A new paper from a research group in India has compared people who have tuberculosis (Tb) with those who have Tb and then developed chronic pulmonary aspergillosis (CPA). CPA develops in patients with Tb quite commonly and for many years it has been speculated that the mould grows on the lung scar tissue left behind by a Tb infection.
The researchers looked at many components of the patient’s immune system to try to see if any differed between the two as this would potentially tell them why one patient might develop CPA while another doesn’t.
Significantly the research team found that those patients who went on to develop CPA had reduced intensity of ‘neutrophil burst’, which is the release of reactive oxygen chemicals that are important in the fight against infection. They also had impaired Th1 cell response which is important as Th1 cells are part of the patient’s normal response to infection and they produce cytokines like interferon-gamma (IFN-γ), interleukin-2 (IL-2), and tumor necrosis factor-alpha (TNF-α). In turn, these trigger cytokines activate macrophages, enhance the phagocytic (pathogen-eating!) ability of immune cells, and stimulate the production of antibodies that mark pathogens for attack.
In short, we now have a clearer understanding of at least one part of the immune system of a CPA patient that isn’t working as well as it should, and which would directly lead to them being more vulnerable to infection.
The next question is ‘why are these patients unable to produce the normal levels of neutrophil burst and Th1 cell response?’ There are several possibilities including:
- Genetic disorder
- Immunosuppressive medication
- Chronic diseases eg diabetes, renal failure, liver disease
- Malnutrition/eg Vitamin D deficiency
- Alcohol abuse
- Severe infection
- HIV
- Exposure to some toxins (eg mercury, lead
- Autoimmune disorder
Some of these may apply to the patients in this study but it is not yet clear which are the most likely. There is more work to do!
What does this mean for treatment of CPA?
The INCAS study, sets out to assess if CPA patients benefit when they are given supplementary doses of interferon-gamma. This is one of the cytokines found to be inhibited in CPA patients in the study discussed above, so if these patients improve it is good evidence that we have found one of the important causes of susceptibility to CPA, and we will already have a medication to partly treat it.