Abnormalities of Peripheral Lymphocyte Subsets in Rheumatoid Arthritis Patients Complicated with Osteoporosis

Abstract

Introduction Osteoporosis (OP) is one of the major comorbidities of rheumatoid arthritis (RA). Recent studies have shown that immune cells modulate bone health and regulate bone remodeling. However, the alterations of lymphocyte subsets in RA patients with OP are unclear. Here, we assessed the absolute numbers and proportions of the subsets in RA sufferers with OP and investigated the clinical significance. Methods A total of 777 RA patients and 117 gender- and age-matched healthy controls (HCs) were enrolled in this study. Patients were divided into RA-non-OP and RA-OP group according to their bone mineral density (BMD) and the history of fragility fracture. Peripheral lymphocyte subsets of participants were assessed by flow cytometry. Results Among 220 (28.31%) RA-OP patients, there were higher levels of erythrocyte sedimentation rate (ESR) ( P = 0.011), C-reactive protein (CRP) ( P = 0.028), rheumatoid factor (RF) ( P = 0.013) and anti-cyclic citrullinated peptide antibody (ACPA) ( P = 0.010), while red blood cells (RBC) ( P = 0.039) were lower than those in RA-non-OP group. Compared with those of HCs and RA-non-OP group, the level of circulating Th17 cells in RA-OP patients was significantly increased ( P < 0.05), while those of Tregs decreased ( P < 0.01), leading to a higher ratio of Th17/Treg ( P < 0.01). Notably, the level of B cells in both RA-non-OP and RA-OP group was reduced, this alteration was more obvious in patients with OP ( P < 0.05). Conclusions Immune disorders characterized by peripheral Th17/Treg imbalance and reduced B cells may contribute directly or indirectly to OP in RA, and this deserves more clinical attention. Supplementary Information The online version contains supplementary material available at 10.1007/s40744-022-00452-x.

Mechanisms of Systemic Osteoporosis in Rheumatoid Arthritis

“…A study using flow cytometry to characterize peripheral blood lymphocyte subsets in RA patients demonstrated a higher Th17:Treg ratio in patients when compared to those without osteoporosis [ 37 ]. Interestingly, in the presence of osteoporosis the number of peripheral blood B cells was reduced.…”

“…Bruno et al, reported a connection between ACPA-positive patients and osteopenia and osteoporosis, respectively [ 59 ]. A publication of Cheng et al, demonstrated that RA-osteoporosis patients showed higher ACPA titers in comparison to non-osteoporotic RA patients [ 37 ]. Apart from ACPAs and RF, anti-carbamylated protein antibodies (anti-CarP) also appeared to be involved in enhancing bone resorption in RA patients [ 54 ].…”