scholarly journals The relationship between cd5-expressing b lymphocytes and serologic abnormalities in rheumatoid arthritis patients and their relatives

1990 ◽  
Vol 33 (3) ◽  
pp. 339-348 ◽  
Author(s):  
P. Youinou ◽  
L. Mackenzie ◽  
P. Katsikis ◽  
G. Merdrignac ◽  
D. A. Isenberg ◽  
...  
2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 206.1-207
Author(s):  
C. Grönwall ◽  
L. Liljefors ◽  
H. Bang ◽  
A. Hensvold ◽  
M. Hansson ◽  
...  

Background:Seropositive rheumatoid arthritis (RA) is characterized by the presence of rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPA) with different fine-specificities. Yet, other serum anti-modified protein autoantibodies (AMPA), e.g. anti-carbamylated (Carb), anti-acetylated (KAc), and anti-malondialdehyde acetaldehyde (MAA) modified protein antibodies, have been described. By using RA patient single-cell derived monoclonal antibodies we have previously shown that individual ACPA clones recognize small distinct citrulline-containing epitopes giving them extensive multireactivity when these epitopes are found in many peptides and proteins. Moreover, certain CCP2+ multireactive ACPA clones bind also to cabamylated and acetylated autoantigens [1].Objectives:To provide a comprehensive evaluation of serum IgG and IgA autoreactivity to different post-translational modifications in RA.Methods:We analyzed 30 different IgG and IgA AMPA reactivities to modified antigens by ELISA and autoantigen arrays, in N=1985 newly diagnosed RA patients and population controls. The study utilized both previously established (i.e IgG and IgA CCP2; IgG ACPA fine-specificities; IgG anti-Carb fibrinogen and Carb FCS; IgG and IgA Cit/Carb/KAc/Orn(Ac)-vimentin), and novel assays (e.g. IgG anti-MAA and IgG anti-acetylated histones). Association with patient characteristics such as smoking and disease activity were explored. The newly developed assays were also evaluated in SLE disease controls and CCP2+ RA-risk individuals without arthritis.Results:Carb and KAc reactivities by different assays were primarily seen in patients also positive for citrulline-reactivity. Modified vimentin (mod-Vim) peptides were used for direct comparison of different AMPA reactivities, revealing that IgA AMPA recognizing mod-Vim was mainly detected in subsets of patients with high IgG anti-Cit-Vim levels and a history of smoking. IgG acetylation reactivity was mainly detected in a subset of patients with Cit and Carb reactivity. Anti-acetylated histone 2B reactivity was RA-specific and associated with high anti-CCP2 IgG levels, multiple ACPA fine-specificities, and smoking. This reactivity was also found to be present in CCP2+ RA-risk individuals without arthritis. Our data further demonstrate that IgG autoreactivity to MAA was increased in RA compared to controls with highest levels in CCP2+ RA, but was not RA-specific, and showed low correlation with other AMPA. Anti-MAA was instead associated with disease activity and was not significantly increased in CCP2+ individuals at risk of RA. Notably, RA patients could be subdivided into four different subsets based on their AMPA IgG and IgA reactivity profiles.Conclusion:We conclude that autoantibodies exhibiting different patterns of ACPA fine-specificities as well as Carb and KAc reactivity are present in RA and may be derived from multireactive B-cell clones. Anti-Carb and anti-KAc could be considered reactivities within the “Cit-umbrella” similar to ACPA fine-specificities, while MAA is distinctly different.References:[1]Sahlström P, Hansson M, Steen J, Amara K, Titcombe PJ, Forsström B, Stålesen R, Israelsson L, Piccoli L, Lundberg K, Klareskog L, Mueller DL, Catrina AI, Skriner K, Malmström V, Grönwall C. Different Hierarchies of Anti-Modified Protein Autoantibody Reactivities in Rheumatoid Arthritis. Arthritis Rheumatol. 2020 Oct;72(10):1643-1657. PMID: 32501655Caroline Grönwall: None declared, Lisa Liljefors: None declared, Holger Bang Employee of: Employee at ORGENTEC Diagnostika GmbH, Aase Hensvold: None declared, Monika Hansson: None declared, Linda Mathsson-Alm Employee of: Employee at Thermo Fisher Scientific, Lena Israelsson: None declared, Anna Svärd: None declared, Cyril CLAVEL: None declared, Elisabet Svenungsson: None declared, Iva Gunnarsson: None declared, Guy Serre: None declared, Saedis Saevarsdottir: None declared, Alf Kastbom: None declared, Lars Alfredsson: None declared, Vivianne Malmström: None declared, Johan Rönnelid: None declared, Anca Catrina: None declared, Karin Lundberg: None declared, Lars Klareskog: None declared


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1017.2-1018
Author(s):  
N. Kelly ◽  
E. Hawkins ◽  
H. O’leary ◽  
K. Quinn ◽  
G. Murphy ◽  
...  

