Increased chromogranin A levels indicate sympathetic hyperactivity in patients with rheumatoid arthritis and systemic lupus erythematosus

OBJECTIVE: Sympathetic hyperactivity is an unfavorable disease consequence in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) due to an increased risk of cardiovascular events. We aimed to identify a serum marker of the sympathetic nervous system, the adrenal chromogranin A (CHGA), in order to study sympathetic hyperactivity in RA and SLE. METHODS: Serum levels of CHGA were measured by radioimmunoassay in healthy subjects and patients with RA and SLE. CHGA immunofluorescence was performed in synovium of patients with RA and controls with osteoarthritis (OA). CHGA levels were measured in plasma, synovial fluid, and synovium superfusate in RA and OA controls. RESULTS: In healthy subjects, systemic CHGA levels correlated positively with age and plasma norepinephrine, indicating the sympathetic origin (p < 0.01). Serum CHGA levels were higher in RA and SLE than in healthy subjects (p < 0.001), which was particularly evident in female patients. Immunofluorescence revealed double-staining of CHGA and elastase-positive neutrophils in the synovium (but not with macrophages, T cells, fibroblasts, B cells, or tyrosine hydroxylase-positive cells). Density of CHGA+ cells was higher in RA synovium compared to OA controls. In OA controls and RA, CHGA levels were similar in plasma and synovial fluid, but levels in synovial tissue superfusate were markedly lower, which indicates that most of the CHGA is of systemic adrenal origin. CONCLUSION: Increased level of CHGA is a good marker of systemic sympathetic hyperactivity.     

Plasma adrenomedullin and proadrenomedullin N-terminal 20 peptide in patients diagnosed as having early rheumatoid arthritis

Abstract

The aim of this study was to investigate plasma adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) level in patients diagnosed with early rheumatoid arthritis (RA). Furthermore, several inflammatory cytokines were measured in those patients to clarify the roles of AM and PAMP. Forty patients diagnosed with early RA (women 46 ± 8.5 years old) and 10 healthy controls (women 57 ± 5 years old) were studied. Plasma levels of AM, PAMP, matrix metalloprotease 3 (MMP-3), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP) were measured using an immunoradiometric assay and enzyme-linked immunosorbent asay (ELISA) methods. The plasma levels of AM (17.5 ± 8.4 fmol/ml) and PAMP (2.01 ± 0.57 fmol/ml) in patients exceeded those in healthy controls (AM 8.6 ± 1.7, PAMP 1.17 ± 0.34 fmol/ml). Moreover, plasma AM and PAMP levels demonstrated a significantly positive correlation with plasma MMP-3 and IL-6 levels. Nevertheless, CRP and TNF-α levels in these patients showed no significant correlation with plasma AM and PAMP levels. These data support the possible role for AM and PAMP in the pathophysiology of early RA.     

Enhanced local production of osteopontin in rheumatoid joints

OBJECTIVE: To investigate the involvement of osteopontin (OPN) in the pathogenesis of rheumatoid arthritis (RA), localization and production of OPN were examined in patients with RA. METHODS: Localization of OPN in the rheumatoid synovium was examined by immunohistochemistry. In vitro OPN production by cultured synovial cells from patients with RA (n = 5) and with osteoarthritis (OA) (n = 5) was assessed by ELISA. OPN concentrations in plasma and synovium were quantified in patients with RA (n = 23) by 2 distinct ELISA systems to measure both thrombin cleaved and non-cleaved OPN. The same experiments were done in patients with OA (n = 15) and healthy volunteers (n = 10) as a control. RESULTS: OPN was highly detected by immunohistochemistry predominantly in the RA synovial lining cells, while less and scattered OPN was detected in OA synovial tissues. ELISA revealed that cultured RA synovial cells secreted significantly more OPN than OA cells. ELISA also showed a marked increase of OPN levels in synovial fluid (SF) of patients with RA and with OA compared to the control plasma OPN levels, although OPN levels were not increased in RA and OA plasma compared to healthy controls. SF OPN levels of patients with RA were significantly higher than those of patients with OA, and correlated with serum C-reactive protein levels. The ratios of thrombin cleaved versus non-cleaved OPN were significantly increased in RA plasma and SF compared with OA plasma and SF and plasma from healthy controls. CONCLUSION: Our results revealed enhanced local production of OPN in rheumatoid joints, suggesting involvement of OPN in the pathogenesis of RA.     

