anti-CCP Research Articles

Reproductive Effect by Rheumatoid Arthritis and Related Autoantibodies.

Rheumatoid arthritis (RA) is a common inflammatory arthritis in women. The effects of RA on the reproductive system are usually overlooked, as RA is not diagnosed until later in reproductive age. Whether RA itself or its related rheumatoid antibodies have an impact on female reproductive function has long been a thought-provoking issue. In brief, relevant epidemiological evidence has shown that women affected by RA are more likely to have coexisting reproductive disorders, including infertility, endometriosis, and premature ovarian insufficiency (POI), or to subsequently develop them. Furthermore, linkage between RA and pregnancy loss (PL) as well as polycystic ovary syndrome (PCOS) is also well known, albeit controversial in available evidence. RA and reproductive disorders appear to share a similar inflammatory immune response and genetic background. The stress experienced by patients with RA may affect their reproductive choices to some extent. Notably, few studies have explored the impact of rheumatoid antibodies such as rheumatoid factors (RFs) and anti-citrullinated protein antibodies (ACPAs) on reproductive disorders. Although it has been mentioned that the rate of RF and/or ACPA positivity is higher in women with a history of PL and POI, the clinical relevance of this relationship and underlying mechanisms still need to be further clarified.

Predictors at diagnosis for start of biologic disease-modifying antirheumatic drugs in patients with early rheumatoid arthritis: a cohort study

ObjectivesTo investigate the relation between patient characteristics at rheumatoid arthritis (RA) diagnosis and subsequent initiation of treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs).DesignA retrospective cohort...

Limited Diagnostic and Prognostic Value of Routine Radiographs in Newly Presenting Arthritis Suspected of Rheumatoid Arthritis: A Retrospective Study.

Current recommendations suggest that patients with newly presenting arthritis suspected of rheumatoid arthritis (RA) should undergo routine radiographs of hands and feet (X-HF) as the presence of RA-associated erosions might be of diagnostic and prognostic value. Our objective was to investigate the prevalence, diagnostic, and prognostic value of RA-associated erosions seen on routine X-HF in a large, recent cohort of patients with newly presenting arthritis. A retrospective cohort study was performed between 2016 and 2019 in patients with newly presenting arthritis suspected of RA. Patients were included if arthritis was present at diagnosis, rheumatoid factor and anticitrullinated protein antibodies were measured, RA was noted in the differential diagnosis, and routine X-HF were conducted. Outcomes were the prevalence of one or more RA-associated erosion(s), and whether diagnostic or prognostic classification were changed by erosivity. Seronegative patients, patients without acute phase reactants, and patients with longer symptom duration were analyzed as subgroups. RA-associated erosions were found in 32 of 724 patients (4.4%, 95% confidence interval [95% CI] 3.1-6.2). Erosions led to a change of diagnostic classification in two patients (0.3%, 95% CI 0.01-1.1) and changed prognostic classification in three patients (0.4%, 95% CI 0.1-1.3). Seronegative patients and patients without elevated acute phase reactants had significantly lower prevalence of erosions (χ2 9.4, P = 0.002, χ2 6.5, P = 0.01). Longer symptom duration was not associated with a different prevalence of erosions (χ2 0.4, P = 0.81). The recommendation of conducting routine X-HF in patients with newly presenting arthritis suspected of RA might be reconsidered due to low prevalence of early erosive disease and lack of diagnostic and prognostic value.

Comparative effectiveness of abatacept versus TNF inhibitors in rheumatoid arthritis patients who are ACPA and shared epitope positive

