Expansion of Alternative Autoantibodies Does Not Follow the Evolution of Anti–Citrullinated Protein Antibodies in Preclinical Rheumatoid Arthritis: An Analysis in At‐Risk First‐Degree Relatives

2021 ◽  
Author(s):  
Vidyanand Anaparti ◽  
Irene Smolik ◽  
Xiaobo Meng ◽  
Liam O’Neil ◽  
Mackenzie A. Jantz ◽  
...  
2021 ◽  
Author(s):  
Mihnea R. Mangalea ◽  
David Paez-Espino ◽  
Kristopher Kieft ◽  
Anushila Chatterjee ◽  
Jennifer A. Seifert ◽  
...  

SUMMARYRheumatoid arthritis (RA) is an autoimmune disease characterized in seropositive individuals by the presence of anti-cyclic citrullinated protein (CCP) antibodies. RA is linked to the intestinal microbiota, yet the association of microbes with CCP serology and their contribution to RA is unclear. We describe intestinal phage communities of individuals at risk for developing RA, with or without anti-CCP antibodies, whose first degree relatives have been diagnosed with RA. We show that at-risk individuals harbor intestinal phage compositions that diverge based on CCP serology, are dominated by Lachnospiraceae phages, and originate from disparate ecosystems. These phages encode unique repertoires of auxiliary metabolic genes (AMGs) which associate with anti-CCP status, suggesting that these phages directly influence the metabolic and immunomodulatory capability of the microbiota. This work sets the stage for the use of phages as preclinical biomarkers and provides insight into a possible microbial-based causation of RA disease development.


2016 ◽  
Vol 75 (Suppl 2) ◽  
pp. 957.2-958
Author(s):  
D. Alpizar-Rodriguez ◽  
R. Müller ◽  
B. Möller ◽  
J. Dudler ◽  
A. Ciurea ◽  
...  

Rheumatology ◽  
2017 ◽  
Vol 56 (9) ◽  
pp. 1579-1585 ◽  
Author(s):  
Deshiré Alpizar-Rodriguez ◽  
Rüdiger B. Mueller ◽  
Burkhard Möller ◽  
Jean Dudler ◽  
Adrian Ciurea ◽  
...  

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
R. E. Costello ◽  
J. H. Humphreys ◽  
J. C. Sergeant ◽  
M. Haris ◽  
F. Stirling ◽  
...  

Abstract Background First-degree relatives (FDRs) of people with rheumatoid arthritis (RA) have a fourfold increased risk of developing RA. The Symptoms in Persons At Risk of Rheumatoid Arthritis (SPARRA) questionnaire was developed to document symptoms in persons at risk of RA. The aims of this study were (1) to describe symptoms in a cohort of FDRs of patients with RA overall and stratified by seropositivity and elevated CRP and (2) to determine if patient characteristics were associated with symptoms suggestive of RA. Methods A cross-sectional study of FDRs of patients with RA, in the PREVeNT-RA study, who completed a study questionnaire, provided a blood sample measured for rheumatoid factor, anti-CCP and CRP and completed the SPARRA questionnaire. Moderate/severe symptoms and symmetrical, small and large joint pain were identified and described. Symptoms associated with both seropositivity and elevated CRP were considered suggestive of RA. Logistic regression was used to determine if symptoms suggestive of RA were associated with patient characteristics. Results Eight hundred seventy participants provided all data, 43 (5%) were seropositive and 122 (14%) had elevated CRP. The most frequently reported symptoms were sleep disturbances (20.3%) and joint pain (17.9%). Symmetrical and small joint pain were 11.3% and 12.8% higher, respectively, in those who were seropositive and 11.5% and 10.7% higher in those with elevated CRP. In the logistic regression model, seropositivity, older age and feeling depressed were associated with increased odds of small and symmetrical joint pain. Conclusions This is the first time the SPARRA questionnaire has been applied in FDRs of patients with RA and has demonstrated that the presence of symmetrical and small joint pain in this group may be useful in identifying people at higher risk of developing RA.


Healthcare ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1326
Author(s):  
Zhain Mustufvi ◽  
Stefan Serban ◽  
James Chesterman ◽  
Kulveer Mankia

There is increasing evidence supporting an association between periodontal disease (PD) and rheumatoid arthritis (RA), both mechanistically and clinically. Trials have shown that treating PD in people with RA may improve RA disease activity. Patients with musculoskeletal symptoms without arthritis, who test positive for cyclic-citrullinated protein antibodies, are at risk of RA (CCP+ at-risk), with seropositivity preceding arthritis onset by months or years. Importantly, there is evidence to suggest that periodontal inflammation may precede joint inflammation in CCP+ at-risk and, therefore, this could be a trigger for RA. There has been increased research interest in RA prevention and the phenotyping of the pre-RA disease phase. This review will examine the merits of identifying individuals who are CCP+ at-risk and performing screening for PD. In addition, we discuss how PD should be treated once identified. Finally, the review will consider future research needed to advance our understanding of this disease association.


2015 ◽  
Vol 74 (Suppl 2) ◽  
pp. 975.2-975
Author(s):  
D. Alpizar-Rodriguez ◽  
R.B. Mueller ◽  
B. Möller ◽  
J. Dudler ◽  
A. Ciurea ◽  
...  

Rheumatology ◽  
2019 ◽  
Vol 58 (Supplement_3) ◽  
Author(s):  
Ruth E Costello ◽  
Mohammad Haris ◽  
Jenny H Humphreys ◽  
Jamie C Sergeant ◽  
Fiona Stirling ◽  
...  

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