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SAT0023 Direct-acting antiviral-based therapy restores immune tolerance in hepatitis c-induced cryoglobulinemia vasculitis
  1. C Comarmond1,
  2. M Garrido2,
  3. A-C Desbois2,
  4. M Costopoulos3,
  5. M Garff-Tavernier Le3,
  6. SN Si Ahmed4,
  7. L Alric5,
  8. H Fontaine6,
  9. B Bellier7,
  10. A Maciejewski7,
  11. M Rosenzwajg7,
  12. D Klatzmann7,
  13. L Musset8,
  14. T Poynard9,
  15. P Cacoub10,
  16. D Saadoun10
  1. 1Internal Medicine and Clinical Immunology
  2. 2INSERM, UMR_s 959, FRE3632, Hôpital Pitié-Salpêtrière
  3. 3Biological Hematology, Groupe Hospitalier Pitié-Salpêtrière, Paris
  4. 4Hepatology, Hôpital d'Orléans, Orléans
  5. 5Internal Medicine, Centre hospitalier universitaire Purpan, Toulouse
  6. 6Hepatology, CHU Cochin
  7. 7INSERM, UMR_s 959, FRE3632
  8. 8Immunology, UF d'Immunochimie et d'autoimmunité
  9. 9Hepatology
  10. 10Internal Medicine and Clinical Immunology, CHU Pitié-Salpêtrière, Paris, France

Abstract

Objectives Interferon-free direct-acting antiviral (DAA)-based therapy has proven to be very effective in patients with hepatitis C virus-cryoglobulinemia vasculitis (HCV-CV). However, their mechanisms of action and their effects on cellular immunity remain poorly defined.

Methods 27 HCV-CV patients treated with DAA therapy, 12 healthy donors (HD) and 12 HCV were included. We investigated the effects of DAA-based therapy on cellular and cytokine abnormalities in HCV-CV patients by flow cytometry, cytokine Multiplex and enzyme-linked immunosorbent assay.

Results Compared with HD and HCV, pre-DAA abnormalities in HCV-CV patients included a decreased percentage of CD4+CD25hiFoxP3+ regulatory T cells (P<0.01) with increases in IgM+CD21-/low memory B cells (P<0.05), CD4+IFNγ+ (P<0.01), CD4+IL17A+ (P<0.01) and CD4+CXCR5+IL21+ follicular helper T cells (Tfh) (P<0.01). IgM+CD21-/low memory B cells were negatively correlated with regulatory T cells (Tregs) (P=0.03), and positively correlated with Tfh (P=0.03) and serum cryoglobulin levels (P=0.01). DAA-based therapy was associated with an increase in Tregs frequency (1.5% ± 0.18% versus 2.1% ± 0.18%), and decreased IgM+CD21-/low memory B cells and Tfh percentage (35.7% ± 6.1% versus 14.9% ± 3.8%, and 12% ± 1.3% versus 8% ± 0.9%, respectively). B lymphocyte stimulator receptor 3 and programmed death-ligand 1 staining expression on B cells increased in HCV-CV after DAA-based therapy (MFI 37±2.4 versus 47±2.6, P<0.01; and 29±7.3 versus 48±9.3, P<0.05 respectively).

Conclusions Our results indicate that DAA-based therapy effectively normalizes many of the disturbances in peripheral B and T lymphocyte homeostasis of HCV-CV patients.

Disclosure of Interest None declared

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