Regulatory T-Cell Deficiency in Rheumatic Heart Disease: A Preliminary Observational Study

Background and aim of the study: Autoimmunity plays an essential role in the pathogenesis of rheumatic heart disease (RHD). The CD4⁺CD25⁺ T cell (Tregs) is the chief regulator of autoimmunity, and is essential for the induction and maintenance of self-tolerance and prevention of autoimmunity. To date, the levels of Tregs in RHD have not been investigated. Hence, the study aim was to monitor levels of circulating Tregs in patients with RHD, and to determine whether these differ according to the extent of valvular involvement. Methods: A total of 100 adult patients with RHD and 50 age- and gender-matched controls were studied. Patients were subdivided according to the extent of left-sided valvular involvement. Those with echocardiographic evidence only of significant mitral valve disease were enrolled in the univalvular group, while those with significant involvement of both mitral and aortic valves were allocated to the multivalvular group.

Levels of circulating Tregs were determined using flow cytometry. Results: Levels of Tregs in total lymphocytes and CD4⁺ T lymphocytes were significantly lower in RHD patients than in controls (3.55 ± 2.28% versus 5.76 ± 4.2%; p <0.001, and 14.4 ± 9.4% versus 18.6 ± 10.4%; p = 0.011, respectively). Within the study group, the proportion of Tregs to total and CD4⁺ T lymphocytes was significantly lower in patients with multivalvular than with univalvular disease (2.7 ± 1.52% versus 4.41 ± 2.58%; p = 0.001 and 11.5 ± 8.5% versus 17.4 ± 9.4%; p = 0.001, respectively). Conclusion: The present study was the first to demonstrate a significant deficiency of circulating Tregs in RHD patients; notably, the reduction was greater in patients with multivalvular than with univalvular involvement.

The Journal of Heart Valve Disease 2013;22:118-125