Course Of RA Research Articles

Belonging, happiness, freedom and empowerment—a qualitative study of patients’ understanding of health in early rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is a chronic, systemic, inflammatory joint disease, that influences patients’ health in different ways, including physical, social, emotional, and psychological aspects. The goal of rheumatology care is to achieve optimal health and personalised care and therefore, it is essential to understand what health means for patients in the early course of RA. The aim of this study was to describe the understanding of health among patients with early RA.MethodsThe study had a descriptive qualitative design with a phenomenographic approach. Phenomenography is used to analyse, describe, and understand various ways people understand or experience a phenomenon, in this study, patients’ understandings of health. Individual semi-structured interviews were conducted with 31 patients (22 women and nine men, aged (38–80) with early RA, defined as a disease duration of < 1 year, and disease-modifying anti-rheumatic drugs (DMARDs) for 3–7 months. The phenomenographic analysis was conducted in 7 steps, and the outcome space presents the variation in understanding and the interrelation among categories. In accordance with the European Alliance of Associations for Rheumatology’s (EULAR) recommendations, a patient research partner participated in all phases of the study.ResultsThe analysis revealed four main descriptive categories: ‘Health as belonging’ was described as experiencing a sense of coherence. ‘Health as happiness’ was understood as feeling joy in everyday life. ‘Health as freedom’ was understood as feeling independent. ‘Health as empowerment’ was understood as feeling capable. Essential health aspects in early RA are comprised of a sense of coherence, joy, independence, and the capability to manage everyday life.ConclusionsThis study revealed that patients’ perception of health in early RA encompasses various facets, including a sense of belonging, happiness, freedom, and empowerment. It highlighted that health is multifaceted and personal, emphasizing the importance of acknowledging this diversity in providing person-centred care. The findings can guide healthcare professionals to deepen patients’ participation in treatment goals, which may lead to better treatment adherence and health outcomes.

Body mass index stratification enables cytokine-based prediction of ACPA status and Power-Doppler disease activity in rheumatoid arthritis.

Rheumatoid arthritis can be classified according to ACPA and RF status. ACPA status may be associated with other pathophysiological differences, e.g., the cytokines driving inflammation. Obesity influences the course of RA, likely involving leptin; the exact mechanisms are not completely understood. This study investigates BMI influence on RA cytokine profiles and the possibility of predicting ACPA status and disease activity measured by Power-Doppler sonography (PDS). Patients were examined using a multi-biomarker disease assay and PDS examination of wrists and MCP and PIP joints and stratified according to ACPA status and BMI, using prediction precision to determine BMI cutoff. Analysis was performed using elastic net regularization of logistic and multiple regression. We then attempted to predict ACPA status/PDS activity based on a bootstrap approach. A total of 120 measurements from 95 patients were performed. ACPA status prediction peaked at BMI 26 kg/m2, with AUC 0.82. PDS activity prediction had a mean average error of < 1.6 PDS points for all groups. In obese patients, cytokine profiles appear to align in ACPA-positive and -negative patients, with leptin playing a greater role in predicting PDS activity, but with some remaining differences. When stratified according to BMI, cytokine patterns can predict ACPA status and PDS activity in RA with a high degree of precision. This indicates that studies into the pathophysiology of RA should take BMI into account, to differentiate between disease- and obesity-associated phenomena. The underlying pathological processes of ACPA-negative and -positive RA appear different. Multi-cytokine evaluations may provide a deeper understanding of disease processes. Key Points • A multi-cytokine approach combined with ultrasonography and modern mathematical methods can contribute to a deeper understanding of the relationship between systemic and joint inflammation. • BMI influences cytokine profiles in rheumatoid arthritis and appears to "override" disease-specific processes. • Using cytokines only, and adjusting for BMI, it is possible to predict the ACPA status and joint inflammation with considerable precision.

