Checkmate for Auto-Antibodies

11. November 2008

Researchers at the University Erlangen-Nuremberg want to use an enzyme to fight autoimmune diseases such as multiple sclerosis, arthritis or the systemic Lupus erythematodes. The special effect: Not the entire immune system will be suppressed, just the damaging auto-antibodies.

The immune system has multifarious functions. Among others it is made to recognize diseases and to fight them. If the immune system gets out of control it might turn against the own body. The auto-antibodies attack body-own tissue and might cause great damage. Autoimmune diseases can affect nearly all tissues and organs or just single organs. At any rate they have a chronic process and a lack of a causal therapy in common.

Aiming at auto-antibodies

In combat against autoimmune diseases, currently the options are mainly limited to antiphlogistics and immune modulation, respectively suppression. The complex interplay of the immune system was not sufficiently understood until now and the targeted attack against the damaging auto-antibodies impossible. A new promising therapy approach was introduced by a team of researchers of Professor Falk Nimmerjahn at the University Erlangen-Nuremberg in cooperation with scientists at the University of Lund in Sweden. As published online in Proceedings of the National Academy of Sciences (PNAS 2008; doi: 10.1073/pnas.0808248105), the researchers succeeded to remove the sugar side chain with the aid of a bacterial enzyme leading to suppression of the proinflammatory activity of auto-antibodies. The enzyme used is endoglycosidase S (EndoS) from Streptococcus pyogenes, the pathogen causing purulent inflammations.

The sugar molecule is the key

Alongside protein modules, the sugar molecule is decisive for the effect of antibodies including the destructive implications of auto-antibodies. Nimmerjahn succeeded before in cooperation with researchers of the Rockefeller University in New York to decode the sugar side chain (PNAS 2007; 104: 8433-8437). They were able to demonstrate that certain sugar remains have a key function deciding over the destructive activity of auto-antibodies. The researchers tested the influence of modified sugar side chains in animal experiments. It turned out that especially sialic acid remains do have a key function. If they are missing, auto-antibodies can develop their full destructive power. Contrary to the assumption that serum proteins are responsible for the activity of auto-antibodies, the researchers also discovered that special cellular receptors (Fc-receptors) can be made accountable for the damaging effects of the auto-antibodies. Already back then, the researcher drew a new picture of therapies for autoimmune diseases.

Reaction also on human antibodies

The successful removal of the sugar side chain of antibodies resulted in animal experiments in the effective suppression of various autoimmune diseases. EndoS injection efficiently removes the IgG-associated sugar molecules. In other autoimmune models as well as in human antibodies, the side chain was removed successfully and the EndoS interfered with auto-antibody mediated proinflammatory processes.

Not to suppress the entire immune system

The advantage of the new therapy approach would be that the enzyme affects special antibodies fully targeted and does not suppress the entire immune system as currently applied treatment methods do. One of the effects of those current treatments is for example an increased susceptibility to infections. But the targeted attack on the sugar side chain did not always turn out the same and depended on individual subclasses of the IgG antibodies which might result in varying effects on patients.

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