Isolation of a phosphorylcholine-containing component from the turbot tapeworm, Bothriocephalus scorpii (Müller), and its reaction with C-reactive protein

A fraction isolated by electrofocusing (pI 4.2) from a saline extract of the turbot parasite, Bothriocephalus scorpii, contained choline and precipitated with a teleost C-reactive protein (CRP) and a phosphorylcholine-binding Balb/c mouse myeloma protein, TEPC-15. Non-dialysable products released from cultured tapeworms also precipitated with the phosphorylcholine-specific precipitins. Ca2+ was required for precipitation with CRP and immunodiffusion lines were confluent with pneumococcal C-polysaccharide and a fungal C substance. Intradermal injection of the phosphorylcholine-containing fraction caused an immediate erythema reaction in all mature turbot tested. The skin reaction is though to be related to the amount of circulating CRP and this protein was present in sera fro all nature turbot giving a positive skin response. There is no evidence for CRP being toxic to the tapeworms and the possibility is discussed that the worms exploit the host CRP for their own survival.     

Regulation of Immune Response by Autogenous Antibody against Receptor

BALB/c mice repeatedly immunized with Pneumococcus R36A vaccine produce antibodies to phosphorylcholine having the TEPC-15 myeloma idiotype (murine IgA myeloma protein that binds phosphorylcholine). The plaque-forming cell response to phosphorylcholine shows a decrease with repeated immunizations. In contrast, spleen cells from multiply immunized mice responded better in vitro than spleen cells from nonimmunized mice. The serum of animals immunized four or five times agglutinates TEPC-15-coated sheep erythrocytes. Inhibition of hemagglutination shows that the agglutinating activity is directed against the TEPC-15 idiotype. Sera from these mice, when added to cultures of normal spleen cells, specifically suppress the response to phosphorylcholine. The suppressive activity in the serum can be removed by solid absorption with TEPC-15. Evidently, repeated immunization with antigen induces two kinds of antibody responses: one directed against antigen and the other directed against the antibody to the antigen. It is proposed that this "auto" antibody against receptor is involved in the regulation of the immune response.     

Utility of serum C-reactive protein in assessing the outcome of infective endocarditis.

AIMS: To evaluate the diagnostic usefulness of serial serum C-reactive protein determinations in monitoring the outcome of infective endocarditis (IE). METHODS AND RESULTS: C-reactive protein, erythrocyte sedimentation rate (ESR), and white blood cell count (WBC) were measured from admission until week 10 in 129 patients with 134 episodes of IE. Need for cardiac surgery and final outcome were assessed until 3 months from admission. Data were evaluated using extensive statistical analyses. The fall in serum C-reactive protein or WBC was significantly faster when a patient had an uncomplicated recovery than when complications developed or death ensued, but no such behaviour was observed in ESR. None of the 80 patients who had normal C-reactive protein by week 10 died of IE. Moreover, none of the 22 patients who had normal C-reactive protein by week 4 needed cardiac surgery and only two of the 33 patients who had normal C-reactive protein by week 6 needed cardiac surgery, both after successful medical treatment of IE. Of the 87 patients whose WBC normalized within 4 weeks, six died and 15 needed valve surgery. CONCLUSION: The normalization of C-reactive protein proved to be a good predictor of a favourable late outcome (surgery, death) of IE. Also WBC count proved useful in the assessment of patients with IE, but the value of ESR was negligible.     

Human pancreatic islet cell specific 38 kilodalton autoantigen identified by cytomegalovirus-induced monoclonal islet cell autoantibody

Summary Our previous finding that about 15% of newly diagnosed patients with Type 1 (insulin-dependent) diabetes mellitus had human cytomegalovirus genome in their lymphocytes and islet cell autoantibodies in their sera, suggests that autoimmune Type 1 diabetes is associated with persistent cytomegalovirus infection under certain circumstances. This investigation was initiated to see if cytomegalovirus can induce islet cell autoantibodies and if the autoantibodies react with any specific islet protein(s). Monoclonal antibodies were generated after immunizing Balb/c mice with human cytomegalovirus. When these monoclonal antibodies were tested for the presence of islet cell antibodies, one (MCMVA-51) of 13 monoclonal antibodies reacted strongly with the islets. The titer of islet cell antibodies was 12000. When this monoclonal antibody was reacted with the proteins from the solubilized fraction of human pancreatic islets using the western immunoblotting technique, a band with a molecular weight of 38 kilodalton was detected. The 38 kilodalton band was not observed when the monoclonal antibody was reacted with the proteins prepared from pancreatic islet tissues of rats and mice or from other human organs including stomach, liver, spleen and brain, indicating that the 38 kilodalton protein is human islet cell-specific. It is concluded that human cytomegalovirus can induce islet cell antibodies that react with a 38 kilodalton human islet cell protein and that this protein component may represent islet cell-specific target antigens associated with perinistent cytomegalovirus infection.     

