Increased natural antibody activity in sera of patients with malignant non-Hodgkin's lymphomas containing paraproteins.

In view of the frequent association between malignant lymphoproliferative diseases and autoimmunity, we studied by ELISA the presence, isotype, and specificity of natural antibodies in sera from 60 patients with malignant non-Hodgkin's lymphomas and 70 healthy controls. The antigens selected were actin, tubulin, myosin, troponin, tropomyosin, keratin, thyroglobulin, single stranded DNA, and the hapten trinitrophenyl. The results of this study were compared with the presence of oligoclonal immunoglobulins in the same sera, as previously detected by Isoelectric Focusing and Immunoblotting. Our results showed that 1) there is a high proportion of autoreactive NHL sera: 28 (46.6%) exhibited high IgG natural antibody activity (Nab) against one or more panel antigens, mostly against keratin, myosin, and tropomyosin, 26 (43.3%) had high IgA Nab activity, mainly against myosin, keratin, and ssDNA, whereas 17 (28.3%) displayed a high IgM Nab activity. The great majority (> 80%) of positive sera was polyspecific, i.e., reacted with at least two panel antigens. 2) A strong correlation exists between the high serum Nab activity and the presence of paraproteins: of the 28 sera exhibiting high IgG Nab activity, 16 (57%) contained oligoclonal IgG, and of the 17 sera exhibiting high IgM Nab activity, 13 (76.4%) contained oligoclonal IgM. The Nabs detected had frequently the same heavy and light chain as the paraproteins. No relationship between the presence of paraproteins with Nab activity and the stage of disease or grade of malignancy was found. We conclude that the high incidence of clonal immunoglobulins of different isotypes with various autoantibody specificities suggests an oligoclonal lymphocyte activation involving Nab producing cells. The significance of such autoreactive clones in NHL patients remains to be elucidated.