Benjamin Terrier1, Wahiba Chaara2, Laurent Dufat3, Guillaume Geri1, Michelle Rosenzwajg4, Lucile Musset5, Damien Sène6, David Saadoun7, Adrien Six8, David Klatzmann1, Patrice Cacoub9. 1. Département Hospitalo-Universitaire (I2B), UPMC Univ Paris 6, UMR 7211, F-75013 Paris, France; CNRS Centre National de la Recherche Scientifique, UMR 7211, F-75013 Paris, France; INSERM, UMRS959, F-75013 Paris, France. 2. Département Hospitalo-Universitaire (I2B), UPMC Univ Paris 6, UMR 7211, F-75013 Paris, France; CNRS Centre National de la Recherche Scientifique, UMR 7211, F-75013 Paris, France; Department of Biotherapy, Groupe Hospitalier Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris 6, F-75013 Paris, France. 3. Department of Immunology, Groupe Hospitalier Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris 6, F-75013 Paris, France. 4. Département Hospitalo-Universitaire (I2B), UPMC Univ Paris 6, UMR 7211, F-75013 Paris, France; CNRS Centre National de la Recherche Scientifique, UMR 7211, F-75013 Paris, France; INSERM, UMRS959, F-75013 Paris, France; Department of Immunology, Groupe Hospitalier Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris 6, F-75013 Paris, France. 5. Department of Biotherapy, Groupe Hospitalier Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris 6, F-75013 Paris, France. 6. Department of Internal Medicine, Groupe Hospitalier Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris 6, F-75013 Paris, France. 7. Département Hospitalo-Universitaire (I2B), UPMC Univ Paris 6, UMR 7211, F-75013 Paris, France; CNRS Centre National de la Recherche Scientifique, UMR 7211, F-75013 Paris, France; INSERM, UMRS959, F-75013 Paris, France; Department of Internal Medicine, Groupe Hospitalier Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris 6, F-75013 Paris, France. 8. Département Hospitalo-Universitaire (I2B), UPMC Univ Paris 6, UMR 7211, F-75013 Paris, France; CNRS Centre National de la Recherche Scientifique, UMR 7211, F-75013 Paris, France. 9. Département Hospitalo-Universitaire (I2B), UPMC Univ Paris 6, UMR 7211, F-75013 Paris, France; CNRS Centre National de la Recherche Scientifique, UMR 7211, F-75013 Paris, France; INSERM, UMRS959, F-75013 Paris, France; Department of Internal Medicine, Groupe Hospitalier Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris 6, F-75013 Paris, France. Electronic address: patrice.cacoub@psl.aphp.fr.
Abstract
BACKGROUND: Hepatitis C virus (HCV) is associated with B-cell disorders, including mixed cryoglobulinemia (MC) and B-cell non-Hodgkin lymphoma (B-NHL). We hypothesized that combination of serum biomarkers could be used to identify B-NHL in HCV patients. METHODS: We measured in 155 HCV infected patients, with and without MC and/or B-NHL, serum levels of eight markers previously described to be increased in patients with B-NHL, i.e. sCD22, sCD27, sIL-2Rα, sCD137, free-light chains of Ig (ratio κ/λ), heavy chains of Ig (ratio IgMκ/IgMλ), gammaglobulins and C4. We used a multiparametric analysis to determine a signature that identifies patients with overt B-NHL. RESULTS: Serum levels were significantly different between patients without MC, patients with asymptomatic MC, patients with MC vasculitis and those with MC vasculitis and B-NHL for all biomarkers except for sCD137. Using multiparametric analysis, we identified a signature involving sCD27, sIL-2Rα, gammaglobulins and C4 levels associated with the presence of overt B-NHL in HCV-infected patients. This signature had a sensitivity of 100%, a specificity of 90%, and positive and negative predictive values of 97 and 100%, respectively for discriminating patients with overt B-NHL and those without B-NHL. CONCLUSION: Our data indicate that serum biomarker signature allows identifying HCV-infected patients presenting with overt B-NHL.
BACKGROUND:Hepatitis C virus (HCV) is associated with B-cell disorders, including mixed cryoglobulinemia (MC) and B-cell non-Hodgkin lymphoma (B-NHL). We hypothesized that combination of serum biomarkers could be used to identify B-NHL in HCVpatients. METHODS: We measured in 155 HCV infectedpatients, with and without MC and/or B-NHL, serum levels of eight markers previously described to be increased in patients with B-NHL, i.e. sCD22, sCD27, sIL-2Rα, sCD137, free-light chains of Ig (ratio κ/λ), heavy chains of Ig (ratio IgMκ/IgMλ), gammaglobulins and C4. We used a multiparametric analysis to determine a signature that identifies patients with overt B-NHL. RESULTS: Serum levels were significantly different between patients without MC, patients with asymptomatic MC, patients with MC vasculitis and those with MC vasculitis and B-NHL for all biomarkers except for sCD137. Using multiparametric analysis, we identified a signature involving sCD27, sIL-2Rα, gammaglobulins and C4 levels associated with the presence of overt B-NHL in HCV-infectedpatients. This signature had a sensitivity of 100%, a specificity of 90%, and positive and negative predictive values of 97 and 100%, respectively for discriminating patients with overt B-NHL and those without B-NHL. CONCLUSION: Our data indicate that serum biomarker signature allows identifying HCV-infectedpatients presenting with overt B-NHL.
Authors: Fatemeh Saberi Hosnijeh; Pieter M Kolijn; Delphine Casabonne; Alexandra Nieters; Marta Solans; Sabine Naudin; Pietro Ferrari; James D Mckay; Elisabete Weiderpass; Vittorio Perduca; Caroline Besson; Francesca Romana Mancini; Giovanna Masala; Vittorio Krogh; Fulvio Ricceri; José M Huerta; Dafina Petrova; Núria Sala; Antonia Trichopoulou; Anna Karakatsani; Carlo La Vecchia; Rudolf Kaaks; Federico Canzian; Dagfinn Aune; Heiner Boeing; Matthias B Schulze; Aurora Perez-Cornago; Anton W Langerak; Vincent H J van der Velden; Roel Vermeulen Journal: Sci Rep Date: 2020-08-14 Impact factor: 4.379