Martin aka paused||M.E.
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A study with Dr. Stingl as a co-author found immune-dysregulation in pwME.
https://www.mdpi.com/2218-273X/11/9/1359/htm
https://www.mdpi.com/2218-273X/11/9/1359/htm
1.Abstract
(...) As part of the routine workup for ME/CFS patients, a differential blood count, leukocyte subtyping, and quantification of immunoglobulins and IgG subclasses, as well as a complement analysis, was performed. Out of 262 ME/CFS patients, 64.9% had a reduction or deficiency in at least one of the listed immune parameters. In contrast, 26.3% showed signs of immune activation or inflammation. A total of 17.6% of the ME/CFS patients had an unclassified antibody deficiency, with IgG3 and IgG4 subclass deficiencies as the most common phenotypes. Reduced MBL (mannose-binding lectin) levels were found in 32% of ME/CFS patients, and MBL deficiency in 7%. In summary, the present results confirmed the relevance of immune dysfunction in ME/CFS patients underlining the involvement of a dysfunctional immune response in the disease. Thus, immune parameters are relevant disease biomarkers, which might lead to targeted therapeutic approaches in the future.
2. Materials and methods
A retrospective data analysis was conducted on medical data of ME/CFS patients treated during the study period March 2019 to August 2020. ME/CFS was diagnosed by a specialized neurologist based on exclusion of other medical conditions associated with profound fatigue and based the IOM criteria for the diagnosis G93.3 ME/CFS.(...)
In case of a suggestive history, immunodiagnostics were performed as part of the routine workup for ME/CFS patients including a differential blood count, leukocyte subtyping, immunoglobulins and IgG subclasses, as well as a complement analysis. During the 18-month study period, 351 ME/CFS patients over 18 years of age were followed-up.(...)
The final evaluation was based on immunodiagnostic data of 262 ME/CFS patients independent of gender distribution. All values were compared to defined laboratory norm levels
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3. Results
(...)
Out of the total number of 262 ME/CFS patients, 170 (64.9%) have a reduction or deficiency in at least one of the listed immune parameters. In contrast, 69 of the patients (26.3%) showed signs of immune activation or inflammation, characterized by the increase of one of the evaluated immune parameters
(...)
IgA, as well as total IgG levels, were decreased in 6.5% of all patients. IgM levels were below the norm values in 4.9% of ME/CFS patients. The most prominent reduction of the IgG subclasses was found for IgG3 in 8% of the patients and for IgG4 in 4.9% of the patients. Reduced MBL levels were detected in 32.1% of all patients, and reduced C3c levels in 16% of all patients
(...)
We observed an unclassified antibody deficiency in 17.6% of all patients. On the level of immunoglobulins and IgG subclasses, the highest percentage was found for an isolated IgG3 subclass deficiency found in 5.7% of all patients. In addition, 2.7% of patients suffered from an isolated IgG4 subclass deficiency and 2.7% of all patients were diagnosed with selective IgA deficiency. MBL deficiency was diagnosed in 6.9% of all patients
(...)
The largest number of patients (n = 8) revealed immunoglobulin reduction with reduced CD3-CD16+CD56+ NK (natural killer) cell counts.
(...)
Elevated levels of CD8-CD57+ NK cells were found in 23 patients and higher levels of CD4+ T-cells were detected in 12 patients. Only four patients had an increase in CD8+ T-cells. When evaluating humoral immune parameters, an increase was found mainly in IgG2 (n = 13). Elevated levels of complement parameters were rarely observed; C3 elevation was observed in one patient and C4 in three patients.
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4. Discussion
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Previous studies have highlighted the link between immune dysfunction and ME/CFS development [6,8,9,15,16,24]. These previous results are confirmed in a comprehensive immune evaluation of 262 ME/CFS patients, revealing mostly a reduction or even immunodeficiency in over 64% of all patients.
(...)
Another remarkable finding in our study is the high frequency of MBL deficiency. In our study, the cut-off level for MBL was defined at <50 ng/mL. Reduced MBL levels were seen in 32.1% of ME/CFS patients, representing the most frequently reduced immune parameter. MBL deficiency, being defined as MBL levels below 50 ng/mL, in combination with severe or recurrent infections, was found in 7%. This highlights the high frequency of MBL deficiency in ME/CFS patients, as MBL deficiency with a cut off value < 100 ng/mL is assumed to be found in 4% of the Caucasian population [16]. Up to this point, the data on MBL deficiency in ME/CFS patients is still limited. A previous study using a cut-off value <100 ng/mL for MBL deficiency found that 15% (n = 43 of 293) of ME/CFS patients were affected by this immunodeficiency. In general, ME/CFS patients had lower MBL levels than healthy controls, and more than half reported an increased susceptibility to upper and lower respiratory tract infections [16].
(...)
In summary, the present results confirm the relevance of immune dysfunction in ME/CFS patients underlining the involvement of a dysfunctional immune response in the disease. Thus, immune parameters are relevant biomarkers in ME/CFS patients to identify patients with potential responses to immune-modulating treatment for future targeted therapy of ME/CFS.
