scholarly journals Anti-carbamylated Protein Antibody Levels Correlate with Anti-Sa (Citrullinated Vimentin) Antibody Levels in Rheumatoid Arthritis

2015 ◽  
Vol 43 (2) ◽  
pp. 273-281 ◽  
Author(s):  
Gregory J. Challener ◽  
Jonathan D. Jones ◽  
Adam J. Pelzek ◽  
B. JoNell Hamilton ◽  
Gilles Boire ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Medical Center ◽  
Cross Reactivity ◽  
University Hospital ◽  
Variable Response ◽  
Antibody Positivity ◽  
Dartmouth Hitchcock Medical ◽  
Antibody Levels ◽  
Citrullinated Peptide

Objective.The presence of anticitrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) indicates a breach in immune tolerance. Recent studies indicate that this breach extends to homocitrullination of lysines with the formation of anti-carbamylated protein (anti-CarP) antibodies. We analyzed the clinical and serologic relationships of anti-CarP in 2 RA cohorts.Methods.Circulating levels of immunoglobulin G anti-CarP antibodies were determined by ELISA in established (Dartmouth-Hitchcock Medical Center) and early (Sherbrooke University Hospital Center) cohorts and evaluated for anticyclic citrullinated peptide antibodies (anti-CCP), specific ACPA, and rheumatoid factor (RF) levels using the Student t test and correlation analysis.Results.We identified elevated anti-CarP antibodies titers in 47.0% of seropositive patients (Dartmouth, n = 164), with relationships to anti-CCP (p < 0.0001) and IgM-RF (p = 0.001). Similarly, 38.2% of seropositive patients from the Sherbrooke cohort (n = 171) had elevated anti-CarP antibodies; titers correlated to anti-CCP (p = 0.01) but not IgM-RF (p = 0.09). A strong correlation with anti-Sa was observed: 47.9% anti-Sa+ patients were anti-CarP antibodies+ versus only 25.4% anti-Sa− in the Sherbrooke cohort (p = 0.0002), and 62.6% anti-Sa+ patients versus 26.9% anti-Sa− were anti-CarP antibodies+ in Dartmouth (p < 0.0001). We found a more variable response for reactivity to citrullinated fibrinogen or to citrullinated peptides from fibrinogen and α enolase.Conclusion.In 2 North American RA cohorts, we observed a high prevalence of anti-CarP antibody positivity. We also describe a surprising and unexpected association of anti-CarP with anti-Sa antibodies that could not be explained by cross-reactivity. Further, considerable heterogeneity exists between anti-CarP reactivity and other citrullinated peptide reactivity, raising the question of how the pathogenesis of antibody responses for carbamylated proteins and citrullinated proteins may be linked in vivo.

Hierarchy in the Avidity and Cross-reactivity of Anti-citrullinated Protein Antibodies in the Serum of Patients With Rheumatoid Arthritis

2020 ◽  
Author(s):  
Akihisa Haraguchi ◽  
Hisakata Yamada ◽  
Takahide Sakuragi ◽  
Tomomi Tsuru ◽  
Masakazu Kondo ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Response ◽  
Serum Antibody ◽  
Cross Reactivity ◽  
Sodium Thiocyanate ◽  
Fine Specificity ◽  
Thiocyanate Solution ◽  
Citrullinated Protein ◽  
Citrullinated Peptide ◽  
Substantial Extent

Abstract BackgroundFine specificity of anti-citrullinated protein antibodies (ACPAs), in which cross-reactivity exists, varies among patients with rheumatoid arthritis (RA), but it is unclear whether the mechanism of ACPA production is same or different among individuals. Since avidity of serum antibody reflects the direction of immune response, we compared the levels of avidity and cross-reactivity between various ACPAs in a cohort of RA patient.MethodsSera from 180 RA patients positive for anti-cyclic citrullinated peptide (CCP) 2 antibody were screened for positivity of antibodies against CCP1, and citrullnated fibrinogen (cFib), enolase (cEno), and vimentin (cVim) peptides. Avidity of the four ACPAs, and some autoantibodies and antibodies against foreign antigens was determined by an elution assay using sodium thiocyanate solution. Cross-reactivity between different ACPAs was estimated by measuring the inhibition of binding by competitor peptides. ResultsThe prevalence of anti-CCP1, anti-cFib, anti-cEno, and anti-cVim antibodies in the anti-CCP2-positive RA cohort were 37.7%, 38.3%, 15.6%, and 23.9%, respectively. The avidity of ACPAs, except for anti-cVim antibody, was significantly lower than that of antibodies against foreign antigens, while there was a large variety in the avidity of other autoantibodies. At individual levels, the avidity of anti-cVim was significantly higher than that of other ACPAs, and there was a significant correlation in the avidity of anti-CCP and anti-cFib antibodies. Substantial extent of cross-reactivity was seen between different ACPAs, which also showed a fixed hierarchy.ConclusionThe fixed hierarchy in the avidity and cross-reactivity between different ACPAs suggests that the mechanism underlying ACPA production is common to all RA patients. Presence of a dominant antigen that induces whole ACPA response is speculated.

scholarly journals Synovial Tissue Sublining CD68 Expression Is a Biomarker of Therapeutic Response in Rheumatoid Arthritis Clinical Trials: Consistency Across Centers

2009 ◽  
Vol 36 (8) ◽  
pp. 1800-1802 ◽  
Author(s):  
BARRY BRESNIHAN ◽  
ELIZA PONTIFEX ◽  
ROGIER M. THURLINGS ◽  
MARJOLEIN VINKENOOG ◽  
HANI EL-GABALAWY ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Early Stage ◽  
Medical Center ◽  
Biological Effects ◽  
Pearson Correlation ◽  
University Hospital ◽  
Mean Values ◽  
The Mean