BackgroundThe HLA-DRB1 shared epitope (SE) is a risk factor for the development of rheumatoid arthritis (RA) and the production of anti-citrullinated protein antibodies (ACPAs) in RA patients. Our objective was to examine the real-world effectiveness of abatacept versus tumor necrosis factor inhibitors (TNFi) in patients with RA who were SE and anti-cyclic citrullinated peptide antibody (anti-CCP3) positive.MethodsAbatacept or TNFi initiators who were SE + and anti-CCP3+ (> 20 U/mL) at or prior to treatment and had moderate or high CDAI score (> 10) at initiation were identified. The primary outcome was mean change in CDAI score over six months. Analyses were conducted in propensity score (PS)-trimmed and -matched populations overall and a biologic-experienced subgroup. Mixed-effects models were used.ResultsIn the overall PS-trimmed (abatacept, n = 170; TNFi, n = 157) and PS-matched cohorts (abatacept, n = 111; TNFi, n = 111), there were numerically greater improvements in mean change in CDAI between abatacept and TNFi but were not statistically significant. Similar trends were seen for biologic-experienced patients, except that statistical significance was reached for mean change in CDAI in the PS-trimmed cohort (abatacept, 12.22 [95% confidence interval (95%CI) 10.13 to 14.31]; TNFi, 9.28 [95%CI 7.08 to 11.48]; p = 0.045).ConclusionIn this real world cohort, there were numerical improvements in efficacy outcomes with abatacept over TNFi in patients with RA who were SE + and ACPA+, similar to results from a clinical trial population The only statistically significant finding after adjusting for covariates was greater improvement in CDAI with abatacept versus TNFi in the bio-experienced PS-trimmed cohort..

Search for predictors of methotrexate toxicity in rheumatoid arthritis

Aim. To determine prognostic markers of methotrexate (MT) toxicity in rheumatoid arthritis (RA).Materials and methods. The study included 294 patients with RA who were prescribed MT at a dose of 10 to 25 mg per week for the first time as basic anti-inflammatory therapy (BPVT). The following adverse events (AEs) were recorded: hepatotoxicity, toxicity from the gastrointestinal tract, blood system. Qualitative parameters were considered as possible predictors of MT intolerance: gender, obesity, smoking, systemic manifestations, as well as rheumatoid factor (RF), antibodies to cyclic citrullinated peptide (ACCP), intake of glucocorticosteroids (GCS), form of administration of MT; and quantitative: age of RA onset, baseline disease activity according to DAS28 (Disease Activity Score 28) and HAQ (Health Assessment Questionnaire), MT dose. Statistical processing was performed by one-factor methods using Pearson’s χ2 test with Yates correction, Fisher’s exact two-tailed test, Mann–Whitney U-test, and Student’s t-test. Multivariate analysis was carried out by binary logistic regression.Results. In a univariate analysis, significant results were obtained for hepatotoxicity: a direct correlation with the use of corticosteroids at the onset (odds ratio (OR) 2.0; 95 % confidence interval (CI) 1.1–3.8, p = 0.03), inversely correlated with MT tablet intake (OR 0.5, 95 % CI 0.2–0.95, p = 0.03). According to the results of multivariate analysis, hepatotoxicity was recorded more often when taking GCS in the debut 2.01 times (95 % CI 1.02–3.96, p = 0.043), and in the presence of ACCP – 3.16 times (95 % CI 1.06–9.45, p = 0.039); and less frequently when taking tableted MT by 2.62 times (95 % CI 0.17–0.84, p = 0.017). Gastrointestinal toxicity tends to be associated with a younger age of RA onset (p = 0.06) and greater RA HAQ activity at onset (p = 0.07).Conclusions. Hepatotoxicity is more expected in patients seropositive for ACCP and GCS treatment in the onset of RA, but is less common when taking MT tablets. AEs from the gastrointestinal tract are associated with a younger age of onset of the disease and a greater degree of activity according to the HAQ index.

Prognostic value of serum protein electrophoresis constituents for arthritis development in anti-citrullinated protein antibody-positive patients with musculoskeletal pain

