Incidence of the Anti-Nuclear Factor in Human Sera
Authors: W. R. M. Alexander, J. M. Bremner, J. J. R. Duthie
Journal: Annals of the Rheumatic Diseases (1960)

Miescher and Fauconnet (1954) reported that the ability of serum from patients suffering from disseminated lupus erythematosus (D.L.E.) to induce the formation of L.E. cells was abolished if the serum was previously incubated with nuclear material. Friou (1957), using the Coons' technique, showed that cells in unfixed sections of tissue exposed to serum from patients with D.L.E. and, subsequently, to fluorescein-conjugated anti-human globulin serum, exhibited nuclear fluorescence. The presence of an anti-nuclear factor (A.N.F.) in this disease has been confirmed by other workers and the subject has recently been reviewed by Holman and Kunkel (1959). Goodman, Fahey, Malmgren, and Brecher (1959) have identified A.N.F. as a gamma globulin, separable from that associated with the formation of L.E. cells. The presence of identical or closelyrelated globulins has now been reported in other diseases, particularly in those characterized by involvement of connective tissues. The results of several investigations are summarized in Table I. Using the Coons' fluorescent antibody technique, A.N.F. was detected in sixty of the 62 cases of D.L.E. tested (97 per cent.) and was also present in a proportion of cases of scleroderma, dermatomyositis and polyarteritis nodosa. The incidence of A.N.F. in rheumatoid arthritis has been variously reported as less than 10 per cent. by Friou (1958a), 16 per cent. by Holborow and Weir (1958), and 48 per cent. by Duthie, Bremner, and Alexander (1959). The series of Bardawil, Toy, Galins, and Bayles (1958) is too small to be significant, but Bardawil, Hall, and Bayles (in a communication to the American Rheumatism Association quoted by Sokoloff, Bloch, Seegmiller, Stollerman, and Yielding, 1959) detected A.N.F. in 39 per cent. of cases of severe rheumatoid arthritis. Fessel (1959), using latex particles coated with nucleoprotein as an indicator, demonstrated A.N.F. in 23 per cent. of 150 rheumatoid sera tested. Few positive results have been obtained in diseases other than those affecting connective tissue, and the observation by Friou (1958a) and Fessel (1959) that A.N.F. was present in a number of sera exhibiting false positive reactions for syphilis is interesting in view of the speculations of Moore (1956) on the possible relationship of biologic false positive reactions to diseases of connective tissue. Weir (1959) reported the presence of A.N.F. in five of 38 sera from patients suffering from hepatic disease and in 10 per cent. of patients with disease of the thyroid gland. A.N.F. has been demonstrated in most cases of D.L.E., but the reported incidence in rheumatoid arthritis has varied widely (Table I, opposite). This suggests that the techniques used in the several investigations differed in sensitivity, but that A.N.F. was always present in sufficiently large amounts in D.L.E. to be detected even by the less sensitive techniques. Friou (1958b), using a semiquantitative method, has already shown that A.N.F. is usually present in higher titre in D.L.E. than in rheumatoid arthritis. It seemed important, in view of these results and the current view that A.N.F. may be of pathogenic significance in D.L.E., to screen a large number of human sera for A.N.F. by a sensitive technique. The results of a survey of 1,116 sera are presented in this report with special reference to the prevalence and possible significance of A.N.F. in rheumatoid arthritis.