In SSc, a recent report indicates that the PD-1 pathway is involved in regulating disease severity (14). …”

Section: Introductionmentioning

confidence: 99%

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Increased Expression and Modulated Regulatory Activity of Coinhibitory Receptors PD‐1, TIGIT, and TIM‐3 in Lymphocytes From Patients With Systemic Sclerosis

Fleury

Belkina

Proctor

et al. 2018

Arthritis & Rheumatology

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Increased Expression and Modulated Regulatory Activity of Coinhibitory Receptors PD‐1, TIGIT, and TIM‐3 in Lymphocytes From Patients With Systemic Sclerosis

Fleury

Belkina

Proctor

et al. 2018

Arthritis & Rheumatology

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“…Programmed death‐1 (PD‐1) is a molecule expressed on various human immune cells, including T cells, B cells, myeloid cells, thymocytes and natural killer (NK) cells . The ligation of programmed death ligand‐1 (PD‐L1) and programmed death ligand‐2 (PD‐L2) to PD‐1 may have an inhibitory effect on target cells (eg T cells), playing an important role in the regulation of immune homeostasis and in maintenance of peripheral immune tolerance . PD‐1 expression correlates with the exhaustion of T cells in cancers and chronic infections .…”

Section: Introductionmentioning

confidence: 99%

Soluble programmed death‐1 is a useful indicator for inflammatory and fibrosis severity in chronic hepatitis B

Zhou

Huang

et al. 2019

Journal of Viral Hepatitis

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SummaryElevated programmed death‐1 (PD‐1) has been found in immune cells in viral infections and plays an important role in infection persistence. The soluble form of PD‐1 (sPD‐1) is involved in tumours and viral infections. The aim of this study was to investigate the role of sPD‐1 in chronic hepatitis B (CHB). A total of two hundred and eighteen CHB patients and sixty healthy controls (HC) were enrolled. Demographic data and clinical parameters were collected. An ELISA assay was used to measure serum sPD‐1 levels, and the relationships between sPD‐1 and clinical/virological characteristics was analysed. sPD‐1 levels in CHB patients were higher (median 4.409 IQR 3.435‐5.306 pg/mL) than those of HC individuals (median 0.3665 IQR 0.2425‐0.5010 pg/mL). Among patients at various disease stages, patients with immune activity showed the highest sPD‐1 levels (median 5.138 IQR 4.329‐5.406 pg/mL). sPD‐1 concentration was associated with HBV markers (HBsAg, HBV DNA and HBeAg) and biochemical parameters (serum aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin [TBil] and gamma glutamyl transferase [γ‐GT] levels) (all P < 0.05). sPD‐1 levels were higher in CHB patients with moderate‐to‐severe inflammation or fibrosis than in those with mild inflammation or fibrosis, regardless of ALT levels. The association between sPD‐1 and disease progression of CHB suggests that sPD‐1 could serve as a new indicator in assessing liver fibrosis. These findings may further aid in determining the initiation of antiviral treatment in patients with normal ALT levels.

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“…Even in this study, highly elevated serum IL‐6 levels were observed in active SSc‐ILD. In our previous study using mice where an immune response was elicited using a topoisomerase I protein, activation of T and B cells and macrophages and induction of lung fibrosis were observed . By contrast, the immune cell activation and fibrosis were significantly suppressed in IL‐6R knockout mice.…”

Section: Discussionmentioning

confidence: 91%

“…Recently, we have successfully integrated the immunoassay into a microchip, applying basic enzyme‐linked immunoassay (ELISA) methodology to the micro‐ELISA system . This system can measure the very low concentration (10–1000 fg/mL) of several cytokines using a bead‐bed immunoassay on a microchip composed of flow channels that are 5–100 μm in depth.…”

Section: Case Reportmentioning

confidence: 99%

Rapid alteration of serum interleukin‐6 levels may predict the reactivity of i.v. cyclophosphamide pulse therapy in systemic sclerosis‐associated interstitial lung disease

Numajiri

Yoshizaki

Fukasawa

et al. 2018

The Journal of Dermatology

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Systemic sclerosis (SSc) is an autoimmune disorder characterized by excessive extracellular matrix deposition. Although SSc-associated interstitial lung disease (ILD) is one of the most important complications as a cause of death in SSc, prediction factors of treatment reactivity in SSc-ILD are still unclear. To assess relationships between interleukin (IL)-6 and reactivity to treatment, we measured serum IL-6 levels in 23 of active SSc-ILD patients under i.v. cyclophosphamide (IVCY) therapy and 20 of stabilized SSc-ILD, using the high-sensitivity enzyme-linked immunoassay system. Serum IL-6 levels in active SSc-ILD patients were significantly higher than those in stabilized SSc-ILD patients. Among active SSc-ILD patients, baseline serum IL-6 levels were not significantly different between IVCY responders and non-responders. Meanwhile, serum IL-6 levels after three IVCY doses out of a total of six were decreased in responders but not in non-responders. Regarding changes of parameters by the three doses of a total of six of IVCY, change in serum IL-6 levels correlated inversely with that in values of pulmonary function test. Thus, the rapid decrease in serum IL-6 levels during a couple of doses may predict the efficacy of IVCY therapy against SSc-ILD.

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Contribution of Soluble Forms of Programmed Death 1 and Programmed Death Ligand 2 to Disease Severity and Progression in Systemic Sclerosis

Abstract: These results suggest that sPD-1 and sPD-L2 contribute to disease development in SSc via the regulation of cognate interactions with T cells and B cells.

Cited by 60 publications

References 44 publications

Increased Expression and Modulated Regulatory Activity of Coinhibitory Receptors PD‐1, TIGIT, and TIM‐3 in Lymphocytes From Patients With Systemic Sclerosis

Increased Expression and Modulated Regulatory Activity of Coinhibitory Receptors PD‐1, TIGIT, and TIM‐3 in Lymphocytes From Patients With Systemic Sclerosis

Soluble programmed death‐1 is a useful indicator for inflammatory and fibrosis severity in chronic hepatitis B

Rapid alteration of serum interleukin‐6 levels may predict the reactivity of i.v. cyclophosphamide pulse therapy in systemic sclerosis‐associated interstitial lung disease

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