T Follicular Regulatory Cells Are Decreased in Patients With Established Treated Rheumatoid Arthritis With Active Disease: Comment on the Article by Liu et al

T follicular regulatory (Tfr) cells: Dissecting the complexity of Tfr‐cell compartments

“…15 In multiple sclerosis, myasthenia gravis, systemic lupus erythematosus, and rheumatoid arthritis, a decreased frequency of bTfr cells was observed. [155][156][157][158] However, a higher frequency of bTfr cells was found in patients with ankylosing spondylitis, systemic lupus erythematosus, and Sjögren's syndrome (SS). [159][160][161][162][163] Importantly, most of the literature describes studies where what is defined as Tfh cells contain both Tfh and CXCR5 + Tfr cells, likewise many other studies identify as Treg cells a mixture of conventional Treg cells together with Tfr cells.…”

Control of Germinal Center Responses by T-Follicular Regulatory Cells

“…In rheumatoid arthritis, increased percentages of cTfr, decreased percentages of Tfh and a corresponding drop in the ratio of Tfh/Tfr was associated with stable disease and reduced levels of autoantibodies, while active disease was correlated to increased cTfr but no change in the Tfh/Tfr ratio (71). However, treatment may cause cTfr numbers to drop resulting in a high Tfh/Tfr ratio but no clear relationship between cTfr numbers and autoantibodies (79). Similarly to untreated RA patients, the Tfh/Tfr ratio was correlated with autoantibody production in SLE patients, although in this case this was due to a loss of Tfr while the proportion of Tfh remained stable (80).…”

Follicular regulatory T cells: a novel target for immunotherapy?

“…Altered frequencies and/or the suppressive capacity of cTfr cells have been elucidated in a multitude of AIDs, including systemic AIDs and organ‐specific AIDs (shown in Table ). Systemic AIDs involve rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), ankylosing spondylitis (AS), IgG4‐related disease (IgG4‐RD) and common variable immune deficiency (CVID) . Organ‐specific AIDs involve multiple sclerosis (MS), myasthenia gravis (MG), Hashimoto's thyroiditis (HT), primary biliary cholangitis (PBC), type 1 diabetes (T1D) and ulcerative colitis (UC) .…”

“…13,46,47 Increased 58,61 and decreased 59,60 frequencies of cTfr cells are found in RA patients, while no significant difference is found in early-stage RA. 62 The frequency of cTfr cells has negative 58,60 or no correlation 59 with disease activity, and the ratio of cTfr/cTfh is correlated with disease activity. 59,61 Moreover, increased cTfr cells with enhanced suppressive function and activated CD45RA À Foxp3 high cTfr subset have been found in patients with RA in stable remission compared with patients with active RA and healthy controls.…”

“…62 The frequency of cTfr cells has negative 58,60 or no correlation 59 with disease activity, and the ratio of cTfr/cTfh is correlated with disease activity. 59,61 Moreover, increased cTfr cells with enhanced suppressive function and activated CD45RA À Foxp3 high cTfr subset have been found in patients with RA in stable remission compared with patients with active RA and healthy controls. 58 Percentages of cTfr and cTfh cells are decreased when prescribed with methotrexate.…”