RF-positive Patients Research Articles

Association of RIPK1 and RIPK2 Gene Polymorphisms with Rheumatoid Arthritis in a Chinese Han Population.

Rheumatoid arthritis (RA) is a systemic autoimmune disease with an obscure pathogenesis. This study aims to identify the susceptibility conferred by specific single nucleotide polymorphisms (SNPs), namely rs17548629 within the RIPK1 gene and rs10094579 within the RIPK2 gene, in RA. Additionally, it investigates the associations between inflammatory markers and biochemical parameters at various stages of the disease. We analyzed 394 patients with RA and 258 normal controls (NCs), examining SNPs within the RIPK1 (rs17548629) and RIPK2 (rs10094579) genes using polymerase chain reaction (PCR) and sequencing techniques. Profiles of RA patients were evaluated for inflammatory markers, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), as well as biochemical parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, glucose, uric acid, and creatinine. Additionally, disease-specific indicators included cyclic citrullinated peptide (CCP), rheumatoid factor (RF), antinuclear antibodies (ANA), and anti-keratin antibodies. The Disease Activity Score 28 (DAS28), based on ESR, was used to categorize RA patients into groups of high, moderate, or low disease activity. We found a significant association between the RIPK1 rs17548629 genotype and RA in the additive model (p < 0.001; OR = 3.23), over-dominant model (p < 0.001; OR = 0.27), and dominant model (p < 0.001; OR = 3.94). The frequency of the C allele at rs17548629 was significantly higher in NCs than in RA patients (p < 0.001; OR = 0.322). When compared with normal controls, the RIPK1 rs17548629 genotype demonstrated significant associations with both anti-CCP-positive RA patients (p < 0.001) and anti-CCP-negative RA patients (p < 0.001). Similarly, this genotype was associated with RF-positive RA patients (p < 0.001). Furthermore, the RIPK2 rs10094579 genotype was significantly associated with CRP levels in RA patients with low disease activity in the over-dominant model (p = 0.029; OR = 0.065, adjusted for age and sex). The presence of the RIPK1 rs17548629 genotype is associated with RA under additive, co-dominant, and dominant models. The T allele mutation at rs17548629 increases the risk of RA in the Chinese population. The RIPK1 rs17548629 genotype was identified as being associated with RF-positive RA patients, whereas no significant association was observed in RF-negative individuals. These findings suggest that this SNP may modulate the risk of RA in an RF-dependent manner. Furthermore, the RIPK2 rs10094579 genotype correlates with CRP levels in RA patients exhibiting low disease activity. This association underscores the necessity for caution when reducing the dosage of therapy in RA patients with low disease activity who carry the CA genotype at RIPK2 rs10094579. Additional research is warranted to explore other genotypes that may influence RA susceptibility and to refine potential treatment strategies.

Clinical and laboratory pattern of patients with systemic lupus erythematosus seropositive for rheumatoid factor.

The aim of the study was to investigate the associations between the presence and level of rheumatoid factor (RF) in the blood serum and the clinical and laboratory characteristics of patients with systemic lupus erythematosus (SLE). This retrospective tricentric cross-sectional study analyzed a Ukrainian contingent of SLE patients. Medical records of 495 patients were evaluated. Rheumatoid factor serum concentration was tested in 206 of them (41.6%) using turbidimetry technique. Clinical manifestations, routine laboratory parameters, specific immunological tests, disease activity (SLEDAI-2K), and damage indices (SLICC/ACR DI) were evaluated. Our study revealed that RF was elevated in 27.7% of patients. The RF-positive patients experienced a longer delay in SLE diagnosis (2.0 vs. 0.5 years, p = 0.046), less frequent kidney involvement (42.1% vs. 59.4%, p = 0.045) and fever (42.1% vs. 59.2%, p = 0.046), and more frequent lymphadenopathy (59.6% vs. 42.3%, p = 0.039) compared to RF-negative patients. Patients with RF positivity had higher levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and antinuclear antibody (ANA) titer, and were more frequently positive for antibodies to Ro/SSA and La/SSB. Rheumatoid factor concentration directly correlated with CRP (r = 0.318; p < 0.01) and ESR (r = 0.228; p = 0.04) levels. However, no associations were found between RF levels and SLEDAI-2K, joint involvement frequency, SLICC/ACR DI or drug therapy content. Univariate logistic regression analysis showed that RF positivity was independently associated with lymphadenopathy, presence of anti-Ro/SSA and anti-La/SSB antibodies, and negatively associated with kidney involvement. In RF-seropositive SLE patients (approximately 28%), the diagnosis is established later compared to RF-seronegative ones; kidney involvement and fever are less common, while lymphadenopathy develops more frequently. Rheumatoid factor seropositivity is associated with higher levels of ESR, CRP, ANA, and the presence of antibodies to Ro/SSA and La/SSB. According to the results of univariate logistic regression analysis, an independent association with RF positivity was confirmed only for kidney involvement, lymphadenopathy, and antibodies to Ro/SSA and La/SSB.

