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Inflammation Research
Erschienen in: Inflammation Research 9/2011

01.09.2011 | Original Research Paper

Expression of IgA class switching gene in tonsillar mononuclear cells in patients with IgA nephropathy

verfasst von: Hong Liu, Youming Peng, Fuyou Liu, Weiwei Xiao, Yu Zhang, Weiwei Li

Erschienen in: Inflammation Research | Ausgabe 9/2011

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Abstract

Background and aim

There are many reports suggesting a relationship between the tonsillar autoimmune response and the pathogenesis of IgA nephropathy (IgAN). Hyperproduction of IgA and IgA1 in tonsils could be caused by activation of the Ig class switching recombination (CSR). αGLT (germline transcripts) plays a critical role in the initiation of switching from Cμ to Cα, resulting in production of IgA. Activation-induced cytidine deaminase (AID) is a molecule essential for CSR and Ig gene conversion. The aim of this study was to investigate IgA and IgA1 levels in the supernatant of tonsillar mononuclear cells (TMCs) and the expression of Iα-Cα germline transcript and AID in TMCs stimulated with lipopolysaccharide or hemolytic streptococcus in IgAN patients and chronic tonsillitis patients.

Methods

27 IgAN patients were admitted into our hospital from Jan. 2009 to Feb. 2010. Another 27 patients with chronic tonsillitis but without renal disease were selected as the control group. Tonsillar lymphocytes were isolated by density gradient centrifugation using Lymphocyte Separation Medium. The amount of IgA or IgA1 secreted in the culture supernatants was determined by specific enzyme-linked immunosorbent assay. Expressions of Iα-Cα germline transcript and AID mRNA were examined by reverse transcription real-time PCR. The AID protein was determined by Western blotting.

Results

The production of IgA and IgA1 protein, especially the ratio of IgA1/IgA in TMCs stimulated with or without 10 μg/ml of lipopolysaccharide or 1 × 108 cfu/ml of hemolytic streptococcus, were significantly increased in the IgAN group compared with that in the non-IgAN group (P < 0.05), and the IgA and IgA1 levels in TMCs stimulated with 10 μg/ml of lipopolysaccharide or 1 × 108 cfu/ml of hemolytic streptococcus were markedly increased in patients with IgAN compared with the control group (P < 0.05).The expressions of Iα-Cα and AID mRNA were significantly upregulated in TMCs stimulated with 10 μg/ml of lipopolysaccharide or 1 × 108 cfu/ml of hemolytic streptococcus in patients with IgAN compared with control group (P < 0.05). The expression of AID protein in TMCs stimulated with or without 10 μg/ml of lipopolysaccharide or 1 × 108 cfu/ml of hemolytic streptococcus was significantly increased in the IgAN group compared with that in the non-IgAN group (P < 0.05). The expression of AID protein in TMCs stimulated with 10 μg/ml of lipopolysaccharide or 1 × 108 cfu/ml of hemolytic streptococcus was significantly increased in patients with IgAN compared with the control group (P < 0.05, P < 0.01).

Conclusion

Lipopolysaccharide or hemolytic streptococcus can induce the production of IgA and IgA1 and the expression of AID and Iα-Cα in TMCs from patients with IgAN. Our results indicate that the TMCs from patients with IgAN are capable of producing high levels of IgA and IgA1 when stimulated with lipopolysaccharide or hemolytic streptococcus, which may be due to the increased expression of AID and Iα-Cα.
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Metadaten
Titel
Expression of IgA class switching gene in tonsillar mononuclear cells in patients with IgA nephropathy
verfasst von
Hong Liu
Youming Peng
Fuyou Liu
Weiwei Xiao
Yu Zhang
Weiwei Li
Publikationsdatum
01.09.2011
Verlag
SP Birkhäuser Verlag Basel
Erschienen in
Inflammation Research / Ausgabe 9/2011
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-011-0347-0

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