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New Treatments for Scleroderma

Autoantibodies have been detected in more than 90% of patients with scleroderma. The antibody titers in these patients are typically lower than the titers in patients with other connective tissue diseases such as SLE. The reactive pattern on FANA usually shows fine or large speckles or threads scloroderma, but nucleolar and occasionally diffuse nuclear staining also occur. Unlike most of the autoantibodies in SLE, the autoantibodies in scleroderma tend to be restricted.


Autoantibody Frequency of Occurrence FANA Pattern in Hep-2 Cells Clinical Associations
ACA 20% to 59% scleroderma diffuse punctate speckled nuclear metaphase plate in dividing cells limited scleroderma, Raynaud's, less pulmonary fibrosis and renal crisis
Scl-70 20% to 30% scleroderma homogeneous nuclear and speckled nucleolar diffuse skin involvement, pulmonary interstitial fibrosis, peripheral vascular disease,? association with cancer
Th/To 4% to 10% scleroderma homogeneous nucleolar ? association with puffy fingers, small-bowel involvement, low thyroid, less arthritis
Fibrillarin (U3-RNP) 6% to 8% scleroderma clumpy nucleolar more common in patients of African descent and with diffuse disease, more severe disease
RNA polymerase I 4% to 20% scleroderma speckled nucleolar diffuse disease
RNA polymerase II 4% scleroderma speckled nucleolar diffuse disease, also found in patients with SLE and overlap
RNA polymerase III 23% scleroderma nuclear speckled diffuse disease
PM-Scl 2% to 5% scleroderma homogeneous nucleolar overlap with PM-DM
ACA = anticentromere antibody; PM-DM = polymyositis-dermatomyositis; SLE = systemic lupus erythematosus.

by molecular techniques, and many of the antigens are involved in ribosomal RNA processing. Scleroderma-specific antibodies include anti-DNA topoisomerase I (Scl-70), anticentromere and kinetochore components, anti-RNA polymerase I, II, and III, antifibrillarin (anti-U3-RNP), and anti-Th/To. Other scleroderma-associated autoantibodies, such as anti-PM-Scl and anti-Ku are characteristically seen in overlap syndromes.

On FANA testing, ACA produce a diffuse, punctate, speckled nuclear staining pattern in cells during interphase, and in dividing cells fluorescence is localized to the metaphase plate. ACA tend to persist and the titer to remain stable over long periods of time, and the antibodies rarely appear de novo in patients with established disease. Four distinct antigens, termed CENP-A, CENP-B, CENP-C, and CENP-D have been identified using sera containing ACA. Antibodies to CENP-B, a 30-kDa protein associated with the kinetochore, constitute the majority.

ACA are usually found in patients with limited scleroderma, who have disease for a long time before diagnosis, limited cutaneous sclerosis, and who have calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia (the CREST syndrome).  ACA have been reported to be present in 49% to 96% of such patients but in only 4% to 8% of patients with diffuse scleroderma. The percentage of patients with ACA positive scleroderma increases with the number of features of the CREST syndrome present. ACA are detected in a few patients with Raynaud's phenomenon alone; such patients have been reported to be at increased risk for limited scleroderma. ACA have also been detected in patients with other disorders, including Raynaud's phenomenon and Sjogren's syndrome, primary biliary cirrhosis, and in one patient with primary pulmonary hypertension, RA, and Raynaud's phenomenon. Almost all patients with ACA have Raynaud's phenomenon. 

ACA-positive patients with limited scleroderma have a considerably reduced frequency of interstitial fibrosis and restrictive disease and also apparently a reduced incidence of renal crisis. There, however, is no significant difference in gastrointestinal tract involvement.

Antitopoisomerase I (anti-Scl-70) antibodies were first detected by double-immunodiffusion assay; the antigen was termed Scl-70 because it was specific for scleroderma and bound a 70-kDa protein in immunoblotting techniques.

Approximately 20% to 30% of patients with scleroderma have antitopoisomerase I.  The antibodies are more frequent in affected patients of black American (39%), Thai (77%), Italian (67%), French (48%), and Mexican-American (47%) heritage. Patients with antitopoisomerase I antibodies are more likely than other affected patients.


Idiopathic inflammatory myopathies constitute a group of disorders in which muscle injury results from inflammation of unknown cause; these disorders include polymyositis, dermatomyositis, inclusion body myositis, myositis associated with another connective tissue disease, and cancer-related myositis. Developing sensitive and specific diagnostic criteria for these rare, heterogeneous diseases has been difficult. Division of patients into clinical groups would provide a useful preliminary framework for thinking about these diseases and their treatment and prognosis. Recently, autoimmune responses to nuclear and cytoplasmic autoantigens that are unique to patients with myositis, the so-called "myositis-specific autoantibodies" (MSA), have proved clinically useful in helping predict signs and symptoms of myositis.