Patients with obesity have more inflamed joints and higher CRP levels during the disease course in ACPA-positive RA but not in ACPA-negative RA

BackgroundObese RA patients have higher disease activity scores (DAS). Previous research showed that obese RA patients have higher tender joint count (TJC) and VAS general health. However, it remains unclear whether DAS components measuring local and systemic inflammation (swollen joint count (SJC), CRP) are increased and if this is present in the total RA population or confined to an ACPA subgroup. As ACPA is suggested to enhance inflammatory responses, we hypothesized that the association of obesity with SJC and CRP is present especially in ACPA-positive RA. We therefore studied associations of obesity with courses of DAS components in ACPA subgroups.MethodsWe studied 649 RA patients (291 ACPA-positive), included in the Leiden Early Arthritis Clinic. Five-year courses of DAS44 and DAS44 components (SJC—44, TJC—53, CRP, VAS (0–100)) were compared between RA patients with normal weight (BMI 18.5–24.9), overweight (25.0–29.9), and obesity (≥ 30.0), stratified for ACPA. Linear/Poisson mixed models with a knot at 4 months were used.ResultsObese RA patients had + 0.32 higher DAS compared to normal weight during the 5-year follow-up. In ACPA-positive RA, obese patients had + 0.43 (95% CI: 0.22, 0.64) higher DAS, whereas in ACPA-negative RA, this difference was smaller and not statistically significant: + 0.19 (95% CI: − 0.01, 0.38). In ACPA-positive RA, all DAS components were significantly higher in obese patients compared to normal weight: SJC + 60% (IRR1.60; 95% CI: 1.18, 2.16), CRP + 3.7 mg/L (95% CI:0.95, 6.53), TJC + 55% (IRR1.55; 95% CI:1.15, 2.10), and VAS + 9 (95% CI: 4.0, 14.2). ACPA-negative obese RA patients tended to have higher TJC (IRR1.22; 95% CI: 0.96, 1.55) and VAS (β4.3; 95% CI: − 0.4, 9.0), while SJC (IRR1.07; 95% CI:0.85, 1.33) and CRP (β0.24; 95% CI: − 1.29, 3.32) were unaffected.ConclusionThe association of obesity with a worse DAS course is mainly present in ACPA-positive RA; especially SJC and CRP levels remain higher in ACPA-positive RA patients with obesity but not ACPA-negative RA patients. This is the first demonstration that obesity influences the disease course of ACPA-positive and ACPA-negative RA differently.

Study on the mechanism of action of Wu Mei Pill in inhibiting rheumatoid arthritis through TLR4-NF-κB pathway

BackgroundWu Mei Pills (WMP) is a traditional Chinese medication that exhibits considerable anti-inflammatory effects. While WMP has been documented for its efficacy in treating RA, its mechanism of action on the condition remains unestablished.MethodsThe chemical composition of WMP was analyzed through UPLC-MS. Next, the enzyme-linked immunosorbent assay, cell scratch, Transwell, and Western blotting techniques were used to investigate its intrinsic mechanism. Lastly, the effect of WMP in inhibiting RA was explored by applying it to CIA rats.ResultUPLC-MS analysis detected 181 compounds in WMP. RA-FLS migration and invasion mechanisms were significantly hindered by serum containing WMP (2%, 8%). Moreover, WMP (0.5 g/kg, 2 g/kg) restricted arthritis and immune organ indices in CIA rats with type II collagen-induced rheumatoid arthritis by blocking TLR4-NF-κB inflammatory pathway activation.ConclusionsWMP is valuable in mitigating the course of RA through inhibiting the classical TLR4-NF-κB inflammatory pathway and reducing the secretion of inflammatory factors in the serum of RA-FLS and CIA rats. Moreover, it regulates the dynamic balance of MMP-2/TIMP-2, MMP-9/TIMP-1, modulates the mechanism of RA-FLS invasion, and safeguards articular cartilage tissues in RA.