Objective Predictors of arthritis development in patients with anti-citrullinated protein antibodies (ACPAs) and musculoskeletal symptoms are needed for risk stratification and to improve clinical outcomes. The aim of this study was to assess the relationship between serum protein electrophoresis (SPE) constituents and the development of clinical arthritis in ACPA-positive patients with musculoskeletal pain. Method We prospectively followed 82 ACPA-positive patients with musculoskeletal pain but no baseline arthritis during a median of 72 months (interquartile range 57–81 months). The primary outcome was arthritis development, as judged by clinical examination. SPE constituents were evaluated in baseline sera by immunoturbidimetric methods. Serum levels of the analysed proteins (albumin, orosomucoid, α1-anti-trypsin, haptoglobin, and immunoglobulins IgA, IgG, and IgM) were related to arthritis development by Cox regression analyses. Results During the follow-up period, 39/82 patients (48%) progressed to arthritis. Median baseline levels of orosomucoid and α1-anti-trypsin were higher in patients who developed arthritis than in those who did not (p = 0.04), while median albumin levels were significantly lower (p = 0.03). Immunoglobulin levels did not differ between the groups. Univariable analysis demonstrated a significantly increased risk of arthritis with elevated baseline haptoglobin [hazard ratio (HR) 2.53, 95% confidence interval (CI) 1.32–4.85, p = 0.005] and orosomucoid levels (HR 2.63, 95% CI 1.09–6.31, p = 0.03). However, neither remained significant in multivariable analysis adjusting for elevated C-reactive protein (CRP) levels. Conclusion SPE does not add prognostic value for arthritis development in ACPA-positive patients with musculoskeletal pain.

Long-term mortality in treated-to-target RA and UA: results of the BeSt and IMPROVED cohort

ObjectivesTo study long-term (up to 20-year) mortality of two treat-to-target trial cohorts in undifferentiated arthritis (UA) and early rheumatoid arthritis (RA).MethodsThe BeSt (BehandelStrategieën) study (n=508, early RA) was performed between...

Clinical significance of behavioral type “a” in patients suffering from rheumatoid arthritis

According to modern concepts, rheumatoid arthritis is a classic psychosomatic disease that leads to a decrease in the quality of life of patients and their early disability. To date, few foreign and domestic studies have examined the relationship between behavioral type “A” and rheumatoid arthritis. The clinical significance of behavioral type A in patients with rheumatoid arthritis has been studied to determine new therapeutic and diagnostic approaches. As part of a one-stage (cross-sectional) study, 74 people suffering from rheumatoid arthritis were examined during the year, which were represented by two groups, in accordance with the diagnosed behavioral type. The first group consisted of 22 patients suffering from rheumatoid arthritis with behavioral type A, and the second group consisted of 52 patients suffering from rheumatoid arthritis with behavioral type B. All patients received standard basic and anti-inflammatory therapy in the form of methotrexate at a dose selected individually. The duration of adequate basic therapy corresponded to the incidence of rheumatoid arthritis in both groups. Patients with behavioral type A were characterized by lower immunological activity, manifested, among other things, by a lower level of antibodies to cyclic citrullinated peptide and C-reactive protein, whereas the frequency of erosive lesions was higher. The presence of behavioral type A in patients with rheumatoid arthritis is a risk factor for the development of atherosclerotic damage. A personal negative quality, i. e. , hostility, which is included as one of the characteristics of behavioral type “A,” has a reliable direct relationship with the number of erosions, and significantly, its value directly correlates with the incidence of rheumatoid arthritis. Thus, the stratification of patients suffering from rheumatoid arthritis, according to the presence of behavioral type “A,” demonstrates the clinical and laboratory features of the disease and may be important for the development of new therapeutic and diagnostic approaches and the provision of therapeutic and preventive interventions in these patients

Rheumatoid Arthritis and Pericardial Effusion - A Unique Major Manifestation.

