Serum biomarker signature identifies patients with B-cell non-Hodgkin lymphoma associated with cryoglobulinemia vasculitis in chronic HCV infection.
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.


CONCLUSIONS
Our data indicate that serum biomarker signature allows identifying HCV-infected patients presenting with overt B-NHL.
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.
Benjamin
B
Terrier
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.
Wahiba
W
Chaara
Department of Immunology, Groupe Hospitalier Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris 6, F-75013 Paris, France.
Laurent
L
Dufat
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.
Guillaume
G
Geri
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.
Michelle
M
Rosenzwajg
Department of Biotherapy, Groupe Hospitalier Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris 6, F-75013 Paris, France.
Lucile
L
Musset
Department of Internal Medicine, Groupe Hospitalier Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris 6, F-75013 Paris, France.
Damien
D
Sène
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.
David
D
Saadoun
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.
Adrien
A
Six
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.
David
D
Klatzmann
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.
Patrice
P
Cacoub
D015415:Biomarkers / Q000097:blood; D003449:Cryoglobulinemia / Q000097:blood* / Q000209:etiology / Q000473:pathology; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000150:complications; D006801:Humans; D016393:Lymphoma, B-Cell / Q000097:blood* / Q000209:etiology; D008228:Lymphoma, Non-Hodgkin / Q000097:blood* / Q000209:etiology; D014657:Vasculitis / Q000097:blood* / Q000209:etiology
D015415:Biomarkers
B-cell non-Hodgkin lymphoma; Biomarkers; Hepatitis C virus; Mixed cryoglobulinemia; Soluble IL-2Rα