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

Respiratory Research

Richard A Lake¹  Bruce WS Robinson¹  Sandra Stevenson¹  Marinella Callow¹  Cleo Robinson¹ 

[1] University Department of Medicine, Western Australian Institute for Medical Research, Queen Elizabeth II Medical Centre, Perth, Western Australia

关键词: diagnostic autoantibodies;    cryptogenic fibrosing alveolitis;    antisynthetase syndrome;   

Others  :  1227463
DOI  :  10.1186/rr46

 received in 2000-11-24, accepted in 2001-01-31,  发布年份 2001

【 摘 要 】

Background

The 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.

Method

In 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 × 10⁵ 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.

Results

All 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.

Conclusion

The 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.

【 授权许可】

   
2001 Robinson et al, licensee BioMed Central Ltd

【 图 表 】

Figure 1.

Figure 2.

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