Anti-carbamylated Protein Antibodies Positivity in Rheumatoid Arthritis and Its Association With Rheumatoid Factor and Anti-cyclic Citrullinated Protein Antibodies.

Background Rheumatoid arthritis (RA) is a widespread autoimmune disease affecting millions of people worldwide. The current markers include anti-cyclic citrullinated peptide (anti-CCP) antibodiesand rheumatoid factor (RF), which are nonspecific and elevated in variousconditions and do not have a prognostic value. They are also elevated in the later stages of the disease. Anti-carbamylated protein (anti-CarP) antibodies have been reported to be associated with joint damage in RA. Therefore, this study aimed to evaluate the sensitivity and specificity of anti-CarP antibodies in individuals with RA and their relationship with inflammatory markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Methods This was a cross-sectional case-control study conducted from April 2020 to March 2021 at the Saveetha Medical College, Chennai, India. The age makeup of the three groups was evaluated: Group 1 comprised anti-CCP and RF-positive patients; Group 2 comprised anti-CCP and RF-negative patients; and Group 3 was the control group, which comprised healthy volunteers. Patient samples, including blood and serum, have been utilized to conduct various assessments aimed at evaluating biomarkers such as CRP, ESR, RF, and autoantibodies like anti-CCP and anti-CarP. Results This study examined the role of various autoantibodies and biomarkers in RA across three distinct groups. Group 1 predominantly consisted of middle-aged individuals, and women constituted the majority in both Group 1 and Group 2, consistent with higher RA prevalence among females. In Group 1, 65.7% of patients tested positive for anti-CarP, while in Group 2, 48.6% tested positiveeven when RF and anti-CCP antibodies were absent. This suggests a potential diagnostic role for anti-CarP antibodies in identifying RA patients early. CRP and ESR levels were significantly elevated in RA patients (Groups 1 and 2) compared to healthy controls (Group 3), indicating higher inflammatory activity in affected individuals. We also observed that anti-CarPantibodies had a specificity of 69.1% and a sensitivity of 78.2%. Positive correlations between the diagnosis of RA and anti-CarP antibody positivity were observed across the groups and correlated well with the inflammatory markers and signs such as joint damage. The data were found to be statistically significant. Conclusions Our study showed a significant correlation between joint damage and CRP levels and a positive correlation between anti-CarP antibodies and ESR and CRP values. These findings suggest that anti-CarP antibodies can offer certain advantages over RF and anti-CCP antibodies in RA diagnosis due to their early detection potential, higher specificity, complementary diagnostic role, and predictive value for disease severity.

The first involved joints and associated factors in patients with rheumatoid arthritis.

