Immune checkpoint molecules performance in ANCA vasculitis.

Autor:	Anton-Pampols P; Nephrology, Bellvitge University Hospital, L'Hospitalet de Llobregat, Spain.; IDIBELL, Barcelona, Spain., Martinez Valenzuela L; Nephrology, Bellvitge University Hospital, L'Hospitalet de Llobregat, Spain lmartinezv@bellvitgehospital.cat.; IDIBELL, Barcelona, Spain., Fernandez Lorente L; Nephrology, Navarre Hospital Complex, Pamplona, Spain.; IdiSNA, Pamplona, Spain., Quero Ramos M; Nephrology, Bellvitge University Hospital, L'Hospitalet de Llobregat, Spain.; IDIBELL, Barcelona, Spain., Gómez Preciado F; Nephrology, Bellvitge University Hospital, L'Hospitalet de Llobregat, Spain.; IDIBELL, Barcelona, Spain., Gomà M; IDIBELL, Barcelona, Spain.; Pathological Anatomy, Bellvitge University Hospital, L'Hospitalet de Llobregat, Spain., Manrique J; Nephrology, Navarre Hospital Complex, Pamplona, Spain.; IdiSNA, Pamplona, Spain., Fulladosa X; Nephrology, Bellvitge University Hospital, L'Hospitalet de Llobregat, Spain.; IDIBELL, Barcelona, Spain., Cruzado JM; Nephrology, Bellvitge University Hospital, L'Hospitalet de Llobregat, Spain.; IDIBELL, Barcelona, Spain., Torras J; Nephrology, Bellvitge University Hospital, L'Hospitalet de Llobregat, Spain.; IDIBELL, Barcelona, Spain., Draibe JB; Nephrology, Bellvitge University Hospital, L'Hospitalet de Llobregat, Spain.; IDIBELL, Barcelona, Spain.
Jazyk:	angličtina
Zdroj:	RMD open [RMD Open] 2024 Nov 13; Vol. 10 (4). Date of Electronic Publication: 2024 Nov 13.
DOI:	10.1136/rmdopen-2024-004660
Abstrakt:	Objective: The PD-1 axis promotes protection against autoimmunity. Immune checkpoint (IC) molecules performance in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) remains unknown. This study aims to assess the IC pathway's role in the AAV's pathophysiology. Methods: We recruited 88 AAV from our centre as a discovery cohort (acute=42, remission=46) and 30 patients from another institution for external validation (acute=16, remission=14).Serum, urine and peripheral blood mononuclear cells (PBMCs) were collected. In vitro IC molecules production by lymphocytes was studied with and without MPO/PR3 antigen stimulus. Cell culture supernatant (SN) was obtained by centrifugation. PD-1, PD-L1 and PD-L2 concentrations were assessed in serum (s), urine (u) and SN of AAV and healthy controls (HC) using a multiplex assay. PD-1 and PD-L1's expression was analysed in six diagnostic kidney biopsies. Results: uPD-1 and uPD-L2's concentration was lower in AAV than HC (p<0.0001, p=0.0075). Acute patients exhibited lower uPD-L2 levels compared with those in remission (p=0.036). Similarly, PBMCs showed reduced PD-1 production than HC (stimulated group p=0.04, unstimulated p=0.0074). Furthermore, patients with inflammatory renal lesions had fewer PD-1-positive interstitial cells/staining intensity compared with those with sclerotic lesions. Contradictorily, sPD-1 and sPD-L1's concentration was higher in AAV than HC (p=0.007, p<0.0001) with acute patients exhibiting elevated sPD-1 levels compared with those in remission (p=0.0051). Serum and urine findings were confirmed in the validation cohort. Conclusions: Results in urine, SN and histology suggest IC pathway abolition during acute disease restored in remission and contribute to understand PD-1 axis's role in AAV proposing it as a new biomarker of disease activity. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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