Background:Rheumatoid arthritis (RA) is a chronic, autoimmune inflammatory condition that affects 0.5% of the adult population worldwide (1). Sedentary behavior (SB) is any waking behavior characterized by an energy expenditure of ≤1.5 METs (metabolic equivalent) and a sitting or reclining posture, e.g. computer use (2) and has a negative impact on health in the RA population (3). Sleep is an important health behavior, but sleep quality is an issue for people living with RA (4, 5). Poor sleep quality is associated with low levels of physical activity in RA (4) however the association between SB and sleep in people who have RA has not been examined previously.Objectives:The aim of this study was to investigate the relationship between SB and sleep in people who have RA.Methods:A cross-sectional study was conducted. Patients were recruited from rheumatology clinics in a large acute public hospital serving a mix of urban and rural populations. Inclusion criteria were diagnosis of RA by a rheumatologist according to the American College of Rheumatology criteria age ≥ 18 and ≤ 80 years; ability to mobilize independently or aided by a stick; and to understand written and spoken English. Demographic data on age, gender, disease duration and medication were recorded. Pain and fatigue were measured by the Visual Analogue Scale (VAS), anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS), and sleep quality was assessed using the Pittsburgh Sleep Quality Index. SB was measured using the ActivPAL4™ activity monitor, over a 7-day wear period. Descriptive statistics were calculated to describe participant characteristics. Relationships between clinical characteristics and SB were examined using Pearson’s correlation coefficients and regression analyses.Results:N=76 participants enrolled in the study with valid data provided by N=72 participants. Mean age of participants was 61.5years (SD10.6) and the majority 63% (n = 47) were female. Participant mean disease duration was 17.8years (SD10.9). Mean SB time was 533.7 (SD100.1) minutes (8.9 hours per day/59.9% of waking hours). Mean sleep quality score was 7.2 (SD5.0) (Table 1). Correlation analysis and regression analysis found no significant correlation between sleep quality and SB variables. Regression analysis demonstrated positive statistical associations for SB time and body mass index (p-value=0.03846, R2 = 0.05143), SB time and pain VAS (p-value=0.009261, R2 = 0.07987), SB time and HADS (p-value = 0.009721, R2 = 0.08097) and SB time and HADSD (p-value = 0.01932, R2 = 0.0643).Conclusion:We found high levels of sedentary behavior and poor sleep quality in people who have RA, however no statistically significant relationship was found in this study. Future research should further explore the complex associations between sedentary behavior and sleep quality in people who have RA.References:[1]Carmona L, et al. Rheumatoid arthritis. Best Pract Res Clin Rheumatol 2010;24:733–745.[2]Anon. Letter to the editor: standardized use of the terms “sedentary” and “sedentary behaviours”. Appl Physiol Nutr Metab = Physiol Appl Nutr Metab 2012;37:540–542.[3]Fenton, S.A.M. et al. Sedentary behaviour is associated with increased long-term cardiovascular risk in patients with rheumatoid arthritis independently of moderate-to-vigorous physical activity. BMC Musculoskelet Disord 18, 131 (2017).[4]McKenna S, et al. Sleep and physical activity: a cross-sectional objective profile of people with rheumatoid arthritis. Rheumatol Int. 2018 May;38(5):845-853.[5]Grabovac, I., et al. 2018. Sleep quality in patients with rheumatoid arthritis and associations with pain, disability, disease duration, and activity. Journal of clinical medicine, 7(10)336.Table 1.Sleep quality in people who have RASleep variableBed Time N(%) before 10pm13(18%) 10pm-12pm43 (60%) after 12pm16 (22%)Hours Sleep mean(SD)6.56 (1.54)Fall Asleep minutes mean(SD)33.3(27.7)Night Waking N(%)45(63%)Self-Rate Sleep mean(SD)2.74 (0.90)Hours Sleep mean(SD)6.56 (1.54)Disclosure of Interests:None declared


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1079.1-1079
Author(s):  
I. Yoshii

