Clearance of cryoglobulins in man.
From the foregoing it is evident that the defective clearance of immune complexes may contribute to tissue damage seen in patients with cryoglobulins. Hypocomplementaemia, decreased erythrocyte CR1, and the nature of the immune complexes may all contribute to decreased binding of immune complexes to erythrocytes with the potential consequence of increased availability for deposition and decreased processing of immune complexes. In addition, in type II cryoglobulinaemia the nature of the immune complex namely IgM RF/IgG complexes, has been shown in some circumstances to fix C3 and C4 inefficiently in spite of detectable fluid phase complement activation. The poor C3 fixation results not only in decreased transport by erythrocytes to the RES but also in inefficient removal of immune complexes by phagocytic cells, since the Fc receptor on these cells would be acting alone without the synergy of occupied complement receptors. Persistence of immune complexes in tissues in these circumstances has two potential consequences. First, the multivalency of IgM may contribute to enlargement of these immune complexes in situ by successive trapping of antigen and antibody complexes; this process may be aided by local factors such as low temperature at the peripheries and increased protein concentration in glomerular capillary loops, which favour "cryo" precipitation. The higher avidity of RF for IgG that is surface bound rather than monomeric would also favor immune complex formation in these circumstances. Second, although there is no opsonization of the immune complex complement activation results in bystander fixation of C4 and C3 to the surrounding tissues resulting in tissue injury.
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Y C
YC
Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Schifferli
J A
JA
D000936:Antigen-Antibody Complex / Q000378:metabolism*; D001692:Biological Transport; D003165:Complement System Proteins / Q000502:physiology; D003450:Cryoglobulins / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D008657:Metabolic Clearance Rate; D012157:Mononuclear Phagocyte System / Q000502:physiology; D011951:Receptors, Complement / Q000502:physiology*; D017463:Receptors, Complement 3b; D012217:Rheumatoid Factor / Q000378:metabolism
D000936:Antigen-Antibody Complex; D003450:Cryoglobulins; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D003165:Complement System Proteins; D012217:Rheumatoid Factor