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 ◽  
...  

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.

2014 ◽  
Author(s):  
Gary S. Firestein ◽  
Anna-Karin H. Ekwall

Rheumatoid arthritis (RA) is among the most common forms of chronic inflammatory arthritis. It affects approximately 1% of adults and is two to three times more prevalent in women than in men. There are no specific laboratory tests for RA; diagnosis depends on a constellation of signs and symptoms that can be supported by serology and radiographs. The disease evolves over many years as a consequence of repeated environmental stress causing inflammation and immune activation followed by a breakdown of tolerance in individuals with a specific genetic background. This review describes the definition of RA; its etiology, including genetics, infections, the role of smoking and citrullination of proteins, and epigenetic mechanisms; and its pathogenesis, including synovial histopathology, bone and cartilage damage, adaptive and innate immunity, and the role of cytokines and intracellular signaling. Tables include the 1987 American Rheumatism Association criteria for the classification of RA and the 2010 American College of Rheumatology/European League Against Rheumatism classification for RA. Figures show citrullinated proteins in airway cells, a section of a proliferative synovium from a patient with a classic RA, and scalloped regions of erosion at the junction between a proliferative inflamed rheumatoid synovium and the bone. This review contains 3 highly rendered figures, 2 tables, and 71 references.


2020 ◽  
Author(s):  
Akihisa Haraguchi ◽  
Hisakata Yamada ◽  
Takahide Sakuragi ◽  
Tomomi Tsuru ◽  
Masakazu Kondo ◽  
...  

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.


2006 ◽  
Vol 55 (4) ◽  
pp. 657-661 ◽  
Author(s):  
Margarita Rodríguez-Mahou ◽  
Francisco Javier López-Longo ◽  
Silvia Sánchez-Ramón ◽  
Ana Estecha ◽  
Aurea García-Segovia ◽  
...  

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Ahmed Al-Shukaili ◽  
Saif Al-Ghafri ◽  
Safia Al-Marhoobi ◽  
Juma Alkaabi

Rheumatoid factor (RF) is currently used in the diagnosis of rheumatoid arthritis (RA). The discovery of anticitrullinated protein autoantibodies has led to the development of various new tests, such as anti-cyclic citrullinated peptide (anti-CCP) antibodies, and anti-mutated citrullinated vimentin (anti-MCV) antibodies, to diagnose RA. The aims of this study were to determine the sensitivity and specificity of anti-MCV antibodies in comparison with anti-CCP antibodies and RF in Omani Arab patients with RA and compare our findings with published values from different ethnic groups. The sensitivity of anti-MCV antibodies was 72% with 87% specificity. For anti-CCP antibodies the sensitivity was 52% and the specificity was 97%. The sensitivity of RF was 57% with 94% specificity. Anti-CCP antibodies have higher diagnostic specificity and positive predictive value than RF and anti-MCV antibodies. Anti-MCV antibodies have the highest sensitivity when compared to anti-CCP antibodies and RF. Anti-MCV antibodies do not appear to be very useful in the diagnosis of RA. However, long-term study is required to find out whether anti-MCV antibodies can be used as predictive test for incidence of RA.


2020 ◽  
pp. 1-3
Author(s):  
Reshmy GS ◽  
Mrudula EV ◽  
Sumitha Prabhu PS ◽  
Ashika MS ◽  
Sumithra N Unni ◽  
...  

Background: Rheumatoid arthritis (RA) is an autoimmune disease associated with chronic inflammation of joints causing deformities and functional impairment. Rheumatoid factor (RF) is an autoantibody specific for the Fc portion of human IgG. RF has low specificity as high false positive results are common in the general population. Anti CCP (Anti-cyclic citrullinated peptide) antibody is also a useful marker to diagnose rheumatoid arthritis and included in one of the criteria of the American College of Rheumatology (ACR) /European League against Rheumatism (EULAR) classification of RA. This study is done to compare the diagnostic utility of Anti CCP and RF test in RA patients. Aim & Objective: Comparison of rheumatoid factor (RF) and Anti cyclic citrullinated peptide (Anti -CCP) antibodies in diagnosis of rheumatoid arthritis- in a tertiary care hospital. Material &Methods: A total of 70 samples were taken from clinically suspected RA patients over a period of 6 months.RF and AntiCCP was checked in all patients Results &Discussion: Out of total 70 samples tested, 51 were seropositive with only Anti CCP positive were 37 (52%) and only RF positive were 6 (8.5%), whereas both Anti CCP and RF positive both positive were 8 (11.4%) Conclusion: Anti CCP antibody test and RF can be used mutually for early diagnose of Rheumatoid arthritis and suitable management can be initiated to decrease future morbidity.


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