Background:Boolean remission criteria is one most popular and stringent criteria in treating patient with rheumatoid arthritis (RA), because it may guarantees a stable clinical course after attaining remission.Objectives:Impact of time span from initiation to achieving Boolean remission on maintaining disease activity, daily activities, and quality of life after attaining Boolean remission was investigated from daily clinical practice data.Methods:685 patients with RA since August 2010 under the T2T strategy were treated. They were monitored for their TJC, SJC, PGA, EGA, CRP, and disease activity indices such as CDAI, SDAI, DAS28, and Boolean criteria at every visit. HAQ-DI score, pain score using visual analog scale (PS-VAS), and EQ-5D were also monitored, and the quality of life score (QOLS) calculated from EQ-5D was determined at every visit from the time of diagnosis (baseline).Of 685 patients, 465 patients had achieved Boolean remission >1 times, and were consecutively followed up for >3 years. These patients were enrolled in the study. Time span from the first visit to first Boolean remission was calculated. The relationship between the time span and each of background parameters, and the relationship between the time span and each of the mean values of the SDAI score, HAQ score, PS-VAS, SHS, and QOLS at the first Boolean remission and thereafter was evaluated statistically.Patients were subsequently divided into the G ≤ 6 and G > 6 groups based on the achievement of first Boolean remission within two groups: time span G ≤ 6 months and G > 6 months. The two groups were compared with regard to the SDAI score, HAQ score, PS-VAS, SHS, and QOLS at first visit and at the time of first Boolean remission, and the mean values of these parameters after remission were evaluated statistically. Moreover, changes of these parameters and the mean Boolean remission rate after the first remission, and SDAI remission rate at the first Boolean remission to thereafter were compared between the two groups statistically.Results:Out of 465 patients, females comprised 343 (73.7%), and the mean age was 67.8 years (range, from 21–95 years). The mean disease duration at first visit was 6.1 years (range, from 1 months–45 years). The mean follow up length was 88.1 months (range: 36–122 months; median: 85 months) and mean time span from the first visit to the first Boolean remission was 8.1 months. The mean SDAI score, HAQ score, PS-VAS, and the QOLS at first visit were 13.3, 0.467, 33.2, and 0.834, respectively. Among the study parameters, PS-VAS and QOLS were significantly correlated with the time span. For parameters at the first Boolean remission, HAQ-DI score, PS-VAS, and QOLS demonstrated significant correlation with the time span, whereas SDAI, HAQ-DI score, PS-VAS, SHS, and QOLS after the Boolean remission demonstrated significant correlation with the time span.The comparison between the G ≤ 6 and the G > 6 groups revealed that the disease duration, HAQ score, and PS-VAS at baseline in the G > 6 were significantly higher than that in the G ≤ 6 group, and QOLS in the G ≤ 6 group was significantly higher than that in the G > 6 group at baseline. Similarly, the HAQ score and PS-VAS at the first Boolean remission in the G > 6 group were significantly higher than that in the G ≤ 6 group, whereas QOLS in the G ≤ 6 group demonstrated no significant difference compared with that in the G > 6 group.The mean value of the SDAI score after the first Boolean remission in the G > 6 group was significantly higher than that in the G ≤ 6 group. Similarly, the SDAI score, HAQ score, and PS-VAS after the first Boolean remission in the G > 6 group were also significantly higher than those in the G ≤ 6 group, and the mean value of the QOLS in the G ≤ 6 group were significantly higher than that in the G > 6 group. The Boolean remission rate and SDAI remission rate after the first Boolean remission were significantly higher in the G ≤ 6 group than those in the G > 6 group.Conclusion:Attaining Boolean remission ≤ 6 months for RA has significant benefit for more stable disease control, that leads good maintenance of ADL.Disclosure of Interests:None declared


1958 ◽  
Vol 1 (6) ◽  
pp. 481-496 ◽  
Author(s):  
Currier McEwen ◽  
Morris Ziff ◽  
Philip Carmel ◽  
Domenick Ditata ◽  
Martin Tanner

Author(s):  
Hideki Ohashi ◽  
Keiichiro Nishida ◽  
Yoshihisa Nasu ◽  
Kenta Saiga ◽  
Ryuichi Nakahara ◽  
...  

