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We conducted the current study to analyze the prevalence and clinical significance of circulating monoclonal immunoglobulins in patients with Sjögren syndrome (SS), focusing on the association with extraglandular features, immunologic markers, hematologic neoplasia, and hepatitis C virus (HCV) infection. We performed serum immunoelectrophoresis in 200 patients with primary SS and 37 patients with HCV-related SS. All patients fulfilled 4 or more of the 1993 European classification criteria for SS.Of the 200 patients with primary SS, 35 (18%) presented circulating monoclonal immunoglobulins. The monoclonal bands identified were 20 IgG (13 κ, 7 λ), 10 IgM (5 κ, 5 λ), 2 IgAκ, and 3 free circulating light chains. Of the 37 SS-HCV patients, 16 (43%) had circulating monoclonal immunoglobulins. The monoclonal bands identified were 10 IgMκ, 5 IgGλ, and 1 free light λ chain. Compared with primary SS patients, SS-HCV patients presented a higher frequency of monoclonal immunoglobulins (43% vs 18%, p = 0.001), with monoclonal IgMκ being the most frequent monoclonal band. Six (12%) of the 51 SS patients with circulating monoclonal immunoglobulins presented hematologic neoplasia, compared with 3 (1.6%) of those without monoclonal immunoglobulins (p = 0.004; odds ratio = 8.13; 95% confidence intervals, 1.64-51.54). In 2 of the 6 patients with monoclonal immunoglobulins and lymphoproliferative disorders, a change of the monoclonal component was detected in previous immunoelectrophoresis determinations before the development of hematologic neoplasia.Circulating monoclonal immunoglobulins were detected in nearly 20% of patients with primary SS, with monoclonal IgG being the most frequent type of immunoglobulin detected. In SS-HCV patients, the prevalence of monoclonal immunoglobulins was higher (43%), with monoclonal IgM being the most frequent type found. SS-HCV patients presented a more restrictive monoclonal expression (limited to either monoclonal IgMκ or monoclonal IgGλ) than primary SS patients, who showed all types of heavy and light chains.