Rheumatic autoantibodies in the sera of patients with paraproteins.

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.

An improved method for labeling monoclonal antibodies with samarium-153: use of the bifunctional chelate 2-(p-isothiocyanatobenzyl)-6- methyldiethylenetriaminepentaacetic acid.

Samarium-153 (153Sm) radioimmunoconjugates of the monoclonal antibody K-1-21 were produced using the bifunctional chelate 2-(p-isothiocyanatobenzyl)-6- methyldiethylenetriaminepentaacetic acid (Mx-DTPA). The specific activity (up to 150 MBq mg-1) and percent retained immunoreactivity (greater than 75%) were similar to that of 153Sm-K-1-21 conjugates formed with cyclic DTPA anhydride (cDTPAa). In vivo biodistribution studies showed specific localization of 153Sm-Mx-DTPA-K-1-21 to target antigen implants and higher blood pool and lower uptake in liver, spleen, kidney, and bone when compared to 153Sm-cDTPAa-K-1-21. The improved in vivo distribution of 153Sm-Mx-DTPA-K-1-21 should result in lower radiotoxicity to nontarget tissues when used for radioimmunotherapy purposes.