The B cell superantigen-like interaction of intravenous immunoglobin (IVIG) with Fab fragments of V-H 3-23 and 3-30/3-30.5 germline gene origin cloned from a patient with Kawasaki disease is enhanced after IVIG therapy

The etiology of Kawasaki disease (KD) is still unknown. Therefore, the diag nosis relies on clinical criteria only. Although a specific therapy for KD is not available, coronary complications can be significantly reduced with the help of intravenous immunoglobulin (IVIG) therapy. It is not clear how MG interacts with the immune system. Previously, we selected a large number of IgG and IgM Fab fragments specifically reacting with IVIG molecules by phage display and antiidiotypic panning from three patients with autoimmune thrombocytopenia, a patient with lupus, and a healthy individual. Sequenci ng revealed that the favored V-H germline gene segments of these MG-bound F abs were 3-23 or 3-30/3-30.5, the most frequently rearranged V-H genes amon g human B cells. The binding pattern suggested a B cell superantigen-like, specific interaction of an IVIG subset with B cells that present B cell rec eptors derives from these two germline genes. The aim of the current study was to investigate whether treatment with MG influences this restricted int eraction. Therefore we cloned and selected Fab fragments from a patient wit h KD before and after MG therapy. A favored selection of antibodies derived from both the 3-23 and the 3-30/3-30.5 germline gene segments as before wa s observed. importantly, the reactivity with IVIG was significantly higher for clones from the library prepared after the IVIG treatment, providing th e first in vivo functional evidence that a subset of IVIG may selectively a ctivate B cells of this germline origin. This mechanism may add to the ther apeutic effect of IVIG; in the treatment of KD. (C) 2001 Academic Press.