Elevated serum Activin A in chronic obstructive pulmonary disease with skeletal muscle wasting

OBJECTIVE: Muscle wasting contributes to the reduced quality of life and increased mortality in chronic obstructive pulmonary disease (COPD). Muscle atrophy in mice with cachexia was caused by Activin A binding to ActRIIB. The role of circulating Activin A leading to muscle atrophy in COPD remains elusive. METHODS: In the present study, we evaluated the relationship between serum levels of Activin A and skeletal muscle wasting in COPD patients. The expression levels of serum Activin A were measured in 78 stable COPD patients and in 60 healthy controls via ELISA, which was also used to determine the expression of circulating TNF-α levels. Total skeletal muscle mass (SMM) was calculated according to a validated formula by age and anthropometric measurements. The fat-free mass index (FFMI) was determined as the fat-free mass (FFM) corrected for body surface area. RESULTS: Compared to the healthy controls, COPD patients had upregulated Activin A expression. The elevated levels of Activin A were correlated with TNF-α expression, while total SMM and FFMI were significantly decreased in COPD patients. Furthermore, serum Activin A expression in COPD patients was negatively associated with both FFMI and BMI. CONCLUSION: The above results showed an association between increased circulating Activin A in COPD patients and the presence of muscle atrophy. Given our previous knowledge, we speculate that Activin A contributes to skeletal muscle wasting in COPD.

Prediction of Pre-eclampsia with maternal mid-trimester activin A and uterine doppler velocimetry

Pre-eclampsia considered as one of the most serious conditions affecting about 8% of pregnant women. Signs usually begin in the second trimester. Delivery of the baby is thought to be the only cure of this condition. This study was conducted to assess the potential value of combining uterine artery Doppler ultrasonography with the measurement of maternal serum activin A at 22-24 weeks' gestation, in the prediction of pregnancies that subsequently develop pre-eclampsia. Seventy normotensive women were prospectively included in this cohort study. Peripheral venous blood samples were obtained and Doppler examination of the uterine arteries was performed between 22 and 24 weeks' gestation. Serum level of activin A was measured by ELISA. Mid-trimester maternal serum activin A and resistance index of uterine artery were significantly higher in women who subsequently developed pre-eclampsia than those remained normotensive. The best cut-off value for predicting pre-eclampsia for activin A based on ROC curve analysis was 15 ng/ml. While, measurement of serum activin-A has a role predicting pre-eclampsia in pregnant women, the midtrimesteric uterine artery Doppler is more applicable and accurate

Value of serum and synovial fluid activin A and inhibin A in some rheumatic diseases

Activin is a growth and differentiation factor of many cell types and has recently been implanted in inflammatory processes. Clinical data demonstrating roles of activin and its antagonist inhibin in inflammatory arthropathies, are lacking. The Study is to measure serum and synovial fluid levels of activin A and inhibin A in patients with rheumatoid arthritis [RA] systemic lupus erythematosus [SLE] and osteoarthritis [OA] and correlate them with disease activity parameters. This study included 60 patients with three rheumatic diseases [20 with RA, 20 with SLE and 20 with OA], as well as ten healthy subjects as a control group. All of them were subjected to complete history, physical and musculoskeletal examination and estimation of disease activity index [DAS- 28] for RA and [SLEDAI] for SLE. The following investigations were done for all subjects; serum and synovial activin A and inhibin A; in addition to complete blood picture, erythrocyte sedimentation rate [ESR], C-reactive protein [CRP],rheumatoid factor [RF], antinuclear antibodies [ANA],anti-dsDNA, serum complement [C 3, 4] and Xrays on affected joints. The mean values of serum activin A were significantly higher in RA, SLE and OA than controls [P<0.001] also in RA and SLE versus OA [P<0.05 for both]. The mean values of serum inhibin A were significantly higher in all studied groups than controls [P<0.05 for RA and OA and P<0.001 for SLE]. Also serum inhibin levels were significantly higher in SLE versus OA P<0.001, but there was no significant differences between RA and SLE. Synovial fluid activin and inhibin A were significantly higher in RA than OA [P<0.05 for both]. Positive correlations were found between serum activin A and disease activity parameters of RA morning stiffness [MS], Ritchie index [RI], ESR, CRP and DAS 28] P<0.05, for all. Also positive correlation was found between serum inhibin A and RI in RA patient [P<0.05]. In SLE, positive correlations were found between serum activin A and inhibin A with ESR [P<0.001 for activin and P<0.05 for inhibin A and SLEDAI [P<0.001 for both activin and inhibin]. No correlation were found between synovial activin and disease activity and negative correlation between synovial inhibin and ESR. The significant increase of serum and synovial activin A and inhibin A in RA and SLE and their positive correlations with disease activity parameters of RA and SLE suggest pro-inflammatory action. However the lack of correlations or negative correlation of their synovial levels with disease activity may indicate their anti inflammatory action, We recommended further studies to detect the exact role of activin A and inhibin A

Study of serum activin a and follistatin in post renal transplant patients: correlation with renal hemodynamics, graft function and survival

Chronic allograft nephropathy [CAN] is a devasting long-term complication of kidney transplantation that is responsible for a significant proportion of graft loss. Activin A, a member of the transforming growth factor-beta [TGF- beta] superfamily of proteins, has a pro-fibrotic activity. The biologic effects of activin A are countered by follistatin, which is a high affinity extracellular binding protein for activin A. To study serum activin A and follistatin levels in the post-renal transplant patients and their correlation to renal hemodynamics, graft function and survival. The study included 20 post-renal transplant patients [Group I] and 20 age and sex matched healthy subjects [Group II] as controls. Serum activin A and serum follistatin were measured by enzyme linked immunosorbent assay [ELISA]. Serum C-reactive protein [S.CRP] was measured by turbidimetry. Serum and urinary alkaline phosphatase [S.ALP, U.ALP] were measured by spectrophotometry. Renal henwdynamics were evaluated by duplex Doppler ultrasonography; resistive and pulsatility indices [RI, PI] were calculated. Ten patients were categorized as chronic allograft nephropathy [CAN; group Ia]. The other ten patients had a stable renal function [non-CAN; group Ib]. There was a statistically significant increase in serum activin A [S.activin A], S.ALP, S.CRP, RI and PI and a statistically significant decrease in U.ALP and follistarin/activin ratio in patients with CAN than healthy controls, versus a statistically significant difference only in S. activin A and follistatin/activin ratio between non-CAN and controls. There was no statistically significant differences in S. follistatin between the studied groups. In post-renal transplant patients, S.activin A showed a statistically significant positive correlation with S. creatinine, S.CRP, RI and PI versus a statistically significant negative correlation with creatinine clearance, U.ALP and follistatin/Activin ratio. U.ALP showed a statistically significant positive correlation with creatinine clearance versus a statistically significant negative correlation with S. creatinine, S. activin A, S.CRP, RI and PI. Enhanced activin A activity together with normal follistatin level and the decrease in follistatin/activin ratio in post-renal transplant patients, showed that there is a dysregulation of activin-follistatin axis with the increase of the unbound biologically active activin A with deterioration of renal function. Also, there is an increased activity of ongoing inflammation accompanied by impaired renal function among renal allograft recipients that led to enhanced renal fibrosis and a degree of tubular dysfunction