Tolerability and efficacy of s.c. IgG self-treatment in ME/CFS patients with IgG/IgG subclass deficiency: a proof-of-concept study, by Carmen Scheibenbogen, Franziska Sotzny, Jelka Hartwig, Sandra Bauer, Helma Freitag, Kirsten Wittke, Wolfram Doehner, Nadja Scherbakov, Madlen Loebel, Patricia Grabowski in J Clin Med. 2021 May 29;10(11):2420 [doi: 10.3390/jcm10112420]
Research abstract:
Background:
Chronic fatigue syndrome (ME/CFS) is a complex disease frequently triggered by infections. IgG substitution may have therapeutic effect both by ameliorating susceptibility to infections and due to immunomodulatory effects.
Methods:
We conducted a proof of concept open trial with s.c. IgG in 17 ME/CFS patients suffering from recurrent infections and mild IgG or IgG subclass deficiency to assess tolerability and efficacy. Patients received s.c. IgG therapy of 0.8 g/kg/month for 12 months with an initial 2 months dose escalation phase of 0.2 g and 0.4 g/kg/month.
Results:
Primary outcome was improvement of fatigue assessed by Chalder Fatigue Scale (CFQ; decrease ≥ 6 points) and of physical functioning assessed by SF-36 (increase ≥ 25 points) at month 12. Of 12 patients receiving treatment per protocol 5 had a clinical response at month 12. Two additional patients had an improvement according to this definition at months 6 and 9. In four patients treatment was ceased due to adverse events and in one patient due to disease worsening. We identified LDH and soluble IL-2 receptor as potential biomarker for response.
Conclusion:
Our data indicate that self-administered s.c. IgG treatment is feasible and led to clinical improvement in a subset of ME/CFS patients.
Limitations
Taken together, our study has several limitations, including a small patient number and a lack of a control arm. The strength of this study is to show the feasibility of a dose escalation s.c. IgG home treatment in ME/CFS patients. Furthermore, it provides first evidence for efficacy of an intermediate dose s.c. IgG treatment and potential biomarkers for response. This warrants an RCT study.
Here, we evaluated patients’ symptomatology and the mitochondrial metabolic parameters in 
Multiple studies have shown that peak oxygen consumption is reduced in the majority of ME/CFS patients, using the golden standard for measuring exercise intolerance: cardiopulmonary exercise testing (CPET). A 
Currently, no biomarkers or established diagnostic tests for ME/CFS exist. In Germany, it is estimated that over 300,000 people are affected by ME/CFS. Research from the United States and the UK shows that patients with ME/CFS are medically underserved, as they face barriers to medical care access and are dissatisfied with medical care.
Multiple studies have shown that peak oxygen consumption is reduced in the majority of myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) patients, using the gold standard for measuring exercise intolerance: cardiopulmonary exercise testing (CPET). A 
12 out of 382 retrieved references were included. Seven studies were randomized controlled trials (RCTs) with one including three reports (1 RCT, 2 single-arms); others were single-arm trials. Interventions included mindfulness-based stress reduction, mindfulness-based cognitive therapy, relaxation, Qigong, cognitive-behavioral stress management, acceptance and commitment therapy and isometric yoga.
Exact low-resolution electromagnetic tomography (
significant differences occurred immediately post-test, which were most pronounced after 24 hours, particularly in the low alpha (8-10 Hz) and low beta (13-18 Hz) frequency sub-bands. Together, the present findings offer support for EEG source localization techniques to investigate PEM. If confirmed, this study could provide a useful instrument for functional diagnosis and evaluation of treatment outcomes.