This study aimed to investigate the first involved joints and associated factors in Turkish patients with rheumatoid arthritis (RA). This retrospective cross-sectional study included 300 newly diagnosed and disease-modifying antirheumatic drug-naïve RA patients (240 females, 60 males; mean age: 54±1.2 years; range, 18 to 82 years). Baseline demographic, clinical, and laboratory data were evaluated between January 2022 and December 2022. The patients were divided into four groups according to autoantibody profile: antibody-negative patients (Group 1; both RF and anti-CCP were negative in this group of patients), RF-positive patients (Group 2), anti-CCP-positive patients (Group 3), and patients with dual seropositivity with RF and antiCCP (Group 4). The patients were also divided into two groups according to the size of the first affected joint: patients with SJI at diagnosis and patients without SJI involvement at diagnosis. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibody positivity rates were 40.3% and 35.6%, respectively. The mean lag time to diagnosis was 25±36 months. At the disease onset, 20% of patients did not have small joint involvement (SJI). Seronegative patients tended to be female (p=0.001), had longer lag time (p=0.001), and had lower levels of C-reactive protein (p=0.025), white blood count (p=0.005), and neutrophil/lymphocyte ratio (p=0.001) compared to the dual seropositive group. Patients presenting with SJI had a younger age (p=0.002), tended to be female (p=0.001), and had lower RF (p=0.034) and anti-CCP (p=0.031) positivity. Only age (p=0.005) and dual seronegativity (RF and anti-CCP; p=0.035) were the independent predictors of SJI in multivariate analysis. The decreasing age and seronegative status were defined as independent risk factors of SJI at the onset of RA. Population-based, prospective studies are needed for earlier diagnosis.

Classification of rheumatoid arthritis: is it time to revise the criteria?

Classification criteria have been developed for rheumatoid arthritis (RA) and other rheumatic diseases in order to gather a homogeneous patient population for clinical studies and facilitate the timely implementation of...

Clinical and serological characteristics of anti-Ro/SS-A and anti-La/SS-B negative primary Sjögren's syndrome: a comparative study.

This study aimed to describe the clinical spectrum of primary Sjögren's syndrome (pSS) patients with anti-Ro/SS-A and anti-La/SS-B negativity. From a single-center study population of consecutive SS patients fulfilling the 2016 ACR-EULAR classification criteria, those with triple seronegativity anti-Ro/SS-A (anti-Sjögren's-syndrome-related antigen A autoantibody), anti-La/SS-B (anti-Sjögren's-syndrome-related antigen B autoantibody), rheumatoid factor (RF) (-) and antinuclear antibody (ANA)(+)] or [anti-Ro/SS-A(-), anti-La/ SS-B(-), RF(+) and ANA(-)] and quad¬ruple seronegativity [anti-Ro/SS-A(-), anti-La/SS-B(-), RF(-) and ANA(-)] were identified retrospectively. Clinical, serological, and laboratory features were compared. A comparison between triple and quadruple seronegative pSS patients was also performed. We included 184 patients (168 women, 16 men) with a mean age at diagnosis of 50.1±13.1 years. The most common subjective presenting features at the time of the diagnosis were dry mouth (94.5%) and dry eye (91.3 %). ANA positivity was 57.0%, and RF positivity was 30.4%. Salivary gland enlargement, arthritis, Raynaud's phenomenon, vasculitis, interstitial lung disease (ILD), neurological involvement, primary biliary cholangitis (PBC), lymphopenia, and thrombocytopenia were observed in ANA+ and RF+ patients but not in seronegative patients (p<0.0001). Arthritis was observed most frequently in RF-positive patients and secondly in ANA-positive patients, whereas arthritis was not observed in seronegative patients (p<0.0001). Autoimmune thyroiditis was present in 65 patients (35.0%), 84.6% of these patients were ANA positive while 12.3% were ANA negative (p=0.0014), RF positivity was 30.7% while RF negativity was 6.15% (p=0.001), 23.0% were both ANA and RF positive while 12.3% were seronegative (p<0.002). Cryoglobulinemia, renal disease, and lymphoma were not observed in any of the patients. We confirm the strong influence of immunological markers on the phenotype of primary SS at diagnosis.

The impact of autoantibodies on the efficacy of biological disease-modifying anti-rheumatic drugs in rheumatoid arthritis: meta-analysis of randomized controlled trials.

