Frequent IgG subclass and mannose binding lectin deficiency in patients with CFS, 2015, Guenther, Scheibenbogen et al

N=1, absolutely not scientific personal anecdote, without knowing anything at all about my MBL value: I was the type who fell ill at a ridiculously high frequency after my ME/CFS onset (EBV), in the first two years. As a result, I was terrified of infections because although all I got was the common cold, even that completely floored me and it floored me very often.

On the other hand, before my ME/CFS started, I had the reputation of having the strongest immune system in the family, someone who was never ill and I had that reputation since my childhood (my sister was ill and is ill very very often on the other hand - no sign of ME/CFS for her so far). I only remember 3 instances of a bad illness in my life: 2 influenza infections, which felt really bad but didn't trigger anything at all, and the EBV infection which didn't feel as torturous to me as the other two, but it triggered ME/CFS. I had colds but rarely and I didn't care about them, because they affected me so little even when I had them.

So in short, to me this change was instantaneous and very noticeable and scary and absolutely unprecedented. But again, I have no idea about my MBL levels, so it may be irrelevant.

 

The first author works in an immunology department where people with things like MBL deficiency probably turn up more often. Ditto subclass deficiencies.

 

3 of those authors are from the Charite in Berlin, where the CFS department is based in the immunology department. One of them gave me my diagnosis. Before I went to the Charite, I had to confirm that I was more susceptible to infections, which I felt was rather unfair to those CFS sufferers who aren't (some hardly ever get anything). They took loads of my blood for use in future studies, so my first thought when I saw this was "I wonder if my blood was in this study?". My second thought is that if they only see CFS patients who have confirmed that they are more susceptible to infections and only collect their blood for studies, what are they going to find?

 

Inexperienced ME patients also often mistake PEM for infections, and may believe they're unusually susceptible when they're not. My friends and I grumbled for years about getting every bug going, but most of the "viruses" were the nasty immune flare caused by overdoing things, being in the luteal phase of the menstrual cycle, or both.

Even after 45 years I can't tell the difference, at least until I start with a hacking cough, a streaming nose, or whatever to confirm that it's a real infection.

 

Permit me to quote from part 4 of my blog, and my discussion with Dr Hanitsch (one of the authors of the above paper):

 

Yes the experiences are similar. I usually have to wait a few days to know the differences between flares and actual reactivation of viruses. Flares last a few days in my case, reactivations of viruses can last for well over a year and includes some bizarre symptoms.

 

I got an appointment back in july even though I said on the questionnaire that I'm not more susceptible to infections. Also, I didnt mention having a viral onsent only that it was an infectious one.

Could be that they only changed it recently to include more subtypes, who knows.

 

Errrr Mr. Edwards. That was a study on “CFS” patients. What do we have to take away from your comment, please?

On topic: my MBL is below the detection limit.

 

The CFS patients had all been referred to an immunodeficiency outpatient clinic - its reasonable to assume their GP's had suspicion of immune involvement, hence the referral to immunology and not another type of clinic. This can lead to a selection bias that skews the results because its not a random and representative cohort.

 

I can't read the full article so that excludes the methods, thanks for clarifying. Normally you're only accepted in this subunit there if you are diagnosed with ME/CFS already. So do they say that this was not the case?

What would have been interesting to know is if their MBL deficiency was genetic?

 

This is of interest to me personally.

I have several immune deficiencies including:
Mannose binding lectin deficiency
B cell deficiency
IgG subgroups 1 & 3 deficiency
IgG deficiency
I had a complete inability to make antibodies against any serovar of Pneumonococus (I was thankfully able to make antibodies to the Pneumovax vaccine
Borderline low IgA
Absence of secretory IgA
And a few others to boot.

What prompted my specialist to look into my immune system was my recurrent infections (sinusitis, tonsillitis, UTIs, skin fungal infections and so on) and my comment that when I get an infection I am completely floored and it feels like to me that "the wrong part of my immune system is working overtime to try and fight it which leaves me debilitated and unable to function." That prompted the IgG subgroup test which was the start of the more through investigation by NHS immunologist. The IgG subgroup deficiency came as a complete surprise to my specialist who sees many ME patients so I suspect that this is not a major issue for many with ME/CFS diagnoses, although probably a small subgroup due to perhaps misdiagnosis. Reading the symptoms of immune deficiency reads very like ME. In an ideal world pwME would be screened for this before ME diagnosis.

I just miss criteria for Common Variable Immune deficiency (CVID). My symptoms are a great deal less with ongoing daily antimicrobials.

Missing this diagnosis for me has had other medical consequences including the development of a very large (by the time it was found) kidney stone which the Chemical Pathologist was clear was 100% due to decades of chronic infections. This kinda made me realise how much I had ended up having to normalise and putting up with. I have repeatedly saught out treatment as needed and necessary for infections but I have oft experienced medics who would try and discourage this as I can see in retrospect that it might have looked odd or excessive. What no one seems to have clocked is that this is the presentation of someone who has immune deficiency. As some immune deficiencies are rare (like b cell deficiency) it does not get much of a look in and many will take decades to get diagnosed or they will be diagnosed when hospitalised with sepsis or other life threatening conditions. Also, specialist, complex tests are necessary for conditions like low b cells, so I suspect few have these tests. Many people have low IgA or MBL etc without issue too so it is not a clear cut situation. And there is a lack of NHS immunologists making it vanishingly unlikely that pwME will be able to access the kind of tests I have had done. As @Jonathan Edwards has highlighted there is likely to be bias in the patient sample.

As to what caused this. That's kinda up for grabs but I never had time off school as a youngster due to infections or debility. I did have one horrible episode of "summer flu" where I had high fever etc and I was unable to recall what had happened to me for about 2 weeks. This happened when I was 11. Bizarrely I was not hospitalised at the time. But I recovered enough to go back to school in the autumn. Not long after that I developed chronic skin fungal conditions along with migraines and the rest is history. What precipitated this summer flu? A tick bite followed by an EM rash while sailing with my dad and brother around the islands off the west of Scotland a week before. Further to this, pretty much all of my immune system deficiencies are needed to mount a robust challenge to borrelia infection (the bacteria responsible for Lyme disease and spread by infected ticks). I suspect that this is not a coincidence but no way of knowing.

In my own practice I have occasionally encountered ME patients with additional recurrent infections type presentation. I have asked several to be referred to immunology. Several times immune deficiency has been picked up.

My view is that this is a rare subgroup of ME patients who are perhaps misdiagnosed who would be better served with correct diagnosis and treatment.

The continous antimicrobial treatment I take has allowed me to complete my doctoral training, re-start professional work and build up to nearly FT working. I can also do vigorous exercise a great deal of the time. A massive and dramatic change from bedbound/housebound for years. Migraines still remain a major pest.

 

Not sure what your question is.

A lot of ME/CFS services are run by immunology/infectious disease departments in the first place - or at least they act as a primary route of referral for suspected ME/CFS. Amolak Bansal is an immunologist. My cousin who saw a lot of ME/CFS was an infectious disease/immunology specialist.
Scheibenbogen is an immunologist.