Clinical and etiological meaning of anti-carbamylated protein antibodies in rheumatoid arthritis

Several autoantibodies against proteins with post-translational modifications have been detected in patients with rheumatoid arthritis (RA) and are called anti-modified protein antibodies (AMPAs). Anti-carbamylated protein antibodies (Anti-CarP Ab) are the second most vigorously researched AMPAs following anti-citrullinated protein/peptide antibodies (ACPA). Anti-CarP Ab and ACPA show cross-reactivity to some extent and frequently co-exist with each other in RA, but are two distinct antibodies. Although the diagnostic efficacy of anti-CarP Ab is inferior to that of ACPA, the diagnostic specificity of RA may improve when used in combination with ACPA and rheumatoid factor. Anti-CarP Ab and ACPA are also useful for identifying patients at high risk of more severe joint destruction and cardiovascular diseases. The high prevalence of the co-existence of both antibodies suggests a common factor in their production, and this is important for the development of RA because both antibodies emerge before the onset of clinical symptoms. Neutrophils may also be crucially involved. It is important to distinguish citrullinated antigens from carbamylated antigens because the methods commonly used to detect the former are now known to be cross-reactive with the latter. Research on anti-CarP Ab will provide novel insights into the pathology and etiology of RA

カルバミル化アルブミンは、抗カルバミル化タンパク抗体の対応抗原の1つである

京都大学0048新制・課程博士博士(医学)甲第20611号医博第4260号新制||医||1023(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 椛島 健治, 教授 竹内 理, 教授 生田 宏一学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Inverse Association between Air Pressure and Rheumatoid Arthritis Synovitis

<div><p>Rheumatoid arthritis (RA) is a bone destructive autoimmune disease. Many patients with RA recognize fluctuations of their joint synovitis according to changes of air pressure, but the correlations between them have never been addressed in large-scale association studies. To address this point we recruited large-scale assessments of RA activity in a Japanese population, and performed an association analysis. Here, a total of 23,064 assessments of RA activity from 2,131 patients were obtained from the KURAMA (Kyoto University Rheumatoid Arthritis Management Alliance) database. Detailed correlations between air pressure and joint swelling or tenderness were analyzed separately for each of the 326 patients with more than 20 assessments to regulate intra-patient correlations. Association studies were also performed for seven consecutive days to identify the strongest correlations. Standardized multiple linear regression analysis was performed to evaluate independent influences from other meteorological factors. As a result, components of composite measures for RA disease activity revealed suggestive negative associations with air pressure. The 326 patients displayed significant negative mean correlations between air pressure and swellings or the sum of swellings and tenderness (p = 0.00068 and 0.00011, respectively). Among the seven consecutive days, the most significant mean negative correlations were observed for air pressure three days before evaluations of RA synovitis (p = 1.7×10⁻⁷, 0.00027, and 8.3×10⁻⁸, for swellings, tenderness and the sum of them, respectively). Standardized multiple linear regression analysis revealed these associations were independent from humidity and temperature. Our findings suggest that air pressure is inversely associated with synovitis in patients with RA.</p></div

Mean correlation coefficients between joint synovitis and air pressure in the 326 patients.

<p>p-values for Student's t-test. SD:standard deviation.</p

Basic characteristics of the subjects in the current study.

<p>Steinbrocker's Stage and Class.</p><p>Current smoker and ex-smoker.</p><p>Patients who have been treated by biological agents between 2005 and 2012.</p><p>SD:standard deviation.</p

The strongest associations between joint synovitis and air pressure three days before joint evaluations.

<p>The 326 patients with more than 20 evaluations were analyzed. A)Associations between air pressure and joint synovitis for the seven consecutive days. Y axis indicates −log₁₀P-value of Student's t-test. X axis indicates days before joint evaluations. B)Volcano plots for distribution of RA patients demonstrating positive or negative associations between joint synovitis and air pressure three days before joint evaluations. X and Y axes indicate Spearman's correlation coefficient and P-value, respectively. Numbers in the panels indicate RA patients showing positive or negative correlation coefficients. Because a part of the patients showed consistent TJC or SJC across all evaluations, the sum of the two numbers in each panel does not make 326.</p

Results of multiple standardized linear regression analysis between air pressure and joint synvoitis.

<p>Results of multiple standardized linear regression analysis between air pressure and joint synvoitis.</p

Correlations between joint synovitis and air pressure in RA patients.

<p>Correlation plots in patients demonstrating the smallest, median and largest correlation coefficients between joint synovitis and air pressure are illustrated in the left, middle and right panels, respectively.</p

Standardized multiple linear regression analysis for air pressure 3 days before evaluations and synovitis among the 326 patients.

<p>p-values for Student's t-test. SD:standard deviation.</p