Frequent IgG subclass and mannose binding lectin deficiency in patients with chronic fatigue syndrome.
Guenther, Sabrina, Loebel, Madlen, Mooslechner, Agnes A et al. · Human immunology · 2015 · DOI
Quick Summary
This study looked at immune system proteins called antibodies and a molecule called mannose binding lectin (MBL) in 300 people with ME/CFS. The researchers found that about 25% of patients had lower-than-normal levels of certain antibodies, while another 25% had higher-than-normal levels. Additionally, 15% had low MBL levels, compared to only 6% in healthy people. These immune defects were connected to frequent respiratory infections in ME/CFS patients.
Why It Matters
Understanding immune defects in ME/CFS may explain why many patients experience recurrent infections and could guide targeted immune therapies. This work provides objective biological markers that support the infectious triggers reported by many ME/CFS patients and opens avenues for personalized treatment approaches based on individual immune profiles.
Observed Findings
25% of CFS patients had decreased serum levels of at least one antibody class or subclass, with IgG3 and IgG4 subclass deficiencies being most common.
Another 25% of CFS patients showed elevated immunoglobulin levels, particularly excess IgM and IgG2.
MBL deficiency was found in 15% of CFS patients compared to 6% in a historical control group.
B-cell numbers and B-cell subset frequencies showed no major alterations in CFS patients.
Humoral immune defects were associated with respiratory tract infections in CFS patients.
Inferred Conclusions
Humoral immune defects are frequent in ME/CFS patients and represent a distinct subtype of immune dysfunction.
IgG subclass and MBL deficiencies may increase susceptibility to recurrent infections commonly reported in ME/CFS.
These immune abnormalities are reproducible across multiple patient cohorts, suggesting they are a consistent feature of the disease.
Remaining Questions
Do these immune defects develop before ME/CFS onset or as a consequence of the disease, and what determines which patients develop which immune profile?
Would immune replacement therapy or targeted interventions addressing these specific defects improve infection rates and ME/CFS symptoms?
What This Study Does Not Prove
This study does not establish causation—whether immune defects cause ME/CFS or result from it. The cross-sectional design cannot determine if these immune abnormalities are primary drivers of disease or secondary effects. It also does not prove that correcting these defects would improve ME/CFS symptoms or outcomes.