Pericardial effusion is common in the setting of rheumatoid arthritis (RA); however, it is rarely its first manifestation. An 82-year-old male presented with abdominal pain, vomiting and fever. Blood analysis revealed elevated systemic inflammatory markers, and an abdominal computed tomography scan revealed non-specific alveolar condensation of the right pulmonary base and pericardial effusion subsequently quantified as medium size by transthoracic echocardiography. A large aetiological panel was requested, with the autoimmunity study revealing high levels of rheumatoid factor (RF) and anti-citrullinated cyclic peptide (anti-CCP) antibodies. Since the patient did not present articular involvement, the initial hypothesis was pericardial effusion due to pneumonia and no specific treatment for RA was started. At follow-up, the pericardial effusion recurred and a pericardiocentesis was performed. The pericardial fluid analysis was sterile, and no malignant cells were identified. A new serological study confirmed high levels of RF and anti-CCP antibodies, and immunomodulatory treatment was initiated. After one year, the pericardial effusion recurred due to non-compliance with immunomodulatory therapy. A surgical pleuro-pericardial window was performed, and the cytological study of the pericardial patch revealed submesothelial thickening and foci of perivascular lymphocytic infiltrate. The patient remained asymptomatic. After exclusion of a large spectrum of infectious and non-infectious causes and the relapse after suspension of immunomodulatory treatment, the most probable aetiology for the pericardial effusion remains RA. Pericardial syndromes can be the first manifestation of AR even in the absence of articular symptoms and this disease must be considered in the aetiological investigation. The occurrence of pericardial effusion in the setting of rheumatoid arthritis (RA) is a usual finding but this form of extra-articular manifestation is possibly the first and only presentation of the disease.In the case of recurrent pericardial effusion, the diagnosis of RA must be considered in the aetiological investigation even in the absence of more common manifestations of the disease.

Identification of circulating autoantibodies to non-modified proteins associated with ACPA status in early rheumatoid arthritis.

To discover autoantibodies to non-modified proteins associated with the presence/absence of anticitrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA). The autoantibody repertoire of 80 ACPA negative and 80 ACPA positive RA subjects from the Swedish population-based Epidemiological Investigation of RA (EIRA) cohort was screened using a suspension bead array built on protein fragments earlier described as autoimmunity targets. Four autoantibodies positive in the initial screening were validated in another set of EIRA samples containing 317 ACPA-positive, 302 ACPA-negative and 372 age- and sex-matched controls. The relationship between the four autoantibodies and lung abnormalities on high-resolution computed tomography (HRTC) was examined in 93 early RA patients from LURA cohort. Association between the autoantibodies, smoking and MHC class II alleles was assessed by logistic regression analysis. : Anti-ANOS1 and anti-MURC IgG levels were associated with ACPA-positive status (OR = 3.02; 95% CI 1.87-4.89; and OR = 1.86; 95% CI 1.16-2.97, respectively) and increased in ACPA-positive patients compared with controls. Anti-ANOS1 IgG was associated with smoking habit (OR = 2.11; 95% CI 1.22-3.69) and anti-MURC IgG with the presence of the MHC class II "shared-epitope" genes (OR = 1.95; 95% CI 1.11-3.46). Anti-TSPYL4 IgG was associated with ACPA-negative (OR = 0.41; 95% CI 0.19-0.89). Anti-TSPYL4 IgG and anti-MAP2K6 IgG levels were increased in the ACPA-negative patients compared with controls. Presence of anti-MAP2K6 IgG and anti-TSPYL4 IgG correlated negatively with HRCT-defined lung abnormalities. These four autoantibodies may be useful in diagnostics and in predicting clinical phenotypes of RA.

Frequency of Positive Anti-CCP Antibodies in Rheumatoid Arthritis Patients with Negative Rheumatoid Factor

Background: Rheumatoid arthritis (RA) is a polyarticular autoimmune disease that affects about 1% of the adult population. The disease is characterized by synoviocyte hyperplasia, mainly synovial fibroblasts, resulting in bone and joint destruction. Recent studies have shown that cytokines and other systemic inflammation mediators have a key role in the development ofrheumatoid arthritis. Recently, Anti-Citrullinated Protein Antibodies (anti-CCP) have come into use for the diagnosis of rheumatoid arthritis (RA). It has been reported that anti-CCP has quite a high specificity for RA (98%), together with sensitivity similar to that for rheumatoid factor (RF). The study aimed to determine the frequency of positive anti-CCP antibodies in rheumatoid arthritis patients with negative rheumatoid factor.
 Methods: 91 patients (both male and females) aged 40-70years with negative RF were clinically diagnosed with rheumatoid arthritis. Patients with positive rheumatoid factor and joint injuries were disclaimed. The consultant pathologist used a second-generation enzyme-linked immunosorbent assay (ELISA) to assess the serum levels of anti-CCP antibodies, >20IU/ ml is considered positive p-value of 0.05 were considered statistically significant.
 Results: In the study, the age range was 40 to 70 years, averaging 53.44 ± 7.16 years. 59 (64.84%) of the patients were between the ages of 40 and 55. Of 91 patients, 56 (61.54%) were women, and 35 (38.46%) were men with aratio of 1.6:1 man to women. In patients with negative rheumatoid factors, 27 (40.66%) patients were found to have the levels of positive anti-CCP antibodies.
 Conclusion: Patients with negative rheumatoid factor showed the high frequency of positive anti-CCP.

