Changes in size, subclass, and metabolic properties of serum immunoglobulin A in liver diseases and in other diseases with high serum immunoglobulin A.

Abstract

A B ST R A CT We have studied the relative contributions of monomeric (m-) and polymeric IgA (p-IgA) and of IgAl and IgA2 to total serum IgA in healthy adults and patients with liver disease (LD) or with other diseases and high serum IgA. Serum concentration of total secretory component (SC) was also determined. In addition, fractional catabolic rates (FCR) and synthetic rates for both m-and p-IgA were measured in nine controls and nine cirrhotics. Our results support four main conclusions: (a) In healthy adults, intravascular p-IgA contributes to only 4-22% (mean 12%) of serum IgA, because its FCR and synthetic rate are approximately two times higher and four times smaller, respectively, than those of intravascular mIgA. (b) In LD, biliary obstruction does not result in a significant increase in serum p-IgA unlike in rats and rabbits, indicating that in humans the SC-dependent biliary transport of p-IgA plays a much less significant role in selective removal of p-IgA from plasma than in rats and rabbits. (c) In contrast to biliary obstruction, parenchymal LD results in a significant and preferential increase in serum p-IgA, which in cirrhotics correlates with a selective reduction of the p-IgA-FCR. This supports a role for the human liver in selective removal of p-IgA from plasma, but another mechanism than the SC-dependent biliary transport should be considered. (d) Total SC, p-IgA, and IgA2 in serum are unlinked parameters, not necessarily reflecting mucosal events. A marked increase in serum SC occurs Address reprint requests to Dr. Delacroix, ICP-MEXP, Brussels, Belgium.

A comparison of anti-HER2 IgA and IgG1 in vivo efficacy is facilitated by high N-glycan sialylation of the IgA

“…In humans, the clearance rates of IgG1 and IgA do not differ as strikingly as in mice (IgG1 half-life is »21 days and IgA half-life is »5 days in humans). 31,32,33 Our preliminary PK studies with IgA from HEK293 cells transiently expressing the antibodies confirmed the published data on poor half-life in mice Figure 7. ADCC assays with IgA1-1g5 and IgA22-4g5 purified as described in Figure 2, IgG1 trastuzumab and isotype controls incubated at 1 mg/mL using isolated human PMN and MNC as effector cells and SK-BR-3 as target cells in a 25:1 ratio.…”

Humoral immune response to influenza vaccination in patients with primary immunoglobulin A nephropathy. An analysis of isotype distribution and size of the influenza-specific antibodies.

“…The percentage of polymeric IgA and IgA 1 antibodies appeared to decrease over time after immunization (P = 0.06 for IgA and 0.01 for IgA 1). (12,14), in the bone marrow (17), in the tonsils (18), and in cultures of peripheral blood lymphocytes (14) from patients with IgAN. The present study shows that this subclass shift is also demonstrable in an antigen-specific study.…”

“…The mesangial deposits were found to contain polymeric IgA by some investigators (7,(19)(20)(21), but not by others (2,5,6,8). In the plasma, polymeric IgA was found to be elevated in two studies (7,22), but no absolute (I 1, 23, 24) or relative (6,12,13,25,26) increase was found by others. These conflicting results can be partially explained by the fact that elevated serum levels of polymeric IgA are found predominantly during attacks of macroscopic hematuria (26).…”

Molecular size heterogeneity of immunoglobulins in health and disease

“…As has been previously reported, patients with alcoholic cirrhosis showed increased proportions and quantities of dimeric IgA (Lopez Traseasa et al.. 1980;Delacroix et al, 1983) and this was also apparent in some patients with IgA nephropathy, rheumatoid arthritis and Feity's syndrome. It was interesting that dimeric IgA was the principle form secreted from PBMC cultures a finding coniirming the conclusion of Kalsi, Delacroix & Hodgson (1983).…”

“…As has been previously reported, patients with alcoholic cirrhosis showed increased proportions and quantities of dimeric IgA (Lopez Traseasa et al.. 1980;Delacroix et al, 1983) and this was also apparent in some patients with IgA nephropathy, rheumatoid arthritis and Feity's syndrome. It was interesting that dimeric IgA was the principle form secreted from PBMC cultures a finding coniirming the conclusion of Kalsi, Delacroix & Hodgson (1983). Low tnolecular weight IgM was identified in a number of autoimmune conditions as previously described (Roberts-Thomson Wernick & Ziff, 1981), The finding of il direct correlation between monomeric IgM and the tolal eirculating IgM level in these polyclonal disorders suggests a disorder of assembly of the IgM subunits during the ongoing IgM immune response characteristic of these conditions.…”