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Localized scleroderma can be divided into three main subtypes: morphea, linear scleroderma, and generalized morphea. Plaque morphea usually has a good prognosis. Variants of morphea, including guttate morphea and atrophoderma of Pasini and Pierini, are seen. Linear scleroderma, whether involving an extremity or the face, is often associated with serological abnormalities. Cosmetic and functional prognosis may be poor. Therapy is usually ineffective. Generalized morphea may be difficult to differentiate from systemic scleroderma. However, progression to systemic scleroderma is uncommon.

We have studied the autoantibodies in the serum of a patient with linear scleroderma that specifically recognize the nuclear envelope of cultured cells. These antibodies bind to conserved determinants of nuclear lamins, the predominant mammalian nuclear envelope proteins. Of the three mammalian nuclear lamin proteins (P70, P68, and P60), only P70 and P60 bind the autoantibodies. In addition, two proteins of the Drosophila embryonic nuclear matrix, P70 and P68, bind these autoantibodies. We have used nuclear matrices to isolate the autoantibodies from the patient's serum that react to the nuclear lamins. At least three different IgG heavy chains were found to be involved in this autoimmune response to nuclear lamins, indicating that this response is not due to the expansion of a single B-cell clone.A strong correlation exists between systemic rheumatic diseases and the presence of circulating autoantibodies to proteinnucleic acid complexes (1). The targets of these autoantibodies include nuclear ribonucleoprotein particles (2), nucleosomes (3), nucleoli (4), kinetochores (5), and others. The range of targets for particular disease syndromes are often limited; for example, systemic lupus erythematosis is often associated with autoantibodies to nuclear ribonucleoprotein particles (2), whereas most scleroderma CREST patients produce autoantibodies to centromeric regions of chromosomes (kinetochores; ref. 5). Surprisingly, little is known of the autoimmune responses or their targets on a molecular level.In an attempt to associate the immunofluorescence pattern of sera from patients with specific autoimmune diseases, we discovered a high-titer serum directed against the nuclear envelope in a patient with linear scleroderma. We designate this serum as LS-1. We have chosen here to characterize this autoimmune response more precisely by identifying the antigens recognized by this serum and by determining the nature and complexity of the antibody response. We have found that this autoimmune response is polyclonal and directed against two of the three predominant polypeptides of the nuclear envelope, known as nuclear lamins (6).Using immunofluorescence and immunotransfers of NaDodSO4 gels, we also have detected nuclear lamins in Drosophila melanogaster embryonic nuclear matrices. This demonstrates that nuclear lamins are present in invertebrates and that these autoantibodies from LS-1 serum must be directed against highly conserved determinants. at 26°C in Echalier's medium (7).Immunofluorescence Microscopy. CHO and Kc cells were grown on glass coverslips (12-mm diameter, Corning), fixed in 1% formaldehyde in phosphate-buffered saline (Pi/NaCl) for 5 min at 22°C, and made permeable to antibodies by washing in 0.1% Triton X-100 (Sigma) in Pi/NaCl. The cells were first exposed to LS-1 serum diluted 1:200 and subsequently to a rhodamine-conjugated goat anti-human IgG (Cappel Laboratories, Cochranville, PA). Cells were photographed with a Zeiss photomicroscope with a X 100 planapo objective.Immunohistochemical Microsc...