A new conformational epitope generated by the binding of recombinant 70-kd protein and U1 RNA to anti-U1 RNP autoantibodies in sera from patients with mixed connective tissue disease

OBJECTIVE: To establish an enzyme-linked immunosorbent assay (ELISA) using a complex of in vitro-transcribed U1 RNA and recombinant 70-kd, A, and C proteins (C-ELISA) to detect anti-U1 RNP antibodies reactive in double immunodiffusion (DID), but not in ELISA using the proteins alone (P-ELISA). METHODS: Sera from 196 patients with mixed connective tissue disease were used to test reactivity in P- and C-ELISAs, and the specificity of the sera was also tested by DID and immunoprecipitation (IP). RESULTS: In P-ELISA, 15 of 196 sera positive for anti-U1 RNP in DID did not react, while all sera reacted in C-ELISA. The reactivity of 15 sera to the U1 RNA was tested by IP and ELISA, and only 3 sera reacted with the U1 RNA. These results indicated that the increased reactivity in C-ELISA was not due to the U1 RNA itself. We confirmed that the 70-kd and A proteins were bound directly to the U1 RNA by IP using antibodies to His-tag, and we tested the reactivity of the sera to the U1 RNA-70-kd protein complex and the U1 RNA-A protein complex by IP. All sera reacted with the U1 RNA-70-kd protein complex, and 1 sample reacted with the U1 RNA-A protein complex. CONCLUSION: These results suggest that some anti-U1 RNP-positive sera specifically recognize the conformational structure altered by the binding of U1 RNA to the proteins, and the ELISA using U1 RNA and recombinant proteins is as useful as the DID method for detecting anti-U1 RNP antibodies.     

C-reactive protein and cardiovascular disease: a critical appraisal

PURPOSE OF REVIEW: C-reactive protein, a nonspecific marker of inflammation, has recently been proposed both as a marker of low-grade inflammation involved in atherogenesis and as a predictor of disease progression. RECENT FINDINGS: The physiologic functions of C-reactive protein as an anti-inflammatory scavenger molecule have begun to emerge. For example, C-reactive protein binds to damaged lipoproteins and facilitates their removal by phagocytes without full complement activation. Increased levels of C-reactive protein may result in direct effects on vascular cells, including induction of cytokines and prothrombotic factors. Several sources of biologic variation in the levels of C-reactive protein have been identified, chief among which are abdominal obesity and the metabolic syndrome. Although previous studies showed a potent independent association of C-reactive protein levels with cardiac events, the strength of association was shown to be much weaker than previously reported in recent large meta-analyses. Therapy with nonspecific anti-inflammatory agents such as statins in patients with coronary artery disease has been found to reduce adverse outcomes in association with reductions in C-reactive protein, on the basis of retrospective analysis of stored blood specimens. SUMMARY: Despite a relatively strong epidemiologic association with future adverse cardiovascular events, the great majority of apparently healthy individuals with elevated C-reactive protein will not experience cardiovascular disease. Even though more than 15 000 articles in PubMed mention C-reactive protein, current knowledge is insufficient to implicate C-reactive protein as a causative factor in atherothrombosis or to enable the recommendation of C-reactive protein testing to guide preventive or therapeutic interventions in cardiovascular diseases.     

High-sensitivity C-reactive protein and cardiovascular risk in patients with coronary heart disease

High-sensitivity C-reactive protein levels have received widespread attention because of a multitude of prospective studies that have shown that high levels of high-sensitivity C-reactive protein identify increased risk of initial cardiovascular events in coronary heart disease patients and increased risk of recurrent cardiac events in patients with stable and unstable angina, patients with acute myocardial infarction, and patients undergoing elective coronary revascularization procedures. In contrast to several other inflammatory markers, high-sensitivity C-reactive protein measurements are standardized and reproducible. The clinical significance of a reliable inflammatory marker includes identification of high-risk individuals, a gauge to monitor the activity of the disease, and a potential therapeutic target to alter the inflammatory component of the disease process. This review focuses on the importance of high-sensitivity C-reactive protein in cardiovascular risk stratification in coronary heart disease patients and discusses several preventive therapies that may reduce cardiovascular risk through reduction in high-sensitivity C-reactive protein.     