Synovial-tissue resident macrophages play proinflammatory functions in the pathogenesis of RA while maintaining the phenotypes in the steady state

Synovial tissue-resident macrophages (STRMs) maintain normal joint homeostasis in a steady state. However, it is unclear whether STRMs still play homeostatic roles or change the functions in the joint of rheumatoid arthritis (RA), where infiltrating peripheral blood monocyte-derived macrophages (PBMoMs) play proinflammatory roles. In the present study, we examined changes in the phenotypes and functions of STRMs in response to RA-related stimuli in vitro. STRMs were prepared from non-inflammatory osteoarthritis (OA) joint synovium, which is histologically indistinguishable from normal joint synovium. PBMoMs were prepared and used for comparison. After stimulation with plate-bound IgG, which mimics anti-citrullinated protein antibody immunocomplex formed in RA joints, or with combinations of RA-related inflammatory mediators, namely tumor necrosis factor-α (TNF-α) and prostaglandin E2 or interferon-γ, PBMoMs downregulated surface markers and genes associated with anti-inflammatory macrophages, and upregulated cytokine and marker genes of proinflammatory macrophages in RA. On the other hand, STRMs hardly changed the expression of surface molecules and marker genes but altered the pattern of cytokine gene expression after stimulation like PBMoMs. Furthermore, in vitro stimulated STRMs promote proinflammatory functions of cocultured synovial fibroblasts. Thus, STRMs might play proinflammatory roles in RA joints, while maintaining their phenotypes in the steady state.

Plasma TNF-α Elevation in Biologic Naive Rheumatoid Arthritis Patients Belonging to a Population with New Mutations in TLR4 and CYP51A1 genes without Association with Disease-Related Antibodies Levels.

In a system biology-based study, we previously reported that IL-6 and IL6R -specific m-RNA levels were elevated in leukocytes of patients with Rheumatoid arthritis (RA). Here, the association of toll-like receptor4 (TLR4) rs 141534085 and cytochrome P450 family 51 subfamily A member 1(CYP51A1) rs6 with tumor necrosis factor-α (TNF- α), rheumatoid factor (RF)- and Anti- cyclic citrullinated peptide (anti-CCP) antibody -positivity was investigated in almost the same subjects. Forty-six patients and 48 normal subjects were recruited in this study. The blood leucocytes TLR4 rs 141534085 and CYP51A1 rs6 -comprising DNA sequences were amplified by using tetra-primer amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR) technique and the PCR products were checked by Sanger DNA sequencing method. ELISA method was used to determine plasma levels of TNF- α, anti-CCP antibody and RF positivity of plasma was evaluated through a latex agglutination test. The TNF- α level was significantly higher in the patient group than control subjects (p= 0.001). Moreover, we were not able to find any correlation between TNF-α levels and RF as well as anti-CCP antibodies when we used the K2/ Fisher's exact test and Pearson test respectively. Our DNA sequencing data revealed the following new mutations in TLR4 rs141534085 comprising regions: A>T in position 1050, T>A in position 1052, and C>A in position 1054; and for CYP51A1 rs6 encompassing region, the new mutations were; G>A in position 21680, the T nucleotide was inserted in position 21762 and the G nucleotide was inserted in position 21763, G>T in position 21764. The data of this study showed that both TLR4 rs141534085 and CYP51A1 rs6 related DNA regions should be considered as hotspot areas in RA pathogenicity. Moreover, these data indicated that, TNF- α did not alter the production of anti-CCP and RF pathogenic antibodies in patients with long-term RA.

