IgA anti-citrullinated protein antibodies (IgA ACPA) are associated with flares during DMARD tapering in rheumatoid arthritis

Rheumatology ◽  
2021 ◽  
Author(s):  
Maria V Sokolova ◽  
Melanie Hagen ◽  
Holger Bang ◽  
Georg Schett ◽  
Juergen Rech ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factor ◽  
Prognostic Markers ◽  
Serum Levels ◽  
Randomized Controlled ◽  
Study Recruitment ◽  
Disease Modifying ◽  
Definition Of ◽  
Citrullinated Protein

Abstract Objectives A substantial proportion of rheumatoid arthritis (RA) patients flare upon withdrawal of disease modifying anti-rheumatic drugs (DMARDs), thus the definition of prognostic markers is crucial. Anti-citrullinated protein antibody (ACPA)-positivity has been identified as a risk factor for flare. However, only the role of IgG is established in this context, while the role of IgA ACPA is poorly defined. We thus aimed to investigate the role of IgA ACPA in flare of RA. Methods Serum levels of IgA1 and IgA2 ACPA at baseline and after 12 months were measured in 108 patients from the randomized controlled RETRO study. RA patients in stable remission for at least 6 months at study recruitment were assigned to either one of the DMARD tapering arms or to continuation of DMARDs. Results In patients remaining in remission but not in the ones who flared, IgA2 ACPA levels and proportion of IgA2 in ACPA (IgA2%ACPA) significantly declined (median of 17.5%; p< 0.0001). This seemed to be independent of the treatment choice, as there was no difference in IgA2 ACPA dynamics between the study arms. IgA2% ACPA was associated with disease activity (DAS28) at flare (r = 0.36; p= 0.046). IgA and IgG ACPA showed a tendency towards independent contribution to the risk of flare with the highest risk if a patient had both antibody classes. Conclusion In this study, IgA ACPA was identified as a risk factor for flare in combination with IgG ACPA. IgA2 ACPA levels were associated with flare severity and declined in patients in stable remission.

ASSOCIATIONS BETWEEN SERUM ANTIBODIES TO PERIODONTAL PATHOGENS AND PRECLINICAL PHASES OF RHEUMATOID ARTHRITIS

Rheumatology ◽  
2021 ◽  
Author(s):  
Daniel Manoil ◽  
Delphine S Courvoisier ◽  
Benoit Gilbert ◽  
Burkhard Möller ◽  
Ulrich A Walker ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Primary Outcome ◽  
Signs And Symptoms ◽  
Serum Levels ◽  
Study Cohort ◽  
Periodontal Pathogens ◽  
Serum Antibodies ◽  
Current Smoking ◽  
Clinical Arthritis ◽  
Citrullinated Protein

Abstract Objectives To examine whether serum antibodies against selected periodontal pathogens are associated with early symptoms of rheumatoid arthritis (RA) development in healthy individuals at risk of developing the disease. Methods Within an ongoing study cohort of first-degree relatives of patients with RA (RA-FDRs), we selected four groups corresponding to specific preclinical phases of RA development (n = 201). (1) RA-FDR controls without signs and symptoms of arthritis nor RA-related autoimmunity (n = 51); (2) RA-FDRs with RA-related autoimmunity (n = 51); (3) RA-FDRs with inflammatory arthralgias without clinical arthritis (n = 51); (4) RA-FDRs who have presented at least one swollen joint (“unclassified arthritis”) (n = 48). Groups were matched for smoking, age, sex and shared epitope status. The primary outcome was IgG serum levels against five selected periodontal pathogens and one commensal oral species assessed using validated-in-house ELISA assays. Associations between IgG measurements and preclinical phases of RA development were examined using Kruskal-Wallis or Mann-Whitney tests (α = 0.05). Results None of the IgGs directed against individual periodontal pathogens significantly differed between the four groups of RA-FDRs. Further analyses of cumulated IgG levels into bacterial clusters representative of periodontal infections, revealed significantly higher IgG titers against periodontopathogens in anti-citrullinated protein antibodies (ACPA)-positive RA-FDRs (p = 0.015). Current smoking displayed a marked trend towards reduced IgG titers against periodontopathogens. Conclusion Our results do not suggest an association between serum IgG titers against individual periodontal pathogens and specific preclinical phases of RA development. However, associations between cumulative IgG titers against periodontopathogens and the presence of ACPAs suggest a synergistic contribution of periodontopathogens to ACPA development.

scholarly journals AB0925-PARE A NARRATIVE REVIEW ASSESSING THE ROLE OF DIETARY SALT AS AN ENVIRONMENTAL RISK FACTOR FOR THE ONSET AND SEVERITY OF RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1484.1-1484
Author(s):  
S. Ahmed ◽  
E. Nikiphorou ◽  
J. Bayliss
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factor ◽  
Autoimmune Disease ◽  
Environmental Risk ◽  
Narrative Review ◽  
Environmental Risk Factor ◽  
T Helper ◽  
Dietary Salt ◽  
Salt Consumption

