Fibromyalgia syndrome (FMS), rheumatoid arthritis (RA) and spondyloarthritis (SpA) all exhibit multifaceted manifestations, and many patients exhibit overlapping comorbidities. However, patients with FMS are distinct from others in that they experience widespread pain, fatigue and mood changes, including anxiety and depression.
Although its hallmark symptom of pain causes rheumatologists to consider FMS a pain disorder, psychiatrists and others consider it a psychosomatic disorder. Unfortunately, the lack of an objective biomarker or pathological evidence of disease has left patients with the feeling that their disease experience is medically unexplained or, perhaps even, inauthentic. The addition of an analysis of mucosal-associated invariant T (MAIT) cells to the currently available diagnostic procedures and criteria may offer an objective standard for distinguishing between the confusingly similar manifestations of these rheumatic diseases.
Chie Sugimoto, PhD, assistant professor at Hokkaido University in Sapporo, Japan, and colleagues recently published the results of their analysis of peripheral blood mononuclear cells (PBMC) in PLoS ONE.1 The investigators sought disease-specific biomarkers that would not only facilitate an objective diagnosis of FMS, but also distinguish it from RA and SpA. They found that patients with FMS, RA and SpA have a decreased population of MAIT cells relative to healthy donors. Serum analysis also revealed that patients with RA had elevated levels of C-reactive protein when compared with serum from patients with FMS and/or SpA.
The investigators sought first to identify a cell-surface antigen on MAIT cells that would distinguish between healthy donors and patients with FMS. They next looked for a cell-surface antigen on MAIT cells that would further differentiate between healthy donors, and patients with FMS, RA and SpA.
They evaluated three chemokine receptors (CCR4, CCR7 and CXCR1), a natural killer receptor (NKp80), a member of the signaling lymphocyte associated molecule family (CD150), a degranulation marker (CD107a) and a co-receptor (CD8β). They found that all of these had the potential to serve as distinguishing biomarkers for patients with FMS. They also found that a memory marker (CD44) and an inflammatory chemokine receptor (CXCR1) could serve as possible biomarkers for RA. Moreover, the homeostatic chemokine receptor (CXCR4) was able to differentiate SpA from FMS.
The researchers next asked whether daily drug intakes affected the frequency of the various MAIT cell subsets and the expression of the cells’ surface markers on MAIT cells from patients with FMS. They found that alteration in drug treatment for patients with FMS resulted in changes in the expression of CCR4, CCR5, CXCR4, CD27 and CD28; inducible costimulatory molecule; the IL-7 receptor α (CD127); CD94; NKp80; an activation marker (CD69); an integrin family member (CD49d) as well as a dipeptidase (CD26). The investigators noted that not all of the antigens that appeared relevant to FMS demonstrated altered expression in response to interruption of drug treatment. They did find, however, that CD28 expression increased in all subsets of MAIT cells when treatment was stopped.