Quantitation of chondroitin 4-sulfate and chondroitin 6-sulfate in pathologic joint fluid.

OBJECTIVE. To investigate the correlation between joint disease and the composition of chondroitin sulfate in the joint fluid, unsaturated disaccharide isomers of chondroitin 4-sulfate (delta di-4S) and chondroitin 6-sulfate (delta di-6S) were measured in joint fluids obtained from patients with osteoarthritis (OA), rheumatoid arthritis (RA), or traumatic arthritis (TA). METHODS. These pathologic joint fluids were digested with chondroitinase ABC, and the delta di-4S and delta di-6S produced were determined by high performance liquid chromatography combined with fluorometry. RESULTS. Total content of delta di-4S plus delta di-6S was 71.8 +/- 30.0 nmoles/ml (mean +/- SD) in OA, 55.4 +/- 29.3 nmoles/ml in RA, and 211 +/- 149 nmoles/ml in TA joint fluids. The ratio of delta di-6S to delta di-4S was 3.81 +/- 0.992 in OA, 1.13 +/- 0.527 in RA, and 5.75 +/- 2.46 in TA joint fluids. Differences between groups were statistically significant. CONCLUSION. These results strongly suggest that the levels of chondroitin sulfate isomers and the delta di-6S: delta di-4S ratio in joint fluid reflect the proteoglycan metabolism of joint tissues, particularly of articular cartilage; hence, they could be used to diagnose joint diseases and to predict articular cartilage destruction from such joint diseases.     

Plasma adrenomedullin and proadrenomedullin N-terminal 20 peptide in patients diagnosed as having early rheumatoid arthritis

The aim of this study was to investigate plasma adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) level in patients diagnosed with early rheumatoid arthritis (RA). Furthermore, several inflammatory cytokines were measured in those patients to clarify the roles of AM and PAMP. Forty patients diagnosed with early RA (women 46 ± 8.5 years old) and 10 healthy controls (women 57 ± 5 years old) were studied. Plasma levels of AM, PAMP, matrix metalloprotease 3 (MMP-3), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP) were measured using an immunoradiometric assay and enzyme-linked immunosorbent asay (ELISA) methods. The plasma levels of AM (17.5 ± 8.4 fmol/ml) and PAMP (2.01 ± 0.57 fmol/ml) in patients exceeded those in healthy controls (AM 8.6 ± 1.7, PAMP 1.17 ± 0.34 fmol/ml). Moreover, plasma AM and PAMP levels demonstrated a significantly positive correlation with plasma MMP-3 and IL-6 levels. Nevertheless, CRP and TNF-α levels in these patients showed no significant correlation with plasma AM and PAMP levels. These data support the possible role for AM and PAMP in the pathophysiology of early RA.     

Ferritin correlates with C-reactive protein and acute phase serum amyloid A in synovial fluid, but not in serum.

OBJECTIVE: To evaluate ferritin concentration in serum and synovial fluid (SF) as a marker of activity of arthritis in comparison with C-reactive protein (CRP) and acute-phase serum amyloid A protein (A-SAA). METHODS: We determined the concentrations of ferritin, CRP and A-SAA in paired serum and SF in 34 rheumatoid arthritis (RA) and 21 osteoarthritis (OA) patients. The erythrocyte sedimentation rate (ESR) was also measured. RESULTS: The serum concentrations of ferritin, CRP and A-SAA were 93 +/- 76 (mean +/- SD) ng/ml, 4 +/- 5 mg/ml, 8 +/- 4 mg/ml in OA and 140 +/- 227, 59 +/- 34, 289 +/- 223 in RA, respectively. There was no significant difference in serum ferritin levels between OA and RA, and serum ferritin did not correlate with ESR, CRP or A-SAA. Both serum CRP and A-SAA levels were significantly higher in RA than in OA (p < 0.0001, p < 0.0001), and correlated with ESR in all arthritis (r = 0.658, p < 0.0001, r = 0.404, p < 0.01), respectively. Serum CRP levels correlated with A-SAA levels in serum (r = 0.727, p < 0.0001). In SF, the concentrations of ferritin, CRP and A-SAA in RA (421 +/- 307, 25 +/- 20 and 39 +/- 41) were significantly higher (p < 0.01, p < 0.0001, p < 0.001) than those in OA (202 +/- 220, 2 +/- 2 and 2 +/- 2), respectively. There were significant correlations among SF ferritin, CRP and A-SAA. CONCLUSION: Ferritin levels in SF but not in serum are significantly elevated in RA more than in OA, and ferritin correlated with CRP or A-SAA in SF, but not in serum. Higher levels of SF ferritin, as well as SF CRP and SF A-SAA, seem to reflect greater degrees of joints inflammation in RA and OA.     

