Correlation of C3D effector molecules concentrations, C1Q-CIC level and clinical activity in patients with rheumatoid arthritis

Complete or partial deficiencies (inherited and acquired) of all complement components, its regulatory proteins and receptors, are associated with autoimmune diseases such as Systemic lupus erithematodes (SLE) and Rheumatoid arthritis (RA). These deficiencies are more common in women than in men. The pathoethiological basis of this phenomenon is still unclear. Metabolism of C3 complement molecules started by their cleavage into C3b and then into C3c and C3d fragments. C3c is rapidly catabolized and cleared, but C3d molecules, because of its small molecular mass (35 kDa), have relatively slow catabolism. For this reason C3d molecules can moved by diffusion in blood circulation from extravascular sites of complement activation. The measurement of C3d concentration in plasma or serum specimens of RA patients can be a useful tool for monitoring of in vivo parallel complement activation, which may be involved in the pathogenesis of rheumatoid arthritis. Measurement of the serum concentration of C3d is thus a useful index of in vivo complement activation or index of disease activity. C3d effector molecules, as degradation products of C3b, tend to bind to B-cell CR-2/CD21receptors and to the surface of bacteria and fungi as well. Because of increased C3 catabolism during RA the level of C3d component is generally increased in plasma from RA patients. In clinical management of RA the monitoring and quantification of C3d levels in combination with C1q-CIC quantification is common in investigation of complement activation. For this reasons, we investigated the level variation of C3d component concentrations in 53 serum specimens taken from RA patients, in correlation with C1q-CIC values and other clinical findings, by ELISA-HYCOR quantitative automated method. Our results suggest that extreme high levels of C3d are always followed by C1q-CIC positivity. Never opposite case did not found. Almost, all RA patients were female. It was established specific level variation of commonly used markers of RA disease activity such as RF (rheumatoid factor), CRP (serum C-reactive protein), CICs, ESR (erythrocyte sedimentation rate) in relation with C3d concentrations in specific cases. On the basis of obtained values specific for markers of RA activity, we described four grades of RA disease activity: I = inactive; grade II= slightly active; grade III = moderately active, grade IV = very active. In our investigations the extremely high values of C3d and C1q-CIC levels in correlation with other clinical findings, in most cases suggest to grade III or moderate disease activity in RA patients. During chemotherapy by corresponding drugs mainly, it was achieved the reduction of disease activity to a level II (slightly active).