Safflower extract (Carthamus tinctorius Linn.) suppresses proinflammatory cytokines level in rheumatoid arthritis mice model stimulated by complete Freund’s adjuvants

Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation of the synovial membrane, and swelling, associated with excessive production of proinflammatory cytokines. In addition, anti-citrullinated protein antibodies is excessively high in RA. Carthamus tinctorius Linn. (C. tinctorius), commonly known as Safflower, is widely used as traditional medicine in Indonesia and has anti-inflammatory properties. This study aims to determine cell viability on HEK293 cells and the anti-RA activity of the ethanol extract of C. tinctorius on reducing edema in animal models of RA mice and to determine the anti-RA activity ethanol extract C. tinctorius against rheumatoid factor (RF) in RA mice. In this study, HEK293 cell line was treated with C. tinctorius extract at various concentrations. In addition, mice’s paws were examined after being injected with complete Freund’s adjuvant (CFA) as an intraplantar RA inducer and treated with 2.5 mg/kg body weight (BW) of methotrexate, and extract C. tinctorius at various concentrations orally once a day for 14 days. Then, the paw’s thickness was measured using a gauge meter, arthritis index scoring was observed daily, and agglutination in the RF test was observed on the 17th and 31st days. The collected data was analyzed using one-way analysis of variance. Moreover, an In-Silico test was carried out by measuring the affinity and stability of C.tintorius extract as an anti-RA agent against the cytokines IL-1β and tumor necrosis factor-alpha. The test results showed C. tinctorius at various concentrations were safe to HEK293 cell lines and the administration of C. tintorius extract at 100, 200, and 400 mg/kg BW doses could reduce paw thickness, arthritis index scoring >1, and no agglutination occurred in the RF test. It can concluded that the C. tintorius extract is safe to HEK293 and has activity against CFA-induced RA.

The double shared epitope: Its impact on clinical features and ultrasound findings in rheumatoid arthritis.

The link between the HLA-DRB1 locus and the risk of rheumatoid arthritis (RA) shown in genome-wide association studies strengthens the shared epitope (SE) hypothesis. We aimed to assess the impact of the double dose of the SE (double SE) on RA and explore its clinical associations, including the response to abatacept. We evaluated RA patients treated with csDMARDs or abatacept for HLA-DRB1 typing, clinical characteristics at baseline, and disease activity and ultrasound findings over 12 months. Patients with the double SE (n = 12) had significantly higher anti-citrullinated protein antibody (ACPA) titers, higher total grayscale (GS) score, and power Doppler (PD) score at baseline than patients without the double SE. Patients with the double SE exhibited reduced rates of SDAI remission and pronounced improvements in multiple disease activity between baseline and 12 months, including SDAI, CDAI, total GS score, and total PD score. When focusing on abatacept-treated patients, the decreases in SDAI, CDAI, and total PD score between baseline and 12 months were significantly larger in patients with the double SE. Patients with the double SE exhibited distinct characteristics, increased disease activity, and improved response to abatacept treatment.

When does obesity exert its effect in conferring risk of developing RA: a large study in cohorts of symptomatic persons at risk

ObjectivesObesity is a known risk factor for developing rheumatoid arthritis (RA). However, it is unclear whether obesity exerts its risk effect during the asymptomatic or the symptomatic clinically suspect arthralgia...

Ameliorative effects of undifferentiated and differentiated BM-MSCs in MIA-induced osteoarthritic Wistar rats: roles of NF-κB and MMPs signaling pathways.