C-reactive protein in patients with chronic stable angina: differences in baseline serum concentration between women and men.

AIMS: Serum C-reactive protein has prognostic significance in apparently healthy men and women and in men with coronary artery disease. Little is known regarding the predictive role of C-reactive protein in women with coronary heart disease. We assessed whether differences exist in C-reactive protein levels and their prognostic value in men compared with women. We also assessed whether C-reactive protein concentrations differed in women receiving hormone replacement therapy vs those on no hormone replacement therapy. METHODS AND RESULTS: We prospectively studied 911 consecutive patients (327 women) with typical exertional angina. All patients underwent clinical, biochemical and angiographic characterization at study entry. Serum C-reactive protein was measured using a highly sensitive assay and correlated with clinical events during follow-up (from 1.0 to 3.7 years). C-reactive protein was significantly higher in women than men (3.0 mg. l(-1)[range 1.3-5.8] vs 2.1 mg. l(-1)[range 1.0-4.2], P<0.001), even after multiple regression adjustment for other risk factors. C-reactive protein was also significantly higher in women receiving hormone replacement therapy than in women not using hormone replacement therapy (P=0.001). C-reactive protein was an independent predictor of cardiovascular risk (logistic regression P=0.033) in the whole group but, despite higher C-reactive protein concentration, women had a similar rate of cardiac events compared to men. CONCLUSIONS: Baseline C-reactive protein levels were higher in women than men but the event rate was similar in men and women. Women on hormone replacement therapy had significantly higher C-reactive protein than women not using hormone replacement therapy. In the group as a whole, increased C-reactive protein was associated with a higher cardiovascular risk.     

The role of C-reactive protein in the resolution of bacterial infection

C-reactive protein is an acute phase protein in man and an important component of the innate immune system. C-reactive protein activates the classical pathway of complement, which is one of its main mechanisms in providing host defense. It has recently been recognized that C-reactive protein interacts with the cells of the immune system by binding to Fc gamma receptors. It may thus bridge the gap between innate and adaptive immunity and provide an early, effective antibacterial response. Furthermore, as it protects against the damaging inflammatory response to lipopolysaccharide and cytokines, it may prevent the lethal side-effects of bacterial products. The recent identification of the interaction of C-reactive protein with Fc gamma receptors will lead to an enhanced understanding of C-reactive protein and its role in both the innate and acquired immune systems.     

New and old cardiovascular risk factors: C-reactive protein, homocysteine, cysteine and von Willebrand factor increase risk, especially in smokers.

BACKGROUND: The relative importance of new risk factors for heart disease singly or in combination is uncertain. We assessed relationships between C-reactive protein, homocysteine, cysteine, von Willebrand factor, activated factor XII and stable heart disease, as well as interaction with established risk factors. METHODS: A case-control study of 260 cases of stable heart disease from the Irish component of the European Action on Secondary Prevention through Intervention to Reduce Events (EUROASPIRE) II cohort and 260 age, sex-matched controls. C-reactive protein, homocysteine, cysteine, von Willebrand factor, activated factor XII and conventional risk factors were assayed or recorded. Interaction effects between new and conventional factors were assessed using additive and multiplicative models. RESULTS: C-reactive protein, homocysteine, cysteine and von Willebrand factor were significantly higher in cases than controls. Comparing the top fifth with the bottom four-fifths showed independent associations between heart disease and C-reactive protein [odds ratio (OR) 1.79; 95% confidence interval (CI) 1.12-2.86; P = 0.01], cysteine (OR 2.00; 95% CI 1.25-3.20; P = 0.004), von Willebrand factor (OR, 3.0; 95% CI 1.9-4.8; P < 0.0001). For homocysteine, the association was independent comparing the top tenth to the bottom nine-tenths (OR 1.95; 95% CI 1.02-3.41; P = 0.04). Activated factor XII was not associated with risk. The association between C-reactive protein and disease was U-shaped and a graded association existed between homocysteine, cysteine, von Willebrand factor and disease. C-reactive protein, homocysteine, cysteine and von Willebrand factor considerably increased risk associated with other factors, particularly smoking. CONCLUSIONS: Independent associations exist between stable heart disease and C-reactive protein, homocysteine, cysteine and von Willebrand factor. Strong combined effects were observed between these and conventional risk factors, particularly smoking. Smoking cessation may profoundly reduce risk associated with other risk factors. We found no evidence of a relationship between activated factor XII and disease.     

