Plasma CAF22 Levels as a Useful Predictor of Muscle Health in Patients with Chronic Obstructive Pulmonary Disease

Qaisar, Rizwan; Karim, Asima; Muhammad, Tahir

doi:10.3390/biology9070166

Cited by 24 publications

(35 citation statements)

References 38 publications

(51 reference statements)

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“…Body mass index (BMI) was calculated as kg/m 2 . Appendicular skeletal muscle mass (ASM) and fat mass were calculated with the bioelectrical impedance analysis scale (RENPHO, Dubai, UAE) as described previously [ 24 ]. ASM was divided by body area to get the appendicular skeletal muscle mass index (ASMI).…”

Section: Methodsmentioning

confidence: 99%

“…No other body movement was allowed during the procedure. Three attempts were performed with each hand with a 60-s rest between each attempt and the highest value was recorded for analysis, as described by us previously [ 24 ].…”

Section: Methodsmentioning

confidence: 99%

“…For analysis of circulating biomarkers, plasma samples were collected in the morning in fasting state and assayed using ELISA kits for Dkk-3 (Cat # ab100502, Abcam) and CAF22 (NTCAF, ELISA, Neurotune, Schlieren-Zurich, Switzerland) according to the manufacturer’s instructions [ 24 ].…”

Section: Methodsmentioning

confidence: 99%

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Circulating Biomarkers of Accelerated Sarcopenia in Respiratory Diseases

Qaisar

Karim

Muhammad

et al. 2020

Biology

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Skeletal muscle dysfunction is a critical finding in many respiratory diseases. However, a definitive biomarker to assess muscle decline in respiratory diseases is not known. We analyzed the association of plasma levels of glycoprotein Dickkopf-3 (Dkk-3), c-terminal agrin fragment-22 (CAF22) and microRNAs miR-21, miR-134a, miR-133 and miR-206 with hand-grip strength (HGS) and appendicular skeletal mass index (ASMI) in male, 54–73-year-old patients with chronic obstructive pulmonary diseases (COPD), asthma or pulmonary TB (n = 83–101/group). Patients with respiratory diseases showed a reduction in HGS and gait speed, while a reduction in ASMI was only found in patients with pulmonary TB. Among the sarcopenia indexes, HGS showed the strongest correlation with plasma CAF22, miR-21 and miR-206 levels while ASMI showed the strongest correlation with Dkk-3 and miR-133 in respiratory diseases. We found a modest-to-significant increase in the plasma markers of inflammation, oxidative stress and muscle damage, which had varying degrees of correlations with Dkk-3, CAF22 and selected micro RNAs (miRs) in respiratory diseases. Taken together, our data show that plasma levels of Dkk-3, CAF22 and selected miRs can be useful tools to assess accelerated sarcopenia phenotype in the elderly with respiratory diseases.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Circulating Biomarkers of Accelerated Sarcopenia in Respiratory Diseases

Qaisar

Karim

Muhammad

et al. 2020

Biology

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“…Sarcopenia and other catabolic conditions disrupt NMJ integrity via proteolytic cleavage of agrin into CAF22 that can be detected in circulation. We have previously shown that plasma CAF22 levels are increased in sarcopenia with pulmonary diseases 9 , 16 . Here, we confirm and extend these findings to sarcopenia with CHF.…”

Section: Discussionmentioning

confidence: 91%

“…Candidate biomarkers for sarcopenia were selected based on the relevant literature and our previous investigations in patients with normal and advanced phases of sarcopenia 9 , 10 , 16 . Among various candidates investigated, circulating levels of P3NP, CAF22, osteonectin, irisin, FABP3 and MIF were significantly different in the COPF and CHF subjects with advanced sarcopenia, when compared to age-matched healthy controls.…”

