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

Research Press Release | April 10, 2015

The disease concept of FMS, SpA , and RA: FMS, SpA, and RA are characterized by widespread pain, which often results in confusion. Note that FMS patients often possess a comorbidity with SpA or RA.
The disease concept of FMS, SpA , and RA: FMS, SpA, and RA are characterized by widespread pain, which often results in confusion. Note that FMS patients often possess a comorbidity with SpA or RA.

Press Release

Fibromyalgia syndrome (FMS) is an obstinate disease with an enigmatic etiology. Since there was no known structural and/or pathological evidence explaining it, many physicians denied its presence, which in turn made patients suffer psychological stress in addition to the physical pain. In this study, we focused on a subset of T cells called MAIT cells, and found that analysis of the frequency of MAIT cells and of the antigen expression profile in MAIT cells allowed us to not only diagnose FMS but also distinguish it from rheumatoid arthritis (RA) and spondyloarthritis (SpA)–both of which show similar indications.


FMS affects 1.5 – 2.0 % of the population in industrialized countries around the world. Although FMS is characterized with indications such as chronic and widespread pain, fatigue, sleeping disturbance, and physical and psychological impairment, there is no concrete structural and/or pathological evidence relevant to the disease. In this respect, many physicians do not accept FMS as a disease, although patients suffer real physical and psychological dysfunction. The diagnosis of FMS is classically based on an examination of the pain-sensitive points in the body, which is rather subjective in nature. Furthermore, FMS often manifests comorbidity with RA or SpA, both of which exhibit a similar sign—a great pain. This facet has not only made a sound diagnosis for FMS difficult, but also confounded FMS with RA and/or SpA. Therefore, more rapid and precise diagnostic markers for FMS that simultaneously distinguish it from RA and SpA have long been sought.


Our study focused on a subset of T cells called Mucosal-associated invariant T (MAIT) cells. MAIT cells are quite abundant in humans, while they are rare in mice. Recent studies have highlighted the important aspects of MAIT cells in infectious immunity and autoimmune-diseases in humans. In order to examine the possibility of using MAIT cells as a diagnostic marker, we measured the frequency of MAIT cells and the mean fluorescent intensity of the antigens in MAIT cells in the peripheral blood from healthy donors (HD), FMS, RA, and SpA patients.

Results MAIT cells are comprised of three subsets: CD4 positive (CD4+), CD4CD8 double negative, and CD8 positive (CD8+) MAIT cells. We found the frequency of CD4+MAIT cells decreased in FMS patients compared with that of HD. When we analyzed more than 60 antigens in MAIT cells with a flow cytometer, we found alternation in expression of 11 antigens in FMS patients compared with that of HD. Similar analysis revealed that the expression profile of 10 antigens allowed a distinction between FMS from RA and SpA. There existed an inverse correlation between the frequency of MAIT cells and the severity of pain in FMS patients. Since FMS patients take anti-convulsant, anti-depressant, or painkillers, the above difference in antigen expression might be attributed to these drugs rather than FMS per se. To exclude such a possibility, we examined the expression profile of the antigens in question prior to and post drug-treatment interruption, and found that such an interruption accompanied alternation in expression of 12 antigens in MAIT cells. Furthermore, such an interval resulted in an increase in CD8+ MAIT cells, implying that MAIT cells play some roles in FMS.
Perspective This study has opened a novel avenue for the objective diagnosis of FMS, which has up until now been difficult due to the absence of concrete structural and/or pathological parameters, the ignorance of physicians, and the problem in differentiating FMS from RA and/or SpA. Rapid diagnosis of FMS will ameliorate quality of life for the patient.
It is also important to keep in mind that most research on novel drug development, including basic research, particularly in immunology, is performed on mice, for which MAIT cells are quite rare, and not on humans for which they are abundant. Exploiting the function of MAIT cells in health and disease will shed light on the etiology and/or pathology of FMS, which in turn will engender the advent of revolutionary drugs.

Hiroshi Wakao, Associate Professor, Hygiene and Cellular Preventive Medicine, School of Medicine, Hokkaido University

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Publications  Mucosal-Associated Invariant T Cell Is a Potential Marker to Distinguish Fibromyalgia Syndrome from Arthritis, PLoS One  (2015.4.8)