rheumatoid factors in primary and reactive macroglobulinaemia.

The occurrence of 1gM (= /32m)-globulins capable of reacting with IgG (= 7S-y)-globulin, the socalled rheumatoid factors, is not restricted to rheumatoid arthritis, but has been reported in a variety of conditions unrelated to the collagen diseases. The importance of these "false positive" reactions lies in the possibility of obtaining more information about the origin of the rheumatoid factors by studying different biological conditions under which these factors can arise. Many of the diseases associated with false positive reactions in the tests for rheumatoid factors belong to the group of chronic infections. Thus a high incidence of false positive reactions has been reported in syphilis (Bloomfield, 1960), leprosy (Cathcart, Williams, Ross, and Calkins, 1961), kala-azar (Kunkel, Simon, and Fudenberg, 1958), tuberculosis (Singer, Plotz, Peralta, and Lyons, 1962) and chronic bronchitis (Bonomo, Tursi, and Pinto 1963), although in none of these instances could this be confirmed by Valkenburg and Hijmans (unpublished). The experimental production of rheumatoid factors by prolonged immunization with certain bacteria by Eyquem, Guyot-Jeannin, and Podliachouk (1959) and Abruzzo and Christian (1961), and with purified proteins either alone or in combination with their specific antibody (Aho and Wager, 1961) has provided some basis for the expectation that chronic infections could be accompanied by the presence of rheumatoid factors. The explanation in all such cases would then be that a prolonged stimulation with y-globulin which is altered by its binding to an antigen, produces rheumatoid factors as antibodies against the y-globulin part of immune complexes. An interesting example is subacute bacterial endocarditis (Williams and Kunkel, 1962), in which the antigen is being constantly fed into the circulation, a situation which is analogous to the experiments of Eyquem and others (1959). In a search for other diseases associated with the occurrence of rheumatoid factors, trypanosomiasis drew our attention because it is an infection of long duration with the peculiarity that there is a permanently high level of IgM-globulin in the serum, at least part of which is of antibody nature (Mattern, Masseyeff, Michel, and Peretti, 1961). As would be expected these IgM-globulins are heterogeneous in electrophoresis in contrast to the paraproteins of Waldenstrom's macroglobulinaemia, to which they bear a certain resemblance in ultracentrifugation (Mattem, Klein, Hijmans, and Radema, 1963). Positive rheumatoid serology might be expected here, in view of the chronic nature of the disease and because of the tendency, which is perhaps dependent on special properties of the antigen, to produce a large amount of IgM antibodies not only at the beginning of the infection but during a prolonged period. If certain properties of the antigen favour the formation of IgM antibodies, this might also apply to the formation of rheumatoid factors. In this connexion it should be remembered that the opinion has been expressed that rheumatoid factor reactions occur particularly in conditions in which IgM-globulins of reactive origin are prominent (Bartfeld, 1960). This hypothesis is opposed by the reported high incidence (Hammack and Holley, 1961; Waldenstrom, Winblad, Hiillen and Liungman, 1964) of positive reactions in Waldenstrom's macroglobulinaemia, a disease in which the pathological IgMglobulin is usually assumed not to be of reactive origin. These macroglobulins show a characteristic narrow zone in electrophoresis which indicates the homogeneity of these so-called paraproteins, in contrast to the well-known heterogeneity produced by multiple antibodies. This report deals with the serological investigation of trypanosomiasis sera in comparison with sera from diseased controls. Sera from patients with chronic splenomegaly were also included in this study, since Francq, Eyquem, Podliachouk, and Jacqueline (1960) reported that such sera show false positive rheumatoid serology. In this typically African syndrome, described by Charmot, Demarchi, Orio, Reynaud, and Vargues (1959), the serum sometimes contains large amounts of IgM-globulin, the origin and function of which is unknown, but which in electrophoresis shows the characteristic heterogeneity of antibodies. In order to investigate