Chondroitin sulfate and abnormal contact system in rheumatoid arthritis.
Rheumatoid arthritis (RA) is a heterogeneous autoimmune disease that affects 1% of the population worldwide. In the K/BxN mouse model of RA, autoantibodies specific for glucose-6-phosphate isomerase (GPI) from these mice can transfer joint-specific inflammation to normal mice. The binding of GPI/autoantibody to the cartilage surface is a prerequisite for autoantibody-induced joint-specific inflammation in the mouse model. Chondroitin sulfate (CS) on cartilage surface is the long sought high-affinity receptor for GPI. The binding affinity and structural differences between mouse paw/ankle CS and knee/elbow CS correlate with the distal to proximal disease severity in these joints. The data presented in this chapter indicate that autoantigen/autoantibodies in blood circulation activate contact system to produce vasodilators to allow immune complex, protein aggregates, and other plasma proteins to get into the joints. Cartilage surface CS binds and retains autoantigen/autoantibodies. The CS/autoantigen/autoantibody complexes could induce C3a and C5a production through contact system activation. C3a and C5a trigger degranulation of mast cells, which further recruit plasma contact system and complement proteins, immune cells, and immune activation factors to facilitate joint-specific tissue destruction. Therefore, either reducing autoantibody production or inhibiting autoantibody-induced contact system activation might be effective in RA prevention.
Zhou
Xiaodong
X
Department of Pathology and Immunology, Washington University Medical School, St. Louis, MO, USA.
Weiser
Peter
P
Pan
Jing
J
Qian
Yi
Y
Lu
Hong
H
Zhang
Lijuan
L
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D001324:Autoantigens / Q000276:immunology*; D004195:Disease Models, Animal; D005956:Glucose-6-Phosphate Isomerase / Q000502:physiology; D006025:Glycosaminoglycans / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout
D001324:Autoantigens; D006025:Glycosaminoglycans; D005956:Glucose-6-Phosphate Isomerase