Showing papers by "Eng M. Tan published in 1989"

Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology

Abstract: Publisher Summary Early studies pointed to the directions for subsequent investigations and there has been continuing identification of other circulating autoantibodies, characterization of their respective cellular antigens, and demonstration of the relationship between autoantibodies and clinical syndromes. The antibodies identified in these studies have been used extensively by investigators in molecular and cell biology as powerful probes for understanding the precursor messenger RNA (mRNA) splicing. Autoantibodies designated SS-A or Ro and SS-B or La were identified in patients with Sjogren's syndrome (SS) and SLE, and have been shown to target intracellular proteins that may be involved with regulation of RNA polymerase III function. Investigators in the field had long perceived that these spontaneously occurring auto-antibodies in human disease would turn out to be useful reagents in cell biology. It was also appreciated that it was necessary to characterize the molecular nature of the auto-antigens so that in addition to the immunochemical properties, their structure and function might be determined. One of the purposes of this chapter is to show that the new molecular biology of cellular antigens and auto-antibodies could now be providing insights into comprehending some features of autoimmunity. In addition, there appears to be a need for the synthesis of the wealth of information that has accumulated and an evaluation of what it might signify.

Anti-fibrillarin autoantibodies in mercury-treated mice.

Abstract: Using indirect immunofluorescence (IF) with HEp-2 cells as a substrate serially bled SJL mice were found to gradually develop a high titre of anti-nucleolar antibodies (ANuA) after 3-5 weeks of s.c. injections of 1.6 mg HgCl2/kg body weight every third day. The ANuA showed a clumpy nucleolar pattern of localization and were composed of all IgG subclasses, but contained, in comparison with the antinuclear antibodies (ANA) in MRL-lpr/lpr mice, significantly lower titres of IgG2a and only traces of IgG3. Immunoblotting analysis using purified mouse liver nucleoli revealed that the sera with ANuA identified the same 34-kD nucleolar protein which was targeted by a human scleroderma serum containing autoantibodies monospecific for fibrillarin. In addition, a fraction of the mercury-treated SJL mice developed serum antibodies reacting with 10-15 and 60-70 kD nucleolar proteins in immunoblotting. The presence of serum autoantibodies reacting with the 10-15 kD proteins correlated with significantly increased titres of anti-histone antibodies of the IgG class in ELISA. Some mercury-treated SJL mice also developed a significantly increased titre of anti-histone antibodies of the IgM class. B10.S mice treated with mercuric chloride consistently developed ANuA, which also targeted a 34-kD nucleolar protein. Since anti-fibrillarin antibodies are specific markers of scleroderma, the present animal model may be valuable for studies of the immunological aberrations which are likely to induce this autoimmune response.

Autoantibodies in scleroderma.

Abstract: In scleroderma a profusion of circulating autoantibodies have now been defined. They include autoantibodies to Scl-70 or DNA topoisomerase 1, and to centromere/kinetochore proteins of 17.80 and 140 kilodaltons. In addition, there are several antigens which are resident primarily in the nucleolus and they are RNA polymerase 1, PM-Scl, fibrillarin and 7-2 ribonucleoprotein. Antibody to Scl-70 has been found primarily in the diffuse form of scleroderma and antibody to the centromere/kinetochore proteins in the CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly and telangiectasia) subset of scleroderma. Autoantibodies to the nucleolar antigens RNA polymerase 1, PM-Scl, fibrillarin and 7-2 RNP have been detected in at least 10% of all patients with scleroderma. For several reasons which are discussed, it appears that the autoantibody response in scleroderma is antigen-driven and further that the autoantigens involved in this disease are present at some time in the nucleolus. These observations may be providing clues to some of the basic mechanisms initiating autoimmunity.