IgM and IgA Rheumatoid Factors Purified from XXXX Sera Boost the Fc Receptor- and Complement-Dependent Effector Functions of the Disease-Specific Anti-Citrullinated Protein Autoantibodies.

@entity1 @entity32 @entity650 @entity558 @entity1356 @entity310 @entity1193 @entity603 @entity687 @entity7134 @entity2939 @entity6824 @entity688 @entity309
UNASSIGNED: Rheumatoid factors (RF) and the disease-specific anti-citrullinated protein autoantibodies ( @entity7134 ) coexist in the joints of @entity309 ( @entity309 ) @entity1 where they probably contribute to @entity603 . We investigated the influence of IgM and IgA RF on the FcR- and complement-dependent effects of @entity7134 immune complexes ( @entity7134 -IC). When stimulated by @entity7134 -IC formed in the presence of IgM RF or IgA RF fractions purified from @entity309 serum pools, @entity6824 -generated macrophages skewed their cytokine response toward @entity32 , with increases in the @entity310 / @entity688 ratio and in @entity650 and @entity687 secretion, and decreases in the @entity1193 / @entity1356 ratio. In the IgM RF-mediated amplification of the inflammatory response of macrophages, the participation of an IgM receptor was excluded, notably by showing that they did not express any established receptor for IgM. Rather, this amplification depended on the IgM RF-mediated recruitment of more IgG into the @entity7134 -IC. However, the macrophages expressed FcaRI and blocking its interaction with IgA inhibited the IgA RF-mediated amplification of @entity310 secretion induced by @entity7134 -IC, showing its major implication in the effects of RF of the IgA class. @entity558 further amplified the @entity310 response of macrophages to RF-containing @entity7134 -IC. Lastly, the presence of IgM or IgA RF increased the capacity of @entity7134 -IC to activate the complement cascade. Therefore, specifically using autoantibodies from @entity309 @entity1 , the strong FcR-mediated or complement-dependent pathogenic potential of IC including both @entity7134 and IgM or IgA RF was established. Simultaneous FcR triggering by these RF-containing @entity7134 -IC and @entity2939 ligation possibly makes a major contribution to @entity309 .
