MAP Mycobacterium Subspecies Linked To Rheumatoid Arthritis

People with rheumatoid arthritis were more likely to have mutations in a particular gene than healthy people, and they were more likely to have traces of Mycobacterium avium subspecies paratuberculosis bacteria, known as MAP, researchers have found.

MAP has previously been linked to other conditions related to immune function, including Crohn’s disease. The bacteria is common in cattle in the US and can be found in contaminated dairy or meat products from infected cows.

The researchers theorise that MAP bacteria may trigger rheumatoid arthritis in people who have genetic mutations. However, that doesn’t mean MAP causes the disease. At this stage it’s just an association worthy of further study.

Rheumatoid Arthritis Links

It is still not clear what causes rheumatoid arthritis, but inherited genes and cigarette smoking are most strongly linked to the disease.

You may have your own personal reasons for not drinking milk or eating beef. But this study does not provide any evidence that avoiding them could prevent rheumatoid arthritis.

The study, conducted by researchers from the University of Central Florida, was a genetic analysis of blood samples carried out in the laboratory. This type of research is helpful in developing early understanding of possible disease pathways and causes of disease. It can sometimes pave the way for future research that may lead to new treatments or prevention.

Effect of SNPs in PTPN2/22 on T-cell response.

Effect of SNPs in PTPN2/22 on T-cell response.
Credit: Robert C. Sharp, et al. CC-BY

The work builds on the background that two inflammatory diseases – Crohn’s and rheumatoid arthritis – share common features. They’re both autoimmune diseases (where the immune system attacks the body’s own tissue), they both have genetic links, and are treated with similar drugs.

Past study has linked MAP with Crohn’s, therefore the researchers were interested in seeing whether they may share common triggers.

Research Protocol

Researchers took blood samples from 132 people, 72 of them with rheumatoid arthritis and the remainder without the condition. The blood samples were tested for:

  • 9 mutations to a gene affecting immune system regulation, called PTPN2/22 (previous research has linked mutations in this gene to rheumatoid arthritis)
  • presence of MAP DNA
  • behaviour of immune system T-cells when exposed to purified MAP protein

Researchers then analysed the results to look at:

  • whether people with rheumatoid arthritis were more likely to have mutations to PTPN2/22 than people without rheumatoid arthritis
  • whether blood from people with genetic mutations was more likely to have traces of MAP DNA
  • how blood cells from different groups reacted to infection

Basic Results

Researchers found that mutations in PTPN2/22 were far more common in people with rheumatoid arthritis than people without:

  • One type of mutation was present in 78.6% of people with rheumatoid arthritis and 60% of people without (odds ratio (OR) 2.28,95% confidence interval (CI) 1.05 to 4.93)

They also found MAP DNA was more common among people with rheumatoid arthritis:

  • 34.3% of people with rheumatoid arthritis had traces of MAP DNA compared to 8.3% of people without rheumatoid arthritis (OR 5.74, 95% CI 1.84 to 17.9)

Blood from people who had genetic mutations was more likely to show a raised T-cell immune response. T-cells are white blood cells (lymphocytes) that recognise abnormal cells or substances and trigger an immune response to destroy them.

There was a 7-fold increase in T-cell activity in blood from people with rheumatoid arthritis and with 2 types of mutations, when the cells were exposed to MAP purified protein, compared to a 3.4-fold increase in T-cell activity in blood from people with rheumatoid arthritis but no mutations.

Conclusions

There are some limitations to bear in mind. The study does not show that MAP caused rheumatoid arthritis – not everyone with the condition had MAP DNA, and some people without rheumatoid arthritis had MAP DNA. It also does not tell us whether people got MAP infection before or after they developed rheumatoid arthritis.

We also don’t know whether the MAP DNA indicated that people had active MAP infection, or whether the traces were from a previous infection that had been cured. The research doesn’t tell us the possible source of this infection.

A reported 50% of cows in the US are infected with MAP, but we don’t know if that’s the case in the UK and shouldn’t assume that beef and dairy products are contaminated or carry risk to the public.

Combined Effect of MAP and PTPN2:rs478582 on IFN-γ Expression in RA.

Combined Effect of MAP and PTPN2:rs478582 on IFN-γ Expression in RA.
Credit: Robert C. Sharp, et al. CC-BY

The lead researcher, speaking in a press release, said:

“We believe that individuals born with this genetic mutation and who are later exposed to MAP through consuming contaminated milk or meat from infected cattle are at a higher risk of developing rheumatoid arthritis. We need to find out why MAP is more predominant in these patients – whether it’s present because they have RA [rheumatoid arthritis], or whether it caused RA in these patients. If we find that out, then we can target treatment toward the MAP bacteria.”

This is a technical, early-stage study that focused on DNA mutations in genes that regulate the immune system. The study found that people with rheumatoid arthritis were more likely to have these mutations, and to have traces of MAP bacteria DNA. However, that doesn’t mean MAP caused rheumatoid arthritis, or that people should worry about eating meat or dairy products.

Rheumatoid arthritis is a complex and largely unexplained disease in which the over-active immune system damages the body’s joints (and sometimes other organs), causing pain and malformation. There is no cure, and the disease can affect people to varying degrees of severity and disability.

Many people need to take a combination of drugs to control symptoms, some of which have side effects, alongside different physical therapies. Better understanding of what causes this disease, and possibly new treatments, would be very welcome.

The research goes some way to improving our understanding of rheumatoid arthritis and suggests new routes for researchers to follow.

Robert C. Sharp, Shazia A. Beg and Saleh A. Naser
Polymorphisms in Protein Tyrosine Phosphatase Non-receptor Type 2 and 22 (PTPN2/22) Are Linked to Hyper-Proliferative T-Cells and Susceptibility to Mycobacteria in Rheumatoid Arthritis
Front. Cell. Infect. Microbiol., 25 January 2018 | https://doi.org/10.3389/fcimb.2018.00011

Top Image: Mycobacterium avium-intracellulare. Credit: Wellcome Collection. CC0

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