Upregulation of kallistatin expression in rheumatoid joints

OBJECTIVE: Previous studies demonstrated suppression of rat ankle arthritis by local injection of kallistatin gene, a negative regulator of angiogenesis. We analyzed circulating levels, synovial concentrations, and tissue localizations of kallistatin in patients with rheumatoid arthritis (RA). METHODS: Paired plasma and joint fluid samples were simultaneously obtained from 24 patients with RA and 14 with osteoarthritis (OA). Synovial tissues from 5 patients with RA and 5 with OA were obtained during surgery. Fibroblast-like synoviocytes (FLS) and mononuclear cells (MNC) were prepared. ELISA was used to measure kallistatin levels of plasma, joint fluid, cell lysate, and synovium homogenate extract. Synovial tissues were subjected to Western blot and immunohistochemical staining. In addition, the tissue kallikrein (TK) levels of plasma and joint fluid samples were also measured by the ELISA. RESULTS: Circulating and synovial levels of kallistatin and TK were elevated in patients with RA. The immunohistochemical assay exhibited stainings of kallistatin on both infiltrating MNC and FLS. Intracellular kallistatin levels were significantly elevated in MNC and FLS from patients with RA. CONCLUSION: Elevated kallistatin levels were demonstrated in patients with RA, particularly in synovial tissues, FLS, and MNC. This report is the first to demonstrate upregulation of kallistatin expression in rheumatoid joints.     

Increased plasma levels of adrenomedullin in patients with systemic inflammatory response syndrome.

We measured the plasma levels of adrenomedullin (AM), a novel vasodilating peptide, in 89 patients with various forms of systemic inflammatory response syndrome (SIRS) and 13 healthy volunteers serving as controls. Plasma levels of AM in SIRS (burns: 20.5 +/- 3. 2 fmol/ml [mean +/- SEM]; pancreatitis: 13.8 +/- 3.8 fmol/ml; trauma: 14.9 +/- 2.5 fmol/ml; traumatic shock: 41.1 +/- 7.8 fmol/ml; severe sepsis: 59.9 +/- 11.2 fmol/ml; septic shock: 193.5 +/- 30.1 fmol/ml) were significantly increased over those of controls (5.1 +/- 0.2 fmol/ml). The patients with traumatic shock or septic shock especially had higher levels of plasma AM than those with trauma or severe sepsis, respectively. These data showed that in patients with SIRS, plasma AM levels increased in proportion to the severity of illness. Subsequently, we measured the plasma levels of mediators such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, plasminogen activator inhibitor (PAI)-1, and thrombomodulin (TM) in patients with traumatic shock and septic shock. A significant correlation was observed between plasma AM and TNF-alpha levels in patients with septic shock, suggesting an important role for AM as well as of TNF-alpha in the pathophysiology of inflammation. Plasma AM and IL-8 levels correlated positively with Acute Physiology and Chronic Health Evaluation (APACHE) II score, peak multiple organ failure (MOF) score during the first month and prognosis in patients with septic shock, as did plasma IL-6 levels in patients with traumatic shock. The plasma AM level might serve as a useful marker for evaluating the severity of disease and as an early predictor of subsequent organ failure and outcome in septic shock.     