Osteoarthritis (OA) is a degenerative joint condition that is persistent. OA affects millions of people throughout the world. Both people and society are heavily economically burdened by osteoarthritis. There is currently no medication that can structurally alter the OA processes or stop the disease from progressing. Stem cells have the potential to revolutionize medicine due to their capacity to differentiate into chondrocytes, capacity to heal tissues and organs including osteoarthritic joints, and immunomodulatory capabilities. Therefore, the goal of the current investigation was to determine how bone marrow-derived mesenchymal stem cells (BM-MSCs) and chondrogenic differentiated mesenchymal stem cells (CD-MSCs) affected the treatment of OA in rats with monosodium iodoacetate (MIA)-induced osteoarthritis. Male Wistar rats were injected three times with MIA (1 mg)/100 µL isotonic saline to induce osteoarthritis in the ankle joint of the right hind leg. Following the MIA injection, the osteoarthritic rats were given weekly treatments of 1 × 106 BM-MSCs and CD-MSCs into the tail vein for three weeks. The obtained results showed that in osteoarthritic rats, BM-MSCs and CD-MSCs dramatically decreased ankle diameter measurements, decreased oxidized glutathione (GSSG) level, and boosted glutathione peroxidase (GPx) and glutathione reductase (GR) activities. Additionally, in rats with MIA-induced OA, BM-MSCs and CD-MSCs dramatically boosted interleukin-10 (IL-10) serum levels while considerably decreasing serum anticitrullinated protein antibodies (ACPA), tumour necrosis factor-α (TNF-α), and interleukin-17 (IL-17) levels as well as ankle transforming growth factor-β1 (TGF-β1) expression. Analysis of histology, immunohistochemistry, and western blots in osteoarthritic joints showed that cartilage breakdown and joint inflammation gradually decreased over time. It is possible to conclude from these results that BM-MSCs and CD-MSCs have anti-arthritic potential in MIA-induced OA, which may be mediated via inhibitory effects on oxidative stress, MMPs and inflammation through suppressing the NF-κB pathway. In osteoarthritis, using CD-MSCs as a treatment is more beneficial therapeutically than using BM-MSCs.

PREVALENCE OF CARPAL TUNNEL SYNDROME IN PATIENTS WITH RHEUMATOID ARTHRITIS AND ITS ASSOCIATION WITH DISEASE SEVERITY

Background: Rheumatoid arthritis (RA) is an auto-immune inflammatory arthritis globally affecting 1% of the population. This study was conducted to see prevalence of carpal tunnel syndrome in patients of RA and its association with disease severity. Methods: One-hundred-fifty-four patients aged 21?80 years, of both gender, with RA were enrolled using non-probability consecutive sampling technique. Patients were divided into two groups of 77 each: active disease group (DAS-28 score >3.2) and LDA/remission group (DAS-28 score ?3.2). RA was defined according to the 2010 ACR Diagnostic Criteria for Rheumatoid Arthritis. Disease severity of RA was determined according to DAS-28 score. Carpal tunnel syndrome (CTS) was diagnosed clinically by specific symptoms and clinical signs. Data were analysed using SPSS-25. Results: Mean age of the patients was 43.6±13.7 years, 102 (66.3%) were female. Mean disease duration was 8.3±6.1 years, and mean DAS-28 score was 4.3±2.1. RA factor was positive in 98 (63.7%) and Anti-CCP antibody in 79 (51.3%). CTS was present in 49 (31.8%) patients. On stratification, CTS was seen in 32 (41.5%) patients with active disease compared with 17 (22.1%) patients with LDA/remission. No statistical association of CTS was seen with age, gender, disease duration, RA factor positivity, Anti-CCP antibody positivity and disease severity. Conclusion: Carpal Tunnel Syndrome was seen in about one-third patients with RA but no statistically significant association was seen with age, gender, disease duration, RA factor or Anti-CCP positivity and disease activity. Pak J Physiol 2023;19(4):32–5

Lipid profile and NT-proBNP changes from pre-clinical to established rheumatoid arthritis: A 12 years follow-up explorative study

