Patients Family Medical History and past/current Medical History and Complement System

Activation of Classical Pathway Complement in Chronic Inflammation

Elevated Levels of Circulating C3d and C4d Split Products in Rheumatoid Arthritis  and  Crohn's Disease

NIELS ERIK PETERSEN, JENS ELMGREEN, B0RGE  TEISNER  and  SVEN-ERIK SVEHAG

From the Institute of Medical Microbiology, University of Odense, Odense and Medical Department TIA, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

ABSTRACT. Petersen NE, Elmgreen J, Teisner B, Svehag S*E (Institute of Medical Microbiology, University of Odense, Odense and Medical Department TTA,  Rigshospita let, University of Copenhagen, Copenhagen, Denmark). Activation of classical pathway complement in chronic inflammation. Elevated levels of circulating C3d and C4d split products in rheumatoid arthritis and Crohn's disease. Acta Med Scand   1988; 223:557--60.

Split products of complement component 3 (C3) and complement component 4 (C4) derived from activation of the alternative and classical complement pathways were meas­ ured in untreated outpatients, 20 with Crohn's disease and 19 with rheumatoid arthritis. Elevated levels of the d split product of C4 (C4d) were observed in 12 of 19 patients with rheumatoid arthritis and in 9 of 20 patients with Crohn's disease. Levels of the d split product of C3 (C3d) were increased in 14 of 19 patients with rheumatoid arthritis and in 6 of 20 Crohn's disease patients. The median values of C4d and C3d were significantly in­ creased in both groups of patients. C3d concentrations correlated  positively  with  C4d levels Crs=0.51--0.56, p<0.005). The complement activation was not reflected in reduced plasma levels of native C3 and C4. The data indicate activation of the classical complement pathway in both rheumatoid arthritis and Crohn's disease. Key U)()rds: Crohn' s disease, rheumatoid  arthritis,  chronic  inflammation, complement  C3, complement C4.

Normal or even increased levels of complement factor 3 (C3) (1), complement factor 4 (C4) and factor B (2) in sera of patients with rheumatoid  arthritis  and  Crohn' s disease  may reflect increased synthesis compensating for enhanced catabolism (3-5).  Immune  com­ plexes may be demonstrated in both conditions (6), but neither the site of complement activation nor the etiological factor(s) have been identified. The nature of the antigenic component  of  immune  complexes  found  in Crohn's  disease  remains unidentified.

The aim of the present study was to define the pathway responsible for elevated levels of the d split product of C3 (C3d) inpatients with Crohn'sdisease. For comparison C3d and the d split product of C4 (C4d) were also measured in patients with definite rheumatoid arthritis.