Objective.To determine whether the correlation between the mean change in disease activity and the mean change in synovial sublining (sl) CD68 expression could be demonstrated across different academic centers.Methods.Synovial biopsies obtained at arthroscopy from patients with rheumatoid arthritis before and 160 days after rituximab therapy were selected and coded. Paired sections were processed independently at Amsterdam Medical Center (AMC) and at St. Vincent’s University Hospital (SVUH), Dublin. Digital image analysis (DIA) was employed at both centers to quantify sublining CD68 expression.Results.After analysis of CD68sl expression at centers in 2 different countries, high levels of intracenter and intercenter agreement were observed. For the pooled sections stained at AMC, the correlation between 2 investigators was R = 0.942, p = 0.000, and for sections stained at SVUH, R = 0.899, p = 0.001. Similarly, the intracenter correlations for ΔCD68sl expression after treatment were R = 0.998, p = 0.000, for sections stained at AMC and R = 0.880, p = 0.000, for sections stained at SVUH. The intercenter correlation for the pooled scores of sections stained at AMC was R = 0.85, p = 0.000, and for the sections stained at SVUH, R = 0.62, p = 0.001. The consistent correlation between ΔDAS (Disease Activity Score) and ΔCD68sl expression across different studies (Pearson correlation = 0.895, p < 0.001) was confirmed. The standardized response mean values for ΔCD68sl, calculated from analyses at both AMC and SVUH, were consistently 0.5 or greater, indicating a moderate to high potential to detect change.Conclusion.The correlation between mean ΔDAS and mean ΔCD68sl expression was confirmed across 2 centers. Examination of serial biopsy samples can be used reliably to screen for interesting biological effects at the site of inflammation at an early stage of drug development.

scholarly journals Is there an association between Anti-Citrullinated Peptide Antibodies and the Severity of Rheumatoid Arthritis Parameters in Algerian Patients?

2020 ◽  
Vol 10 (4) ◽  
pp. 17-24
Author(s):  
Siheme OUALI ◽  
Khalida ZEMRI ◽  
Ferial SELLAM ◽  
Noria HARIR ◽  
Zahira BENIASSA ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Severity ◽  
Disease Duration ◽  
University Hospital ◽  
Laboratory Assessment ◽  
Functional Rehabilitation ◽  
Strong Relation ◽  
The University ◽  
Citrullinated Peptide

Objectives: The aim of this study was to demonstrate the relationships between anti-citrullinated peptide/protein antibodies status and clinical characteristics, disease severity, radiological damages and laboratory assessment in Algerian patients with Rheumatoid arthritis, as well as their importance like a predictive factor for the diagnosis of Rheumatoid arthritis (RA). Methods: 281 patients diagnosed with RA according to ACR 1987 criteria in the  internal medicine and Functional Rehabilitation departments (the University Hospital of Sidi Bel Abbes) were enrolled in the study based on medical records including age, gender, disease duration, disease activity score (DAS28), joint damages, laboratory tests and treatment. All data were processed and analyzed via SPSS 22.0. Results: 86.5% of patients were females with a mean age and disease duration of respectively 52.665±12.3477, 4.19±4.050.  Patients with Anti-CCP positive (79.7%) presented a high disease activity (p<0.0001), a long disease duration (p=0.016) and a erosion damages (p<0.0001). we did not found any significant relation between gender, hands damages and CRP..A logistic regression showed that the presence of Anti-CCP was associated with Erosion, disease activity, age and RF presence. Conclusion: There was a strong relation between Anti-CCP antibodies status and the development of RA in Algerian patients. It could be considered as a useful predictor of disease severity.  

The Anti-mutated Citrullinated Vimentin Response Classifies Patients with Rheumatoid Arthritis into Broad and Narrow Responders

2009 ◽  
Vol 36 (12) ◽  
pp. 2670-2674 ◽  
Author(s):  
ROBBY ENGELMANN ◽  
JAN BRANDT ◽  
MARTIN EGGERT ◽  
KIRSTEN KARBERG ◽  
ANDREAS KRAUSE ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cross Reactivity ◽  
Antibody Diversity ◽  
Elisa System ◽  
Peptide Antigens ◽  
American College Of Rheumatology ◽  
Specific Igg4 ◽  
Citrullinated Vimentin ◽  
Citrullinated Peptide

Objective.Autoantibodies against citrullinated peptide antigens (ACPA) are routinely determined to diagnose rheumatoid arthritis (RA) and are predictive of a more severe course of the disease. We here set out to address an involvement of ACPA in the pathogenesis of RA and investigated the recognition pattern of antibodies against 2 citrullinated antigens in more detail.Methods.The sera of 77 patients fulfilling the American College of Rheumatology criteria for RA were analyzed for subclass titers of anti-mutated citrullinated vimentin (MCV) and anticyclic citrullinated peptide (CCP) antibodies by combining subclass specific detection antibodies with commercially available CCP and MCV ELISA plates. Cross-reactivities between anti-MCV and anti-CCP antibodies were detected using a sequential ELISA system.Results.IgG1, IgG3, and IgG4 titers among anti-MCV and anti-CCP antibodies correlated significantly. Cross-reactivity of MCV-specific antibodies against CCP could be detected in 8 of 16 patients’ sera; however, cross-binding of MCV-specific IgG4 was weaker compared to total IgG.Conclusion.The inherent capacity of IgG4 to exchange F(ab) arms provides insight into the anti-MCV antibody diversity and suggests a classification of ACPA positive patients into broad and narrow responders.

Sign in / Sign up

Export Citation Format

Share Document