Abstracts
2000 Digestive Disease Week

# 2318 Impairment of Mucosal Immunity by Parenteral Nutrition: Decreased Nasotracheal Influenza-Specific Secretory IgA Levels and Transport in Parenterally Fed Mice.
Kathryn B. Renegar, Kenneth Allan Kudsk, R. Chance Dewitt, Yong Wu, Brock K. King, Memphis, TN

IgA is the most important component in mucosal specific immunity. It is transported intraluminally by secretory component (SC) on mucosal epithelial cells after production by B cells or plasma cells in the lamina propria (LP). Mucosal IgA protection is influenced by enteral feeding or lack of it. Parenteral nutrition (IV-TPN) decreases the size of LP lymphoid tissue and decreases intestinal and respiratory IgA, implying reduced production. However, IV-TPN also affects the mucosa which could affect SC and IgA transport. This work investigates whether dietary alteration of IgA is due to reduced production, decreased transport, or both, by measuring mucosal transport of IV-administered polymeric IgA (pIgA) relative to IgG via the selective transport index (STI=nasal pIgA/serum pIgA ¥serum IgG-1/nasal IgG-1). Intact mucosa is relatively impermeable to IgG (STI < 1); an STI of 1.0 indicates comparable pIgA and IgG transport while STI > 1 indicates selective transport of pIgA. Expt. 1: Mice were randomized to chow (n=15) or IV-TPN (n=17) and, after 5 days, given a mixture of pIgA (1700 mg) and IgG (1460 mg). Nasal washes and serum were collected for ELISA analysis. Expt. 2: Eight mice immunized against H1N1 were fed IV-TPN for 5 days (which impairs the immunity), randomized to receive IV viral-specific pIgA or nonspecific antibody and given H1N1 virus intranasally 4 hours later. Viral cultures were obtained at 42 hours to determine immunity. Unimmunized controls were also tested. Results: Expt. 1: The STI of IVTPN animals dropped significantly (1164 ± 859 vs 4633 ± 297, p<0.005), indicating impaired mucosal transport. However, in Expt. 2, 4 of 4, mice administered viral-specific pIgA eliminated the virus (reflecting immunity and adequate transport) while 4/4 animals given nonspecific antibody had virus present (p<0.05). All unimmunized mice had virus present. Conclusion: Reduced respiratory IgA with IV-TPN is affected by both changes in GALT and impaired mucosal transport. However, residual transport is adequate for protection if adequate IgA is present. Thus, production is the limiting factor in maintaining respiratory IgA-mediated antiviral defenses.