Determining prevalence of inhibitory antibodies against Pseudomonas

  • Research type

    Research Study

  • Full title

    An observational study of the prevalence and clinical significance of blocking antibodies in patients with chronic Gram negative bacteria

  • IRAS ID

    218360

  • Contact name

    Ian Henderson

  • Contact email

    i.r.henderson@bham.ac.uk

  • Sponsor organisation

    University of Birmingham

  • Duration of Study in the UK

    2 years, 0 months, 1 days

  • Research summary

    Pseudomonas aeruginosa is a Gram-negative bacterium and chronic P. aeruginosa lung infections commonly occur in patients suffering from bronchiectasis. Infection with Pseudomonas has been indicated as a risk factor for declining lung function, increased morbidity and mortality as well as being associated with reduced quality of life. Once P. aeruginosa infection is established, it is almost impossible to eradicate and becomes progressively more resistant to antibiotics.

    Recently, we identified a sub-population of patients, with bronchiectasis who had chronic P. aeruginosa lung infections. These patients possessed high blood levels of a specific type of antibody (IgG2 specific for the O polysaccharide of LPS). However, while antibody normally protects against infection we found that this antibody prevented the immune system from killing the bacteria. This is not the first report of such a phenomenon and corresponds to other reports of blocking antibodies against Gram-negative bacteria in the literature.

    We hypothesised that removal of inhibitory antibody might restore patients immune killing of the P. aeruginosa and improve patient health. We recently reported that plasmaphoresis to remove blocking antibody resulted in a significant improvement in health status in 2 patients with bronchiectasis and blocking antibodies. This rescue therapy was the only treatment available for a seriously ill patient group with a poor prognosis.

    Therefore we now wish to use this study to examine the frequencey of blocking antibodies as well as their clinical relevance in patient groups at risk of Gram-negtive bacterial infections, including individuals with lung disorders such as Bronchiectasis, COPD, Cystic Fibrosis but also chronic kidney disease and diabetes.

    Ultimatley we want to identify a clinical test to identify patients with inhibitory antibodies, determine the clinical relevance and determine how to best treat these patients.

  • REC name

    London - Dulwich Research Ethics Committee

  • REC reference

    18/LO/1158

  • Date of REC Opinion

    16 Jul 2018

  • REC opinion

    Further Information Favourable Opinion