Mixed monoclonal cryoglobulinemia and monoclonal rheumatoid factor cross‐reactive idiotypes as predictive factors for the development of lymphoma in primary Sjögren's syndrome

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Abstract
Objective. To prospectively investigate whether mixed monoclonal cryoglobulinemia (MMC) and monoclonal rheumatoid factor (mRF)–associated crossreactive idiotypes (CRI) serve as predictive factors for the development of lymphoma in patients with primary Sjögren's syndrome (SS).Methods. One hundred three consecutive patients with primary SS were evaluated from 1986 to 1991. In all patients, the amount of cryoglobulin was measured by ultraviolet absorption at 280 nm and 260 nm. The type of cryoglobulinemia was identified by agarose gel electrophoresis, combined with immunofixation. Sera from all patients were evaluated by enzyme‐linked immunosorbent assay, using the corresponding monoclonal or polyclonal antibodies, for the presence of immunoglobulins bearing the idiotypes 17109 (VκIIIb associated), G‐6 (VH1 associated), and 3rd SS (a rabbit polyclonal antibody raised against the Fab fragment of an IgMκ mRF from a patient with primary SS). Data analysis was performed by logistic regression.Results. Eighteen of the patients with primary SS (17.4%) had MMC during the first evaluation. There was a statistically significant correlation between the presence of MMC and a higher prevalence of autoantibodies to Ro/SS‐A and La/SS‐B, as well as extraglandular manifestations. During a 5‐year period, 7 patients developed lymphoma. Six of the 7 (86%) had MMC before the appearance of lymphoma, compared with 12 of 96 (12.4%) of the remainder (r = 0.421, P < 0.0009). Patients who developed lymphoma had higher amounts of cryoglobulin than those who did not (mean ± SD 53.4 ± 44.7 mg/dl versus 26.8 ± 20.6 mg/dl). CRIs 17109 and G‐6 were also correlated with lymphoma development (r = 0.321, P < 0.006 and r = 0.22, P < 0.03, respectively). For both CRIs, this correlation was dependent on the presence of MMC, since a stepwise multiple comparison analysis revealed that their individual significance was abolished when their correlation with lymphoma in association with MMC was assessed.Conclusion. The determination of MMC can be used as a laboratory predictive factor for lymphoma development in primary SS. CRIs 17109 and G‐6 may also be used to predict lymphoma development, especially when the monoclonal component is absent.