Influence of Therapy with Sartans on TGFβ Serum Levels in Children with Marfan's Syndrome: Preliminary Results of the TiGer For Kids Study (TGFβ Study)

Background: Diagnosis and treatment of Marfan's syndrome (MFS) require the interaction of a wide range of medical disciplines due to multisystemic symptoms. So far, laboratory findings have a subordinate role for diagnosis and therapy guidance. Current studies postulate that TGFβ signaling cascades play a crucial role in the pathogenesis of MFS. Adult MFS patients showed increased serum TGFβ levels which decrease under drug treatment. In children, these correlations have not yet been investigated. We performed the TiGer for kids study (TGFβ study) to investigate the role of TGFβ in pediatric patients. Here, we present our preliminary findings concerning TGFβ levels in pediatric MFS patients under sartan treatment.

Method: Since 2008, 672 children presented to our pediatric Marfan's clinic, of which 152 showed a heterozygous pathogenic FBN1 variant. Between 2017 and 2020, 31 pediatric MFS patients (6.1 ± 5.6 years, male: 52%) with a proven FBN1 variant were recruited into the TiGer for kids study. In 11 patients (5.5 ± 3.8 years, male: 73%), medical prophylaxis with the Valsartan was indicated. In this group, we performed successive TGFβ measurement when medication was administered for the first time, repetitive during the first 12 hours, followed by a 12-month follow-up. As a control cohort, we measured TGFβ levels in 125 healthy children (9.4 ± 5.7 years; male: 58%).

Results: Baseline TGFβ levels were 6137 (95% CI: 5,360; 6,914) pg/mL in MFS patients without medication and 6,526 (95% CI: 6,027; 7,026) pg/mL in healthy children (p > 0.05). We observed that the TGFβ serum levels reached a significant nadir 6 hours after sartan administration with an average reduction of 1,288 pg/mL (95% CI: 85; 2,491, p < 0.05), followed by a return toward baseline at the 11.5-hour mark (delta from baseline = 590 pg/mL [95% CI: −2,932; 1,751, p > 0.05]). Follow-up measurements of TGFβ at random times of the day after 12 months did not show a significant decrease of TGFβ levels in comparison to baseline.

Conclusion: In our patient cohort with sartans TGFβ levels were effectively suppressed by the treatment during the day with a nadir 6 hours after drug administration. The pathogenesis of MFS determined by TGFβ can thus be influenced in a relevant way. As an important conclusion of our study, the application of sartans twice daily seems reasonable and essential for a constant TGFβ suppression. Whether TGFβ levels are suitable as a screening parameter or for therapy monitoring is still unclear and needs further investigation with a larger collective.

Publication History

Article published online:
12 February 2022