Section: Resultsmentioning

confidence: 99%

Prediction of sarcopenia using a battery of circulating biomarkers

Qaisar

Karim

Muhammad

et al. 2021

Sci Rep

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Loss of muscle mass and strength with aging, termed sarcopenia is accelerated in several comorbidities including chronic heart failure (CHF) and chronic obstructive pulmonary diseases (COPD). However, the effective circulating biomarkers to accurately diagnose and assess sarcopenia are not known. We recruited male healthy controls and patients with CHF and COPD (n = 81–87/group), aged 55–74 years. Sarcopenia was clinically identified based on hand-grip strength, appendicular skeletal muscle index and physical capacity as recommended by the European working group for sarcopenia. The serum levels of amino-terminal pro-peptide of type-III procollagen, c-terminal agrin fragment-22, osteonectin, irisin, fatty acid-binding protein-3 and macrophage migration inhibitory factor were significantly different between healthy controls and patients with CHF and COPD. Risk scores for individual biomarkers were calculated by logistic regressions and combined into a cumulative risk score. The median cutoff value of 3.86 was used to divide subjects into high- and low-risk groups for sarcopenia with the area under the curve of 0.793 (95% CI = 0.738–0.845, p < 0.001). A significantly higher incidence of clinical sarcopenia was found in high-risk group. Taken together, the battery of biomarkers can be an effective tool in the early diagnosis and assessment of sarcopenia.

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C‐terminal agrin fragment as a biomarker of muscle wasting and weakness: a narrative review

Monti

Sarto

Sartori

et al. 2023

J cachexia sarcopenia muscle

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Ageing is accompanied by an inexorable loss of muscle mass and functionality and represents a major risk factor for numerous diseases such as cancer, diabetes and cardiovascular and pulmonary diseases. This progressive loss of muscle mass and function may also result in the insurgence of a clinical syndrome termed sarcopenia, exacerbated by inactivity and disease. Sarcopenia and muscle weakness yield the risk of falls and injuries, heavily impacting on health and social costs. Thus, screening, monitoring and prevention of conditions inducing muscle wasting and weakness are essential to improve life quality in the ageing modern society. To this aim, the reliability of easily accessible and non-invasive bloodderived biomarkers is being evaluated. C-terminal agrin fragment (CAF) has been widely investigated as a neuromuscular junction (NMJ)-related biomarker of muscle dysfunction. This narrative review summarizes and critically discusses, for the first time, the studies measuring CAF concentration in young and older, healthy and diseased individuals, cross-sectionally and in response to inactivity and physical exercise, providing possible explanations behind the discrepancies observed in the literature. To identify the studies investigating CAF in the above-mentioned conditions, all the publications found in PubMed, written in English and measuring this biomarker in blood from 2013 (when CAF was firstly measured in human serum) to 2022 were included in this review. CAF increases with age and in sarcopenic individuals when compared with age-matched, non-sarcopenic peers. In addition, CAF was found to be higher than controls in other muscle wasting conditions, such as diabetes, COPD, chronic heart failure and stroke, and in pancreatic and colorectal cancer cachectic patients. As agrin is also expressed in kidney glomeruli, chronic kidney disease and transplantation were shown to have a profound impact on CAF independently from muscle wasting. CAF concentration raises following inactivity and seems to be lowered or maintained by exercise training. Finally, CAF was reported to be cross-sectionally correlated to appendicular lean mass, handgrip and gait speed; whether longitudinal changes in CAF are associated with those in muscle mass or performance following physical exercise is still controversial. CAF seems a reliable marker to assess muscle wasting in ageing and disease, also correlating with measurements of appendicular lean mass and muscle function. Future research should aim at enlarging sample size and accurately reporting the medical history of each patient, to normalize for any condition, including chronic kidney disease, that may influence the circulating concentration of this biomarker.

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Plasma CAF22 Levels as a Useful Predictor of Muscle Health in Patients with Chronic Obstructive Pulmonary Disease

Cited by 24 publications

References 38 publications

Circulating Biomarkers of Accelerated Sarcopenia in Respiratory Diseases

Circulating Biomarkers of Accelerated Sarcopenia in Respiratory Diseases

Prediction of sarcopenia using a battery of circulating biomarkers

C‐terminal agrin fragment as a biomarker of muscle wasting and weakness: a narrative review

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