Clinical features of patients with osteoarthritic knees followed by development of rheumatoid arthritis]

We investigated clinical features of patients with osteoarthritic knees followed by development of rheumatoid arthritis (RA) after several year's interval. The subjects were 16 knees of 8 patients with osteoarthritis (OA) including one man and 7 women. The mean age at development of OA knee was 62.8 years (range; 45-73). The mean age at later development of RA was 66.0 years (range; 52-79). The mean follow-up period was 96.4 months (range; 28-191). We evaluated clinical features using the 1987 revised Criteria of the American College of Rheumatology (ACR), laboratory dates including RF, CRP, ESR, the number of joints with RA, and femorotibial angle (FTA). The mean number of features of patients which was fulfilled with the ACR criteria was 3.3 +/- 1.6 at the onset of RA. Only four patients were seropositive through the total follow-up period. The serum level of RF, CRP, and ESR were reduced at the follow-up period. The mean number of the joints involved in RA was 11.0 +/- 5.1 (range; 4-22) and wrist and shoulder joints were involved more frequently than other joints except knees. High tibial osteotomy (HTO) was performed on 5 knees of 3 patients and the mean degree of FTA was 168.8 +/- 1.9 degrees just after surgery. However, 36 months after development of RA, joint destruction and valgus deformity occurred on 3 knees and the mean degree of FTA of 5 knees was ended up to 159.6 +/- 11.3 degrees. Our experiences suggested that RF, CRP, ESR and lesions of other joints should be carefully evaluated in the OA patients with seropositivity or knee hydrarthrosis and that histological analysis for synovium should be assessed by the biopsy at time of HTO or arthroscopic surgery to improve accuracy of diagnosis.     

Rheumatoid arthritis synovial fluid fibroblasts express TRAIL-R2 (DR5) that is functionally active

OBJECTIVE: To examine fibroblasts grown from the synovial fluid of rheumatoid arthritis (RA) patients for TRAIL-R2 expression, and for susceptibility to apoptosis induced by an agonistic anti-TRAIL-R2 monoclonal antibody (mAb). METHODS: The expression of TRAIL-R2 (DR5) was determined by flow cytometry on fibroblasts grown from the synovial fluid of patients with RA, osteoarthritis (OA), seronegative arthritis, and unclassified monarthritis or oligoarthritis, and on fibroblasts from the synovial membrane of RA and OA patients. Susceptibility to apoptosis mediated by an agonistic anti-TRAIL-R2 mAb was determined by alamar blue bioassay, fluorescence microscopy (annexin V/propidium iodide staining), and caspase activation. RESULTS: Fibroblasts grew from 35 of 50 RA synovial fluid samples, of which 26 were DR5(+) (mean [+/-SD] fluorescence intensity [MFI] 18.74 +/- 2.5). Fibroblasts also grew from 15 of 30 seronegative arthritis synovial fluid samples, 28 of 40 OA synovial fluid samples, and 8 of 20 unclassified monarthritis or oligoarthritis synovial fluid samples; all of these were DR5- (MFI 0.32 +/- 0.02). All 10 of the fibroblast lines from joint replacement surgery or synovectomy specimens of RA patients were DR5(+) (MFI 20.3 +/- 3.2). All fibroblast lines from the synovium of 10 OA patients were DR5-, as were fibroblasts from the skin of 5 healthy subjects. DR5(+) fibroblast cultures underwent apoptosis when treated in vitro with an agonistic anti-DR5 antibody. CONCLUSION: Fibroblasts grown from the synovial fluid and synovial membrane of RA patients express TRAIL-R2 that is functionally active. An agonistic anti-TRAIL-R2 antibody that does not induce hepatocyte toxicity may be an alternative strategy for treatment of RA.     

High CCL18/PARC expression in articular cartilage and synovial tissue of patients with rheumatoid arthritis