Effect of exercise training on plasma levels of C-reactive protein in healthy adults: the HERITAGE Family Study.

AIMS: To study the effect of exercise training on plasma C-reactive protein, a marker of inflammation. METHODS AND RESULTS: We performed a 20 week standardized exercise training programme in 652 sedentary healthy white and black men and women. C-reactive protein was measured with a high sensitivity assay. The study sample was stratified according to baseline C-reactive protein levels using a recommended classification (low <1.0 mg/L, n=265; moderate 1.0-3.0 mg/L, n=225; high >3.0 mg/L, n=162). The median C-reactive protein reduction was 1.34 mg/L in the high baseline C-reactive protein group. C-reactive protein levels did not change in the low or moderate baseline C-reactive protein groups. The difference among the C-reactive protein groups was significant adjusting for all correlates of baseline C-reactive protein (P<0.001) and additionally for changes in body weight, glucose, insulin, LDL cholesterol, HDL cholesterol, triglycerides, systolic and diastolic blood pressure, and maximal oxygen uptake (P<0.001). The C-reactive protein reduction in the high baseline C-reactive protein group was consistent across all population groups (P<0.001 for difference among baseline C-reactive protein groups). CONCLUSION: Plasma C-reactive protein levels are reduced in response to exercise training in sedentary healthy adults with high initial C-reactive protein levels. This finding may partly explain the effectiveness of regular physical activity in the prevention and treatment of cardiovascular and metabolic diseases.     

Antibody to two forms of dihydrolipoamide acetyltransferase (PDC-E2) in primary biliary cirrhosis

ABSTRACT— Dihydrolipoamide acetyltransferase, the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2), is the major autoantigen in primary biliary cirrhosis. By immunoblotting with sera from patients with primary biliary cirrhosis, we observed a double band, of molecular weight 70 and 74 kD for PDC-E2, when a preparation of bovine heart mitochondria was not boiled prior to electrophoresis. This double band could also be detected using antisera raised in rats or rabbits against intact PDC or PDC-E2, but not in antisera raised against a synthetic decamer representing the lipoic acid binding sequence of PDC-E2; the latter reacted only with the 74 kD component. Antibody eluted from either the 70 or 74 kD component reacted with both 70 and 74 kD components. By ELISA, sera from patients with primary biliary cirrhosis reacted more strongly with a non-boiled than a boiled PDC-E2, whereas immune animal sera reacted equally with both preparations. Thus, according to whether preparations of PDC are boiled or not, two conformationally alternative forms of the PDC-E2 protein can be revealed by immunoblotting. The two forms in non-boiled preparations migrate at molecular weights corresponding to 70 and 74 kD.     

Association between pulse pressure and C-reactive protein among apparently healthy US adults

Elevated pulse pressure has been associated with an increased risk of cardiovascular disease, which is increasingly being seen as an inflammatory disease. Thus, the mechanism underlying the link between elevated pulse pressure and cardiovascular disease risk may be inflammation. However, investigators have not examined the relationship between pulse pressure and C-reactive protein, an inflammation marker that has been closely linked to cardiovascular risk. We examined the cross-sectional relationship between pulse pressure and C-reactive protein among 9867 healthy persons 17 years of age or older who participated in the Third National Health and Nutrition Examination Survey. The association between pulse pressure and the odds of having an elevated C-reactive protein level (> or = 0.66 mg/dL) was assessed by logistic regression. In a model that adjusted for systolic blood pressure, demographic factors, cholesterol, measures of obesity, smoking, alcohol consumption, physical activity, and antihypertensive medication use, a 10 mm Hg increase in pulse pressure was associated with a 15% increase in the odds of having an elevated C-reactive protein level (odds ratio, 1.15; 95% confidence interval, 1.01 to 1.31; P=0.04). When the same model was re-run adjusting for diastolic blood pressure instead of systolic blood pressure, a 10 mm Hg rise in pulse pressure was associated with a significant 12% increase in the odds of having an elevated C-reactive protein level. Systolic and diastolic blood pressure were unrelated to C-reactive protein once pulse pressure had been accounted for. Our results suggest that increases in pulse pressure are associated with elevated C-reactive protein levels among apparently healthy US adults, independent of systolic and diastolic blood pressure.     

