Serum transforming growth factor beta in endomyocardialo fibrosis patients and healthy Ugandan individuals

Abstract

Introduction: Transforming Growth Factor-beta (TGF-β) plays a critical role in the production of extra cellular matrix and, excessive productions of these leads to fibrosis. Endo-Myocardial Fibrosis (EMF) is a fibrotic disease of the heart common in the tropics. First described in 1948, the aetiology of EMF still remains largely unknown. EMF bears a poor prognosis and treatment is essentially symptomatic. Better understanding of serum TGF-β levels in EMF patients will contribute to improvement in the management of EMF patients.

Objective: To compare serum TGF-β levels between EMF patients and healthy Ugandan individuals, the association between serum TGF-β and eosinophils among EMF patients and relationship between selected clinical features of EMF with serum TGF- β levels.

Methodology: A cross sectional comparative study was conducted in the Cardiac units of Mulago National Referral hospital. Initial screening was done to rule out other disease conditions known to affect TGF- β levels. A total of 60 participants were enrolled after screening for eligibility; 30 had EMF and 30 were healthy individuals; consent/assent was obtained from all participants in the study. Socio-demographic characteristics were obtained and echocardiography done for all participants in the two groups. Blood was drawn for total eosinophil count and serum TGF-β determination using TGF- β ELISA kit. Data was entered into EPI data 3.1 and transferred to STATA version 10 for analysis. Using the two sample t-test mean serum TGF-β was compared between healthy Ugandan individuals and patients with EMF. Bi-variate and multivariate analysis was done to determine association between dependent and independent variables.

Results: Mean serum TGF-β levels in EMF patients in Mulago Hospital were significantly lower (461.3pg/ml ±48.8) compared to that of healthy individuals (986.9pg/ml ±105.9) (P < 0.001). Significantly high levels of eosinophils were found among EMF patients, compared to healthy participants (p=0.006). No statistically significant relationship was found between eosinophilia in EMF patients and serum TGF-β (p=0.945). There was a statistically significantly lower serum TGF- β level among EMF patients with a raised JVP, irregular rhythm and a murmur (p- value < 0.05).

Conclusion: EMF patients in Mulago Hospital have lower serum levels of TGF-β and high levels of eosinophils compared to their accompanying healthy individuals. There is no association between eosinophils in EMF and serum TGF- β. Raised JVP, heart murmurs and irregular rhythm were significantly associated with low serum TGF-β levels among EMF patients.

Recommendations: We recommend further exploration of serum TGF- β in untreated patients, to determine if low levels of TGF-β have an effect on the disease progression, and if modifying TGF-β would modify disease. With these findings, it is not very clear what the role of corticosteroids is, in the management of EMF, therefore the need for further exploration to determine the relationship between TGF-β levels and prednisolone use in EMF. The interplay between eosinophils and TGF- β in EMF and the role played by TGF-β in the pathogenesis of EMF need further evaluation.