3.5
#29-OR
NUMBER OF HLA-DRB GENES INFLUENCES LEVELS OF ENDOTOXIN CORE ANTIBODIES.
David M. Turner, PhD , Mohammed Rashid MSc , Mala Siva FRCA , Robert Stephens FRCA , Angela Casbard MSc , Colin Brown PhD , Juliette Brown PhD , Michael G. Mythen, MD and Cristina V. Navarrete, PhD . London United Kingdom, National Blood Service, NW9 5BG, H&I ; London United Kingdom, University College London, Immunology and Molecular Pathology ; London United Kingdom, University College London, W1T 3AA, Centre for Anaesthesia and Cambridge United Kingdom, National Blood Service, Clinical Studies Unit .

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Interindividual levels of IgG and IgM endotoxin core antibodies (EndoCAb) are known to vary in both healthy and patient populations. Low EndoCAb levels have been shown to be associated with complications following major surgery. 497 plateletpheresis donors were screened to establish EndoCAb levels in a local population and HLA-DRB typing was performed to investigate links with antibody production.
IgM and IgG EndoCAb were assessed by ELISA. HLA-DRB typing was performed using Dynal Reli reverse SSOP. Broad HLA-DR specificities were initially compared to production of IgM and IgG antibodies. HLA-DR1 and DR8 were associated with lower IgG antibody production. This prompted an analysis of EndoCAb levels against numbers of HLA-DRB genes (2, 3 or 4 genes). A linear regression test for trend analysis showed that there was a relationship between the number of DRB genes and the production of IgG EndoCAb, p=0.012 (2 genes = 100.8MU/ml, 3 genes = 135.05 MU/ml and 4 genes = 156.24 MU/ml).
Although little is known about the pathways leading to endotoxin antibody production, these results indicate a role for HLA-class II molecules. Lipopolysaccharide (LPS) has been shown to colocalise with class II molecules in late endosomes. The class II association observed could be a result of a requirement for class II presentation of LPS-binding protein epitopes to helper T cells, or of the role class II molecules play in trafficking CD1d to endosomes where binding of glycolipid antigens can occur. This HLA gene dose effect may enable identification of surgical patients who would benefit from transfusion of hyperimmune EndoCAb plasma.