A study comparing 140 people with ME/CFS and 44 matched sedentary controls has found that haptoglobin (Hp) – a protein that plays a crucial role in recycling iron and protecting the body from the harm caused during oxidative stress – may be linked to post exertional malaise (PEM).
In this study the majority of those with ME/CFS were ‘severely affected housebound individuals’ – often this group are not represented in research. Importantly, all participants provided their informed consent meaning that they were aware of what would be asked of them during the project before they agreed to take part.
The research team, led by Atefeh Moezzi and Anastasiya Ushenikina, identified that, following a non-invasive stress test to induce PEM, participants who met the Canadian Consensus Criteria (CCC) for ME/CFS had lower levels of haptoglobin compared with healthy controls.
Interestingly, low levels of haptoglobin have been linked with several diseases including a condition in which red blood cells are destroyed faster than they are produced (haemolytic anaemia), liver disease, and certain autoimmune conditions such as lupus and rheumatoid arthritis.
Furthermore, in the paper, the authors explain that there are two version of the gene that makes haptoglobin (Hp1 and Hp2), and depending on the genetics of an individual, haptoglobin can exist in one of three forms (phenotypes):
- Hp 1-1
- Hp 2-1
- Hp 2-2
Each type of haptoglobin plays an important role in the body, but Hp 1 appears to be the most efficient. Notably, Hp 2 is thought to be associated with lower antioxidant capacity, and has been linked with oxidative stress and low-grade inflammation.
Additionally, it is thought that people with higher levels of Hp 2-1 or Hp 2-2 may have poorer outcomes when they become unwell. For example, the Hp 2-2 type has been associated with acute pain caused by the blockage of blood flow in children with sickle cell anaemia.
In the study by Moezzi and colleagues, results suggested that those with ME/CFS who had the Hp 2-1 phenotype had the highest susceptibility to PEM, and the poorest performance on tests assessing cognitive function related to PEM.
In summary, the findings from the study by Moezzi and colleagues suggest people with ME/CFS may have lower levels of haptoglobin, and that haptoglobin phenotype (Hp 1-1, Hp 2-1, or Hp 2-2) could be linked to the severity of PEM; in this exploratory study, those with Hp 2-1 experienced the most severe PEM.
While the researchers emphasise the robustness of their findings, there are limitations which must be taken into consideration, including that the participants were all ‘Caucasian (French-Canadian) individuals of European ancestry‘. More research is needed to assess whether the same observations would occur for larger and more diverse cohorts of people with ME/CFS, and to assess whether results may be different between groups (for example for different ME/CFS severity levels, for males and females, and for different ethnic groups).
