PO26 - Immune checkpoint alterations in B cells and NK cells of obese sarcoidosis patients revealed by EBUS/TBNA lymph node and peripheral blood analysis.
Agata Raniszewska-Borys (Poland)1; Iwona Kwiecień (Poland)1; Elżbieta Rutkowska (Poland)1; Rafał Sokołowski (Poland)2; Karina Jahnz-Różyk (Poland)2; Piotr Rzepecki (Poland)3;
1 - Department of Internal Medicine and Hematology, Laboratory of Flow Cytometry, Military Institute of Medicine- National Research Institute, Warsaw, Poland; 2 - Department of Internal Medicine, Pulmonology, Allergology, Clinical Immunology and Rare Diseases, Military Institute of Medicine- National Research Institute, Warsaw, Poland; 3 - Department of Internal Medicine and Hematology, Military Institute of Medicine- National Research Institute, Warsaw, Poland;
Keywords: Obesity; Immunoregulation; EBUS/TBNA;
Select the theme: Genetics and Immunopathology: Advances in Contemporary Understanding and Prospects for Future Research
Type: Original Papers
Presentation: Poster Presentation

Introduction: Obesity has emerged as a potential modifier of sarcoidosis (SA) risk and severity, likely through chronic low-grade inflammation and altered immunometabolic signalling. While previous work has demonstrated obesity related abnormalities in T cell phenotype in SA, the impact of BMI on B and NK cell immunoregulation at sites of granulomatous inflammation remains poorly understood.

Objectives: To evaluate the expression of immunomodulatory molecules on B cells and NK cells in obese and non obese SA patients, and to determine whether these immunophenotypic alterations correlate with pulmonary function.

Materials and Methods: Fifty seven treatment naïve SA patients underwent diagnostic evaluation with EBUS/TBNA. Flow cytometric immunophenotyping was performed on lymph node (LN) aspirates and peripheral blood (PB). Patients were stratified into obese (BMI ≥30 kg/m²; n=18) and non obese (BMI <30 kg/m²; n=39) groups. Pulmonary function was assessed using spirometry and diffusing capacity for carbon monoxide (DLCO). Expression of LAG-3, CTLA-4, TIM-3, PD-1, and CD28 on B cells and NK cells was quantified as a percentage of positive cells and GeoMean fluorescence intensity using multiparameter flow cytometry.

Results: Obese SA patients exhibited significantly higher percentages and GeoMean expression of PD-1⁺ B cells (44.9% vs 35.2%, p<0.05) and TIM-3⁺ B cells (63.6% vs 38.4%) in LNs compared with non-obese patients. Additionally, obese patients demonstrated increased percentages (51.9% vs. 37.2%) and GeoMean (4724 vs. 2950) of TIM 3⁺ NK cells. A negative correlation was observed between DLCO and the proportion of TIM-3⁺ NK cells in EBUS (r = -0.62) and PB (r = -0.55) in obese patients, suggesting a link between obesity-associated immune alterations and impaired gas exchange.

Conclusions: Obesity is associated with a distinct pattern of immune checkpoint upregulation on B cells and NK cells in LNs of SA patients. These findings indicate that BMI may amplify local immunoregulatory dysfunction and contribute to reduced pulmonary function.