Aim: Obese and overweight patients may be prone to adverse outcomes following lung Tx. We sought to determine the relationship between body mass index (BMI) in patients listed for lung Tx and their Treg function.

Methods: We assessed BMI and the suppressive function of FOXP3+ Treg cells in 52 patients listed for lung transplantation. Their mean age was 57.8±1.5 years, 53% were males, 37 were obese or overweight (ob/ow) and 15 had normal weight.

Results: The ob/ow group had no differences in race, age, gender or primary lung diagnoses compared with patients with normal weights. Both groups had comparable percentages of Tregs within the CD4+ T cell subset and normal Treg viability. However, differences in Treg suppressive function, determined by area-under-curve analysis using healthy CD4+ and CD8+ responder T cells, were noted between groups. Treg function was significantly impaired in the ob/ow group (37.8±4.0 units vs. 71.1±9.6 units in normal weight group for CD4+ responders, p=0.001; and 33.4±3.7 units in ob/ow vs. 65.1±8.4 units in normal weight group for CD8+ responders, p=0.0002). Moreover, the BMI of pre-Tx patients demonstrated strong negative correlations with Treg suppressive function: r=-0.472, p=0.002 for CD4+responders and r=-0.523, p=0.0005 for CD8+ responders, Pearson). As ob/ow patients commonly received therapy with statins and ACE inhibitors (ACEi), and such drugs are suggested to have negative effects on Treg function, we also analyzed whether the impaired function of Tregs in ob/ow patients was confounded by their statins and/or ACEi use. We found that statins and ACEi users indeed had impaired Treg function, but statins and ACEi-free patients still had the same, strong and statistically significant inverse correlations between their Treg suppressive functions and BMI.

Conclusion: Obesity may play an important role in immunological events in lung allograft recipients due to direct negative effects on recipient Treg function. While these effects are likely multifactorial, the recognition that obesity may be linked with predisposition to adverse outcomes adds to our understanding of the complex host/graft relationships in clinical lung Tx recipients.

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