TY - JOUR
T1 - Broad requirement for terminal sialic acid residues and FcγRIIB for the preventive and therapeutic activity of intravenous immunoglobulins in vivo
AU - Schwab, Inessa
AU - Mihai, Sidonia
AU - Seeling, Michaela
AU - Kasperkiewicz, Michael
AU - Ludwig, Ralf J.
AU - Nimmerjahn, Falk
PY - 2014/1/1
Y1 - 2014/1/1
N2 - Intravenous immunoglobulin (IVIg) therapy is widely used to treat a variety of autoimmune diseases including immunothrombocytopenia, chronic inflammatory demyelinating polyneuropathy, and more recently autoimmune skin blistering diseases. Despite this well-documented clinical success, the precise molecular and cellular mechanisms underlying this immunomodulatory activity are discussed controversially. In particular, the clinically relevant therapeutic pathway of IVIg-mediated immune modulation has not been studied in detail. In the present study, we use four independent in vivo model systems of auto-Ab-mediated autoimmune disease to identify a common pathway explaining IVIg activity under therapeutic conditions in vivo. We show that irrespective of the in vivo model system, IVIg activity is strictly dependent on the presence of terminal sialic acid residues and the inhibitory FcγRIIB under preventive as well as therapeutic treatment conditions. In contrast, specific ICAM3 grabbing nonintegrin related 1, previously demonstrated to be essential under preventative treatment conditions, showed a disease-specific impact on IVIg-mediated resolution of established autoimmune disease.
AB - Intravenous immunoglobulin (IVIg) therapy is widely used to treat a variety of autoimmune diseases including immunothrombocytopenia, chronic inflammatory demyelinating polyneuropathy, and more recently autoimmune skin blistering diseases. Despite this well-documented clinical success, the precise molecular and cellular mechanisms underlying this immunomodulatory activity are discussed controversially. In particular, the clinically relevant therapeutic pathway of IVIg-mediated immune modulation has not been studied in detail. In the present study, we use four independent in vivo model systems of auto-Ab-mediated autoimmune disease to identify a common pathway explaining IVIg activity under therapeutic conditions in vivo. We show that irrespective of the in vivo model system, IVIg activity is strictly dependent on the presence of terminal sialic acid residues and the inhibitory FcγRIIB under preventive as well as therapeutic treatment conditions. In contrast, specific ICAM3 grabbing nonintegrin related 1, previously demonstrated to be essential under preventative treatment conditions, showed a disease-specific impact on IVIg-mediated resolution of established autoimmune disease.
UR - http://www.scopus.com/inward/record.url?scp=84899573297&partnerID=8YFLogxK
U2 - 10.1002/eji.201344230
DO - 10.1002/eji.201344230
M3 - Journal articles
C2 - 24505033
AN - SCOPUS:84899573297
VL - 44
SP - 1444
EP - 1453
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 5
ER -