The Leukocyte Protein L1 in Plasma and Synovial Fluid from Patients with Rheumatoid Arthritis and Osteoarthritis

Abstract

L1 is a major granulocyte and monocyte protein, released during activation and turnover of such cells. Blood and synovial fluid (SF) from 41 patients with rheumatoid arthritis (RA) and 6 patients with osteoarthritis (OA), were analyzed for L1 and the acute phase proteins C-reactive protein, orosomucoid, haptoglobin, alpha 1-antitrypsin and albumin as well as for differential leukocyte count. L1 levels in plasma and SF showed highly significant differences (p less than 0.0001), between the RA and OA patients. All the OA patients had normal plasma concentrations of L1 and low concentrations of L1 in SF. All the RA patients had elevated plasma levels of L1 and high L1 concentrations in SF. In the RA patients, the ratios between the protein concentrations in SF and blood were 3.29 for L1 and less than or equal to 0.64 for the acute phase proteins. In the SF, the L1 levels did not correlate with the monocyte count, while a low, positive correlation was found between L1 and the granulocyte count. The high L1 concentrations observed in SF from RA patients probably reflected an increased turnover of leukocytes in the inflamed joints. In SF from RA patients, high L1 concentrations were found in joints with a high amount of swelling. The present study suggests that L1 may represent a marker of both local and systemic inflammation.

Calprotectin (S100A8/S100A9), an Inflammatory Protein Complex from Neutrophils with a Broad Apoptosis-Inducing Activity

“…The calprotectin-upregulated pathological states were also listed in more detail in a review by Johne et al 21) Berntzen et al reported that in healthy human serum/ plasma, the concentration of calprotectin was less than 1 mg/ml, while the plasma concentration of patients with rheumatoid arthritis (RA) was reportedly increased to approximately 10-fold higher concentrations as mean values. 30) In contrast, no substantial increase was observed in osteoarthritis. 30) An increase in blood calprotectin concentration was also reported in patients with Crohn's disease, 34) colorectal carcinoma, 35) cystic fibrosis, 36,37) multiple sclerosis, 38) human immunodeficiency virus (HIV) infection, 39) and patients who had undergone major surgery.…”

“…30) In contrast, no substantial increase was observed in osteoarthritis. 30) An increase in blood calprotectin concentration was also reported in patients with Crohn's disease, 34) colorectal carcinoma, 35) cystic fibrosis, 36,37) multiple sclerosis, 38) human immunodeficiency virus (HIV) infection, 39) and patients who had undergone major surgery. 42) A more intense increase in calprotectin concentration has been observed in body fluid from local inflammatory sites than in blood.…”

“…42) A more intense increase in calprotectin concentration has been observed in body fluid from local inflammatory sites than in blood. For instance, the concentration in the synovial fluid of RA patients was reported to often increase by more than 100 mg/ml 30) ; the cerebrospinal fluid with an opportunistic infection in HIV-infected patients reportedly contained 30-350 mg/ml of calprotectin. 44) The concentration of the factor thus often increases by more than 100-fold above the normal state.…”

“…11,[29][30][31][32][33][34][35][36][37][38][39][40][41] Examples of the inflammatory states in which extracellular calprotectin reportedly increases are depicted in Table 1. The calprotectin-upregulated pathological states were also listed in more detail in a review by Johne et al 21) Berntzen et al reported that in healthy human serum/ plasma, the concentration of calprotectin was less than 1 mg/ml, while the plasma concentration of patients with rheumatoid arthritis (RA) was reportedly increased to approximately 10-fold higher concentrations as mean values.…”

Serum Calprotectin Versus Acute‐Phase Reactants in the Discrimination of Inflammatory Disease Activity in Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Inhibitors

“…Calprotectin induces the secretion of both IL-6 and TNF in a dose-dependent manner (10). Higher calprotectin levels have been found in synovial fluid and serum from RA and PsA patients compared with healthy controls and osteoarthritis patients (11). Calprotectin serum levels correlate with disease activity, predict relapse, and are independently associated with radiographic progression in RA (12)(13)(14).…”