Autoantibodies directed to intracellular antigens are serological hall
marks of systemic rheumatic diseases. Identification of circulating au
toantibodies is helpful in establishing the correct diagnosis, indicat
ing the prognosis and providing a guide to treatment and follow-up. So
me autoantibodies are included in diagnostic and classification criter
ia for diseases such as anti-Sm antigen and anti-double-stranded DNA a
ntibodies in systemic lupus erythematosus, anti-U1 nuclear ribonucleop
rotein antibodies in mixed connective tissue disease, and anti-SS-A/Ro
and anti-SS-B/La antibodies in Sjogren's syndrome. Over the past 30 y
ears, the identification of new autoantibody systems was advanced by t
he initiation or adaptation of novel techniques such as double immunod
iffusion to detect antibodies to saline-soluble nuclear antigens, extr
action-reconstitution and ELISA techniques to detect histone and chrom
atin antibodies, immunoblotting and immunoprecipitation to detect a wi
de range of antibodies directed against naturally occurring and recomb
inant proteins. These techniques have been made possible by advances i
n cellular and molecular biology and in turn, the sera from index pati
ents have been important reagents to identify novel intracellular macr
omolecules. This paper will focus on the clinical relevance of several
autoantibody systems described by Tan and his colleagues over the pas
t 30 years.