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Mucosal-associated invariant T cell is a potential marker to distinguish fibromyalgia syndrome from arthritis.

Sugimoto C, Konno T, Wakao R, Fujita H, Fujita H, Wakao H - PLoS ONE (2015)

Bottom Line: There was a decrease in the MAIT cell population in FMS, RA, and SpA compared with HD.Among the cell surface antigens in MAIT cells, three chemokine receptors, CCR4, CCR7, and CXCR1, a natural killer (NK) receptor, NKp80, a signaling lymphocyte associated molecule (SLAM) family, CD150, a degrunulation marker, CD107a, and a coreceptor, CD8β emerged as potential biomarkers for FMS to distinguish from HD.Furthermore, the drug treatment interruption resulted in alternation of the expression of CCR4, CCR5, CXCR4, CD27, CD28, inducible costimulatory molecule (ICOS), CD127 (IL-7 receptor α), CD94, NKp80, an activation marker, CD69, an integrin family member, CD49d, and a dipeptidase, CD26, in FMS.

View Article: PubMed Central - PubMed

Affiliation: Department of Hygiene & Cellular Preventive Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, 060-8638, Japan.

ABSTRACT

Background: Fibromyalgia (FM) is defined as a widely distributed pain. While many rheumatologists and pain physicians have considered it to be a pain disorder, psychiatry, psychology, and general medicine have deemed it to be a syndrome (FMS) or psychosomatic disorder. The lack of concrete structural and/or pathological evidence has made patients suffer prejudice that FMS is a medically unexplained symptom, implying inauthenticity. Furthermore, FMS often exhibits comorbidity with rheumatoid arthritis (RA) or spondyloarthritis (SpA), both of which show similar indications. In this study, disease specific biomarkers were sought in blood samples from patients to facilitate objective diagnoses of FMS, and distinguish it from RA and SpA.

Methods: Peripheral blood mononuclear cells (PBMCs) from patients and healthy donors (HD) were subjected to multicolor flow cytometric analysis. The percentage of mucosal-associated invariant T (MAIT) cells in PBMCs and the mean fluorescent intensity (MFI) of cell surface antigen expression in MAIT cells were analyzed.

Results: There was a decrease in the MAIT cell population in FMS, RA, and SpA compared with HD. Among the cell surface antigens in MAIT cells, three chemokine receptors, CCR4, CCR7, and CXCR1, a natural killer (NK) receptor, NKp80, a signaling lymphocyte associated molecule (SLAM) family, CD150, a degrunulation marker, CD107a, and a coreceptor, CD8β emerged as potential biomarkers for FMS to distinguish from HD. Additionally, a memory marker, CD44 and an inflammatory chemokine receptor, CXCR1 appeared possible markers for RA, while a homeostatic chemokine receptor, CXCR4 deserved for SpA to differentiate from FMS. Furthermore, the drug treatment interruption resulted in alternation of the expression of CCR4, CCR5, CXCR4, CD27, CD28, inducible costimulatory molecule (ICOS), CD127 (IL-7 receptor α), CD94, NKp80, an activation marker, CD69, an integrin family member, CD49d, and a dipeptidase, CD26, in FMS.

Conclusions: Combined with the currently available diagnostic procedures and criteria, analysis of MAIT cells offers a more objective standard for the diagnosis of FMS, RA, and SpA, which exhibit multifaceted and confusingly similar clinical manifestations.

No MeSH data available.


Related in: MedlinePlus

Biochemical and physical parameters in FMS, RA, and SpA.A: Serum CRP concentrations in FMS, RA, and SpA (left panel).: Serum MMP-3 concentrations in FMS, RA, and SpA (right panel). B: PVAS in FMS, RA, and SpA (left panel).: FVAS in FMS, RA, and SpA (right panel). A-B. Horizontal line: Median; boxes: 25th percentile and 75th percentile; whiskers: Minimum and Maximum. Asterisk shows the group-pairs exhibiting significance. *: P< 0.05, **: P < 0.01, ***: P<0.001 (P value adjusted after the Kruskal-Wallis test with the Dunn's multicomponent test). C: Correlation between PVAS/FVAS and MAIT cell percentage (% of Vα7.2+CD161high cells among CD3+ cells) in a cohort of 26 FMS (left panels), of 21 RA (middle panels), and of 36 SpA (right panels) patients. The correlation was analyzed with the Spearman rank correlation test. *: P< 0.05, r: correlation coefficient.
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pone.0121124.g004: Biochemical and physical parameters in FMS, RA, and SpA.A: Serum CRP concentrations in FMS, RA, and SpA (left panel).: Serum MMP-3 concentrations in FMS, RA, and SpA (right panel). B: PVAS in FMS, RA, and SpA (left panel).: FVAS in FMS, RA, and SpA (right panel). A-B. Horizontal line: Median; boxes: 25th percentile and 75th percentile; whiskers: Minimum and Maximum. Asterisk shows the group-pairs exhibiting significance. *: P< 0.05, **: P < 0.01, ***: P<0.001 (P value adjusted after the Kruskal-Wallis test with the Dunn's multicomponent test). C: Correlation between PVAS/FVAS and MAIT cell percentage (% of Vα7.2+CD161high cells among CD3+ cells) in a cohort of 26 FMS (left panels), of 21 RA (middle panels), and of 36 SpA (right panels) patients. The correlation was analyzed with the Spearman rank correlation test. *: P< 0.05, r: correlation coefficient.