Dorsal dislocation of metatarsophalangeal (MTP) joints of the lesser toe frequently occurs in patients with rheumatoid arthritis (RA), and may cause painful and uncomfortable plantar callosities and ulceration. The current study examined the reliability and clinical relevance of a novel radiographic parameter (the MTP overlap distance [MOD]) in evaluating the severity of MTP joint dislocation. The subjects of the current study were 147 RA patients (276 feet; 1104 toes). MOD, defined as the overlap distance of the metatarsal head and the proximal end of the phalanx, was measured on plain radiographs. The relationship between the MOD and clinical complaints (forefoot pain and/or callosity formation) was analyzed to create a severity grading system. As a result, toes with callosities had a significantly larger MOD. ROC analysis revealed that the MOD had a high AUC for predicting an asymptomatic foot (−0.70) and callosities (0.89). MOD grades were defined as follows: grade 1, 0 ≤ MOD < 5 mm; grade 2, 5 ≤ MOD < 10 mm; and grade 3, MOD ≥ 10 mm. The intra- and inter-observer reliability of the MOD grade had high reproducibility. Furthermore, the MOD and MOD grade improved significantly after joint-preserving surgeries for lesser toe deformities. Our results suggest that MOD and MOD grade might be useful tools for the evaluation of deformities of the lesser toe and the effect of surgical intervention for MTP joints in patients with RA.


2021 ◽  
Author(s):  
Ying Lu ◽  
Chongbo Hao ◽  
Shanshan Yu ◽  
Zuan Ma ◽  
Xuelian Fu ◽  
...  

Abstract Background: Abnormal proliferation of fibroblast-like synoviocytes (FLSs) in the synovial lining layer is the primary cause of synovial hyperplasia and joint destruction in rheumatoid arthritis (RA). Currently, the relationship between metabolic abnormalities and FLS proliferation is a new focus of investigation. However, little is known regarding the relationship between amino acid metabolism and RA. Methods: The concentrations of amino acids and cytokines in the synovial fluid of RA (n=9) and osteoarthritis (OA,n=9) were detected by LC-MS/MS and CBA assay, respectively. The mRNA and protein expression of CAT-1 were determined in FLSs isolated from RA and OA patients by real-time PCR and western blotting. MTT assay, cell cycle, apoptosis, invasion and cytokine secretion were determined in FLSs knocked down of CAT-1 using siRNA or treated with D-arginine under normoxic and hypoxic culture conditions. A mouse collagen-induced arthritis (CIA) model was applied to test the therapeutic potential of blocking the uptake of L-arginine in vivo.Results: L-arginine was upregulated in the synovial fluid of RA patients and was positively correlated with elevation of the cytokines IL-1β, IL-6 and IL-8. Further examination demonstrated that cationic amino acid transporter-1 (CAT-1) was the primary transporter for L-arginine and was overexpressed on RA FLSs compared to OA FLSs. Moreover, knockdown of CAT-1 using siRNA or inhibition of L-arginine uptake using D-arginine significantly suppressed L-arginine metabolism, cell proliferation, migration and cytokine secretion in RA FLSs under normoxic and hypoxic culture conditions in vitro but increased cell apoptosis in a dose-dependent manner. Meanwhile, in vivo assays revealed that an L-arginine-free diet or blocking the uptake of L-arginine using D-arginine suppressed arthritis progression in CIA mice. Conclusion: CAT-1 is upregulated and promotes FLS proliferation by taking up L-arginine, thereby promoting RA progression.


2021 ◽  
Vol 12 ◽  
Author(s):  
Sha Wu ◽  
Xiao-Feng Li ◽  
Yuan-Yuan Wu ◽  
Su-Qin Yin ◽  
Cheng Huang ◽  
...  

Rheumatoid arthritis (RA), one of the most common autoimmune diseases, is characterized by immune cell infiltration, fibroblast-like synovial cell hyperproliferation, and cartilage and bone destruction. To date, numerous studies have demonstrated that immune cells are one of the key targets for the treatment of RA. N6-methyladenosine (m6A) is the most common internal modification to eukaryotic mRNA, which is involved in the splicing, stability, export, and degradation of RNA metabolism. m6A methylated-related genes are divided into writers, erasers, and readers, and they are critical for the regulation of cell life. They play a significant role in various biological processes, such as virus replication and cell differentiation by controlling gene expression. Furthermore, a growing number of studies have indicated that m6A is associated with the occurrence of numerous diseases, such as lung cancer, bladder cancer, gastric cancer, acute myeloid leukemia, and hepatocellular carcinoma. In this review, we summarize the history of m6A research and recent progress on RA research concerning m6A enzymes. The relationship between m6A enzymes, immune cells, and RA suggests that m6A modification offers evidence for the pathogenesis of RA, which will help in the development of new therapies for RA.


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