Proteomic Investigation in Plasma from Women with Fibromyalgia in Response to a 15-wk Resistance Exercise Intervention

Supplemental digital content is available in the text.


Supplementary Digital Content (SDC)
Clinical and exercise-related data Post exercise FM vs. CON Post exercise compared to CON, FM had significant higher pain intensity (VAS), fatigue (MFI all subscales), FIQ total score, pain catastrophizing thoughts (PCS), and psychological distress (HADS total). Further, significant reduced PPT was found in FM compared to CON. No significance difference in pain acceptance (CPAQ) was seen between the two groups (SDC Table 1).
Post exercise, FM had significant reduced physical capacity compared to CON as described by the variables SixMWT and handgrip force (both sides). No significant differences were found between the two groups in the variables knee extension force and elbow strength (both sides) (SDC Table 1).
Baseline vs. post exercise in CON The CON group significantly improved their physical fatigue, walking distance, knee extension force, and handgrip force on the left side after 15 weeks of resistance exercise (SDC Table 1). Table 1. Presented data includes participants who performed 15-week resistance exercise, and which plasma samples were analyzed with proteomics at both time points. FM = 21, CON= 24. These data have been published elsewhere although not the same number of participants [11,20].  Protein S100-A8 P05109 S100A8 S10A8 Protein S100-A9 P06702 S100A9 S10A9

Potential subgroups of FM related to clinical characteristics and exercise variables
A within-group separation could be seen in the FM group both at baseline (Fig. 1 a, Score plot) and post exercise (Fig. 2 a, Score plot). To get an overview and compare the proteome profile at baseline and post exercise in FM alone, a PCA was performed including all proteins from both time points (SDC Fig. 2). The PCA consisted of two significant PCs with a R 2 = 0.53 and Q 2 = 0.38. A clear separation in the plasma proteome profile was noted between baseline and post exercise (SDC Fig. 2b, loading plot) as well as a subgroup division within FM (SDC Fig. 2 a, score plot). To further evaluate the differences between the two subgroups of FM patients (classified as subgroup 1 and 2) seen in the PCA analysis (SDC Fig. 2, score plot) and in the score plots of the two OPLS-DA models ( Fig. 1 and 2), background and exercise-related data were first compared. At baseline, significant differences existed between the two groups in FM duration, number of tender points, and mental fatigue (SDC  Table 2.
Several biological processes with an FDR < 0.05 were present and both networks had proteins related to stress. In subgroup 1 (shorter FM duration) the proteins were further involved in blood coagulation and immune response, whereas in subgroup 2 (longer FM duration) the proteins were involved in leucocyte-mediated immunity, immune system process, and inflammatory response (SDC Fig. 4 c). No significant models were obtained when regressing the knee extension force or handgrip force variables for all FM or when divided into subgroups at baseline. SDC Fig. 4. Subgroup division of FM duration at baseline. OPLS models of FM duration and significant plasma proteins of respective FM subgroup. The subgroup division is based on the score plot of the OPLS-DA model at baseline (Fig. 1 a, upper right quadrant = subgroup 1, and lower right quadrant = subgroup 2). a) In the score plot of respective subgroup, the larger the square the longer FM duration. Numbers 1 and 2 shows participant who have performed resistance exercise and which are included in the subgroup division seen in the PCA score plot in SDC Fig. 2 a. b) Loading plot of each FM subgroup showing significant protein with VIPpred ≥ 1.2 and p(corr) ≥ 0.4. c) Protein network of significant proteins from respective subgroup. The color nodes in subgroup 1 represents: Red = response to stress, yellow = blood coagulation, green = immune response. For subgroup 2 the colored nodes represent: Green = immune system process, blue = inflammatory response, red = response to stress, purple = leucocyte-mediated immunity. Abbreviated protein names in loading plots and STRING networks are explained in SDC Table 2.
SDC Fig. 5. OPLS models of knee extension force post exercise subgroup 2 including protein network. a) Score blot of knee extension force mean right and left side for subgroup 2 (with longer FM duration). The larger the square, the higher knee extension force. b) Loading plots of significant proteins with VIPpred ≥ 1.2 and p(corr) ≥ 0.66 from each model. c) STRING Protein network including all significant proteins from the OPLS model of both right and left side of knee extension force. The colored nodes represent red = wound healing, purple = tissue generation, and blue = inflammatory response. Abbreviated protein names in loading plots and STRING networks are found in SDC Table 2.