Effect of oral clodronate on structural damage and bone turnover in rheumatoid arthritis.

OBJECTIVES: To study the effect of oral clodronate on structural damage and bone metabolism in rheumatoid arthritis (RA). METHODS: In this 2-year proof-of-concept study, sixty patients with at least moderately active RA were randomised to receive anti-rheumatic therapy alone or together with oral clodronate 1600 mg daily. Radiographs of hands and feet and serum samples for bone biomarkers were studied at baseline and at 24 months. RESULTS: At 24 months, progression of radiographic joint damage was similar in the 2 groups. Clodronate suppressed carboxyterminal cross-linked peptide of type I collagen (p=0.03) and aminoterminal propeptide of type I procollagen (p=0.01). Eight patients (27%) withdrew from clodronate therapy due to adverse drug reactions. CONCLUSIONS: Oral clodronate did not retard the focal bone damage in RA despite its beneficial effect on overall bone metabolism, as judged by the decrease in the reference bone biomarkers.

Stability of chemical and immunochemical analytes in uncentrifuged plasma samples.

BACKGROUND: The stability of analyte concentrations in plasma after prolonged contact with blood cells in uncentrifuged lithium-heparin gel tubes was studied. METHODS: To investigate the stability of concentrations of 26 chemistry and 15 immunochemistry analytes, the simultaneously drawn samples (n = 50) were measured after 6 h storage at +8 degrees C and +22 degrees C in whole blood and after immediate separation of plasma. The analyte concentrations were measured with a Roche Modular PPEE analyser using reagents from Roche Diagnostics. RESULTS: After prolonged contact with cells a clinically significant change was only observed for potassium where the mean value increased from 4.0 mmol/L to 4.8 mmol/L (P < 0.001) when stored at +8 degrees C. CONCLUSION: Immediate separation of plasma from cells is recommended. However, when prolonged contact of plasma with cell is unavoidable, samples can be kept uncentrifuged for up to 6 h at +8 degrees C or at +22 degrees C. The stability of potassium, however, is temperature-dependent and cannot be measured from refrigerated blood samples.

Sensitivity and specificity of autoantibodies binding to citrullinated carboxyterminal telopeptides of types I and II collagens in an early arthritis series.

OBJECTIVE: To assess the specificity and sensitivity of autoantibodies binding to citrullinated carboxyterminal telopeptides of types I and II collagens in an early arthritis series. METHODS: A cohort of 146 patients from the Kuopio 2000 Arthritis Survey having RA, AS, PsA, ReA, uSpA or undifferentiated arthritis were studied. Autoantibodies binding citrullinated types I and II carboxytelopeptides were measured in two different inhibition ELISA assays. Sera from 135 adult persons were used as controls. RESULTS: In RA, the sensitivities were 0.83 with long type I telopeptide and 0.78 with long type II telopeptide and the respective specificities were 0.94 and 0.93, while the corresponding values in other inflammatory joint diseases were much lower. The likelihood ratio in RA increased with longer peptides from 4.20 to 14.06 for type I telopeptide and from 2.74 to 11.67 for type II telopeptide. CONCLUSION: The antibody assay using long telopeptide from type I collagen was the most specific and sensitive method in every diagnostic category, although in the arthritides other than RA, binding was much less abundant and possibly citrulline-independent.

Change of diagnoses and outcome of patients with early inflammatory joint diseases during a mean 13-month follow-up.