Role of interleukin-6 in acute pancreatitis. Comparison with C-reactive protein and phospholipase A.

Plasma values of immunoreactive interleukin-6, C-reactive protein and phospholipase A have been determined in serial samples from 24 patients with acute pancreatitis ('mild' pancreatitis nine, 'severe' pancreatitis 15). Median plasma concentrations of interleukin-6, C-reactive protein, and phospholipase A activity were significantly higher in patients with 'severe' illness (p < 0.001) than those with 'mild' illness. A particularly marked increase in interleukin-6 was found in two patients with necrotising pancreatitis and fatal outcome. Significant correlations between plasma concentrations of interleukin-6 and phospholipase A (p = 0.0218) and C-reactive protein and phospholipase A activity (p < 0.0001) were found in patients with 'severe' disease. These findings in a limited number of patients with acute pancreatitis are promising in that raised interleukin-6 correlated with clinical severity and with two other established markers, C-reactive protein, and phospholipase A activity.     

Characterization of C-reactive protein and the complement subcomponent C1t as homologous proteins displaying cyclic pentameric symmetry (pentraxins).

Partial amino acid sequences of rabbit C-reactive protein, a peptide derived from human C-reactive protein by cyanogen bromide cleavage, and the C1t subcomponent of the human complement component C1 have been determined. Extensive sequence homology between these proteins establish their evolutionary relationships. In addition, examination of C-reactive proteins by negative-stain electron microscopy revealed that the protein is composed of five subunits arranged in cyclic symmetry. This structure is similar to that reported for both C1t and the amyloid P-component. The extensive structural relationship suggests similar or overlapping functions and the term pentraxin is proposed to describe these homologous proteins.     

Admission C-reactive protein levels and 30-day mortality in patients with acute myocardial infarction

BACKGROUND: Elevated C-reactive protein levels are associated with an increased risk of subsequent cardiovascular events in patients with unstable angina. However, limited information is available concerning the value of C-reactive protein levels in patients with acute myocardial infarction. METHODS: We prospectively studied 448 consecutive patients (mean [+/- SD] age, 60 +/- 12 years) with acute myocardial infarction. Serum C-reactive protein levels were measured within 12 to 24 hours of symptom onset, and divided into tertiles. Infarct size was determined by echocardiographic examination that was performed on day 2 or 3. Patients were followed for 30 days for mortality and subsequent cardiac events. RESULTS: At 30 days, 4 deaths (3%) occurred in patients in the lowest C-reactive protein tertile, 15 (10%) in patients in the middle tertile (P = 0.02 vs. the lowest tertile), and 33 (22%) in patients in the highest tertile (P <0.001 vs. the lowest tertile). In a multivariate analysis, C-reactive protein in the upper tertile was associated with 30-day mortality (relative risk = 3.0; 95% confidence interval [CI]: 1.3 to 7.2; P = 0.01) and the development of heart failure (odds ratio = 2.6; 95% CI: 1.5 to 4.6; P = 0.0006). C-reactive protein levels were not associated with the development of postinfarction angina, recurrent myocardial infarction, or the need for revascularization. CONCLUSION: Plasma C-reactive protein level obtained within 12 to 24 hours of symptom onset is an independent marker of 30-day mortality and the development of heart failure in patients with acute myocardial infarction. These findings suggest that C-reactive protein levels may be related to inflammatory processes associated with infarct expansion and postinfarction ventricular remodeling.     

瑞舒伐他汀对不稳定型心绞痛患者C反应蛋白的影响

目的探讨瑞舒伐他汀对不稳定型心绞痛患者血清C反应蛋白水平的影响。方法 60例不稳定型心绞痛患者随机分为瑞舒伐他汀组(治疗组)及对照组。采用免疫浊度法检测两组患者治疗前后血浆C反应蛋白水平并比较两组治疗的总有效率。结果两组治疗前后C反应蛋白水平差异有统计学意义(P<0.05),但治疗组较对照组改善更显著(P<0.05)。治疗组显效21例,有效8例,无效1例,总有效率为96.0%;对照组显效15例,有效7例,无效8例,总有效率为73.0%;两组比较差异有统计学意义(P<0.05)。结论瑞舒伐他汀可显著降低不稳定型心绞痛患者血浆C反应蛋白水平,改善冠心病患者的预后。     

Amyloid fibril protein related to prealbumin in familial amyloidotic polyneuropathy.

