Nuclear antigenic structures.

Nuclear envelope. Improved light and electron microscopic techniques have provided a vast amount of new information about nuclear structures in the last decade (4). It is well recognized that the nucleus is surrounded by a double membrane consisting of (a) an outer layer which is continuous with the endoplasmic reticulum and the many important structures that associate with this reticulum and (b) an inner laminar layer (Fig. 1). The endoplasmic reticulum layer meets the inner laminar layer of the nucleus at the nuclear pores, which vary in number depending on the physiological state of the nucleus. Even the nuclear pores have a complex structure which may regulate the inflow and outflow of nuclear elements, although rigorous proof for this is not yet established. Chromatin. Depending on one’s point of view, virtually all the elements within the inner or laminar layer of the nuclear envelope can be considered to be chromatin. Chromatin exists in several states including the decondensed euchromatin which is usually distributed throughout the nucleus and the condensed chromatin (previously referred to as “heterochromatin”) which is associated with the inner layer of the nuclear envelope except at the nuclear pores, the chromocenters and the perinucleolar chromatin. Each of these elements probably has special roles but their specific functions have not been identified. It is usually considered that condensed chromatin is “inactive”. With “anti-DNA’’ autoantibodies, all the DNA-containing chromatin structures are decorated, but in the usual ANA slides they are not sharply differentiated. The nucleolus. The major nuclear structure in most cells is the nucleolus (Fig. 2), the site of ribosome biogenesis. In addition to the outer layer of condensed chromatin, the nucleolus contains within it the arborized rDNA, the template for synthesis of rRNA. This complex biosynthetic process involved in “reading” the rDNA genes includes controls at upstream “promoter” regions and “enhancer regions”. Important protein cofactors are involved in the activity of the specific nucleolar enzyme, RNA polymerase I. Antibodies to nucleolar elements. Antibodies to RNA polymerase I and its multiple subunits have been isolated and monoclonal antibodies to several subunits are also available. In addition, antibodies have been developed to specific nucleolar proteins such as proteins C23 (1 10b.2) and B23 (3715.2) which are phosphoproteins (5) associated with the rDNA and preribosomal RNP particles (Figs. 3, 4). The nucleolus also contains a specific U-snRNA, the U3 RNA, which like all other U-snRNAs is packaged with specific proteins in the form of an RNP particle. It has been suggested that U3 RNP plays a key role in the specific cleavage of 45s RNA and 35s RNA to subcomponents, particularly the 5.8s RNA. Scleroderma antibodies. For unknown reasons, patients with scleroderma develop antinucleolar antibodies of several types including anti-RNA and anti-protein antibodies (19). Recently, a variety of protein antigens have been identified with anti-scleroderma antibodies. Some appear to be subunits of RNA polymerase I and NII kinase. The others remain to be classified. Other nuclear particles. A variety of nuclear structures have been identified by electron microscopy. These include the perichromatin granules (PCGs) which are identified by a