OBJECTIVE: To assess the state of the disease and verify the diagnoses during a 7-24-month follow-up of adult patients with newly diagnosed inflammatory joint diseases in a defined population. METHODS: Patients with previously undiagnosed synovitis in at least one peripheral joint or signs of inflammation in sacroiliac, glenohumeral or hip joints were enrolled on their first hospital visit in 2000 and followed-up for up to 24 months in Kuopio. RESULTS: A total of 138/173 adult patients completed a mean 13-month follow-up. During the follow-up the diagnosis was specified for 15/81 (19%) patients previously classified as undifferentiated arthritis (UA). Eight patients developed rheumatoid arthritis (RA). Of 28 patients with RA, 92% were on disease-modifying anti-rheumatic drugs (DMARDs) and 75% had a combination treatment with two or more DMARDs. According to the diagnosis at baseline, 75% of cases with RA, 38% with spondyloarthropathies (SpAs) and 42% with UA had active synovitis or arthralgia at follow-up. In multivariate analysis, older patients at disease onset were less likely to be in remission (p = 0.011). CONCLUSION: The diagnosis could be specified for 19% of patients with UA. Fifteen of 20 patients with RA had an active disease despite treatment with DMARDs. Patients with SpAs and UA had a better short-term outcome. Patients with active disease need aggressive therapy in all age groups.

Inhibitory characteristics of citrullinated telopeptides of type I and II collagens for autoantibody binding in patients with rheumatoid arthritis.

OBJECTIVE: To study how soluble citrullinated telopeptides of type I and II collagens inhibit the binding of autoantibodies to the respective antigens immobilized onto solid phase, and to use modifications of previous methods to re-analyse rheumatoid arthritis (RA) and control serum samples. METHODS: Autoantibody binding was inhibited with normal or citrullinated carboxytelopeptides using enzyme-linked immunosorbent assay (ELISA) methods. Serum samples were available from 120 patients with RA and 81 controls. RESULTS: Autoantibodies that bind normal C-telopeptides were not inhibited with soluble normal or citrullinated telopeptides. However, the antibodies that bind only citrullinated telopeptides could be inhibited with corresponding citrullinated telopeptides. Thus, it is not necessary to study the binding of autoantibodies to normal collagens if the specificity of their binding is assessed by immunological inhibition. For type I telopeptide, there are two arginines, the latter of which, when citrullinated, is important for binding. For type II telopeptide, there is one arginine, which is important when citrullinated. The other amino acids, e.g. the last alanine, have only a slight effect on binding. These improved methods differentiate better between RA patients, who have specific citrullinated autoantibodies, and controls than previous ELISA methods. CONCLUSIONS: Based on inhibition assay, it is possible to measure the autoantibodies binding specifically to citrullinated telopeptides of type I and II collagens. When only one assay is involved, variance is decreased and the overall performance is easier than before.

Are there autoantibodies reacting against citrullinated peptides derived from type I and type II collagens in patients with rheumatoid arthritis?

OBJECTIVES: To assess the possible presence in patients with rheumatoid arthritis (RA) of autoantibodies recognising citrullinated peptides derived from type I and II collagens. METHODS: Firstly, the binding of four pairs of synthetic peptides (arginine-containing and artificially citrullinated forms) related to different regions of human type II collagen were tested with sera from 120 patients with RA and 81 controls. Secondly, two similar pairs of peptides related to the carboxy terminal telopeptides of the alpha1 and alpha2 chains of human type I collagen were tested. RESULTS: 42-53% of the RA sera showed increased binding of arginine peptides related to type II collagen. However, 12 RA sera bound the citrullinated form of the alpha1(II) telopeptide more strongly than the corresponding arginine peptide. 20 RA sera bound the citrullinated carboxytelopeptide from the alpha1 chain of type I collagen (alpha1(I) telopeptide) more strongly than the respective arginine peptide. The correlation between the autoantibodies to type I and II collagen telopeptides was r(s) = 0.576, p < 0.001. Anti-cyclic citrullinated peptide (anti-CCP) assay was positive in 71/120 (59%) patients with RA. An anti-CCP assay detects a different subgroup of antibodies than anti-telopeptide assays. However, both anti-telopeptide and anti-CCP antibodies were increased in patients with RA. CONCLUSION: Some patients with RA were identified whose sera contained antibodies that specifically bound citrullinated peptides related to the carboxy terminal telopeptides of the alpha1 and alpha2 chains of type I collagen and the alpha1 chains of type II collagen (sequences YYXA, FYXA, and YMXA, where X stands for citrulline).