Macro creatine kinase BB isoenzyme in serum: most likely an antigen-autoantibody complex

Abstract

Nine sera containing an abnormal creatine kinase BB isoenzyme, “macro CK-BB”, were examined. Immunoglobulin precipitation after addition of radio-labelled CK-BB suggested that in eight of the sera the enzyme was linked to an immunoglobulin G. Results obtained with papain-digested and with pepsin-digested IgG suggested that the binding of CK-BB occurred in the antigen-binding region (the “Fab-region”) of JgG. Each of the two antigen-binding fragments of IgG, obtained by papain-digestion, were CK-BB specific, since they complexed this isoenzyme equally well when excess CK-MM and CK-MB was added. From Scatchard plots the affinity constant for binding of CK-BB to IgG and the BB-binding capacity of four of the sera was calculated. The affinity constant was high and differed little between the sera (range 0.7 ± 10¹¹-⁻1.6 ± 10¹¹ l/mol). The BB-binding capacity differed widely (range 21—900 μg of CK-BB per litre of serum), but in each serum it roughly paralleled the activity of the macro CK-BB complex. The results suggest that in eight of the nine sera examined the BB-binding IgG is an antibody with activity directed towards CK-BB.

Key Words:

• affinity constant
• binding capacity
• creatine kinase
• immunoglobulin G
• papain
• pepsin
• radioimmunoassay
• Scatchard plot