Elevated serum granzyme B levels are associated with disease activity and joint damage in patients with rheumatoid arthritis

Abstract

Objectives Little is known about the roles of granzyme B in rheumatoid arthritis (RA). We aimed to evaluate the serum level of granzyme B in patients with RA and determine relationships with clinical features and joint destruction of RA. Methods We enrolled 100 patients with RA, 50 patients with osteoarthritis (OA), and 50 healthy controls (HC). Granzyme B serum concentrations were measured by ELISA; we then analyzed associations between granzyme B levels, clinical features, and joint destruction by calculating Sharp scores and disease activity as measured by Disease Activity Score-28 based on erythrocyte sedimentation rate (DAS28-ESR) in patients with RA. Results Compared with HC and patients with OA, serum granzyme B levels in patients with RA were remarkably elevated. Serum granzyme B levels did not differ between patients with OA and HC. Granzyme B levels correlated with ESR, rheumatoid factor, swollen joint counts, joint erosion scores, total Sharp scores, and DAS28-ESR. Moreover, patients with RA with high disease activity had higher granzyme B levels. Conclusions Serum granzyme B levels were elevated significantly in patients with RA and correlated positively with disease activity and joint destruction. Serum granzyme B may have potential applications in laboratory evaluation of patients with RA.

Potential role of extracellular granzyme B in wet age-related macular degeneration and fuchs endothelial corneal dystrophy

“…Despite its recognized presence in the extracellular space, no effective endogenous extracellular GrB inhibitors have been identified in humans. Thus, it appears that GrB activity in the extracellular space is minimally regulated, which may help explain why GrB is implicated in a number of diseased states ( Choy et al, 2003 ; Ngan et al, 2009 ; Turner et al, 2019 ; Matsubara et al, 2020 ; Qiao et al, 2020 ).…”

“…The normal and pathological functions of GrB have been investigated in a variety of organs and tissues and have implicated GrB in the process of tissue aging, as well as in a variety of age-related diseases (eg. cardiovascular disease, COPD, arthritis) ( Hendel et al, 2010 ; Bao et al, 2018 ; Qiao et al, 2020 ; Zeglinski and Granville, 2020 ). However, little investigation has been conducted on GrB activity in ocular age-related diseases.…”

Effect of family caregiver nursing education on patients with rheumatoid arthritis and its impact factors: A randomized controlled trial

“…Initially, we selected biochemical indicators of inflammation for evaluation due to their importance in the pathogenesis of RA[ 22 ]. In addition to the two traditional indicators of CRP and ESR[ 23 ], we also included TNF-α, an emerging marker of RA[ 16 ].…”

Dual roles of granzyme B

“…For patients presenting with aGVHD, the size of the GZMB + Treg population was a strong predictor of aGVHD at 30+ days after subjection to allogeneic haematopoietic stem cell transplantation. 62 Apart from these findings, the level of extracellular/soluble GZMB is reportedly elevated in atherosclerotic lesions, 63 bronchoalveolar lavage fluid of patients with chronic obstructive pulmonary disease, [64][65][66] allergen-challenged patients with atopic asthma, 67 the serum, plasma and synovial fluid of patients with rheumatoid arthritis (RA), 68,69 acute-phase plasma of typhoid patients, 70 plasma of acute myocardial infarction patients, 71 serum of obese subjects, 72 and patients with type 2 diabetes and low-grade systemic inflammation. 73 Moreover, the abundance of GZMB-expressing Eomes + T helper cells increased in the pathogenesis of secondary progressive multiple sclerosis.…”