PubMed · 8619739
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R H Seder, V P Berardi. 1996. Proficiency testing program for Lyme disease.. https://pubmed.ncbi.nlm.nih.gov/8619739/
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The recognition reactions between a synthetic disaccharide alpha-Kdo-(2-->4)-alpha-Kdo-(2-->O)-allyl and two monoclonal antibodies (mAbs) were studied by NMR, yielding two distinct bound conformations of the carbohydrate ligand. One mAb, S23-24, recognizes the disaccharides alpha-Kdo-(2-->4)-alpha-Kdo-(2-->O)-allyl and alpha-Kdo-(2-->8)-alpha-Kdo-(2-->O)-allyl with similar affinities, whereas mAb S25-2 binds to the disaccharide alpha-Kdo-(2-->8)-alpha-Kdo-(2-->O)-allyl with an approximately 10-fold higher affinity than to the disaccharide alpha-Kdo-(2-->4)-alpha-Kdo-(2-->O)-allyl. Compared to S25-2, S23-24 binds to alpha-Kdo-(2-->4)-alpha-Kdo-(2-->O)-allyl with an approximately 50-fold increased affinity. We used NMR experiments that are based on the transferred NOE effect, specifically, trNOESY, trROESY, QUIET-trNOESY, and MINSY experiments, to show that the (2-->8)-specific mAb, S25-2, stabilizes a conformation of the alpha-(2-->4)-linked disaccharide that is not highly populated in solution. S23-24 recognizes two conformations of alpha-Kdo-(2-->4)-alpha-Kdo-(2-->O)-allyl, one that is highly populated in aqueous solution and another conformation that is similar to the one bound by S25-2. This is the first example where it is experimentally shown that a carbohydrate ligand may adopt different bioactive conformations upon interaction with mAbs with different fine specificities. Our NMR studies indicate that a careful examination of spin diffusion is critical for the analysis of bioactive conformations of carbohydrate ligands.
OBJECTIVES: To investigate the effect of Chlamydia pneumoniae infection on future development of ischaemic heart disease and mortality. DESIGN: Prospective longitudinal study. SETTING: Caerphilly, South Wales. SUBJECTS: Plasma specimens were collected during 1979-83 from 1773 men aged 45-59 years. These were tested for IgG and IgA antibodies to C pneumoniae (TW183) by microimmunofluorescence. OUTCOME MEASURES: 13 year mortality and incident ischaemic heart disease events were ascertained from death certificates, hospital records, and electrocardiographic changes at follow up every 4 to 5 years. RESULTS: 642 men (36.2%) had IgG antibodies at a titre of >/=1 in 16, of whom 362 (20.4% of all men) also had detectable IgA antibodies. The prevalence of ischaemic heart disease (a history of past or current disease) at entry was similar at all IgG antibody titres but was positively related to IgA antibody titre. IgA antibody titre was positively correlated with plasma viscosity but not with other cardiovascular risk factors. Incidence of ischaemic heart disease was not associated with either IgG antibody titre or IgA antibody titre, but there were stronger and significant relations of IgA antibodies with all cause mortality and fatal ischaemic heart disease, which persisted after adjustment for conventional cardiovascular risk factors. The odds ratios associated with detectable IgA antibodies were 1.07 (95% confidence interval 0.75 to 1.53) for all incident ischaemic heart disease, 1. 83 (1.17 to 2.85) for fatal ischaemic heart disease, and 1.50 (1.10 to 2.04) for all cause mortality. CONCLUSION: This is the first prospective demonstration of an association between IgA antibodies to C pneumoniae, a putative marker of chronic infection, and subsequent risk of death from ischaemic heart disease. In contrast to earlier case-control studies, IgG antibodies were not associated with either prevalent or incident ischaemic heart disease.
The importance of the injection technique in booster vaccination was investigated in an open randomized study with 252 10-year-old Swedish school-children receiving routine DT vaccination either by subcutaneous or by intramuscular route in the upper arm. The adolescents had previously been primed with DT vaccine at 3, 5 and 12 months of age. Adverse reactions, monitored for 2 weeks, showed the same low rates for systemic reactions in both groups, while the intramuscular administration gave significantly less redness (p < 0.001), swelling (p < 0.001), itching (p < 0.01) and pain (p < 0.05). These reactions were also of shorter duration (p < 0.01 to p < 0.001). Girls were found to have more pain and itching than boys (p < 0.001). No significant differences in antibody responses between the two administration routes were found in the 99 samples drawn 2 weeks after the booster. However, girls were found to have a lower response to diphtheria toxoid than boys (p = 0.009). Local reactions to a booster can thus be significantly reduced by choice of injection technique, which may be necessary if increased dosages and/or further valences are to be given to adolescents and adults.