C-reactive protein (CRP) interacts with phosphorylcholine (PC), Fc receptors, complement factor C1q and cell nuclear constituents, yet its biological roles are insufficiently understood.The aim was to characterize CRP-induced complement activation by ellipsometry. PC conjugated with keyhole limpet hemocyanin (PC-KLH) was immobilized to cross-linked fibrinogen. A low-CRP serum with different amounts of added CRP was exposed to the PCsurfaces. The total serum protein deposition was quantified and deposition of IgG, C1q, C3c, C4, factor H and CRP detected with polyclonal antibodies. The binding of serum CRP to PC-KLH dose-dependently triggered activation of the classical pathway. Unexpectedly, the activation was efficiently down-regulated at CRP levels >150 mg/L. Using radial immunodiffusion, CRP-C1q interaction was observed in serum samples with high CRP concentrations. We propose that the underlying mechanism depends on fluid-phase interaction between C1q and CRP. This might constitute another level of complement regulation, which has implications for systemic lupus erythematosus where CRP is often low despite flare-ups.

Beware of antibodies to dietary proteins in "antigen-specific" immunoassays! Falsely positive anti-cytokine antibody tests due to reactivity with bovine serum albumin in rheumatoid arthritis (the Swedish TIRA project)

Rheumatoid factor (RF), i.e. a family of autoantibodies against the Fc part of IgG, is an important seromarker of rheumatoid arthritis (RA). Traditional particle agglutination without disclosing the antibody isotype remains the predominating diagnostic method in clinical routine. Although IgG‐RF attracts pathogenic interest, its detection remains technically challenging. The present study aimed at developing a set of tests identifying IgG‐RFs directed against the four IgG subclasses. IgG‐RF against either subclass of human IgG‐Fc were analysed with four novel enzyme‐linked immunosorbent assays (ELISAs) utilizing four recombinant human Fc‐gamma fragments (hIgG1–4) as sources of antigen. Sera from 40 patients with recent onset RA (20 seropositive and 20 seronegative by IgM‐RF and IgA‐RF‐isotype‐specific ELISA) were analysed. Sera from 20 healthy blood donors served as reference. Among the IgM‐/IgA‐RF‐positive RA‐sera, IgG‐RF was found directed against hIgG1 and hIgG2, but not against hIgG3 or hIgG4. Significant correlations were seen between IgG‐RF against hIgG2‐Fc and IgM‐RF (r = 0.666) levels. Further prospective studies are warranted to elucidate any correlation to disease course and outcome.