ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1440

The Myeloperoxidase (MPO) Anti-Neutrophilic Cytoplasmic Antibody (ANCA) Binding Epitope, MPO447-459 Induces CD4 T-cell Proliferation in Patients with MPO-ANCA-associated Vasculitis

Matthew Terrill1, Hendrik Nel2, Yassmin Musthaffa3, Wong Richard4, Ross Francis5, David Johnson5, Greg Keir6, David Gillis7 and Ranjeny Thomas8, 1University of Queensland Diamantina Institute and Princess Alexandra Hospital, Rheumatology Department, Brisbane- Australia, Moffat beach, Queensland, Australia, 2University of Queensland Diamantina Institute, Brisbane, Queensland, Australia, 3University of Queensland Diamantina Institute, Brisbane, Australia, 4Immunology Department, Princess Alexandra Hospital, Brisbane- Australia, Brisbane, Australia, 5Renal Department, Princess Alexandra Hospital, Brisbane- Australia., Brisbane, Queensland, Australia, 6Respiratory Department, Princess Alexandra Hospital, Brisbane- Australia., Brisbane, Queensland, Australia, 7Immunopathology Department, Royal Women’s and Children’s Hospital, Brisbane- Australia., Brisbane, Queensland, Australia, 8University of Queensland Diamantina Institute and Rheumatology Department, Princess Alexandra Hospital, Brisbane – Australia., Brisbane, Australia

Meeting: ACR Convergence 2020

Keywords: , , , ,

Session Information

Date: Sunday, November 8, 2020

Title: Vasculitis – ANCA-Associated Poster

Session Type: Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: In Myeloperoxidase (MPO) Anti Neutrophilic Cytoplasmic Antibody (ANCA)-Associated Vasculitis (MPO-AAV), murine and human studies suggest that the MPO435-465 region, which includes ANCA-binding MPO447-459, the CD4 MPO435-454 epitope and CD8 MPO457-465 epitope; is an immunogenic hotspot within the MPO heavy chain. To map the MPO peptide proliferative response in peripheral blood (PB) of MPO-AAV, we developed a T cell proliferation assay based on CFSE dilution, and assayed responses to MPO heavy chain peptides in participants with MPO-AAV, and age and sex-matched healthy controls.

Methods: MPO-AAV participants were included if they had a positive MPO-ANCA and Birmingham Vasculitis Activity Score (BVAS) ≥ 1 at diagnosis. We collected PB, isolated and froze mononuclear cells, thawed and stained them with CFSE, and cultured them for 7 days with no peptide, anti-CD3, tetanus toxoid, MPO peptides or pools of 10 overlapping 15mer MPO peptides derived from the MPO279-745 heavy chain. The % proliferating CD3+CD4+ and CD8+ T cells in response to antigen or anti-CD3 was calculated by flow cytometry. The cell division index (CDI) was calculated as % divided in peptide-stimulated relative to % divided in unstimulated samples. All were genotyped for HLA-DR, DP and DQ.

Results: Nineteen participants with MPO-AAV were included, with mean age 65.32 (95% CI: 57.36- 73.27) and 14/19 were male (11 MPA, 3 GPA, 5 renal limited disease). Five had active disease. Of the healthy participants, mean age was 56.70 (95% CI: 43.32- 70.08), and 7/9 were male. MPO-AAV patients had a significantly greater CD4+ T cell CDI to MPO447-459 than healthy controls (p=0.015), with median CDI 3.20 (95% CI: 0.96- 5.80) in MPO-AAV and 0.67 (95% CI: 0.07- 0.89) in controls. CDI was greater in patients with remitted disease (median CDI 3.93, 95% CI: 0.52- 13.00), than in patients with active disease (median CDI 1.72, 95% CI: 0.96-3.89), but CDI did not correlate with ANCA titre. Within the MPO heavy chain, there was no significant increase in CDI among MPO-AAV patients towards any epitope other than MPO447-461. CDI to MPO435-365 among MPO-AAV patients with remitted disease was increased relative to patients with active disease. No peptide stimulated a significantly increased CD8+ proliferative response. HLA-DPB1*04:01 was enriched among patients with MPO-AAV (10/13; 76.92%) relative to controls (2/6; 33.33%), odds ratio 6.67 (95% CI: 0.79- 56.21). Carriage of this allele did not influence CDI to MPO447-459.

Conclusion: CD4+ T cells from patients with MPO-AAV proliferate specifically to the MPO447-459 epitope within the MPO heavy chain, and this response is greater after remission. An increased CDI to MPO435-465 suggests that MPO447-459 can be processed in culture from the longer peptide. T cell immunomodulation may be a suitable strategy for remitted MPO-AAV.

Disclosure: M. Terrill, None; H. Nel, None; Y. Musthaffa, None; W. Richard, None; R. Francis, None; D. Johnson, None; G. Keir, None; D. Gillis, None; R. Thomas, Abbvie, 8, BMS, 5, 8, Janssen-Cilag, 8.

To cite this abstract in AMA style:

Terrill M, Nel H, Musthaffa Y, Richard W, Francis R, Johnson D, Keir G, Gillis D, Thomas R. The Myeloperoxidase (MPO) Anti-Neutrophilic Cytoplasmic Antibody (ANCA) Binding Epitope, MPO447-459 Induces CD4 T-cell Proliferation in Patients with MPO-ANCA-associated Vasculitis [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/the-myeloperoxidase-mpo-anti-neutrophilic-cytoplasmic-antibody-anca-binding-epitope-mpo447-459-induces-cd4-t-cell-proliferation-in-patients-with-mpo-anca-associated-vasculitis/. Accessed .

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