OBJECTIVE: We studied the role of CCL18/pulmonary and activation-regulated chemokine (PARC) in rheumatoid arthritis (RA). METHODS: Human cartilage tissues and synovial membranes were obtained from patients with RA and with osteoarthritis (OA). Sera samples were obtained from RA patients, OA patients, healthy controls, and patients with flu, and synovial fluid (SF) from patients with RA and OA. Real-time PCR was performed with RNA from cartilage samples. Immunohistochemical analysis of CCL18/PARC was done with RA and OA cartilage and synovial tissue. Levels of CCL18/PARC in serum and SF were evaluated by ELISA. RESULTS: CCL18/PARC mRNA was expressed at significantly higher levels in RA cartilage than in OA (p = 0.0001) and control (p < 0.0001) samples. CCL18/PARC mRNA expression was much higher in RA synovial membrane than OA samples (p = 0.0001). All RA cartilage and synovial tissue samples exhibited medium to strong staining for CCL18/PARC. Serum levels of CCL18/PARC were higher in RA patients (156.21 +/- 125.73 ng/ml, n = 71) than in OA patients (64.54 +/- 40.90 ng/ml, n = 12) and controls (28.04 +/- 10.96 ng/ml, n = 20). Levels of CCL18/PARC in RA SF (275.20 +/- 228.16 ng/ml, n = 15) were higher than in OA (33.13 +/- 14.84 ng/ml, n = 6; p = 0.0198). CCL18/PARC levels correlated significantly with rheumatoid factor levels (r = 0.431, p = 0.0040), but not with matrix metalloproteinase-3, erythrocyte sedimentation rate, and C-reactive protein. CONCLUSION: CCL18/PARC was highly expressed in RA articular cartilage and synovial tissue compared with OA samples. Our data indicated that CCL18/PARC levels are not related to the conditions of generalized inflammation, but are related to the pathogenesis of RA.     

Dyslipoproteinemia in patients with active rheumatoid arthritis: effects of disease activity, sex, and menopausal status on lipid profiles

OBJECTIVE: To investigate the lipid profiles in patients with active rheumatoid arthritis (RA) and to assess the relationship of inflammatory disease activity markers, sex, and menopausal status with lipid profiles. METHODS: Three groups of patients with active RA (n = 184) were studied: men (n = 61, mean age 50.8 +/- 4.81 yrs), premenopausal women (n = 58, mean age 39.2 +/- 2.44 yrs), and postmenopausal women (n = 65, mean age 60.4 +/- 2.14 yrs), and healthy controls (n = 161): men (n = 65, mean age 50.9 +/- 3.42 yrs), premenopausal women (n = 47, mean age 40.3 +/- 1.66 yrs), and postmenopausal women (n = 49, mean age 61.3 +/- 3.16 yrs). We measured fasting plasma levels of total cholesterol (TC), triglyceride (TG), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), lipoprotein (a) [LP(a)], apolipoprotein A1 (apo A1), apolipoprotein B (apo B), and erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). RESULTS: Male RA patients had significantly higher apo B/apo A1 and LP(a) and lower HDL-C than male controls. Female RA patients had significantly higher TC, LDL-C, and LP(a) than female controls. Premenopausal RA patients had significantly higher LDL-C, TC/HDL-C, LDL-C/HDL-C, and apo B/apo A1 and lower TG and HDL-C than premenopausal controls. Postmenopausal RA women had significantly higher TG and LP(a) and lower TC than postmenopausal controls. Female RA patients had higher HDL-C, apo A1, and TC/HDL-C and lower apo B/apo A1 than male RA patients. Postmenopausal RA patients had significantly higher TC, TG, TC/HDL-C, apo B, LP(a), and LDL-C/HDL-C than premenopausal RA patients. CRP correlated positively with TC/HDL-C, LDL-C/HDL-C, and apo B/apo A1 and negatively with HDL-C in male RA patients. In female RA patients CRP had positive correlation with TC/HDL-C and LDL-C/HDL-C and negative correlation with HDL-C. CONCLUSION: These findings suggest that patients with active RA have altered lipid profiles and that disease activity, sex, and menopausal status affect lipid profiles, and these would be expected to change the pattern of atherosclerotic events in RA.     

