Private specificities can dominate the humoral response to self-antigens in patients with cryptogenic fibrosing alveolitisReportar como inadecuado




Private specificities can dominate the humoral response to self-antigens in patients with cryptogenic fibrosing alveolitis - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Respiratory Research

, 2:119

First Online: 20 February 2001Received: 24 November 2000Revised: 29 January 2001Accepted: 31 January 2001

Abstract

BackgroundThe pathogenetic mechanisms that underlie the interstitial lung disease cryptogenic fibrosing alveolitis CFA may involve an immunological reaction to unidentified antigens in the lung, resulting in tissue damage.

MethodIn order to identify the range of target autoantigens, we used expression cloning, employing serum from an index patient as the probe against an expressed cDNA library that was derived from a tumour cell line. We screened over 5 × 10 recombinants and obtained sequence information on three antigens that had provoked strong responses with immunoglobulin heavy chain class switching, presumably as a consequence of T-cell recognition.

ResultsAll of the antigens were identifiable by comparison with sequence data from the US National Center for Biotechnology Information. Alanyl tRNA synthetase ATS was picked on six occasions; five of these incidences reflected independent recombination events, indicating that the library was not biased. Antibodies to ATS anti-PL-12 represent the most common reactivity that defines the antisynthetase syndrome, which is typically expressed as polymyositis, dermatomyositis and interstitial lung disease ILD. The index patient never showed symptoms other than those associated with alveolitis, even though sera obtained from him over a period of 2 years contained antibodies with the same specificity. Autoantibodies to ATS were never detected in serial bleeds from 11 other patients with CFA, and neither did we detect antibodies to the other two antigens identified from the serum of the index patient.

ConclusionThe humoral response in patients with CFA can be dominated by autoantibodies with private specificities. This suggests that the antibodies are epiphenomenal and are a secondary feature of tissue damage induced by some other mechanism.

Keywordsantisynthetase syndrome cryptogenic fibrosing alveolitis diagnostic autoantibodies AbbreviationsATSalanyl tRNA synthetase

CFAcryptogenic fibrosing alveolitis

ESTexpressed sequence tag

IGBP1α4 immunoglobulin-binding protein

ILDinterstitial lung disease

SAGEserial analysis of gene expression

SLEsystemic lupus erythematosus.

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Autor: Cleo Robinson - Marinella Callow - Sandra Stevenson - Bruce WS Robinson - Richard A Lake

Fuente: https://link.springer.com/



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