Clearance of Polymeric IgA Aggregates in Humans

Roccatello, Dario; Picciotto, Giuseppe; Coppo, Rosanna; Piccoli, Giuseppe; Molino, Andrea; Cacace, Gianluigi; Amore, Alessandro; Amoroso, Antonio; Quattrocchio, Giacomo; Sena, Luigi Massimino

doi:10.1016/s0272-6386(89)80167-2

Cited by 26 publications

(8 citation statements)

References 27 publications

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“…[19][20][21] In addition, Yasumori 22 has represented the cases of decreased pIgR expression in the duodenum and impaired secretory-IgA-secretion in extra fluid in two of the 10 IgAN patients after duodenal biopsy. Therefore, decreased pIgR expression should also be found in some IgAN patients like ddY High mice.…”

Section: Discussionmentioning

confidence: 99%

Age-dependent decrease of polymeric Ig receptor expression and IgA elevation in ddY mice: a possible cause of IgA nephropathy

et al. 2003

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Individual animals in the closed colony population of ddY mice were analyzed to clarify the major cause of agedependent elevation of serum IgA and the appearance of human IgA nephropathy (IgAN)-like symptoms. Based on the serum IgA levels, the mice were classified into two subgroups. One was a high serum IgA group with some manifestations of IgAN through aging (ddY High ), and the other was a normal serum IgA group without IgAN (ddY Norm ). The ratio of urinary IgA to serum IgA was significantly reduced in ddY High mice, suggesting an impaired IgA clearance via secretion through the epithelial barrier. The actual clearance rate of the intravenously injected dimeric IgA in ddY High mice was found to be slower than that in ddY Norm mice. Furthermore, we found that the polymeric Ig receptors (pIgRs) that mediate transcytosis of IgA were poorly expressed in the glomeruli as well as in the intestine of ddY High mice, whereas the pIgRs were more abundantly expressed in ddY Norm mice. In addition, the comparative study using polymerase chain reaction showed that decreased pIgR expression occurred at the transcriptional level in the ddY High population. Taken together, these results suggest that a systemic defect in pIgR expression may result in impaired IgA secretion and accumulation of IgA in the serum of ddY High mice. The age-dependent changes of pIgR expression in the dimeric IgA secretion sites of ddY High mice suggest a possible cause for the elevation of serum IgA level and the pathogenesis of IgAN-like disease.

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Section: Discussionmentioning

confidence: 99%

Age-dependent decrease of polymeric Ig receptor expression and IgA elevation in ddY mice: a possible cause of IgA nephropathy

et al. 2003

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“…Studies on the clearance of IgA in IgAN patients have led to conflicting results. Roccatello and colleagues [13] found a decreased clearance in IgAN patients, suggesting a defective clearance mechanism, while Rifai et al [14] could not find any defect.…”

Section: Introductionmentioning

confidence: 96%

Complement enhances the clearance of large‐sized soluble IgA aggregates in rats

et al. 1991

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In the present study the involvement of the complement system (C) in the clearance of soluble IgA aggregates in the rat was studied. Monoclonal monomeric IgA (mIgA) antibody (which does not activate C) or aggregated polymeric IgA (aIgA; which activates C) were administered intravenously to phosphate-buffered saline-treated and complement-depleted [Cobra venom factor (CVF)-treated] rats and assessed for clearance from the circulation. In control rats, mIgA was cleared in a biphasic fashion with a first half-life (T1/2) of 29.5 +/- 14.2 min and a second T1/2 of 230 +/- 176 min. No differences were observed in clearance of mIgA in CVF-treated rats as compared to PBS-treated rats. In PBS-treated rats, aIgA with a size between 20 S and 150 S disappeared very rapidly from the circulation with a first T1/2 of 1.1 +/- 0.4 min and a second T1/2 of 23.2 +/- 11.3 min. In CVF-treated rats the clearance of aIgA was significantly delayed as compared to that in control rats, namely with a first T1/2 of 7.3 +/- 2.6 min and a second T1/2 of 64.2 +/- 19.4 min. Immunohistochemical studies of the liver (which is the main site of clearance of aIgA) revealed that Kupffer cells (KC) are mainly responsible for the uptake of aIgA. Furthermore, in PBS-treated rats aIgA deposition was accompanied by C3 deposition in the KC. In CVF-treated rats, the percentage of KC containing aIgA was significantly lower during the first 16 min after aIgA administration as compared to PBS treated rats. In addition no detectable C3 was found in KC of CVF-treated rats. These results indicate that KC play an important role in the clearance of large molecular weight IgA in rats and that C facilitates the clearance of these complexes from the circulation.

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“…IgA ICs in patients with IgA nephropathy [52,53]. Despite normal blood clearance rates and normal values for total hepatic uptake of IgA ICs in patients with IgA nephro pathy [52], defective hepatic IgA IC clearance cannot be ruled out as a cause of this condition.…”

Section: Discussionmentioning

confidence: 99%

Different Elimination of Circulating IgA Immune Complexes in Rat and Guinea Pig

Johansson

1994

Int Arch Allergy Immunol

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Soluble IgA immune complexes, formed between ¹²⁵I-labelled dinitrophenyl-conjugated human serum albumin and mouse IgA anti-dinitrophenyl antibodies (MOPC 315), were given intravenously to rats and guinea pigs. Blood clearance kinetics and organ distribution of radioactivity were measured after 15 min. Radioactivity was quantified in isolated parenchymal cells, Kupffer cells (KCs) and liver endothelial cells. IgA complexing did not affect the antigen blood clearance kinetics in either species. In rats, IgA increased the total hepatic antigen uptake, owing to a vast increase in the uptake by parenchymal cells. No IgA-mediated effect could be shown in KCs, still about 40–50% of the hepatic uptake was confined to KCs. In guinea pigs there was also an IgA-mediated increase in hepatic uptake, but here the increase could be ascribed to the KCs alone.

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Clearance of Polymeric IgA Aggregates in Humans

Cited by 26 publications

References 27 publications

Age-dependent decrease of polymeric Ig receptor expression and IgA elevation in ddY mice: a possible cause of IgA nephropathy

Age-dependent decrease of polymeric Ig receptor expression and IgA elevation in ddY mice: a possible cause of IgA nephropathy

Complement enhances the clearance of large‐sized soluble IgA aggregates in rats

Different Elimination of Circulating IgA Immune Complexes in Rat and Guinea Pig

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