PALLAVI L. NADIG, MD
DM FELLOW
ALLERGY IMMUNOLOGY UNIT, ADVANCED PEDIATRICS CENTER, POSTGRADUATE INSTITUTE OF MEDICAL EDUCATION AND RESEARCH
CHANDIGARH, Chandigarh, India
Background: The role of immune checkpoint inhibitory receptors is being increasingly recognised in inflammatory disorders. Programmed death ligand (PDL1) is an immune checkpoint molecule that inhibits T cell activating signals and mitigates inflammation along with other co-inhibitory receptors. Defects in this pathway are associated with autoimmune diseases, including vasculitis. This study aimed to determine the expression of immune checkpoint molecule PD-L1 on monocytes in a cohort of patients with Kawasaki disease (KD) and compare it with other pediatric vasculitides [Polyarteritis nodosa( PAN) and IgA vasculitis ( IgAV)] as well as with age-matched healthy and disease (active systemic juvenile idiopathic arthritis and systemic lupus erythematosus) controls.
Methods: The study was conducted in the Allergy Immunology Unit, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh from July 2022 to December 2023. Monocytes from patients with pediatric vasculitidis (n=32; KD-25, PAN-3; IgAV-3), and healthy age-matched controls (n=30) and disease controls (n=9) were tested for surface expression of PD-L1 on CD14+ monocytes using in-vitro culture at resting state and after stimulation with interferon-gamma at 50 IU/ml.
Results: We found that patients with KD (complete KD =14; incomplete =11) tended to exhibit lower percentage of PD-L1+ monocytes both in the resting as well as stimulated state compared to healthy controls and disease controls (31.95% versus 45.88% vs 39.45%; p=0.134), and showed a significantly reduced expression of PD-L1 upon stimulation when compared to healthy and disease controls (D MFI 71.49 versus 707.26, p=0.139, SI index: 1.07 vs 1.25, p=0.019). PD-L1 expression on CD14+ monocytes was significantly lower in treatment naïve patients (n=22) when compared to convalescent patients both in resting and stimulated states (D MFI- 60.715 versus 707.26, p= 0.041; SI index 1.05 versus 1.26, p=0.007)
Among the vasculitides subtypes, children with KD had the highest expression of PD-L1, followed by IgAV and PAN. There was no statistically significant difference between the children with, and without coronary artery abnormalities (n=7). Children with complete KD tended to have lower PD-L1 expression when compared to incomplete KD, but the difference was not statistically significant. PD-L1 expression negatively correlated with erythrocyte sedimentation rates in the treatment naïve group.
Conclusion: PD-L1 expression on monocytes in KD is significantly reduced both in unstimulated and stimulated states compared to healthy controls and disease controls. These findings suggest an underlying defect in the PD1-PD-L1 pathway that may play a role in disease pathogenesis, particularly immune dysregulation and disease activity.