Abstract
Multiple myeloma (MM) remains an incurable plasma cell malignancy. While its origin is enigmatic, an association with infectious pathogens including hepatitis C virus (HCV) has been suggested. Here we report nine patients with monoclonal gammopathy of undetermined significance (MGUS) or MM with previous HCV infection, six of whom received antiviral treatment. We studied the evolution of the gammopathy disease, according to anti-HCV treatment and antigen specificity of purified monoclonal immunoglobulin, determined using the INNO-LIA™ HCV Score assay, dot-blot assays, and a multiplex infectious antigen microarray. The monoclonal immunoglobulin from 6/9 patients reacted against HCV. Four of these patients received antiviral treatment and had a better evolution than untreated patients. Following antiviral treatment, one patient with MM in third relapse achieved complete remission with minimal residual disease negativity. For two patients who did not receive antiviral treatment, disease progressed. For the two patients whose monoclonal immunoglobulin did not react against HCV, antiviral treatment was not effective for MGUS or MM disease. Our results suggest a causal relationship between HCV infection and MGUS and MM progression. When HCV was eliminated, chronic antigen-stimulation disappeared, allowing control of clonal plasma cells. This opens new possibilities of treatment for MGUS and myeloma.
Highlights
Multiple myeloma (MM) is a common hematologic malignancy (1.2% of all tumors) characterized by the clonal expansion and transformed plasma cells in the bone marrow
We demonstrate for the first time that in cases where the monoclonal Ig reacted against hepatitis C virus (HCV), treating the HCV infection improved monoclonal gammopathy of undetermined significance (MGUS) and MM disease
For patient P1, who suffered from MM in third relapse at the time of anti-HCV treatment, eradication of HCV (Figure 1A) was associated with complete remission (CR) of MM in the absence of new anti-MM therapy
Summary
Multiple myeloma (MM) is a common hematologic malignancy (1.2% of all tumors) characterized by the clonal expansion and transformed plasma cells in the bone marrow. The primary function of plasma cells is to produce and secrete large amounts of immunoglobulins (Ig) that mediate humoral immunity against infection. Healthy plasma cells differentiate from immature B cells when they recognize an antigen foreign to the organism. This process occurs in the germinal centers of the secondary lymphoid organs, where B cells proliferate and select somatic hypermutations that have high affinity with the external antigen. In MM, monoclonal plasma cells secrete large quantities of a single Ig, monoclonal Ig, which serves as a marker of the disease and triggers much of the symptomatology [4]
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