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               682                                                                             Immunology—Autoimmunity


                      TABLE II Examples of Subcellular Structures and Domains Recognized by Autoantibodies a
                           Autoantibody              Molecular specificity           Subcellular structure
                      Nuclear components
                        Antichromatin          Nucleosomal and subnucleosomal  Chromatin
                                                 complexes of histones and DNA
                        Anti-nuclear pore      210-kDa glycoprotein (gp210)    Nuclear pore
                        Antilamin              Nuclear lamins A, B, C          Nuclear lamina
                        Anticentromere         Centromere proteins (CENP) A, B, C, F  Centromere
                        Anti-p80 coilin        p80-coilin (80-kDa protein)     Coiled or cajal body
                        Anti-PIKA              p23- to 25-kDa proteins         Polymorphic interphase kayrosomal
                                                                                association (PIKA)
                        Anti-NuMA              238-kDa protein                 Mitotic spindle apparatus
                      Nucleolar components
                        Antifibrillarin         34-kDa fibrillarin               Dense fibrillar component of nucleolus
                        Anti-RNA polymerase 1  RNA polymerase 1                Fibrillari center of nucleolus
                        Anti-Pm-Scl            75- and 100-kDa proteins of the  Granular component of nucleolus
                                                 Pm–Scl complex
                        Anti-NOR 90            90-kDa doublet of (human)       Nucleolar organizer region (NOR)
                                                 upstream binding factor (hUBF)
                      Cytosolic components
                        Antimitochondria       Pyruvate dehydrogenase complex  Mitochondria
                        Antiribosome           Ribosomal P proteins (P 0 ,P 1 ,P 2 )  Ribosomes
                        Anti-Golgi             95- and 160-kDa golgins         Golgi apparatus
                        Antiendosome           180-kDa protein                 Early endosomes
                        Antimicrosomal         Cytochrome P450 superfamily     Microsomes
                        cANCA                  Serine proteinase (proteinase 3)  Lysosomes
                        Antimidbody            38-kDa protein                  Midbody
                        Anti-centrosome/centriole  Pericentrin (48 kDa)        Centrosome/centriole
                        a  NuMA, nuclear mitotic apparatus; Pm–Scl, polymyositis–scleroderma; cANCA, cytoplasmic antineutrophil cytoplasmic
                      antibody.

                 The molecular spectrum of autoantigenic targets (see  although rare, have proven to be a useful marker for the
               Tables  I  and  II)  together  with  their  exquisite  antigenic  fibrillar center of the nucleolus. A growing appreciation
               specificity has made autoantibodies valuable reagents in  of the antigenic diversity of cellular constituents, together
               molecular and cellular biology. The most visually impres-  with improvements in fluorescent microscopy, has led to
               sive demonstration of the usefulness of autoantibodies as  identification of autoantibodies reacting with a variety of
               biological probes is the indirect immunofluorescence (IIF)  subnuclear domains and compartments, some consider-
               test. Using this technique (see Section II.A), an increas-  ably smaller than the nucleolus. The coiled body, a small
               ing number of autoantibody specificities are being iden-  circular subnuclear structure originally described by the
               tified that recognize cellular substructures and domains  Spanish cytologist Santiago Ramon y Cajal in 1903, and
               (Table II and Fig. 1). Autoantibodies against chromatin  now named the Cajal body, is an example. Cajal bod-
               and DNA can be used to identify the cell nucleus. Other  ies can be identified using autoantibodies that react with
               nuclear structures such as the nuclear lamina, which un-  p80 coilin (Fig. 1d), an 80-kDa protein highly enriched
               derlies the nuclear envelope, can be identified by anti-  in Cajal bodies. Using other autoantibodies in colocaliza-
               lamin autoantibodies as a ring-like fluorescence around  tion studies, it has been found that Cajal bodies contain
               the nucleus (Fig. 1a). The nucleolus and its subdomains  other proteins, including fibrillarin (previously thought
               can be identified by a variety of autoantibodies (Table II).  to be restricted to the nucleolus and prenucleolar bod-
               Antifibrillarin autoantibodies, which recognize the highly  ies). Autoantibodies have also been identified that react
               conserved 34-kDa fibrillarin [a component of some small  with subcellular structures other than the nucleus (Fig. 1).
               nucleolar RNP (snoRNP) particles], identify the dense fib-  Prior knowledge of the existence and relative distribu-
               rillar component. Autoantibodies to RNA polymerase I,  tions of these subcellular organelles was instrumental in
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