To investigate the efficacy of bDMARDs in patients with RA with RF/ACPA compared with patients without these autoantibodies. Previous systematic literature reviews performed by EULAR RA management task forces were searched for qualifying RCTs. RCTs investigating the efficacy of bDMARDs and including both autoantibody-positive (≤80% of total population) and -negative RA patients were eligible. For trials comparing bDMARD+csDMARD vs csDMARD, relative risks (RR) comparing two groups (RF + vs RF-, ACPA+ vs ACPA-) were calculated for efficacy outcomes for each arm. Subsequently, relative risk ratios (RRRs) were computed, as the ratio of RR of the bDMARD-arm and the RR from the non-bDMARD-arm. Pooled effects were obtained with random effect meta-analyses. Data from 28 eligible RCTs were analyzed, pooling 23 studies in three subgroups: 6 including csDMARD-naïve patients, 14 csDMARD-IR, and 3 TNFi-IR patients. In csDMARD-naïve and csDMARD-IR patients, seropositivity was not associated with a better response to bDMARDs: pooled 6-month ACR20 RRRs 1.02 (0.88-1.18) and 1.09 (0.90-1.32), respectively. Other outcomes showed no difference between groups either. In TNFi-IR patients, based on 3 trials, the 6-month ACR20 RRR was 2.28 (1.31-3.95), favoring efficacy in seropositive patients. Other outcomes mostly showed no significant difference between the groups. Based on the mode of action, efficacy was comparable between RF-positive and RF-negative patients for both TNFi and non-TNFi treatment and also for the individual bDMARDs. The effect of bDMARDs is generally comparable in patients with and without RF/ACPA, regardless of the patient population, the mechanism of action or individual drug used.

Heterophilic Interference of Rheumatoid Factor in TSH Immunometric Assay: A Cross-Sectional Observational Study.

Considering the inherent vulnerability of immunoassays for heterophilic interference and the potential of Rheumatoid Factor (RF) to act as a heterophile-like antibody, we conducted this study to investigate if RF leads to any such heterophilic interference in seropositive rheumatoid arthritis (RA) patients. The study was done on the TSH assay as it is a noncompetitive, double antibody sandwich assay, which is known to be vulnerable to heterophilic interference. In this cross-sectional observational study, eighty-four consecutive newly diagnosed RF-positive RA patients underwent TSH, Free T4, and anti-TPO estimation using the chemiluminescence technique (CLIA) on Siemens Immulite 1000 platform. The samples were screened for TSH interference using four methods: 1) analysis on a different platform, 2) assessment of linearity using doubling dilutions, 3) polyethylene glycol (PEG) precipitation, and 4) addition of a commercial blocker. Ten samples had a loss of linearity on serial dilution, indicating potential interference. After heterophile blocker treatment, five cases exhibited interference. One patient had diagnostic interpretation discordance on the second platform. No sample on PEG precipitation suggested the influence of antibodies. It is worth noting that even in cases where interference was suspected, the clinical interpretation was largely unaffected by the correction of TSH values based on mean dilution or measurement after heterophile blocker treatment. RF can cause heterophilic interference in TSH immunoassays used commercially. However, in most cases, this interference does not affect clinical decision-making.

Molecular B-cell clonality assay in minor salivary glands as a useful tool for the lymphoma risk assessment in Sjögren's syndrome

ObjectivesNon-Hodgkin's lymphoma (NHL) risk assessment is crucial in Sjögren's syndrome (SS). We studied the prevalence of clonal immunoglobulin gene rearrangements in minor salivary glands (MSG) and their correlations with lymphoma occurrence and with previously established NHL predictors. MethodsMolecular B-cell expansion was studied in fresh-frozen MSG of 207 patients with either suspected SS or with suspected lymphoma during SS, using a standardised multiplex PCR assay combined with heteroduplex analysis by microcapillary electrophoresis. The assignation of clonal cases was based on EuroClonality consortium guidelines. ResultsAmong 207 studied patients, 31 (15%) had MSG monoclonal B-cell infiltration. Monoclonality was significantly more frequent in patients with SS (28/123, 22.8%) compared with patients without SS (3/84, 3.6%, P<0.001). Monoclonal B-cell infiltration in MSG of SS patients correlated significantly with ongoing salivary gland NHL, salivary gland swelling, CD4+ T-cell lymphopenia, rheumatoid factor (RF) activity, low complement levels and type 2 mixed cryoglobulinemia. The accumulation of biological risk factors was associated with a higher rate of MSG B-cell monoclonality given that patients with only positive RF had no probability of MSG B-cell monoclonality, RF-positive patients with 1 or 2 other risk factors had a 25.0% and 85.7% probability of MSG B-cell monoclonality, respectively. ConclusionThe detection of MSG monoclonal B-cell expansion by this easy-to-perform molecular assay is useful, both at the time of diagnosis and during the course of SS. Monoclonal B-cell expansion is associated with a subset of SS patients presenting either ongoing lymphoma or other established lymphoma predictive factors.

