Abstract
The findings of controlled trials on use of intravenous immunoglobulin G (IV IgG) to treat myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are generally viewed as representing mixed results. On detailed review, a clearer picture emerges, which suggests that the potential therapeutic value of this intervention has been underestimated. Our analysis is consistent with the propositions that: (1) IgG is highly effective for a proportion of patients with severe and well-characterised ME/CFS; (2) responders can be predicted with a high degree of accuracy based on markers of immune dysfunction. Rigorous steps were taken in the research trials to record adverse events, with transient symptom exacerbation commonly experienced in both intervention and placebo control groups, suggesting that this reflected the impact of participation on people with an illness characterised by post-exertional symptom exacerbation. Worsening of certain specific symptoms, notably headache, did occur more commonly with IgG and may have been concomitant to effective treatment, being associated with clinical improvement. The findings emerging from this review are supported by clinical observations relating to treatment of patients with severe and very severe ME/CFS, for whom intramuscular and subcutaneous administration provide alternative options. We conclude that: (1) there is a strong case for this area of research to be revived; (2) pending further research, clinicians would be justified in offering a course of IgG to selected ME/CFS patients at the more severe end of the spectrum. As the majority of trial participants had experienced an acute viral or viral-like onset, we further suggest that IgG treatment may be pertinent to the care of some patients who remain ill following infection with SARS-CoV-2 virus.
Highlights
Interest in researching immunoglobulin (IgG) therapy in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/chronic fatigue syndrome’ (CFS)) began in the mid-1980s, prompted by emerging evidence of immunoregulatory defects including disordered cell-mediated immunity (CMI) [1,2,3,4,5,6,7,8,9] and immunoglobulin subclass deficiencies [1,10,11,12]
A documented viral onset in some patients [2,13,14], the demonstration of enteroviral RNA in muscle tissue [15] and the presence of enteroviral antigen in serum [16] were viewed as supporting the hypothesis that myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may develop as a consequence of failed clearance of viral or other antigens [13,17] and strengthened the case for investigating an intervention predicated on the presence of immunologic dysfunction
The analysis conducted implies that Myalgic encephalomyelitis’ (ME)/CFS patients who have scope to benefit from Immunoglobulin G (IgG) may be predicted in advance with a high degree of accuracy
Summary
Interest in researching immunoglobulin (IgG) therapy in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) began in the mid-1980s, prompted by emerging evidence of immunoregulatory defects including disordered cell-mediated immunity (CMI) [1,2,3,4,5,6,7,8,9] and immunoglobulin subclass deficiencies [1,10,11,12]. High-dose intravenous (IV) IgG was known to ameliorate other disorders of immune regulation [1,18,19,20] and positive findings in a crossover study of intramuscular IgG therapy in patients with ‘chronic mononucleosis syndrome’ [21], in tandem with numerous individual case reports of beneficial outcome following IV IgG in patients with ME/CFS [18], provided further encouragement for this line of enquiry. Following publication in 1997 of the last of these, [24] asserting an “ineffective” conclusion, interest in researching this treatment in patients with ME/CFS waned
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