类风湿关节炎患者滑液和血浆中尿激酶型纤溶酶原激活物及其受体测定的临床意义

目的 检测尿激酶型纤溶酶原激活物（uPA）及其受体uPAR在类风湿关节炎（RA）患者滑液和血浆中的含量,并结合临床和实验室资料分析其实际意义。方法 运用酶联免疫吸附法（ELISA）双抗体夹心法分别测定46例RA、8例骨关节炎（OA）和12名健康对照个体的血浆以及15例RA患者滑液中的uPA和uPAR含量,同时将类风湿因子阳性（RF^ ）和阴性（RF^-）组之间uPA和uPAR含量进行比较,并采用直线相关与回归方法分析血浆和滑膜中uPA、uPAR的含量与相评价RA病情活动指标之间的相互关系。结果 RA患者滑液中uPA、uPAR的含量均显著高于其自身血浆（P＜0．001,P＜0．01）;RA血浆中uPA、uPAR的含量又明显高于OA组（P＜0．05,P＜0．0001）和正常对照组（P＜0．0001,P＜0．001);RF^ 和RF^-组之间uPA、uPAR在滑液和血浆中的含量差异均无显著性（P＞0．05）。RA滑液和血浆中uPA、uPAR在滑液和血浆中的含量差异均无显著性（P＞0．05）。RA滑液和血浆中uPA、uPAR的含量还与反映RA病情活动的指标C反应蛋白（CRP）和类风湿因子（RF）之间均呈正相关;RA滑液中uPA、uPAR的含量还与关节肿胀个正相关。结论 RA患者滑液和血浆中uPA和uPAR的含量是反映RA病情活动的有用指标,提示uPA和uPAR基因可能通过降解细胞外基质的蛋白裂解作用参与RA的免疫作用机制并发挥重要作用。     

Cartilage Oligomeric Matrix Protein (COMP): Die Rolle eines nichtkollagenen Knorpel-Matrix- Proteins als Marker der Krankheitsaktivität und Gelenkzerstörung bei Patienten mit rheumatoider Arthritis und Arthrose

Today, we can assess criteria to predict the tissue destruction and progression of Rheumatoid Arthritis (RA) and Osteoarthritis (OA) only in a late stage of the disease. It would be an advantage to have biochemical markers of disease activity and joint destruction to optimize therapy. PATIENTS AND METHODS: In this cross-sectional study with 37 RA and 20 OA patients (disease duration 119 +/- 130 months for RA and 41 +/- 73 months for OA), ESR, CRP, disease activity score (DAS), the functional status of RA (American College of Rheumatology), and the radiological scoring systems of Larsen and Kellgren/Lawrence, respectively, were used as parameters for disease activity and joint destruction. Cartilage oligomeric matrix protein (COMP) was measured with an enzyme-linked immunosorbent assay (ELISA) in serum and synovial fluid, COMP fragments with immunoblot in the synovial fluid. RESULTS: The mean COMP value in synovial fluid was 38 ug/ml (RA) and 46 ug/ml (OA); 6.5 ug/ml (RA) and 3.4 ug/ml (OA) in serum. RA patients had a higher amount of small COMP fragments in synovial fluid than OA patients. In RA patients, there was a significant positive correlation between disease activity (DAS) and COMP in synovial fluid and serum, a negative correlation between functional status of RA and serum COMP and between radiologic joint destruction of the knee and serum COMP. In OA patients, there was a significant correlation of joint space width and synovial fluid COMP. DISCUSSION: A high clinical disease activity (DAS) correlated with high COMP values in serum and synovial fluid and with increasing proteolytic activity (higher amount of small COMP fragments especially in RA). An increased turnover of cartilage matrix in joint inflammation might explain this correlation. The correlation of decreased COMP with decreased functional status in RA and increased joint destruction is compatible with a loss of cartilage and less turnover. The correlation between joint space width and increased COMP in OA patients with short disease duration might be explained with a higher turnover of the cartilage matrix in the early stage of the disease.     

Increased levels of circulating intercellular adhesion molecule 1 in the sera of patients with rheumatoid arthritis

