Submitted by: Pritikanta Paul, MD
Edited by: Rebecca O’Bryan, MD
Gros M, Nunes AM, Daoudlarian D, et al. Identification of serum interleukin 6 levels as a disease severity biomarker in facioscapulohumeral muscular dystrophy. J Neuromuscul Dis
. 2022;9(1):83-93. doi: 10.3233/JND-210711.
Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common inherited myopathies, presenting as slowly progressive, often asymmetric muscle weakness. Although a gain-of-toxic function secondary to aberrant DUX4
expression is the known etiology, exact pathomechanism is not known. Inflammatory reactions are sometimes seen in muscle biopsies, leading to speculation of the role of inflammatory pathway activation in disease pathogenesis. This retrospective study analyzed serum cytokines in 100 FSHD1 patients to identify potential biomarkers.
Levels of 20 serum pro-inflammatory and regulatory cytokines were measured in patients and compared with healthy controls. Also, association between cytokine levels and clinical scores was analyzed. Serum interleukin-6 (IL-6) levels correlated negatively with disease severity. No differences were found in serum IL-6 levels between the male and female groups, but a significant difference in serum IL-6 levels was noted between heathy volunteers and FSHD patients overall, and also when comparing healthy volunteers with FSHD patients within male and female subgroups. The findings were further demonstrated in a mice model showing serum IL-6 levels were significantly increased in the severe FSHD-like model.
Amongst the previous studies looking at disease biomarkers in FSHD, this current study shows a reliable correlation of a biomarker with the disease severity. The authors also note that increased IL-6 has been described in other neuromuscular disease. Thus, the exact role of IL-6 in neuromuscular pathology is poorly understood. Further studies are needed to confirm similar findings to identify potential therapeutic targets.
FSHD is the second most common genetic myopathy and further understanding of disease mechanism is needed to identify reliable biomarkers and hence potential treatment. Like many other neuromuscular diseases, there is a need for a non-invasive biomarker which can help monitor treatment response for clinical trials in FSHD.
This is a great study design showing a correlation between a biomarker with disease severity and demonstrating the same in an animal model. Similar studies showing elevated complement proteins in FSHD patients have been reported in the recent past. Thus, this type of study helps us identify a precision-based treatment target. Further awareness and studies are required to confirm the study findings.