Serum KL-6 as predictive and prognostic marker of interstitial lung disease in childhood connective tissue diseases: a pilot study

El-Beheidy, Rabab; Domouky, Ayat M.; Zidan, Haidy E.; Amer, Y. A.

doi:10.4081/reumatismo.2021.1399

Cited by 3 publications

(2 citation statements)

References 33 publications

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“…In this study, after treatment of patients in the study group, lung function indicators were significantly better than those in the control group, while the KL-6 level was noticeably lower than that in the control group. Pirfenidone is a new type of smallmolecule drug used to treat pulmonary fibrosis, and it has antioxidant, anti-inflammatory, and antifibrotic activity (31). Initially, pirfenidone was recommended by many experts and multiple guidelines worldwide for the treatment of IPF.…”

Section: Discussionmentioning

confidence: 99%

Pirfenidone inhibits cell fibrosis in connective tissue disease-associated interstitial lung disease by targeting the TNF-α/STAT3/KL6 pathway

Zuo¹,

Liu²,

Xu³

et al. 2022

J Thorac Dis

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Background: To explore the effect and mechanism of pirfenidone in inhibiting pulmonary fibrosis in connective tissue disease-associated interstitial lung disease (CTD-ILD). Methods: From 2018 to 2020, 50 CTD-ILD patients were enrolled in the clinical study. Based on whether pirfenidone was used during treatment, patients were enrolled into the pirfenidone group and the control group. Pulmonary function tests were compared before and after treatment. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the expression of tumor necrosis factor-α (TNF-α), signal transducer and activator of transcription 3 (STAT3), and Krebs Von den Lungen-6 (KL-6) in venous blood before and after treatment. Rat type II (RLE-6TN) lung epithelial cells were cultivated for in vitro experiments, and they were sorted into the control group, bleomycin group, pirfenidone group, TNF-α group, Stattic group, and TNF-α/Stattic combined treatment group. For the in vitro experiments, 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide (MTT) tests were used to evaluate cell proliferation, Reverse Transcription-Polymerase Chain Reaction(RT-PCR) was performed to detect STAT3 and KL-6 mRNA expression levels, ELISA was utilized to detect TNF-α and E-cadherin expression levels, and Western blotting (WB) was performed to determine α-smooth muscle actin (α-SMA), vimentin, TNF-α, STAT3, phosphorylated signal transducer and activator of transcription 3 (PSTAT3) and KL-6 expression.Results: In the clinical study, the pulmonary function indices including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow (PEF) and partial pressure (PaO 2 ) of the patients in the study group were superior to those in the control group (P<0.05). The serum TNF-α, STAT3 and KL-6 levels in the study group were significantly lower than those in the control group (P<0.05). In the in vitro experiments, the α-SMA, vimentin, STAT3 and KL-6 levels in the treatment group were significantly lower than those in the bleomycin group (P<0.05). Compared with those in the pirfenidone group, the α-SMA, vimentin, STAT3 and KL-6 levels in the TNF-α-treated group were significantly upregulated (P<0.05). Meanwhile, cell viability was further upregulated (P<0.05), and the expression of STAT3 and KL-6 was further decreased in the Stattic-treated group (P<0.05). In the group treated with infliximab combined with Stattic, TNF-α expression was significantly increased (P<0.05), cell activity was significantly restored (P<0.05), and the STAT3, KL-6 and E-cadherin expression levels were inhibited (P<0.05).Conclusions: Pirfenidone improved pulmonary function 1 and decreased TNF-α, STAT3, and KL-6 expression in CTD-ILD patients. Moreover, pirfenidone inhibits cell fibrosis through the TNF-α/STAT3/ Mucin 1(MUC1) pathway.