Association Of Cellular Communication Network Factor 3 (CCN3) With Rheumatoid Arthritis Disease And It's Severity (Case-Control Study)

Background: An inflammatory condition that affects the joints in the limbs is rheumatoid arthritis. The most common symptom is chronic, recurrent joint inflammation. When patients are advanced, joint deformities and impairments may cause major impediments in the cardiac, skin, as well as other tissues and organs. A protein called cellular CCN3 is implicated in many biological processes such as cell adhesion, migration, as well as proliferation. Additionally, CCN3 has a role in a number of pathological processes, such as fibrosis, angiogenesis, and wound healing. CCN3 can be released from the cytoplasm. CCN3 may also be an inflammatory component in the course of RA. Future therapy approaches that focus on the activities and mechanisms of action of these proteins may result from better knowledge of how CCN proteins alter the pathophysiological processes underlying these types of arthritis and successfully reduce patients' pain (Wei et al., 2020). It was discovered that RA sera and tissues had increased levels of all CCN family members. IL6 production and CCN3 expression are correlated with disease activity (Giusti &amp; Scotlandi, 2021).&#x0D; Methods: Between November 2021 and April 2022, a study including 70 patients with RA who met four or more 2010 American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) classification criteria for the condition and 70 healthy persons serving as control groups was conducted. All subjects had their disease activity score (DAS28-ESR), clinical activity index (CDAI), and rheumatoid factors (RF) detected by latex agglutination. By using an enzyme-linked immunosorbent assay, the levels of anti-cyclic citrullinated peptide (ACCP) and CCN3 in human serum samples were determined (ELISA).The age group of both the patients and the controls included in this study was 20-70. RA was found to be high in individuals of the age group &gt;40 years, at a percentage of 71.4%. The mean age was 46.2±10.3 years for patients and 1.7±0.5 for controls.Results: The results clearly showed high serum CCN3 levels in patient groups with RA compared to control (P = 0.0001). CCN3 and ACCP have a significantly positive association at control (P = 0.0001). According to DAS28-ESR, there were significantly increased concentrations of CCN3 in severe patients at P values of 0.0001 in comparison to mild patients.&#x0D; Conclusions: The biomarker CCN3 is a good prognostic marker for the severity of RA.&#x0D;

ANATOMICAL VARIATIONS IN ARTERIAL SUPPLY OF THUMB AND INDEX FINGER IN CADAVERIC HANDS

Human hand is highly evolved in terms of complexity and variations. In this modern medical era, vascular anatomy of the human hand has clinical importance in medical, surgical and radiological sciences. The intention of the current study is to determine the variations which occur as the radial artery branches thus making a contribution to the arterial supply of the index finger and the thumb. The study design was descriptive case series, carried out in the Department of Anatomy in King Edward Medical University from December 2018 to May 2019 on 30 cadaveric limbs. Vivisection of the cadaveric hands was performed following Cunningham’s Manual of practical anatomy. The origin and the course of RA, UA and MA were dissected and identified with further exploration of the blood supply of the index finger and the thumb. All details were entered in a predesigned proforma, and the dissected limbs were photographed. Data was analyzed to find the frequencies of superficial palmar arch as well as the arterial supply of thumb and index finger were also expressed in frequencies. Great variation was observed in the arterial supply to palmar aspect of index finger and thumb. Main contributing artery being radial artery in majority of cases through its common palmar or proper palmar branches arising from SPA or SPBRA. Ulnar artery and median artery were also observed to be supplying these areas in 6.6% and 3.3% cases respectively. The median artery when present was replacing the radial artery on palmar aspect of hand. The dorsum, however, was supplied by the princeps pollicis and the radialis indicis branches of radial artery in all the cases. We concluded that in about 1/3rd (11/30 are incomplete SPA) of our studied sample, arterial supply of the index finger and the thumb is highly dependent on radial artery and should any damage occur to it, vitality of these useful structures will be compromised.