Mentions: Analysis of serum showed that RA had elevated levels of C-reactive protein (CRP) compared with FMS and/or SpA (Fig. 4A and S4A–B Table). Matrix metalloproteinase (MMP)-3 level in FMS was significantly lower than that in RA and SpA (Fig. 4A and S4A–B Table). Thus, CRP and MMP-3 might be potential biomarkers for distinguishing the diseases. Despite biomarkers such as CRP and rheumatoid factors, 20–50% of RA patients are devoid of them [10]. This means that there is a continuing need for a novel biomarker(s) for RA. In this respect, CCR7 may be a potential one for RA to distinguish from HD in total MAIT cells, and in CD8+ MAIT cells (Fig. 3 and Table 3 and S3 Table). When pain visual analog scale (PVAS) was compared, FMS and SpA showed a greater value than RA (Fig. 4B and S4A–B Table). Similarly, FMS exhibited a greater fatigue visual analog scale (FVAS) than RA (Fig. 4B and S4A–B Table). Intriguingly, there existed an inversed correlation between PVAS and the MAIT cell frequency in FMS, suggesting that MAIT cells would somehow be implicated in the pathology of FMS (Fig. 4C). Combined with data from the cell surface antigen analysis in MAIT cells, CRP, MMP-3, PVAS and FVAS may serve as auxiliary markers to distinguish FMS from RA and/or SpA.


Mucosal-associated invariant T cell is a potential marker to distinguish fibromyalgia syndrome from arthritis.

Sugimoto C, Konno T, Wakao R, Fujita H, Fujita H, Wakao H - PLoS ONE (2015)

Biochemical and physical parameters in FMS, RA, and SpA.A: Serum CRP concentrations in FMS, RA, and SpA (left panel).: Serum MMP-3 concentrations in FMS, RA, and SpA (right panel). B: PVAS in FMS, RA, and SpA (left panel).: FVAS in FMS, RA, and SpA (right panel). A-B. Horizontal line: Median; boxes: 25th percentile and 75th percentile; whiskers: Minimum and Maximum. Asterisk shows the group-pairs exhibiting significance. *: P< 0.05, **: P < 0.01, ***: P<0.001 (P value adjusted after the Kruskal-Wallis test with the Dunn's multicomponent test). C: Correlation between PVAS/FVAS and MAIT cell percentage (% of Vα7.2+CD161high cells among CD3+ cells) in a cohort of 26 FMS (left panels), of 21 RA (middle panels), and of 36 SpA (right panels) patients. The correlation was analyzed with the Spearman rank correlation test. *: P< 0.05, r: correlation coefficient.
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pone.0121124.g004: Biochemical and physical parameters in FMS, RA, and SpA.A: Serum CRP concentrations in FMS, RA, and SpA (left panel).: Serum MMP-3 concentrations in FMS, RA, and SpA (right panel). B: PVAS in FMS, RA, and SpA (left panel).: FVAS in FMS, RA, and SpA (right panel). A-B. Horizontal line: Median; boxes: 25th percentile and 75th percentile; whiskers: Minimum and Maximum. Asterisk shows the group-pairs exhibiting significance. *: P< 0.05, **: P < 0.01, ***: P<0.001 (P value adjusted after the Kruskal-Wallis test with the Dunn's multicomponent test). C: Correlation between PVAS/FVAS and MAIT cell percentage (% of Vα7.2+CD161high cells among CD3+ cells) in a cohort of 26 FMS (left panels), of 21 RA (middle panels), and of 36 SpA (right panels) patients. The correlation was analyzed with the Spearman rank correlation test. *: P< 0.05, r: correlation coefficient.
Mentions: Analysis of serum showed that RA had elevated levels of C-reactive protein (CRP) compared with FMS and/or SpA (Fig. 4A and S4A–B Table). Matrix metalloproteinase (MMP)-3 level in FMS was significantly lower than that in RA and SpA (Fig. 4A and S4A–B Table). Thus, CRP and MMP-3 might be potential biomarkers for distinguishing the diseases. Despite biomarkers such as CRP and rheumatoid factors, 20–50% of RA patients are devoid of them [10]. This means that there is a continuing need for a novel biomarker(s) for RA. In this respect, CCR7 may be a potential one for RA to distinguish from HD in total MAIT cells, and in CD8+ MAIT cells (Fig. 3 and Table 3 and S3 Table). When pain visual analog scale (PVAS) was compared, FMS and SpA showed a greater value than RA (Fig. 4B and S4A–B Table). Similarly, FMS exhibited a greater fatigue visual analog scale (FVAS) than RA (Fig. 4B and S4A–B Table). Intriguingly, there existed an inversed correlation between PVAS and the MAIT cell frequency in FMS, suggesting that MAIT cells would somehow be implicated in the pathology of FMS (Fig. 4C). Combined with data from the cell surface antigen analysis in MAIT cells, CRP, MMP-3, PVAS and FVAS may serve as auxiliary markers to distinguish FMS from RA and/or SpA.

