Autoantibodies anti-dsDNA

The most common adverse reaction to etanercept is mild to moderate erythema, pain, or pruritus at the injection site (37%). Headaches and abdominal pain can also occur. New positive autoantibodies, such as antinuclear antibodies (ANA), anti-dsDNA antibodies, and anticardiolipin antibodies, can develop in patients treated with etanercept. Although there is so far no association between this and the development of autoimmune diseases or malignancies, long-term studies have yet to be done. Rare cases of pancytopenia may be associated with this drug. Although clinical trials showed no increased risk of infection with etanercept treatment, postmarketing reports of serious infections, sepsis, and associated fatalities exist. 

Mechanism of Anti-dsDNA, Anti-Ro/SSA, and Anti-La/SSB Autoantibody... 

There are also therapies based on knowledge of the pathogenesis of SLE, mainly for the removal of anti-dsDNA autoantibodies. We will discuss these therapies in a later section. 

Direct evidence of DNA as an antigen source to drive autoantibody production was derived from experiments using combined DNA-protein as an immunogen to immunize mice. The mice immunized with the DNA-peptide complex produce anti-dsDNA antibodies with pathogenic properties (D7). 

Anti-dsDNA antibodies can cause cytotoxic effects in various cultured cells in vitro. They can trigger apoptosis in cultured mesangial and endothelial cells (T9, L3). Monoclonal anti-DNA autoantibodies produced by human-human hybridoma also revealed cytotoxicity to primary cultures of lymphocytes (SI 1). 

Anti-dsDNA antibodies are both specific and pathogenic to SLE. As mentioned previously, these autoantibodies are produced by an antigen-driven mechanism. They are organ-specific, especially kidney. We will discuss the close relationship between anti-dsDNA and lupus nephritis and the proposed mechanism by which anti-dsDNA leads to lupus nephritis. 

Compared with anti-dsDNA, relatively fewer studies have been performed on anti-Ro/La antibodies. However, the unique ability to demonstrate the pathogenic role of autoantibodies causing disease provides us a chance to explore the mechanism of human autoimmune disease. The possibly most important task is to identify the cofactors making the infants of mothers with anti-Ro/La vulnerable to developing neonatal lupus syndromes. 

Arbuckle MR, James JA, Kohlhase KF, Rubertone MV, Dennis GJ, Harley JB. Development of anti-dsDNA autoantibodies prior to clinical diagnosis of systemic lupus erythematosus. Scand J Immunol 2001 54(1 2) 211-219. 

Despite a good overall safety profile, anti-TNF antibodies can induce a number of adverse effects, including autoimmunity and infections. A trial in the treatment of Crohn s disease noted infusion reactions, transient increased of anti-dsDNA antibodies, and serum sickness-like delayed hypersensitivity with retreatment. Induction of human-antichimeric-antibodies was suggested as the cause of some of the infusion reactions [90]. A prospective study in 35 patients with Crohn s disease showed induction of ANA and anti-dsDNA autoantibodies in 53% and 35% of infliximab-treated patients [91]. A single patient showed clinical features consistent with drug-induced lupus, including the presence of ANA and anti-dsDNA autoantibodies, which quickly resolved after discontinuation of infliximab. Reports on renal adverse effects of anti-TNF antibodies are very rare. Saint Marcoux described the occurrence of crescentic GN in as few as 2 patients out of a cohort of 39 patients, treated with an anti-TNF antibody for rheumatoid arthritis [92]. A case report by Chin et al. [93] described the case of a 29-year-old Australia-born Vietnamese who presented with nephrotic syndrome. A renal biopsy showed membranous nephropathy. Symptoms attenuated after discontinuation of infliximab therapy. 

Systemic lupus erythematosus (SLE). A chronic, remitting-relapsing inflammatory autoimmune disease affecting multiple organ systems, such as the skin, joints, serosal membranes, kidneys, blood cells, and central nervous system. The disease is very heterogeneous in clinical expression and serological factors. Autoantibodies directed against nuclear components ( - antinuclear antibodies) are typically detected. Anti-dsDNA, anti-Sm, and antiphospholipid antibodies are used as classification criteria. 

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