ObjectivesThe aim of the current study was to explore the changes in lipid and NT-proBNP levels in rheumatoid arthritis (RA) patients through different phases of the disease: from the pre-clinical stage and RA onset up to the treatment phase with biological disease-modifying anti-rheumatic drugs (bDMARDS). MethodsThirty-eight consecutive patients, initially with arthralgia and rheumatoid factor and/or anti-citrullinated protein antibodies without arthritis, who later developed RA and eventually started treatment with bDMARDs, were included. Lipid spectrum and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were measured longitudinally from several months before diagnosis through treatment with bDMARDs. ResultsFrom baseline, C-reactive protein (CPR) initially increased sharply, decreasing with the start of biological treatment. Low-density lipoprotein-cholesterol (LDL-c) remained stable, high-density lipoprotein-cholesterol (HDL-c) increased, apolipoprotein A1 (ApoA1 and lipoprotein (a) (Lp(a)), and total cholesterol (TC)/HDL-c ratio and apolipoprotein B (ApoB) decreased during follow-up. NT-proBNP closely followed progression of CRP. TC, LDL-c, TC/HDL-c ratio, ApoA and ApoB inverse correlated with CRP, while Lp(a) positively correlated. HDL-c and triglycerides showed no correlation. ConclusionChanges in the lipid profile and NT-proBNP in RA patients seem to be related to inflammation, with changes reflecting an increase in CVD risk occurring along with rises in CRP levels. These changes seem to already be present at diagnosis, indicating the need for timely control of inflammation.

The use of hepcidin as a marker for diagnosing the type of anemia in patients with high activity of rheumatoid arthritis

Anemia is still one of the most common comorbidities that affects the prognosis of the underlying disease and the quality of life of patients.Objective: to evaluate the value of serum hepcidin level determination for the differential diagnosis of anemia of chronic disease/inflammation (ACD) in patients with active rheumatoid arthritis (RA).Material and methods. The study included 47 patients with RA with anemia consecutively admitted to V.A. Nasonova Research Institute of Rheumatology for inpatient treatment. According to WHO recommendations, the criterion for anemia was a decrease in hemoglobin level ˂ 120 g/l in women and ˂ 130 g/l in men. The control group consisted of 29 patients without anemia. In all patients, the DAS28 index was determined, and clinical and biochemical blood parameters were examined: serum iron, total iron-binding capacity of serum, hepcidin, cytokines, including interleukin (IL) 6 and tumor necrosis factor α (TNFα).Results and discussion. Of 47 patients with active RA and anemia, only 13 (28%) were diagnosed with isolated ACD. Iron deficiency anemia (IDA) was found in 17 (36%), the remaining 17 patients had a mixed genesis of anemia (ACD + IDA). Patients with isolated ACD had a statistically significant higher level of hepcidin(120.3±56.1 pg/ml) compared to the control group (90.3±37.9 pg/ml) and to patients with RA + IDA. In isolated ACD, the levels of IL6, TNFα, rheumatoid factor and antibodies to cyclic citrullinated peptide were 2 times higher (p<0.05) than in RA with iron deficiency (both in IDA and in mixed genesis of anemia). Only in isolated ACD did the hepcidin level correlate with the IL6 concentrations (r=0.8); no such correlation was found in patients with IDA and anemia of mixed origin or in patients without anemia. No correlation with TNFα levels was found in any subgroup. Conclusion. Hepcidin levels are an informative indicator for the differential diagnosis of the type of anemia during active inflammation. In RA patients with ACD, the maximum hepcidin concentration in blood serum was determined, and in IDA it was found to be lower than the reference values. The importance of the hepcidin – IL6 axis and the lack of influence of the proinflammatory cytokine TNFα on iron metabolism were demonstrated. Keywords: hepcidin; anemia; difficult-to-treat patient; rheumatoid arthritis> ˂ 0.05) than in RA with iron deficiency (both in IDA and in mixed genesis of anemia). Only in isolated ACD did the hepcidin level correlate with the IL6 concentrations (r=0.8); no such correlation was found in patients with IDA and anemia of mixed origin or in patients without anemia. No correlation with TNFα levels was found in any subgroup.Conclusion. Hepcidin levels are an informative indicator for the differential diagnosis of the type of anemia during active inflammation. In RA patients with ACD, the maximum hepcidin concentration in blood serum was determined, and in IDA it was found to be lower than the reference values. The importance of the hepcidin – IL6 axis and the lack of influence of the proinflammatory cytokine TNFα on iron metabolism were demonstrated.