Somatic Mutations Modulate Autoantibodies against Galactose-Deficient IgA1 in IgA Nephropathy

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F16%3A33162260" target="_blank" >RIV/61989592:15110/16:33162260 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1681/ASN.2014101044" target="_blank" >http://dx.doi.org/10.1681/ASN.2014101044</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1681/ASN.2014101044" target="_blank" >10.1681/ASN.2014101044</a>

Result language

angličtina

Original language name

Somatic Mutations Modulate Autoantibodies against Galactose-Deficient IgA1 in IgA Nephropathy

Original language description

Autoantibodies against galactose-deficient IgA1 drive formation of pathogenic immune complexes in IgA nephropathy. IgG autoantibodies against galactosedeficient IgA1 in patients with IgA nephropathy have a specific amino-acid sequence, Y1CS3, in the complementarity-determining region 3 of the heavy chain variable region compared with a Y1CA3 sequence in similar isotype-matched IgG from healthy controls. We previously found that the S3 residue is critical for binding galactose-deficient IgA1. To determine whether this difference is due to a rare germline sequence, we amplified and sequenced the corresponding germline variable region genes from peripheral blood mononuclear cells of seven patients with IgA nephropathy and six healthy controls fromwhomwe had cloned single-cell lines secreting monoclonal IgG specific for galactose-deficient IgA1. Sanger DNA sequencing revealed that complementarity-determining region 3 in the variable region of the germline genes encoded the Y1C(A/V)3 amino-acid sequence. Thus, the A/V.S substitution in the complementarity-determining region 3 of anti-galactose- deficient-IgA1 autoantibodies of the patients with IgA nephropathy is not a rare germline gene variant. Modeling analyses indicated that the S3 hydroxyl group spans the complementarity-determining region 3 loop stem, stabilizing the adjacent b-sheet and stem structure, important features for effective binding to galactosedeficient IgA1. Understanding processes leading to production of the autoantibodies may offer new approaches to treat IgA nephropathy.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

EC - Immunology

OECD FORD branch

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Project

<a href="/en/project/EE2.3.20.0164" target="_blank" >EE2.3.20.0164: International research network</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of the American Society of Nephrology

ISSN

1046-6673

e-ISSN

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Volume of the periodical

27

Issue of the periodical within the volume

11

Country of publishing house

US - UNITED STATES

Number of pages

7

Pages from-to

3278-3284

UT code for WoS article

000386538300009

EID of the result in the Scopus database

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