Once-monthly hemin suppresses inflammatory and autoreactive CD4+ T cell responses to robustly ameliorate experimental rheumatoid arthritis

SummaryRheumatoid arthritis (RA) is an inflammatory autoimmune disease that would permanently damage the affected joints. Unfortunately, a large proportion of RA patients fail to respond adequately to current treatments. Here, repurposing hemin and its ultra-long-acting formulation were explored for the effective treatment of RA in animal models. We provided evidence that hemin prevented the onset and ameliorated the clinical course of RA. Notably, hemin treatment rescued the dysregulated gene expression in animal models of RA, resulting in attenuation of Th1/Th17 cell-mediated responses and proinflammatory cytokines. Moreover, we further formulated hemin into the in-situ forming implant, and a single injection of the ultra-long-acting hemin exerted potent disease-modifying effects for at least six weeks with a remarkable dose reduction. Taken together, given the potent anti-inflammatory and immunosuppressive effects, the once-monthly hemin injection holds promise for rapid clinical translation, and represents a potential strategy to treat RA and possibly other autoimmune diseases.

The relationship of ADAMTSL2 and LRPAP1 gene methylation level with rheumatoid arthritis activity.

The role of epigenetic mechanisms in the pathogenesis and course of RA as well as response to treatment is increasingly being emphasised. The aim of our study was to determine the ADAMTSL2 and LRPAP1 gene methylation levels in RA patients' serum divided according to disease activity and in comparison with the results with the control group. Quantitative real-time methylation-specific PCR was used to analyse the methylation status of the investigated genes. We observed a significant difference in the methylation levels of both the ADAMTSL2 and the LRPAP1 genes in patients with high RA activity compared to patients in remission. ADAMTSL2 methylation status was inversely correlated with DAS28. High disease activity was associated with lower methylation levels than in remission as well as in the control group. Different results were obtained for the methylation levels of the LRPAP1 gene. High disease activity and the control group were characterised by a higher level of LRPAP1 gene methylation compared to patients in remission. We have proven that methylation may play an important role in the course and severity of RA. The level of ADAMTSL2 and LRPAP1 gene methylation might impact the development of disease and reflect the activity of RA.

A dose-dependent beneficial effect of methotrexate on the risk of interstitial lung disease in rheumatoid arthritis patients.

The aim of the study was to assess the influence of different factors, including treatment, on the risk of ILD in the course of RA. A total of 109 RA patients were included in the analysis. High-resolution computed tomography (HRCT) of chest was obtained in each patient. Patients were classified as having ILD (ILD group) or not (N-ILD group). The ILD was graded using the semi-quantitative Warrick scale of fibrosis. Warrick extent score (WES) and Warrick severity score (WSS) were calculated separately for each patient, then combined to obtain a global score (WGS). In univariate analysis the presence of ILD was associated positively with age (P = 5x10-6) and negatively with MTX treatment (P = 0.0013), mean MTX dose per year of treatment (P = 0.003) and number of DMARDs used (P = 0.046). On multivariate analysis only age and treatment with MTX were independently associated with the presence of ILD. WGS was significantly lower in patients treated with MTX in a dose of ≥15 mg/week (MTX≥15 group) as compared to patients treated with lower doses of MTX (0<MTX<15 group) or not treated with MTX (N-MTX group) (P = 0.04 and P = 0.037, respectively). The ILD prevalence was higher in N-MTX group than in 0<MTX<15 group (P = 0.0036) and MTX≥15 group (0.0007). The difference in ILD prevalence between MTX≥15 and 0<MTX<15 groups was not significant, but the latter group had higher WES (P = 0.044) and trended to have higher WSS and WGS. We found a beneficial effect of MTX on RA-ILD. Importantly, this effect seems to be dose dependent.

