Prognostic value of cryoglobulins, protein electrophoresis, and serum immunoglobulins for lymphoma development in patients with Sjögren’s syndrome. A retrospective cohort study

Abstract

Background: Patients with Sjögren’s syndrome (SS) have a considerable higher risk of lymphoma development.Objectives: To determine the incidence of lymphoma and the value of biomarkers to predict lymphoma development in patients with SS.Methods: Clinical files of all patients with a presumed diagnosis of SS between 1991 and 2016 were retrospectively reviewed for the development of lymphoma. Biochemical data were plotted as a function of the relative time before and after the lymphoma diagnosis (for patients who developed lymphoma) or before the last available blood test (for patients who did not develop lymphoma). Correlations between several biochemical parameters and development of lymphoma were analyzed by logistic regression. In order to evaluate the evolution of cryoglobulins, a random effect model with random intercepts was used.Results: Sixteen patients developed a lymphoma (prevalence 8.9%; median follow-up 6 years). Cryoglobulins were significantly higher in these patients (n = 16), when compared to the rest of patients (n = 164) without lymphoma (121 ± 250 versus 8 ± 24.9 mg/L for IgG; 231 ± 422 versus 13 ± 30 mg/L for IgM; 10 ± 20 versus 1 ± 4 mg/L for IgA in the cryoprecipitate). Cryoglobulin-levels were significantly more increasing (p-values for IgG = 0.0007; for IgM = 0.0123; and for IgA in the cryoprecipitate <0.0001) in the time period before the lymphoma diagnosis (patients with lymphoma) compared to the time period before the last available blood test (patients without lymphoma). Also low (i.e. under the detection limit) C3 (OR 13.9) or C4 (OR 7.1) levels, a progressively decreasing total complement activity (OR 6.6), progressively decreasing gammaglobulins (OR 13.4), a persistent detection of monoclonal bands (OR 14.6) on protein electrophoresis, a persistent low or decreasing serum IgG (OR 18), and decreasing IgM-serum levels (OR 17.7) were significantly associated with lymphoma.Conclusion: Periodically follow-up of laboratory markers, such as cryogloblins, over time proved to be an accurate way to predict lymphoma.