Thursday, 17 August 2017

H. Pylori: good, bad, ugly, or not quite sure?

Many people think that MS is triggered by exposure to infectious agents in our environment. The most well-known putative trigger is EBV, but there has also been debate surrounding the role of H. Pylori, an enteric pathogen better known for its role in causing peptic ulcers. Epidemiological evidence has been conflicting on whether H. Pylori infection protects against MS, increases the risk of MS, or has no association at all.

A nice new study systematically examined the amounts of anti-H. Pylori antibody in a big cohort of 139 pwMS, 39 pwParkinson's Disease, 21 pwAlzheimer's Disease, and 68 controls without any neurological diseases. The key advantage of this study is that they looked at antibodies against a wide range of H. Pylori antigens, the fragments of the bug exposed to the immune system.

The key findings were:
- Anti-flagellin antibodies were less common in MS than controls. 
- Anti-VacA antibodies were more common in SPMS than controls.
- Anti-p54, anti-p29-UreA and anti-p26 correlated with EDSS.
- Anti-p41, p54-flagellin, p29-UreA, p67-FSH, and p120-CagA were less common in RRMS than control.
- Anti-p26 and anti-p17 correlated with number of relapses.

This is big news - it demonstrates that the antibody response to H. Pylori infection differs between pwMS and controls, between pwRRMS and pwSPMS, and is correlated with disease activity.

How do we interpret this?

There are a few possible explanations. My initial thoughts:
- Exposure to H. Pylori is protective against MS
- Exposure to VacA (a secreted bacterial protein) increases the risk of SPMS
- An underlying problem with immune regulation in people who are at-risk of developing MS affects the immune response to H. Pylori (this could be genetic e.g. MHC polymorphisms, environmental e.g. a consequence of EBV infection, etc...)
- DMTs affect the immune response to H. Pylori
- A combination of some/all of the above!

These don't explain why higher titres of certain anti-H. Pylori antibodies would correlate with disability and relapses. 

In short I'm not quite sure what these data mean but they are certainly interesting. If anti-H. pylori antibodies are protective then vaccination might even be on the cards as a preventative strategy.

To assess whether Helicobacter pylori (Hp) antibody (ab) reactivity against individual Hp antigens is pathogenetically relevant to multiple sclerosis (MS), we systematically investigated prevalence and clinical significance of abs against 14 immunodominant and subdominant Hp antigens by ELISA and immunoblotting in 139 consecutive MS patients with relapsing-remitting (RRMS, n = 102) or secondary progressive (SPMS, n = 37). Sera from 39 patients with Parkinson’s disease (PD), 21 with Alzheimer’s disease (ALZ) and 68 healthy controls (HCs), were also tested. Anti-flagellin (18.3%) and anti-p41 (25.0%) abs in MS were less frequent than in HCs (39.4%, 48.5%, respectively). Abs against 5 of the 14 antigens were less frequent in RRMS than HCs, including p41, p54-flagellin, p29-UreA, p67-FSH, and p120-CagA. Anti-VacA abs were more frequent in SPMS than in HCs (42.1 vs 12.1%, p = 0.019). Anti-p54, anti-p29-UreA and anti-p26 correlated with extended disability status scale (EDSS) (p = 0.017, p = 0.005, p = 0.002, respectively). Anti-p26 and anti-p17 correlated with the number of relapses (p = 0.037 and p = 0.047, respectively). This is the first comprehensive analysis of ab reactivities against most Hp antigens in MS patients. Ab responses differ between MS and HCs and between RRMS and SPMS, being more prevalent in SPMS than RRMS, thus suggesting an association between anti-Hp and the former type of MS.

1 comment:

  1. Interesting post
    In 2014 i did an stomach endoscopy and had heartburn, dx with a little
    Hiatal hernia negative for H,pylori

    2016 dx with ms ,did again endoscopy and this time positive H.pylori
    Also between those years i take ppi drug


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