THU0113 ANTI CARBAMYLATED PROTEIN ANTIBODY IN INDIAN POPULATION WITH RHEUMATOID ARTHRITIS – A BETTER PREDICTOR OF DISEASE OUTCOME

Background:While diagnosis of RA relies mainly on detection of RF and ACCP antibodies at present, anti carbamylated protein antibody which has strong association with severe joint damage and poorer disease outcome1can be found in even healthy individuals years before onset of symptoms of RA2,3thus enabling early initiation of DMARDs and reducing complications of RA.4Objectives:Assess prevalence of anti-CarP Ab in RA patients in India and assess correlation between joint involvement, X-ray erosions and extra articular features between anti-CarP Ab positive and negative RA patients.Methods:Cross-sectional study (2017-2019) conducted among 150 RA patients who met 2010 ACR/EULAR criteria in tertiary referral hospital. Tests for CRP, RF and ACCP were done, DAS28-CRP scores were calculated at presentation &amp; X-ray images of hands and feet obtained.Anti-CarP Ab was tested using ELISA. Cut-off level for positivity was defined using ROC curve as 13.48 U/mL, with specificity 92.73%, sensitivity 85.26%, PPV 95.29% and NPV 78.46%.Results:Venn diagram representing overlap of sero-markersStudy population had 18% males, 82% females, 72% RF+ cases (108), 78% ACCP+ cases (117) and 47.3% anti-CarP Ab+ cases (71).48% of the 25 seronegative (RF-ACCP-) cases tested positive for anti-CarP Ab, indicating its ability in diagnosing more RA cases in conjunction with present markers.Testing association between RF and anti-CarP Ab and between ACCP and anti-CarP Ab proved to be statistically insignificant showing that anti-CarP Ab is independent of the incumbent markers in diagnosing RA.69.4% of RA patients with high disease activity (DAS &gt;3.2) were positive for anti-CarP Ab and showed statistically significant association.Association between DAS28 CRP and anti-CarP AbAlso while 39 of 71 (54.9%) anti-CarP Ab positive RA cases had joint deformities and 23 of 71 (32.4%) of anti-CarP Ab positive cases had extra articular involvement and were statistically significant, 27 of 71 anti-CarP Ab positive cases showed joint erosions in X-ray but was not statistically significant.In comparison, only extra articular involvement showed a statistical significance in ACCP positive patients whereas joint deformities and joint erosions on X-rays showed no correlation to ACCP.Joint DeformityTotalΧ2p valueAbsentPresentanti-CarP antibodyNegative5029795.0090.02563.3%36.7%100.0%Positive32397145.1%54.9%100.0%Total8268150Extra articular featuresTotalΧ2p valueAbsentPresentanti-CarP antibodyNegative6811797.2780.00786.1%13.9%100.0%Positive48237167.6%32.4%100.0%Total11634150Conclusion:Anti-CarP antibody positivity is indicative of increased disease activity (DAS28-CRP score), joint deformities and extra articular involvement in RA patients. Aside from its presence demonstrated early in the course of RA through other studies, its ability in diagnosing RA cases in otherwise seronegative (RF and ACCP negative) population and the high sensitivity, specificity and diagnostic accuracy exhibited paves the way for its routine use as a diagnostic tool in conjunction with RF and ACCP for diagnosing RA and predicting disease outcome.

