Autoantibodies to CRP were reported previously in patients suffering from toxic oil syndrome. This syndrome resembles autoimmune diseases such as systemic lupus erythematosus (SLE) or systemic scleroderma. We therefore examined the prevalence of antibodies to CRP and other acute-phase proteins in autoimmune diseases, including SLE, subacute cutaneous lupus erythematosus (SCLE), systemic scleroderma (SSc), and primary biliary cirrhosis (PBC), as well as in bone marrow transplantation-induced chronic graft-versus-host disease and eosinophilia-myalgia syndrome. IgG antibodies to CRP were found in 78% of SLE and in 30% of SCLE patients, while 16% of patients with PBC were positive. In up to 45% of patients with SSc predominantly IgG antibodies to ceruloplasmin were detectable. Lack of systemic involvement as in discoid lupus erythematosus and localized scleroderma (morphea) correlated with low or absent antibody formation. However, no correlation was found between anti-acute-phase protein antibodies with liver disease or other organ involvement. Adsorption studies revealed that non-native epitopes on the CRP molecule, termed modified CRP, are the main target of antibodies. Chronic inflammatory tissue injury in systemic autoimmune disease might increase the presentation of cryptic epitopes of CRP to the threshold required for T cell activation.
Chronic graft-versus-host disease after bone marrow transplantation presents, in a few cases, as mild to severe scleroderma-like changes. Patients with chronic graft-versus-host disease with and without sclerodermatous skin changes were analysed for antinuclear autoantibodies (ANA) and antinucleolar autoantibodies (ANoA) and the results correlated with disease symptoms and histocompatibility locus antigen (HLA) pattern. Nineteen patients with chronic graft-versus-host disease and scleroderma-like skin changes, 18 with chronic graft-versus-host disease without scleroderma, and 17 controls on immunosuppressive treatment were screened for ANA and ANoA using enzyme-linked immunosorbent assay, immunodiffusion and immunoblot techniques. Four patients with severe scleroderma had antibodies to topoisomerase I, two had antibodies against PM-Scl, both characteristic serological findings in idiopathic systemic scleroderma. One patient had La/SSB antibodies and, in three cases, antibodies to the nucleolar antigen C23 (nucleolin) could be identified. A possible correlation between antinucleolin antibodies and disease activity was observed. HLA-A1, -B1, and -B2 were found significantly more often in patients with scleroderma-like symptoms in comparison to patients without scleroderma-like symptoms. Chronic graft-versus-host disease with scleroderma-like manifestations can be associated with the occurrence of ANA specific for idiopathic scleroderma. The development of scleroderma after bone marrow transplantation might have a HLA-linked genetic background.
Chronic graft-versus-host disease after bone marrow transplantation presents, in a few cases, as mild to severe scleroderma-like changes. Patients with chronic graft-versus-host disease with and without sclerodermatous skin changes were analysed for antinuclear autoantibodies (ANA) and antinucleolar autoantibodies (ANoA) and the results correlated with disease symptoms and histocompatibility locus antigen (HLA) pattern. Nineteen patients with chronic graft-versus-host disease and scleroderma-like skin changes, 18 with chronic graft-versus-host disease without scleroderma, and 17 controls on immunosuppressive treatment were screened for ANA and ANoA using enzyme-linked immunosorbent assay, immunodiffusion and immunoblot techniques. Four patients with severe scleroderma had antibodies to topoisomerase I, two had antibodies against PM-Scl, both characteristic serological findings in idiopathic systemic scleroderma. One patient had La/SSB antibodies and, in three cases, antibodies to the nucleolar antigen C23 (nucleolin) could be identified. A possible correlation between antinucleolin antibodies and disease activity was observed. HLA-A1, -B1, and -B2 were found significantly more often in patients with scleroderma-like symptoms in comparison to patients without scleroderma-like symptoms. Chronic graft-versus-host disease with scleroderma-like manifestations can be associated with the occurrence of ANA specific for idiopathic scleroderma. The development of scleroderma after bone marrow transplantation might have a HLA-linked genetic background.
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