The Differential Expressions and Associations of Intracellular and Extracellular GRP78/Bip with Disease Activity and Progression in Rheumatoid Arthritis Patients

GRP78/BiP, a stress-induced protein and autoantigen in rheumatoid arthritis (RA), exhibits different expressions in various biological fluids and tissues, namely serum, synovial fluid (SF), and synovium, all of which are pertinent to the disease activity and progression of RA; however, there is a scarcity of data linking both intracellular and extracellular GRP78/Bip to the disease activity and progression of RA within the realm of rheumatology. This study was undertaken to investigate the differential expression of intracellular and extracellular GRP78/Bip in serum, SF, and synovium, and to determine their association with disease activity and progression in patients with RA. Patients with RA, osteoarthritis (OA), and traumatic meniscal injury (TMI) without radiographic OA were consecutively recruited for the study at our hospital. Among the patients with RA, six different subgroups were established based on their disease activity and progression. Disease activity was measured using the DAS28 criterion, while disease progression was evaluated using the Steinbrocker classification grade. This study conducted a comprehensive analysis of the differential expressions of GRP78/Bip in multiple sample types, including serum, SF, and synovium, with the specific emphasis on their associations with disease activity and progression in RA. The expression levels of GRP78/Bip, TNF-α, and IL-10 were significantly elevated in serum, SF, and synovium of patients with RA when compared to both the CON and iCON groups(P<0.05). During the status of disease activity, serum and synovium exhibited increased levels of GRP78/Bip, TNF-α, and IL-10 compared to periods of disease remission (P<0.05). However, in SF, the levels of GRP78/Bip and IL-10 were reduced, while TNF-α levels were elevated during disease activity status as opposed to the remission status (P<0.05). In serum and synovium of patients with RA, positive correlations were observed between the levels of GRP78/Bip expression and the stages of disease progression, along with TNF-α and IL-10 levels. Additionally, in SF, positive correlations were identified between the expression levels of GRP78/Bip and the concentrations of TNF-α and IL-10; conversely, a negative correlation was noted between GRP78/Bip expression and stages of disease progression. The differential expressions of GRP78/Bip in serum, SF, and synovium indicated that the potential role and function of GRP78/Bip might vary depending on its location within the specific biological fluids and tissues. The presence of intracellular and extracellular GRP78/Bip was associated with disease activity and progression of RA, 2 suggesting the involvement of GRP78/Bip in the pathogenesis and development of this debilitating autoimmune disorder, as well as its potential as a biomarker for monitoring disease activity and progression.