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. 2024 Nov 13;10(4):e004660.
doi: 10.1136/rmdopen-2024-004660.

Immune checkpoint molecules performance in ANCA vasculitis

Paula Anton-Pampols  1   2 , Laura Martinez Valenzuela  3   2 , Loreto Fernandez Lorente  4   5 , Maria Quero Ramos  1   2 , Francisco Gómez Preciado  1   2 , Montserrat Gomà  2   6 , Joaquin Manrique  4   5 , Xavier Fulladosa  1   2 , Josep M Cruzado  1   2 , Juan Torras  1   2 , Juliana Bordignon Draibe  1   2
Affiliations

Immune checkpoint molecules performance in ANCA vasculitis

Paula Anton-Pampols et al. RMD Open. .

Abstract

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.

Keywords: Autoimmunity; Systemic vasculitis; Vasculitis.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1. (A) Serum levels of PD-1 in AAV and HC. (B) Mean of serum PD-1 in acute and remission patients and in HC. (C) Serum concentration of PD-L1 in AAV and HC. Values correspond to discovery cohort.
Figure 2
Figure 2. (A) Urine levels of PD-1 in AAV and HC. (B) Concentration of uPD-1 in acute, remission patients, and HC. (C) Mean of uPD-L2 in AAV and HC. (D) Concentration of uPD-L2 in acute, remission patients, and HC. Values correspond to discovery cohort.
Figure 3
Figure 3. Urine levels of PD-1 in the same group of patients in acute and then in remission phase. Values correspond to discovery cohort.
Figure 4
Figure 4. (A) Mean of PD-1 in supernatant cell culture of PBMCs (SNPD-1) in AAV and HC (unestimulated group). (B) Concentration of SNPD-1 in acute, remission patients, and in HC (unestimulated group). (C) Mean of SNPD-1 in AAV and HC in the MPO/PR3 antigen-stimulated group. (D) Concentration of SNPD-1 in acute, remission patients, and in HC in the MPO/PR3 antigen-stimulated group. Values correspond to discovery cohort. PBMCs, peripheral blood mononuclear cells; MPO, myeloperoxidase; PR3, proteinase 3.
Figure 5
Figure 5. This figure shows the presence of PD-1 in interstitial compartment in both sclerotic (A) and crescentic (B) biopsies.
Figure 6
Figure 6. Positivity of PD-1 interstitial cell and intensity PD-1 staining is shown as % of total patients.
See this image and copyright information in PMC

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