Neutrophil phagocytosis in Alpha 1 Anti trypsin Deficiency
Research type
Research Study
Full title
Neutrophil Phagocytosis in Alpha 1 Anti trypsin Deficiency
IRAS ID
254124
Contact name
Elizabeth Sapey
Contact email
Sponsor organisation
University of Birmingham
Duration of Study in the UK
2 years, 0 months, 0 days
Research summary
Research Summary:
Alpha 1 Anti-trypsin Deficiency (AATD) is a rare genetic condition where the lack of a protein in the circulating blood and lung tissue allows the early development of emphysema, even in people who have never smoked. Some patients go on to have repeated chest infections and some are colonised with bacteria, with bacteria present in their lungs all the time. The most common bacteria found in patients with AATD is called Haemophilus, and the presence of this bacteria is associated with a faster decline in lung health and increased inflammation. There is no vaccine for the type of haemophilus which causes chest infections in AATD and short courses of antibiotics are ineffective in clearing colonisation, once established and antibiotic resistance is an increasing concern.Infections are usually cleared by immune cells called neutrophils (a process called "phagocytosis", but in AATD there is evidence that these cells are unable to effectively clear and kill haemophilus. It is not understood why these cells are less able to clear haemophilus in AATD and this study seeks to identify the mechanism which underpins this defect.
We will study blood and sputum samples collected from patients with AATD and matched controls who do not have AATD to determine how common this failure of phagocytosis is in AATD, and what the mechanism is. If we can identify the cause of this immune defect, we may be able to improve haemophilus bacterial killing using novel techniques or therapeutic targets.
This research was designed with the help of patients with AATD and highlighted as a priority by them.
Summary of Results:
Alpha 1 Antitrypsin Deficiency (AATD) is a condition where people are unable to make a functional protein called Alpha 1 Anti trypsin (AAT), which protects the lungs from excessive inflammation and damage by immune cells. People with AATD are prone to recurrent chest infections but it was unclear why. This study collected immune cells from patients with AATD and assessed how well they were able to find and kill bacteria that are commonly found in lung infections. We found that the bacteria were able to "hide" from immune cells, as the lack of AAT prevented binding between the immune cells and the bacteria. This offers a potentially new way to treat infections in AATD which will be explored in further studies.REC name
West Midlands - South Birmingham Research Ethics Committee
REC reference
18/WM/0365
Date of REC Opinion
11 Jan 2019
REC opinion
Further Information Favourable Opinion