Session Title: Infection-related Rheumatic Disease
Session Type: Abstract Submissions (ACR)
Background/Purpose: Hepatitis C virus (HCV) is associated with B-cell disorders, including mixed cryoglobulinemia (MC) and B-cell non-Hodgkin lymphoma (B-NHL). Early diagnosis of B-NHL in HCV-infected patients, in particular those with MC vasculitis, is critical to determine the optimal therapeutic management.
Aim: We hypothesized that combination of serum biomarkers could be used to identify B-NHL associated with MC in patients with chronic HCV infection.
Methods: 155 HCV infected patients have been included [median age 62 (31-85) years, M/F 70/85], with and without MC and/or B-NHL [57 patients without MC, 17 patients with asymptomatic MC, 62 patients with MC vasculitis, and 19 patients with MC vasculitis and B-NHL]. We measured serum levels of 8 markers previously described to be increased in patients with B-NHL i.e. soluble CD22, soluble CD27, soluble IL-2Ra, soluble CD137, free-light chains of immunoglobulins, heavy chains of immunoglobulins, gammaglobulins and C4 complement fraction. We used a multiparametric analysis in order to determine a signature that identifies patients with overt B-NHL associated with MC in chronic HCV infection.
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: soluble CD22 (6.7 vs. 11.9 vs. 20.8 vs. 36.4 ng/ml, P<0.0001), soluble CD27 (71.9 vs. 75.7 vs. 122.9 vs. 263.9 U/ml, P<0.0001), soluble IL-2Ra (877 vs. 1035 vs. 2206 vs. 4044 pg/ml, P<0.0001), soluble CD137 (296 vs. 426 vs. 539 vs. 763 pg/ml, P<0.0001), free-light chains of immunoglobulins (ratio k/l 1.13 vs. 1.08 vs. 1.79 vs. 3.01, P<0.0001), heavy chains of immunoglobulins (ratio IgMk/IgMl 1.90 vs. 1.85 vs. 4.85 vs. 31.3, P<0.0001), gammaglobulins (14.1 vs. 17.0 vs. 12.1 vs. 6.0 g/l, P<0.0001) and C4 complement fraction (0.23 vs. 0.16 vs. 0.07 vs. 0.04 g/l, P<0.0001).
Using multiparametric analysis, we identified a signature involving soluble CD27, soluble IL-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 63%, and positive and negative predictive values of 94 and 100% for discriminating patients with overt B-NHL and those without B-NHL.
Conclusion: Overall, our data indicate that serum biomarkers signature allows identifying patients presenting with overt B-NHL associated with mixed cryoglobulinemia vasculitis in chronic HCV infection, and requiring invasive explorations in order to demonstrate the presence of malignant lymphoma.
M. Rosenzwajg Sr.,
D. Sene Sr.,
D. Klatzmann Sr.,
P. Cacoub Sr.,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-biomarkers-signature-identifies-patients-with-overt-b-cell-non-hodgkin-lymphoma-associated-with-mixed-cryoglobulinemia-in-chronic-hcv-infection/