Objectdive. We sought to assess whether circulating levels of intercellular adhesion molecule 1 (ICAM-1) in patients with rheumatoid arthritis (RA) are elevated and correlate with clinical measures of disease activity and whether this ICAM-1 originates from the synovium. Methods. Circulating ICAM-1 (cICAM-1) levels were determined by sandwich enzyme-linked immunosorbent assay of serum from 61 RA, 18 osteoarthritis (OA), and 11 inflammatory arthritis (IA) patients. In addition, paired serum and synovial fluid samples were collected from 17 RA, 9 OA, and 4 IA patients. The stability of cICAM-1 was assessed by overnight incubation at 37°C. Finally, the potential degradative effects of synovial fluid proteases were assessed by incubation of recombinant soluble ICAM-1 with patient synovial fluid. Results. RA sera contained significantly greater (P < 0.001) levels of cICAM-1 compared with RA synovial fluid and compared with sera or synovial fluid from the OA and IA patients. Circulating ICAM-1 levels were unaffected by overnight incubation at 37°C and were unaffected by exposure to RA, OA, or IA synovial fluid. Serum levels of cICAM-1 demonstrated a weak, but significant (P < 0.05) correlation with the joint score and erythrocyte sedimentation rate in 25 RA patients treated with nonsteroidal antiinflammatory drugs. Conclusion. The greatest elevations of cICAM-1 were seen in RA patient sera. In both RA and OA, synovial fluid cICAM-1 levels were consistently lower than serum levels, suggesting that cICAM-1 did not originate in the synovium. Because the production of cICAM-1 can be increased by cytokines (e.g., interleukin-1, tumor necrosis factor α), elevated levels of circulating ICAM-1 in RA may be reflective of systemic exposure to elevated cytokine levels.     

血清淀粉样蛋白A在类风湿关节炎患者体内表达的研究

目的 通过检测血清淀粉样蛋白A(SAA)在类风湿关节炎(RA)患者血清、关节液及滑膜中的表达,探讨其在RA发病机制中的作用.方法 采用酶联免疫吸附试验(ELISA)分别检测RA、骨关节炎患者和健康对照人群血清以及RA与骨关节炎患者关节液中SAA的水平;蛋白印迹法测定SAA在血清中的表达;免疫组织化学技术检测RA和骨关节炎滑膜中SAA的表达.应用t检验或Kruska-Wallis秩和检验进行统计分析.结果 RA血清中SAA含量[(318±132) μg/L]显著高于骨关节炎[(127±47) μg/L]和健康对照组[(127±41) μg/L,P均＜0.01].RA关节液中SAA含量[(571±473) μg/L]显著高于骨关节炎[(129±33) μg/L,t=2.46,P=0.04].蛋白印迹法结果显示各组血清样品中均有SAA条带;RA的SAA表达明显高于其他2组.病理结果显示SAA在RA关节滑膜高表达,位于血管内皮细胞、滑膜成纤维细胞、巨噬细胞以及血管周围;在骨关节炎,SAA仅见于关节血管周围和成纤维细胞.结论 RA血清和关节液中SAA的含量显著增高;SAA在RA滑膜组织中高表达,且表达位置与骨关节炎有明显差别,提示SAA可能参与了RA的炎症反应和关节损害.     

类风湿关节炎外周血单个核细胞和滑膜中人类软骨糖蛋白-39的研究

目的　通过观察人类软骨糖蛋白 39(HCgp 39)mRNA在类风湿关节炎 (RA)外周血单个核细胞 (PBMC)和滑膜中的表达水平 ,寻找反映RA早期骨破坏的敏感指标。方法　采集 31例RA、6例骨关节炎 (OA)、10例血清阴性脊柱关节病 (SpA)、5例系统性红斑狼疮 (SLE)以及 10例健康人新鲜抗凝静脉血 ,分离单个核细胞 ,并采集 7例RA、5例OA的滑膜 ,行半定量逆转录 (RT) PCR。结果　RA患者PBMC中HCgp 39mRNA行RT PCR与内对照tubulin共扩增后吸光度比值为0 86 90± 0 5 2 4 0 ,与OA(P =0 0 2 4 )、SpA(P =0 0 4 9)、SLE(P =0 0 4 3)以及健康对照 (P =0 0 33)相比差异均有显著性。而OA、SpA、SLE与健康对照之间差异无显著性。RA滑膜HCgp 39mRNA行RT PCR与tubulin共扩增后吸光度比值为 1 986 3± 1 9397,与OA相比差异有显著性 (P =0 0 4 )。在RA和OA中 ,同一患者的PBMC与滑膜HCgp 39mRNA表达差异无显著性。 结论　HCgp 39mRNA在RA患者PBMC和滑膜的表达明显高于其他炎症性关节病 ,提示HCgp 39可能是RA发病机制中重要的自身抗原 ,它的异常表达可能是造成T细胞介导自身免疫反应的机制之一。