Anti-nuclear factor as an auto-antibody

Abstract

The study of a factor which can be demonstrated using Coons indirect fluorescent antibody technique, in the serum of patients with Systemic Lupus Erythematosus (and some other diseases) has been described. An outline of the historical development of the concept of auto-immune disease has been presented, incorporating the technical advances which assisted in elucidation of auto-immune phenomena and an indication of the possible relevance of these to systemic lupus. The main technique used in the study, fluorescence microscopy, was described in detail. A study of the sera of 845 individuals revealed the presence of the factor in 62 of 63 cases of systemic lupus (58 of these were L.E. cell positive), 19 of 132 cases of Rheumatoid Arthritis, 14 of 110 cases of Thyroid Disease, 5 of 39 cases of Liver Disease, 10 of 75 cases of Discoid Lupus, and 5 of 258 cases in the control groups. Quantitation of the factor by serial dilution showed that; the majority of systemic lupus sera had a high titre, while the remaining diseases showed moderate or low amounts of activity. A comparison with other reported series revealed a variation in sensitivity of the test in different hands, and the possible interpretations of occasional low titre findings were outlined. The 171 results with the indirect fluorescent antibody technique were compared with other ways of showing anti-nuclear .ctivity. Histochemical, absorption and precipitation studies on sera with anti-nuclear activity suggest that the nuclear antigen concerned in most instances was a complex of D.N.A. and histone, and a similarity to the L.E. cell factor was noted in this respect. It was concluded that the fluorescent antibody technique whilst not able to distinguish easily between the reactions to the several nuclear components which have been implicated, was a sensitive and reliable method of detecting the factor in human sera, and that it would be difficult to sustain a firm diagnosis of systemic lupus in the absence of a positive test. A study of the nature of the factor by eleotrophbretic, chromatographic, ultracentrifugal and thiol degradation methods, indicated that it was an immunoglobulin of the 7 S type in the sera from the caseeof systemic lupus examined and that it was either of this type or of 19 S macroglobulin type in Rheumatoid Arthritis, Liver or Thyroid Disease; a few sera from Rheumatoid Arthritis cases appeared to contain a mixture of the two types. These findings were compared with reports of similar studies, stressing the importance of analysing the "pure" fractions obtained by these procedures with sensitive immunodiffusion techniques.