Cross-reactivity and pathogenicity of anti-DNA autoantibodies in systemic lupus erythematosus

Abstract

Autoantibodies to DNA were discovered over 40 years ago following the discovery a few years earlier of the 'LE' cell phenomenon by Hargraves and colleagues in 1948. These investigators noted that, when leucocytes were incubated with serum from lupus patients, changes in the nucleus could be seen together with phagocytosis of nuclear remnants by polymorphonuclear leucocytes. Since that time numerous studies in many laboratories have investigated almost every aspect of anti-DNA antibodies, partly to identify what determines their pathology. Whilst a subset of anti-DNA antibodies, especially anti-native, or double-stranded DNA (dsDNA) antibodies constitutes a hallmark of lupus disease and a diagnostic criterion, it is now clear that not all anti-DNA autoantibodies are of pathogenic relevance. Moreover, anti-DNA autoantibodies may also be found in other connective tissue disorders. Here we briefly review studies presented at the fifth international workshop on anti-DNA autoantibodies held in London to highlight relevant properties of pathogenic anti-DNA antibodies.

Specific cross-reaction of anti-dsDNA antibody with platelet integrin GPIIIa49-66

“…Anti-dsDNA autoantibodies are considered as not only a diagnostic marker but also a pathogenic factor for SLE [15]. Previous reports have shown that those anti-dsDNA antibodies may cross-react with a variety of epitopes in different proteins [16–27].…”

Elevated levels of serum antibodies against alpha-1, 6-glucan in patients with systemic lupus erythematosus or rheumatoid arthritis

“…Perhaps there is substantial cross-reactivity between dextran and dsDNA, and this notion would help to explain the fact that dextran can adsorb and remove anti-dsDNA antibody from sera of SLE patients. However, anti-dsDNA antibodies crossreact with many different antigens such as heparan sulfate, snRNP proteins, α-actinin and nephritogenic potential (Mageed and Zack, 2002;Zhao et al, 2005). The crossreactivity with dextran is relatively low and should not affect the outcome of this study.…”

Monoclonal auto-antibodies and sera of autoimmune patients react with Plasmodium falciparum and inhibit its in vitro growth

“…Furthermore, auto-Abs found during the course of AID can also cross-react with different self-structures in the host. For example, anti-DNA auto-Ab from SLE patients can bind to α-laminin, α-actinin, myosin and the NR2 glutamate receptor (DeGiorgio et al 2001, Mageed & Zack 2002, and the "same" anti-DNA auto-Ab from primary biliary cirrhosis patients can cross-react with mitochondrial antigens (Shimoda et al 2003). In the same way, anti-cardiolipin (anti-M1) antibodies can bind to phospholipids and β 2 glycoprotein I (Harris & Pierangeli 1994).…”