Bottom Line: There was a decrease in the MAIT cell population in FMS, RA, and SpA compared with HD.Among the cell surface antigens in MAIT cells, three chemokine receptors, CCR4, CCR7, and CXCR1, a natural killer (NK) receptor, NKp80, a signaling lymphocyte associated molecule (SLAM) family, CD150, a degrunulation marker, CD107a, and a coreceptor, CD8β emerged as potential biomarkers for FMS to distinguish from HD.Furthermore, the drug treatment interruption resulted in alternation of the expression of CCR4, CCR5, CXCR4, CD27, CD28, inducible costimulatory molecule (ICOS), CD127 (IL-7 receptor α), CD94, NKp80, an activation marker, CD69, an integrin family member, CD49d, and a dipeptidase, CD26, in FMS.

View Article: PubMed Central - PubMed

Affiliation: Department of Hygiene & Cellular Preventive Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, 060-8638, Japan.

ABSTRACT

Background: Fibromyalgia (FM) is defined as a widely distributed pain. While many rheumatologists and pain physicians have considered it to be a pain disorder, psychiatry, psychology, and general medicine have deemed it to be a syndrome (FMS) or psychosomatic disorder. The lack of concrete structural and/or pathological evidence has made patients suffer prejudice that FMS is a medically unexplained symptom, implying inauthenticity. Furthermore, FMS often exhibits comorbidity with rheumatoid arthritis (RA) or spondyloarthritis (SpA), both of which show similar indications. In this study, disease specific biomarkers were sought in blood samples from patients to facilitate objective diagnoses of FMS, and distinguish it from RA and SpA.

Methods: Peripheral blood mononuclear cells (PBMCs) from patients and healthy donors (HD) were subjected to multicolor flow cytometric analysis. The percentage of mucosal-associated invariant T (MAIT) cells in PBMCs and the mean fluorescent intensity (MFI) of cell surface antigen expression in MAIT cells were analyzed.

Results: There was a decrease in the MAIT cell population in FMS, RA, and SpA compared with HD. Among the cell surface antigens in MAIT cells, three chemokine receptors, CCR4, CCR7, and CXCR1, a natural killer (NK) receptor, NKp80, a signaling lymphocyte associated molecule (SLAM) family, CD150, a degrunulation marker, CD107a, and a coreceptor, CD8β emerged as potential biomarkers for FMS to distinguish from HD. Additionally, a memory marker, CD44 and an inflammatory chemokine receptor, CXCR1 appeared possible markers for RA, while a homeostatic chemokine receptor, CXCR4 deserved for SpA to differentiate from FMS. Furthermore, the drug treatment interruption resulted in alternation of the expression of CCR4, CCR5, CXCR4, CD27, CD28, inducible costimulatory molecule (ICOS), CD127 (IL-7 receptor α), CD94, NKp80, an activation marker, CD69, an integrin family member, CD49d, and a dipeptidase, CD26, in FMS.

Conclusions: Combined with the currently available diagnostic procedures and criteria, analysis of MAIT cells offers a more objective standard for the diagnosis of FMS, RA, and SpA, which exhibit multifaceted and confusingly similar clinical manifestations.

No MeSH data available.


Related in: MedlinePlus