Background:The role of dietary salt consumption in the etiopathogenesis of Rheumatoid Arthritis (RA), and autoimmune disease in general, has received renewed interest. This has been fueled by the increased prevalence of autoimmune disease worldwide correlating with western diets and heightened consumption of salt rich foods and also studies at the cellular level demonstrating induction of IL 17 producing T helper cells (Th17) by dietary salt.Objectives:To conduct a narrative review of observational studies and clinical trials on the role of dietary salt as an environmental risk factor for the onset and development of RA.Methods:A comprehensive search was done of the literature from 2010 to 2021, using the search terms dietary salt and RA; the native interfaces EBSCO and Ovid were used. Databases searched included Pubmed, Embase, EMCare, Medline and CINAHL using a Population, Exposure and Outcome framework; the MESH terms RA, risk factors, nutrition and salt were used. Data was extracted by an independent reviewer.Results:Out of the 72 studies initially identified, 50 were included in this review. Studies in murine models have demonstrated that high concentrations of sodium chloride promote the differentiation of T helper lymphocytes, via the serum- and glucocorticoid- inducible kinase 1 (SGK1) mediator towards the proinflammatory Th17 driven immune response. Six studies were carried out in human subjects. Study design ranged from cross sectional observational to nested case control studies. Sodium intake amongst participants characterized as having high intake, or being placed in the higher quartiles, ranged from 4.5-5grams per day. 5 out of 6 studies demonstrated that increased dietary salt consumption is associated with earlier onset RA. One study suggested an association between high salt intake and erosive disease at diagnosis and the development of anti-citrullinated protein antibodies (ACPA), although evidence was weak and from a single study only. Another study found that increased consumption of salt was only associated with risk of RA in smokers, highlighting the need to explore confounding variables further.Conclusion:This narrative review of the literature provides some evidence that supports a role of excess dietary salt consumption as a risk factor for the onset and severity of RA.Disclosure of Interests:None declared

scholarly journals Angiotensin-Converting Enzyme (ACE) D Allele as a Risk Factor for Increase Serum Interleukin-6 and Interleukin-8 in Psoriasis Patients

2018 ◽  
Vol 6 (5) ◽  
pp. 772-776 ◽  
Author(s):  
Ahmed I. Abd Elneam ◽  
Mohammed Saleh Al-Dhubaibi ◽  
Ali Ismaiel Ali Abd Alrheam
Keyword(s):  
Risk Factor ◽  
Healthy Subjects ◽  
Serum Levels ◽  
Converting Enzyme ◽  
Inflammatory Skin Disease ◽  
Ace Polymorphism ◽  
Ace Gene ◽  
Ace Gene Polymorphism ◽  
The Relationship

BACKGROUND: Psoriasis is a chronic, recurrent inflammatory skin disease. It is characterised by autoimmune, environmental factors and complex genetic disorder.AIM: To explore the role of IL-6, IL-8, and ACE I/D polymorphism in the pathogenesis of Psoriasis and investigation of the relationship between ACE polymorphism and occurrence of psoriasis.PATIENTS AND METHODS: In this study, we took 73 psoriasis patients and 47 healthy patients as a control. These two groups subjected to analysis for ACE gene I/D polymorphism by PCR and biochemical methods.RESULTS: The serum levels of ACE, IL-8 and IL-6 were statistically significantly higher in psoriasis patients compared to healthy subjects (P < 0.001). ID and DD polymorphism were more common in psoriasis patients than healthy subjects. Also, D allele was significantly over-represented in patients compared to controls (52.7% Vs 35.1%).CONCLUSION: ACE gene polymorphism might grant susceptibility to develop psoriasis.

Rheumatoid Arthritis: Etiology and Pathogenesis

2014 ◽  
Author(s):  
Gary S. Firestein ◽  
Anna-Karin H. Ekwall
Keyword(s):  
Rheumatoid Arthritis ◽  
Intracellular Signaling ◽  
Cartilage Damage ◽  
Signs And Symptoms ◽  
American College Of Rheumatology ◽  
European League Against Rheumatism ◽  
Citrullinated Proteins ◽  
Definition Of

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.

EULAR definition of “arthralgia suspicious for progression to rheumatoid arthritis” in a large cohort of patients included in a program for rapid diagnosis: role of auto-antibodies and ultrasound

2020 ◽  
Vol 39 (5) ◽  
pp. 1493-1499 ◽  
Author(s):  
Santiago Ruta ◽  
Einer Sanchez Prado ◽  
Jessica Torres Chichande ◽  
Alvaro Ruta ◽  
Facundo Salvatori ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Rapid Diagnosis ◽  
Large Cohort ◽  
Definition Of

CHANGES THE CYTOKINE PROFILE AND CALCIUM-REGULATING HORMONES IN RHEUMATOID ARTHRITIS

2019 ◽  
Vol 64 (11) ◽  
pp. 673-676
Author(s):  
Asmaya Saftar Huseynova
Keyword(s):  
Rheumatoid Arthritis ◽  
Parathyroid Hormone ◽  
Bone Loss ◽  
Hypovitaminosis D ◽  
Serum Levels ◽  
Control Group ◽  
Tnf Α ◽  
High Production ◽  
Serological Variant

The aim was to study the level of some cytokines (İL-2, İL-6, İL-8 TNFα) and calcium regulating hormones (calcitonin, parathyroid hormone, 25 (OH) D) in the blood of patients with rheumatoid arthritis (RA) depending on rheumatoid factor (RF) and the assessment of the role of the revealed violations in the pathogenesis of bone loss in this pathology. For this purpose, 74 patients with RA (59 women, 15 men) aged from 27 to 71 were examined. On the basis of RF in the blood serum, the patients were divided into 2 groups: seronegative and seropositive RA. The control group included 16 healthy individuals (13 women, 3 men). The results obtained that the serological variant of RA affects the serum levels of proinflammatory cytokines and calcium-regulating hormones: more pronounced changes were found in seropositive RA. The high production of IL-2, IL-6, IL-8, TNF-α and parathyroid hormone detected in both groups of patients undoubtedly contributes to the mechanisms of bone loss in RA. In both groups we detected hypovitaminosis D. This results recommended to use this vitamin in the complex treatment of RA.

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