An abnormal but functionally active complement component c9 protein found in an irish family with subtotal c9 deficiency
Orren, Ann O'Hara, Ann M. Morgan, B. Paul Moran, Anthony P. Wurzner, Reinhard
Orren, Ann
O'Hara, Ann M.
Morgan, B. Paul
Moran, Anthony P.
Wurzner, Reinhard
Repository DOI
Publication Date
2003-03-01
Type
Article
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Citation
Orren, Ann; O'Hara, Ann M. Morgan, B. Paul; Moran, Anthony P.; Wurzner, Reinhard (2003). An abnormal but functionally active complement component c9 protein found in an irish family with subtotal c9 deficiency. Immunology 108 (3), 384-390
Abstract
Two independently segregating C9 genetic defects have previously been reported in two siblings in an Irish family with subtotal C9 deficiency. One defect would lead to an abnormal C9 protein, with replacement of a cysteine by a glycine (C98G). The second defect is a premature stop codon at amino acid 406 which would lead to a truncated C9. However, at least one of two abnormal proteins was present in the circulation of the proband at 0.2% of normal C9 concentration. In this study, the abnormal protein was shown to have a molecular weight approximately equal to that of normal C9, and to carry the binding site for monoclonal antibody (mAb) Mc42 which is known to react with an epitope at amino acid positions 412-426, distal to 406. Therefore, the subtotal C9 protein carries the C98G defect. The protein was incorporated into the terminal complement complex, and was active in haemolytic, bactericidal and lipopolysaccharide release assays. A quantitative haemolytic assay indicated even slightly greater haemolytic efficiency than normal C9. Epitope mapping with six antihuman C9 mAbs showed the abnormal protein to react to these antibodies in the same way as normal C9. However, none of these mAbs have epitopes within the lipoprotein receptor A module, where the C98G defect is located. The role of this region in C9 functionality is still unclear. In conclusion, we have shown that the lack of a cysteine led to the production of a protein present in the circulation at very much reduced levels, but which was fully functionally active.
Funder
Publisher
Wiley-Blackwell
Publisher DOI
10.1046/j.1365-2567.2003.01587.x
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Attribution-NonCommercial-NoDerivs 3.0 Ireland