Immune checkpoint molecules performance in ANCA vasculitis

Area of Science:

• Immunology
• Nephrology
• Autoimmunity

Background:

• The PD-1 axis is crucial for preventing autoimmunity.
• The role of immune checkpoint (IC) molecules in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is not well understood.
• Understanding IC molecules in AAV could reveal new therapeutic targets and biomarkers.

Purpose of the Study:

• To investigate the role of the IC pathway, specifically PD-1, PD-L1, and PD-L2, in the pathophysiology of AAV.
• To assess IC molecule concentrations in serum, urine, and peripheral blood mononuclear cells (PBMCs) of AAV patients compared to healthy controls.
• To analyze the expression of PD-1 and PD-L1 in kidney biopsies of AAV patients.

Main Methods:

• Collected serum, urine, and PBMCs from 88 AAV patients (discovery cohort) and 30 healthy controls (HC).
• Validated findings in an external cohort of 30 AAV patients.
• Measured PD-1, PD-L1, and PD-L2 concentrations using a multiplex assay and analyzed PD-1/PD-L1 expression in kidney biopsies.

Main Results:

• Urinary PD-1 (uPD-1) and PD-L2 (uPD-L2) were lower in AAV patients than HC, with lower uPD-L2 in acute AAV versus remission.
• PBMCs showed reduced PD-1 production in AAV patients.
• Serum PD-1 (sPD-1) and PD-L1 (sPD-L1) were higher in AAV patients than HC, with elevated sPD-1 in acute AAV versus remission.
• Kidney biopsy analysis revealed fewer PD-1-positive cells in inflammatory lesions compared to sclerotic lesions.

Conclusions:

• The study suggests a potential abolition of the IC pathway during active AAV, which is restored during remission.
• Findings indicate that the PD-1 axis plays a significant role in AAV pathophysiology.
• The PD-1 axis may serve as a novel biomarker for assessing AAV disease activity.