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Rheumatic autoantibodies in the sera of patients with paraproteins
K L Hardiman1, S Horn, A Manoharan
1Department of Rheumatology, St. George Hospital, Sydney, Australia.
Objective:
A high incidence of autoantibody activity has been previously described in the sera of patients with paraproteins. In this study we determined the incidence of autoantibodies of particular interest to rheumatologists (including antinuclear antibodies (ANA), anti-DNA, rheumatoid factor (RF), anticardiolipin antibodies (aCL) and the Sjögren's-related antibodies anti-SS.A/Ro and anti-SS.B/La) in the sera of patients with paraproteins, and the frequency with which the autoantibody activity isotype and the paraprotein isotype were identical.
Methods:
ANA was determined by indirect immunofluorescence on HEp2 cells, anti-DNA by the Farr and Crithidia assays, aCL by ELISA, RF by nephelometry, antibodies to the extractable nuclear antigens (anti-ENA) by counter-immunoelectrophoresis (CIE), and anti-SS.B by immunoblot using a recombinant human SS.B antigen source. Incidences of these antibodies was compared in 3 groups of sera: 98 myeloma, 27 monoclonal gammopathy of uncertain significance (MGUS), and 24 age matched controls, using confidence interval analysis.
Results:
There was no significant difference between the incidence of ANAs in paraprotein sera (8.8%) and control sera (16%). Neither was there a significant incidence of RF or aCL in the paraprotein sera. No anti-DNA antibodies were found and no anti-SS.B antibodies were found either with CIE or immunoblotting. Of the 11 ANAs detected in the paraprotein sera, isotype specific immunofluorescence suggested that 6 were monoclonal autoantibodies.
Conclusions:
These results indicate that the incidence of rheumatic autoantibodies is not raised in paraprotein sera compared to control sera. In particular, we could not confirm previous reports of a high incidence of anti-SS.B antibodies. However, of the ANAs detected half were monoclonal, unlike the polyclonality of the ANAs in the control group. That 4.8% of the paraproteins were monoclonal ANAs suggests that the process leading to paraproteinemia may activate usually silent autoreactive B cells as well as the normal B cell repertoire.