Amyloid fibrils were concentrated from the kidney, thyroid, and peripheral nerve of six patients with familial amyloidotic polyneuropathy (FAP). The fibril concentrates were solubilized in 6 M guanidine.HCl and fractionated on Sephadex G-100 columns. The elution profile of all FAP amyloid fibril concentrates revealed a protein of apparent Mr of 14,000, designated the FAP protein, that was absent from normal human tissues treated by the same procedure and from fibrils of a primary amyloidosis liver. Antisera against whole denatured fibril concentrates prepared in rabbits reacted with the FAP protein and a component in normal human serum corresponding to prealbumin. It was further established that the FAP protein shared common antigenic determinants with human prealbumin by its reaction of identity with normal prealbumin using commercial antisera against human prealbumin. Amyloid AL or AA proteins could not be identified in FAP fibrils by sensitive immunochemical assay methods. These results suggest that the FAP protein is a unique and significant component of the FAP amyloid fibrils and that it is closely related to the 13,745 Mr prealbumin subunit.     

Genetic determinants of C-reactive protein in COPD.

Chronic obstructive pulmonary disease (COPD) is associated with a systemic inflammatory state, marked by elevations in serum inflammatory markers including C-reactive protein (CRP). The present study sought to determine epidemiological predictors of CRP levels, to estimate the genetic influence on CRP levels, and to identify genetic variants that affect CRP in a family-based study of COPD. CRP was measured by a high-sensitivity assay in participants from the Boston Early-Onset COPD Study. Predictors of CRP level were determined using multilevel linear models. Variance component analysis was used to estimate heritability and to perform genome-wide linkage analysis for CRP levels. Two variants in the surfactant protein B (SFTPB) gene were tested for association with CRP levels. Increased age, female sex, higher body mass index, greater smoking pack-yrs and reduced forced expiratory volume in one second were all associated with increased CRP levels. There was a significant genetic influence on CRP (heritability = 0.25). Genome-wide linkage analysis revealed several potentially interesting chromosomal regions, though no significant evidence for linkage was found. A short tandem repeat marker near SFTPB was significantly associated with CRP levels. There is a genetic influence on C-reactive protein levels in chronic obstructive pulmonary disease patients. Preliminary evidence suggests an association of the surfactant protein B gene with systemic inflammation in chronic obstructive pulmonary disease.     

Autoantibodies to osteopontin in patients with osteoarthritis and rheumatoid arthritis

OBJECTIVE: Osteopontin (OPN), secreted mainly from chondrocytes, is suggested to be involved in the ossification and remodeling of bone and also in regulation of cytokine profiles. We investigated whether patients with osteoarthritis (OA) and rheumatoid arthritis (RA) display autoimmunity against OPN. METHODS: Recombinant human OPN (rhOPN) was prepared as a fusion protein with beta-galactosidase using E. coli. Serum samples from patients with OA or RA and from age matched healthy donors were tested for autoantibodies to rhOPN using ELISA and Western blotting. Reactivity of the same samples to purified native human OPN (nhOPN) was investigated by ELISA separately, to evaluate conformational epitopes. RESULTS: By ELISA, autoantibodies to rhOPN were found in one (0.95%) of 105 patients with OA and 2 (2.3%) of 88 patients with RA. These autoantibodies to rhOPN were confirmed by Western blotting. In contrast, 11 (9.5%) of 105 OA serum and 13 (15%) of 88 RA serum samples reacted to nhOPN. The anti-OPN positive RA patients showed high serum levels of rheumatoid factor and C-reactive protein and accelerated erythrocyte sedimentation rate compared to the anti-OPN negative group, although the differences did not achieve statistical significance. CONCLUSION: Our data showed that OPN is one of the autoantigens in OA and RA. Preferential recognition of nhOPN to rhOPN indicates that major epitope(s) of OPN would be conformational. Clinically, existence of the anti-OPN antibodies may be linked to disease severity in RA.