Polymeric IgA

Thus, the tetravalency, anti-inflammatory properties and molecular stability of slgA make it particularly suitable for protective passive immunity when applied to mucosal surfaces. To date, the clinical evaluation of slgA protection in humans and animal models has been very limited. Indeed most studies have employed monomeric IgA monoclonal antibodies [3,15]. Hence, differences in IgA and IgG protective activities at the mucosal level have often not been observed [15]. Only a few studies have demonstrated the superior activity of polymeric IgA or slgA compared with monomeric IgG or IgA [16]. In order to determine the efficacy of slgA, future animal experiments and clinical trials are needed to compare the activities of IgG monoclonal antibodies and their slgA counterparts. The ability to engineer slgAs in plants will allow these comparisons to be made [17]. 

The major antibody isotype in external secretions is sIgA, and the total amount of IgA synthesized is twice the amount of IgG produced daily in humans. IgA cells represent up to 80% of the entire mucosal lymphoid cell population. sIgA in mucosal secretions results from polymeric IgA transported across mucosal epithelium via binding to the pIgRreceptor (also known as the secretory component). The receptor is eventually cleaved and results in an IgAipIgR complex, referred to as sIgA (Figure 7.2) (Rojas and Apodaca, 2002). 

SC is now known to be a proteolytic fragment of a receptor (poly(Ig) receptor), synthesised in glandular epithelial cells, that mediates transport of polymeric IgA (and IgM) into external excretions (512). This receptor is present on the surface of epithelial cells at several sites in the body (gut, liver, mammary glands, etc.) and binds to polymeric IgA (and IgM). This receptor-ligand complex then undergoes... 

Parenchymal liver cells Kupffer cells Liver endothelial cells Leucocytes Galactose, polymeric IgA, cholesterol ester-VLDL, LDL Mannose-fucose, galactose (particles), (oxidized) LDL Mannose, acetylated LDL Chemotactic peptide, complement C3b... 

The polymeric IgA receptor/secretory component (plgA-R/SC, also designated plgR) mediated transport represents another, less common and less utilized, form of specialized endosomal epithelial transcytosis. plgR are found... 

Kaetzel CS, Robinson JK, Lamm ME. Epithelial transcytosis of monomeric IgA and IgG cross-linked through antigen to polymeric IgA. A role for monomeric antibodies in the mucosal immune system. / Immunol 1994 152(l) 72-6. 

Ball JM, Moldoveanu Z, Melsen LR, et al. A polarized human endometrial cell line that binds and transports polymeric IgA. In Vitro Cell Dev Biol Anim 1995 31(3) 196-206. 

IL-4 induces an antiinflammatory effect by its ability to suppress production of proinflammatory cytokines (IL-1, TNFa, and IL-6) and to favor the release of IL-1RA. This antiinflammatory action is evident on activated monocytes and/or macrophages, namely the inhibition of IL-6 production. Indeed, not all target cells may be influenced in this way (e.g., IL-4 may be capable of regulating intestinal epithelial cell proliferation without altering the capacity of these cells to function in the inflammatory response by secreting IL-6). IL-4 and IFNy also synergistically increase total polymeric IgA receptor levels in human intestinal epithelial cells. ... 

Denning GM. IL-4 and IFN-y synergistically increase total polymeric IgA receptor levels in human intestinal epithelial cells. Role of protein tyrosine kinases. J Immunol 1996 156 4807-14. 

In some samples more than one paraprotein band will be found (see Fig. 14). This may be due to many causes (1) postsecretory alterations, either by (a) e.g, deamidation (K6), (b) polymerization (IgA... 

Hepatocytes Galactose-terminated (neo)glycoproteins, LDL, polymeric IgA, high-density lipoprotein, epidermal growth factor, transferrin... 

Restriction of dietary gluten is effective in patients with celiac disease, but not in patients with no identifiable nephritogenic antigens. Phenytoin was evaluated because of its ability to reduce the amount of polymeric IgA in the circulation. Although phenytoin reduced serum IgA concentrations and frequency of macroscopic hematuria, the glomerular lesions deteriorated in some of the patients despite treatment. Removal of the tonsils, which produce IgAi and may contribute to IgA nephropathy, may reduce proteinuria and hematuria however, the beneficial effect of tonsillectomy on renal function longterm has not yet been substantiated. ... 

J chain is synthesized by the same cells that produce the immunoglobulin to which it is attached (188,189). It is linked to IgM or to polymeric IgA shortly before secretion from a lymphoid cell. In the case of a myeloma tumor secreting both monomeric and dimeric IgA, the amount of dimer produced appears to be a function of the quantity of J chain available (189,190). 

Antiserum against isolated J chain reacts well with IgM or polymeric IgA only after the immunoglobulin has been reduced and alkylated thus, the J chain is either not exposed or is in an unreactive conformation in the native molecule (181). The J chain has similar antigenic properties whether or not its four disulfide bonds have been reduced this suggests that its conformation is not greatly affected by the status of those bonds (M.E. Koshland, personal communication). 

Other useful criteria include the following (a) Arrangement of 4-chain disulfide bonded monomers (e.g., the pentameric structure characteristic of IgM), and carbohydrate content (b) the number of domains in the H chain (c) the presence of a secretory component (for IgA) or J chain (IgM and polymeric IgA) synthesis by a secretory immune system associated with epithelial tissues (for IgA) (d) heat lability, sensitization of skin with a relativity long latent period, prolonged persistence in skin, and a molecular weight somewhat greater than that of IgG (for IgE) (e) attachment to mast cells and basophilic leukocytes (IgE). 

J chain is present in the IgM of the pheasant, marine toad, catfish, chicken, and each of a large variety of mammals (49,51). It is also present in the polymeric IgA of the chicken and of various mammals... 

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