Denatured-jacalin derivatives with selective recognition for O-linked glycosides (ST,T, Tn,and STn Type) on IgA1 hinge region

Immunoglobulin A1 (IgA1) concentration in the plasma of patients with IgA nephropathy (IgAN) as the cause of renal failure is higher than that in the plasma of normal controls. IgA1 with abnormal sugars is considered to deposit in the glomerular mesangium, aggravating nephritis in IgAN. Jacalin is a lectin that recognizes sugars on IgA1. However, its selective-recognition for normal-type (ST type, NeuAc-α(2,3)-Gal-β(1,3)-GalNAc) and abnormal-type (T type, Gal-β(1,3)-GalNAc; Tn type, GalNAc; STn type, NeuAc-α(2,6)-GalNAc) sugars α-O-linked to serine/threonine in IgA1 is weak. Therefore, jacalin cannot be used for recognizing specific sugar types on IgA1. We attempted to develop a new recognition method for specific sugar types on IgA1 by utilizing the multirecognition capability of jacalin. Its binding abilities were regulated by heat denaturation with suitable template sugar (galactose or N-acetylgalactosamine). Further, we successfully prepared denatured-jacalin derivatives, which recognized ST-/T-type sugars on IgA1, by sugar-immobilized affinity chromatography. Enzyme-linked immunosorbent assay of denatured-jacalin derivatives, showed the ratios of abnormal sugars on IgA1 in the plasma of IgAN patients and normal controls to be approximately 60% and 20%, respectively. The results proved that profiling of sugar types in IgAN can successfully be performed by solely using jacalin derivatives.