Abstract
The etiology of Kawasaki disease (KD) is still unknown, but an infectious origin and involvement of IgA B cells has been suggested. Coronary complications of KD can be reduced with IVIG therapy. It is not clear how IVIG interacts with the immune system. Previously, we selected a large number of IgG and IgM Fab specifically bound by IVIG molecules using phage display and antiidiotypic panning from three patients with autoimmune thrombocytopenia (Eur.J.Immunol. 1998; 28:4236-4247), a patient with lupus and from a healthy individual (Clin.Exp.Immunol. 2000; 121:37-46). The favoured VH germ-line gene segments of these IVIG-bound Fabs were 3-23 or 3-30/3-30.5, the most frequently rearranged VH genes among 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 receptors derived from these two germ-line genes (Arthritis Rheum. 2000, 43, 2722-2732). Here, to investigate whether or not treatment with IVIG influences this restricted interaction, we cloned and selected Fab fragments from a patient with KD before and after IVIG therapy. A favoured selection of IgG antibodies derived from both the 3-23 or 3-30/3-30.5 germ-line genes as before was observed. Importantly, the reactivity with IVIG was significantly higher for clones from the library prepared after the IVIG treatment, providing the first in vivo functional evidence that a subset of IVIG may selectively activate B cells of this germ-line origin (Clin. Immunol. 2001, 99, 18-29). This mechanism may add to the therapeutic effect of IVIG in the treatment of KD. In contrast, an IgA library from the same patient revealed only selection of 3-07 germ-line derived clones by IVIG. IVIG selected IgG clones of 3-07 origin showed a decrease after IVIG therapy, suggesting that those antibodies or their targets may be involved in the cause of KD.
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Fischer, P., Leucht, S., Pape, I. et al. Enhanced B Cell Superantigen-like Interaction of IVIG with IgG but not IgA Cloned from a KD Patient after IVIG Therapy. Pediatr Res 53, 160 (2003). https://doi.org/10.1203/00006450-200301000-00041
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DOI: https://doi.org/10.1203/00006450-200301000-00041