Relative contribution of contact and complement activation to inflammatory reactions in arthritic joints.
Although both the complement and contact system are thought to contribute to the inflammatory reaction in arthritic joints, only activation of complement has so far been well established, whereas contact activation and its contribution to arthritis has not been systematically explored. Complement and contact activation were assessed in 71 patients with inflammatory arthropathies and 11 with osteoarthritis using sensitive assays for C3a, and C1-inhibitor (C1INH)-kallikrein and C1INH-factor XIIa complexes respectively. Increased plasma concentrations of kallikrein-and factor XIIa-C1INH complexes were found in two and seven of the 71 patients with inflammatory arthropathies, respectively, and in none of the patients with osteoarthritis. Increased synovial fluid concentrations of kallikrein and factor XIIa complexes occurred in 13 and 15 patients with inflammatory joint diseases respectively, and in two patients with osteoarthritis. Contact system parameters did not correlate with clinical symptoms, local activity, or neutrophil activation. In contrast, synovial fluid concentrations of C3a and C1INH-C1 complexes were increased in all patients and in 20 patients with inflammatory arthropathies respectively, and were higher in patients with a higher local activity score. Synovial fluid C3a correlated with parameters of neutrophil activation such as lactoferrin. Increased plasma concentrations of C3a and C1INH-C1 complexes occurred in 13 and 11 patients with inflammatory joint diseases, and in one and two patients with osteoarthritis respectively. Plasma concentrations of C3a correlated with the number of painful joints. Thus contact activation occurs only sporadically in patients with arthritis and contributes little if anything to the local inflammatory reaction and neutrophil activation. These latter events are significantly related to the extent of complement activation.
Abbink
J J
JJ
Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Kamp
A M
AM
Nuijens
J H
JH
Erenberg
A J
AJ
Swaak
A J
AJ
Hack
C E
CE
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism; D001777:Blood Coagulation / Q000502:physiology*; D002449:Cell Aggregation / Q000502:physiology; D003167:Complement Activation / Q000276:immunology*; D003174:Complement C1 Inactivator Proteins / Q000378:metabolism; D015926:Complement C3a / Q000032:analysis; D015956:Factor XIIa / Q000378:metabolism; D005260:Female; D006801:Humans; D007610:Kallikreins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology; D010003:Osteoarthritis / Q000276:immunology; D011288:Prekallikrein / Q000032:analysis; D013582:Synovial Fluid / Q000276:immunology
D003174:Complement C1 Inactivator Proteins; D015926:Complement C3a; D011288:Prekallikrein; D007610:Kallikreins; D015956:Factor XIIa