Rheumatoid arthritis bone marrow environment supports Th17 response

BackgroundRheumatoid arthritis (RA) is a systemic, autoimmune disease leading to joint destruction and ultimately disability. Bone marrow (BM) is an important compartment in RA, where pathological processes from “outside the joint” can occur. IL-17 is a cytokine that exerts proinflammatory effects and participates in the process of bone destruction. It is believed that IL-17 is involved in pathogenesis of RA. However, little is known about the biology of this cytokine in BM. In the present study we investigated Th17-related cytokines in RA BM.MethodsBM samples were obtained from RA and osteoarthritis (OA) patients during total hip replacement surgery. Levels of IL-17AF, IL-17AA, IL-17FF, IL-1β, IL-6, IL-23, TGF-β and CCL20 in BM plasma were determined by specific enzyme-linked immunosorbent assay tests. Percentage of IL-17-producing cells in BM was evaluated by flow cytometry. The effect of IL-15 stimulation on IL-17 production by BM mononuclear cells was examined in vitro.ResultsIncreased levels of IL-17AF were observed in BM plasma of RA patients in comparison to OA patients. Increased concentrations of IL-1β, IL-6 and CCL20 were observed in RA compared to OA BM plasma. Concordant with these findings, significantly increased percentages of CD3+CD4+IL-17+ and CD3+CD4+IL-17+IFN-γ+ cells were present in RA BM in comparison to OA BM samples. Finally, abundant in RA BM, IL-15 increased IL-17 production by cultured BM mononuclear cells.ConclusionsIn the course of RA, the BM microenvironment can promote the development of Th17 cell responses and overproduction of IL-17AF that may lead to increased inflammation and tissue destruction in RA BM.

Effect of Human Herpesviruses 6 and 7 Infection on the Clinical Course of Rheumatoid Arthritis / Cilvēka Herpesvīrusa 6 Un 7 Infekcijas Ietekme Uz Reimatoīdā Artrīta Klīnisko Gaitu

Abstract Rheumatoid arthritis (RA) is a chronic systemic autoimmune inflammatory disease affecting joints and causing symmetrical chronic progressive aseptic synovitis and erosive-destructive changes. Viruses and viral infections are considered to be the main risk factors for autoimmune disease development (especially for individuals with genetic predisposition). The goal of this study was to evaluate the frequency of HHV-6 and HHV-7 persistent infection and its activity phase in RA and osteoarthritis (OA) patients, and healthy persons. We examined also the influence of HHV-6 and -7 infections on RA activity, aggressiveness, radiographical stage, and frequency of complications as well as the presence of HHV-6 infection markers in synovial fluid and synovial tissues of RA joints of affected patients. Despite the lack of significant correlation between frequency of persistent single HHV-6, single HHV-7, and concurrent HHV-6 and HHV-7 infection and RA clinical course, we found that both active and latent HHV-6 and/or HHV-7 infection increased RA activity and progression in several clinical and laboratory parameters. Regarding the severity of the course of RA, we observed also a high prevalence of RA complications in the patient group with active single HHV-6 infection and also a more severe radiographical stage in RA patients with active concurrent HHV-6 and HHV-7 infection. Moreover, viral infection markers were found in synovial fluid and synovial tissues of affected joints of RA patients. This suggests that HHV-6 and/or HHV-7 infection has effect on the disease clinical course, but virus reactivation may be a consequence of immunosuppressive treatment.

OP0167 Evidence That Both the Disease Course & Structural Outcomes in RA Have Become Less Severe over Time. A 25-Year Longitudinal Data Analysis Based on Two Consecutive UK Inception Cohorts

BackgroundEvidence suggests that disease expression and course in RA has become less severe. It is unclear whether this is due to changes in disease phenotype/expression or reflects earlier more effective...

FRI0318 Two-Year Retention and Effectiveness of IV Abatacept in Real-Life Setting: Results from the Action Study

BackgroundInitial results from the real-world ACTION study suggest that abatacept (ABA) is clinically effective and well tolerated in pts with RA, with good pt retention over 12 mths.1ObjectivesTo assess retention...

AB0138 Time-Course of Microvascular versus Macrovascular Endothelial Dysfunction in Rat Adjuvant-Induced Arthritis

BackgroundRheumatoid arthritis (RA) is associated with increased risk for cardiovascular disease (CVD). Whereas ample evidence demonstrated the presence of endothelial dysfunction (ED) in RA, it is still unclear how early...

THU0069 Ultrasound-Guided Assessement of Axillary Lymph Node Reactivity/Structural Heterogeneity in Rheumatoid Arthritis: Relationship with Disease Activity and Joint Inflammation

BackgroundThere is growing evidence in the murine system suggesting that joint-draining lymph nodes (LN) and the afferent lymphatic system are relevant patho-phisiologic components of chronic arthritis acting through the control...