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Section: Discussionmentioning

confidence: 99%

Pirfenidone inhibits cell fibrosis in connective tissue disease-associated interstitial lung disease by targeting the TNF-α/STAT3/KL6 pathway

Zuo¹,

Liu²,

Xu³

et al. 2022

J Thorac Dis

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“…El-Beheidy et al assessed serum KL-6, a high-molecular-weight mucin-like protein produced by alveolar type-2 pneumocytes, as a potential marker of interstitial lung disease (ILD) in connective tissue disease (CTD) patients (40 CTD patients, 20 with ILD; 20 healthy controls). KL-6 levels were elevated in CTD patients with ILD [127], but differences between CTDs were not investigated because of small sample size.…”

Section: Monitoring Of Juvenile-onset Systemic Lupus Erythematosusmentioning

confidence: 99%

Current views on lupus in children

Smith

Lythgoe²,

Hedrich

2022

Current Opinion in Rheumatology

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Purpose of reviewThis manuscript provides an update on clinical and pathophysiological features of juvenile-onset systemic lupus erythematosis (jSLE), challenges applying adult-derived classification criteria, and recent advances in treatment and care.Recent findingsSignificant scientific advances have improved the understanding of genetic factors (both genetic causes and risk alleles) and associated phenotypic features. Panels of urine/blood biomarker candidates aid in diagnosing jSLE, monitoring disease activity and predicting treatment response. Available classification criteria have been extensively assessed, with differences in clinical and immunological phenotypes of patients across age groups and ethnicities affecting their performance in jSLE. Therapeutic options remain limited and are based on protocols for adult-onset SLE patients. International efforts to inform development of a treat-to-target (T2T) approach for jSLE have yielded cohort-level evidence that target attainment reduces the risk of severe flare and new damage, and treatment compliance.SummaryRecent studies have significantly improved our understanding of jSLE pathogenesis, highlighting important differences between jSLE and adult SLE, and providing the basis of biomarker development and target-directed individualized treatment and care. Future work focused on development of a T2T approach in jSLE is eagerly awaited.

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Undercover lung damage in pediatrics - a hot spot in morbidity caused by collagenoses

Lupu,

Sasaran,

Jechel

et al. 2024

Front. Immunol.

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Connective tissue represents the support matrix and the connection between tissues and organs. In its composition, collagen, the major structural protein, is the main component of the skin, bones, tendons and ligaments. Especially at the pediatric age, its damage in the context of pathologies such as systemic lupus erythematosus, scleroderma or dermatomyositis can have a significant negative impact on the development and optimal functioning of the body. The consequences can extend to various structures (e.g., joints, skin, eyes, lungs, heart, kidneys). Of these, we retain and reveal later in our manuscript, mainly the respiratory involvement. Manifested in various forms that can damage the chest wall, pleura, interstitium or vascularization, lung damage in pediatric systemic inflammatory diseases is underdeveloped in the literature compared to that described in adults. Under the threat of severe evolution, sometimes rapidly progressive and leading to death, it is necessary to increase the popularization of information aimed at physiopathological triggering and maintenance mechanisms, diagnostic means, and therapeutic directions among medical specialists. In addition, we emphasize the need for interdisciplinary collaboration, especially between pediatricians, rheumatologists, infectious disease specialists, pulmonologists, and immunologists. Through our narrative review we aimed to bring up to date, in a concise and easy to assimilate, general principles regarding the pulmonary impact of collagenoses using the most recent articles published in international libraries, duplicated by previous articles, of reference for the targeted pathologies.

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Serum KL-6 as predictive and prognostic marker of interstitial lung disease in childhood connective tissue diseases: a pilot study

Cited by 3 publications

References 33 publications

Pirfenidone inhibits cell fibrosis in connective tissue disease-associated interstitial lung disease by targeting the TNF-α/STAT3/KL6 pathway

Pirfenidone inhibits cell fibrosis in connective tissue disease-associated interstitial lung disease by targeting the TNF-α/STAT3/KL6 pathway

Current views on lupus in children

Undercover lung damage in pediatrics - a hot spot in morbidity caused by collagenoses

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