The range and specificity of antinuclear antibodies in systemic lupus erythematosus.

Antibodies to nine calf thymus nuclear antigens were sought by complement fixation methods in twenty-four sera from sixteen patients with systemic lupus erythematosus. These antigens included whole nuclei, native and heat denatured DNA, particulate and soluble nucleoprotein and Sm antigen. Soluble antigens were also tested by tanned red-cell agglutination tests. A wide variation in the presence and titres of antibodies to these various antigens was found in the sera studied even when from the same patient but at different times. To further test the range and specificity of antinuclear antibodies in SLE, nineteen ribonucleosides, nucleotides and monophosphoric dinucleotides were coupled to human serum albumin and used as antigens in precipitin studies. A wide variation of reactivity was also found in each serum. Exquisite specificity became apparent, capable of reacting with a nucleoside but not with the corresponding nucleotide or vice versa, with a dinucleotide but not with the nucleotides or nucleosides which it contained, with a given dinucleotide but not with the opposite sequence. Antinuclear antibodies in systemic lupus are, therefore, markedly heterogeneous. Those to a `single' antigen such as DNA may be directed to antigenic sites which may variously be at the bases, single or in sequence, at the site of union of base and sugar–phosphate moiety, at the backbone of deoxyribophosphate or actually dependent on the secondary structure.