AB0174 Relationship of matrix metalloproteinase-3 concentration with clinical, laboratory and ultrasonographic markers of rheumatoid arthritis activity

BackgroundRheumatoid arthritis (RA) is a disease of the connective tissue, in the course of which the occurrence of symmetrical peripheral joints arthritis is the main symptom. It may lead to...

SP0158 Comorbidity in Rheumatic Diseases

More than half of the patients with rheumatoid arthritis seen in daily care have one or more comorbid conditions. These may be coincidental medical conditions as expected in the age...

CAG Repeat Polymorphism in the Androgen Receptor Gene in Women with Rheumatoid Arthritis

Rheumatoid arthritis (RA) is the most common chronic, autoimmune, inflammatory disease, with a genetic and hormonal background. The prevalence of women among patients with RA suggests the important role of sex hormones in the pathogenesis of RA. We examined the association between CAG repeat polymorphism in the androgen receptor (AR) gene and susceptibility to RA and its clinical features in white women. The study groups consisted of 325 female patients with RA and 238 female controls. CAG repeat polymorphism was determined using polymerase chain reaction and subsequent fragment analysis by capillary electrophoresis. The number of CAG repeats in patients did not differ from that of controls (22.1 ± 2.9 vs 21.9 ± 2.9, respectively; p = 0.26), but the presence of articular erosions was associated with a lower number of repeats in the shorter allele of patients with RA (20.4 ± 2.2 vs 21.2 ± 2.4; p = 0.031). When alleles with < 22 CAG were classified as short (S) and those with ≥ 22 CAG as long (L), the age at diagnosis of RA was lower in women with S-S genotype in comparison to combined S-L + L-L genotypes (43.0 ± 14.6 yrs vs 47.6 ± 12.5 yrs; p = 0.021). In patients with the L-L genotype, the frequency of erosive disease (OR 0.45, 95% CI 0.25-0.80, p = 0.0085) and extraarticular manifestations (OR 0.50, 95% CI 0.26-0.98, p = 0.047) was lower in comparison to carriers of the S allele. In multivariate analysis, the L-L genotype was an independent factor associated with a lower risk of erosions (OR 0.44, 95% CI 0.22-0.90, p = 0.024). The results suggest the association of short AR (CAG)(n) alleles with earlier onset and a more aggressive course of RA.

Older age of rheumatoid arthritis onset is associated with higher activation status of peripheral blood CD4+ T cells and disease activity

Rheumatoid arthritis (RA) is a chronic inflammatory disease, with a clinical manifestation both systemic and in joints. It has been suggested that age at disease onset and/or patients' age have influence on disease activity and clinical outcome. The reasons for the different course of RA in older people are not known; however, the activation status of peripheral blood lymphocytes could be responsible. Our aim was to relate expression of activation markers in peripheral blood CD4(+) T cells of RA patients with patients' age and/or onset age and disease activity measured by DAS28. Seventy RA patients were included into the immunological study. Two separation criteria were performed: based on age of RA onset and on the biological age of patients. We examined different activation markers, CD69, CD25, CD95 and human leucocyte antigen D-related (HLA-DR), on the CD4(+) T cell surface. Division of RA patients in 10-year intervals at 40, 50 and 60 years revealed that RA patients with later disease onset were characterized by higher DAS28. This phenomenon was not limited to the division at 60 years of age but, surprisingly, the major differences were found for the 40-year onset division. Analysis of all four components of DAS28 revealed that disease activity in older disease onset was dependent on all components. Older-onset RA patients had a higher percentage of CD4(+) CD25(+) and CD4(+) CD95(+) T cells. Summarizing the major differences in DAS28 and activation status of CD4(+) T cells observed for onset of disease at 40 years seems to be the most informative about the immunological status of RA patients.