Xenogenic humoral responses to islets transplanted in biohybrid diffusion chambers

It has been hypothesized that chronic antigen leakage from the hybrid artificial pancreas could stimulate a host humoral response. Such antibodies could be induced by antigens shed from the islet cell surface, or by proteins secreted by live cells or liberated after cell death. To determine if this humoral response occurs, porcine (n = 15) or canine (n = 7) islets were seeded (2-5 x 10(4) equivalent islet number, density 30 islets/mm3) into diffusion chambers fabricated from permselective acrylic membranes (nominal M(r) exclusion of 80,000). The chambers were implanted intraperitoneally into streptozotocin-induced diabetic rats. Sera were collected at various intervals (0-12 weeks) and tested against isolated canine and porcine islets, for tissue specificity and interspecies cross-reactivity by fluorescence immunocytochemistry. No immunofluorescence (or only weak background staining) was obtained when islets were exposed to horse sera, or to sera obtained before to xenodevice implantation. Within 2-6 weeks, however, the postimplantation sera showed strong immunoreactivity. The antibodies were found to be reactive to multiple tissues, and to possess little or no interspecies cross-reactivity. The appearance of these xenoantibodies coincided with the appearance of circulating soluble immune complexes. However, none of the respiratory, cutaneous, or gastrointestinal manifestations that are characteristic of an anaphylactic reaction, or of the diseases of immediate-type hypersensitivity, were observed, even after intraperitoneal injection of additional naked islet tissue. Renal glomeruli did not stain for IgG or C3 in islet recipients. These results suggest that islet cell antigens crossed the membrane and stimulated antibody formation in the host, although they did not appear to cause renal or immune complex disease during the course of this study.