Herpesviruses serology distinguishes different subgroups of patients from the ME/cfs Biobank. (2021) Dominguez et al

Note:this article is provisionally accepted

Abstract:

The evidence of an association between Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and chronic herpesviruses infections remains inconclusive.

Two possible reasons for this lack of consistent evidence are the large heterogeneity of the patients’ population with different disease triggers and the use of arbitrary cutoffs for defining seropositivity.

In this work we re-analyzed previously published serological data related to 7 herpesvirus antigens. These data were collected as part of the United Kingdom ME/CFS Biobank (UKMEB).

In our re-analysis, patients with ME/CFS were subdivided into four major subgroups related to the disease triggers: S0 - 42 patients who did not know their disease trigger; S1 - 43 patients who reported a non-infection trigger; S2 - 93 patients who reported an infection trigger, but that infection was not confirmed by a lab test; and S3 - 48 patients who reported an infection trigger and that infection was confirmed by a lab test.

In accordance with a sensitivity analysis, the data were compared to those from 99 healthy controls allowing the seropositivity cutoffs to vary within a wide range of possible values.

We found a negative association between S1 and seropositivity to Epstein-Barr virus (VCA and EBNA1 antigens) and Varicella-Zoster virus.

However, the significance of this finding was affected by the seropositivity cutoff used.

We also found that S3 had a lower seroprevalence to the human cytomegalovirus when compared to healthy controls for all cutoffs used for seropositivity.

In summary, herpesviruses serology could distinguish subgroups of ME/CFS patients according to their disease trigger

Link to abstract here

 

I might have misunderstood, but are they saying that groups which could be already be sorted by patient interview could be sorted by herpes serology?

Surely you need to take a large group of patients and then show you can sort them by a blood test.

 

The full paper has now published and available here

 

When they talk about a "confirmed infection," I'm guessing that they mean a specific pathogen was identified by a test. However, I think that a complete blood count (cbc) can pretty much "confirm" that the body is responding to an infection, even if it can't tell you what the specific infection is. I guess I'm just saying that I think there is a difference between "confirming" that there is an infection and "identifying" what that infection is.

 

Here is an example of ‘confirmed infection’ (the follow up blood work showed IgM non reactive and IgG positive)
In the case of a CBC, if your baseline white blood count is in the lower range, a raise could still be within normal range and therefore not ‘confirm’ the symptoms of fever and what not. An elevated WBC would not be a confirmation of an infection- just a sign to look further as appropriate.

 

When I relapsed from taking immunomodulators and reactivated HHV6 and EBV, my WBC shot up to 11. My 'normal' WBC for many years before that event averaged around 3.6, and a few times went down to 2.8.

 

Not forgetting of course that "correlation is not causation". It also might be more accurate to say that: 'a complete blood count can confirm that the body is responding to an apparent infection' - allowing that in the absence of an identified infective agent something other than infection may be causing an "out of usual range" count. Lupus falls into that category but that should of course be recognised in the test appraisal - for ME/CFS currently unrecognised autoimmune impacts on the cbc may need to be considered.

 

What kills me is patients in the S2 who had an undetermined infectious onset may not have been receiving a proper work up to confirm what what the cause of their infection.

 

FWIW, I guess I was thinking of a cbc with a differential, which shows the proportion of different white blood cells in addition to the total. From what I've read, when WBC's are high and the percentage of neutrophils are significantly elevated, it suggests a bacterial infection; if the percentage of neutrophils are are significantly lower than normal, it suggests a viral infection. I'm not sure if neutrophil variation like this happens outside of an infection. If it does, then it would obviously not be an absolute indication of either a bacterial or viral infection.

 

From: https://www.medicalnewstoday.com/articles/323982#causes

"Having an abnormally high level of neutrophils in the blood is known as neutrophilic leukocytosis, also known as neutrophilia.

Rises in neutrophil levels usually occur naturally due to infections or injuries. However, neutrophil blood levels may also increase in response to:

• some medications, such as corticosteroids, beta-2-agonists, and epinephrine
• some cancers
• physical or emotional stress
• surgery or accidents
• smoking tobacco
• pregnancy
• obesity
• genetic conditions, such as Down syndrome
• surgical removal of the spleen

Some inflammatory conditions can increase neutrophil levels, including rheumatoid arthritis, inflammatory bowel disease, hepatitis, and vasculitis.
................................

An abnormally low blood level of neutrophils is a condition called neutropenia.

A drop in neutrophil blood levels typically occurs when the body uses immune cells faster than it produces them or the bone marrow is not producing them correctly.

An enlarged spleen may also cause a decrease in neutrophil levels because the spleen traps and destroys neutrophils and other blood cells.

Some conditions and procedures that cause the body to use neutrophils too quickly include:

• severe or chronic bacterial infections
• allergic disorders
• certain drug treatments
• autoimmune disorders

Some specific conditions, procedures, and drugs that interfere with neutrophil production include:

• cancer
• viral infections, such as influenza
• bacteria infections, such as tuberculosis
• myelofibrosis, a disorder that involves bone marrow scarring
• vitamin B-12 deficiency
• radiation therapy involving bone marrow
• phenytoin and sulfa drugs
• chemotherapy medications
• toxins, such as benzenes and insecticides
• aplastic anemia, when the bone marrow stops producing enough blood cells
• severe congenital neutropenia, a group of disorders where neutrophils cannot mature
• cyclic neutropenia, which causes cell levels to rise and fall
• chronic benign neutropenia, which causes low cell levels for no apparent reason"

 

Yes you are correct re the WBC differential, where neutrophils and lymphocytes may point to different kinds of infections. But it remains a sign of infection and typically needs to be confirmed by other clinical signs and potentially by blood work if warranted. Unfortunately often times doctors don’t bother testing when it comes to viral illness or even gastro-intestinal illness and the usual self-management is recommended until resolution of symptoms.

 

Overworked and under resourced path labs relying on technicians given production line schedules providing reports signed off by overwhelmed specialists provided to GPs lacking skill or resources to critically appraise. Check - Repeat.