How common is remission in rheumatoid factor-positive juvenile idiopathic arthritis patients? The multicenter Pediatric Rheumatology Academy (PeRA) research group experience

ObjectiveRheumatoid factor (RF)-positive polyarthritis is the least common type of juvenile idiopathic arthritis (JIA). Functional disability in RF-positive polyarthritis patients is much more severe than in patients with other subtypes; but data on this subtype alone is limited. This study aimed to analyze clinical features, long-term follow-up, treatment response, and remission status in a large multicenter cohort of RF-positive polyarthritis patients.MethodsThis retrospective study included RF-positive polyarthritis patients that were followed up for ≥ 6 months between 2017 and 2022 by the Pediatric Rheumatology Academy (PeRA)-Research Group (RG). Data on patient demographics, clinical and laboratory characteristics were obtained from medical charts. JIA treatments and duration of treatment were also recorded. The patients were divided into 2 groups based on methotrexate (MTX) response, as follows: group 1: MTX responsive, group 2: MTX unresponsive. Clinical and laboratory findings were compared between the 2 groups.ResultsThe study included 56 (45 female and 11 male) patients. The median age at onset of RF-positive polyarthritis was 13.2 years [(interquartile range) (IQR): 9.0–15.0 years] and the median duration of follow-up was 41.5 months (IQR: 19.5–75.7 months). Symmetrical arthritis affecting the metacarpophalangeal and proximal interphalangeal joints of the hands was commonly observed. Subcutaneous MTX was the preferred initial treatment; however, it was ineffective in 39 (69.6%) of the patients. Of 25 patients followed for 24 months, 56% still had active disease at 24 months.ConclusionDuring 2 years of treatment, 44% of RF-positive polyarthritis patients have inactive disease, and they should be considered as a distinct and important clinical entity requiring aggressive and early treatment.

Elevated serum soluble CD27 levels are associated with both disease activity and humoral immune activity in patients with rheumatoid arthritis.

To investigate the serum level of soluble CD27 (sCD27) and its potential clinical significance in rheumatoid arthritis (RA). Serum sCD27 levels in RA patients, idiopathic inflammatory myopathy (IIM) patients, systemic lupus erythematosus (SLE) patients and healthy controls (HCs) were detected by enzyme-linked immunosorbent assay. The medical information and laboratory data of the patients were collected. Serum sCD27 levels in RA patients with different clinical features were analysed, as was the correlation between the clinical data and serum sCD27 levels. Independent samples t test, the Mann-Whitney U-test or Wilcoxon signed-rank test, and Spearman correlation were used for statistical analysis. Levels of sCD27 were elevated in RA patients (3898 [2525, 5834] pg/mL) compared with IIM patients (2467 [1939, 3324] pg/mL) or HCs (1659 ± 648 pg/mL) (p 0.001). In addition, serum sCD27 levels correlated with age, erythrocyte sedimentation rate, C-reactive protein (CRP), rheumatoid factor (RF), immunoglobulin A, immunoglobulin G, complement 4 and disease activity score in 28 joints in RA patients. Levels of sCD27 were higher in RF-positive RA patients (6054 ± 5842 pg/mL) than in RF-negative patients (3902 ± 2098 pg/mL), and a similar finding was also observed in anti-cyclic citrullinated peptide (anti-CCP) antibody-positive (5810 ± 5671 pg/mL) and anti-CCP-negative (4183 ± 2187 pg/mL) RA patients. Serum ESR, RF, IgA, IgG levels and DAS28-CRP were elevated in RA patients with higher sCD27 levels than in those with lower sCD27 levels (p<0.01). Serum sCD27 might be a promising biomarker that reflects both disease activity and humoral immunity activity in RA.

The assessment of rheumatoid factor levels and hemogram parameters as predictors for rheumatologic disease.

Many markers are used for clinical diagnosis in rheumatic diseases; rheumatoid factor (RF) is the most frequently used marker. However, RF is not specific to rheumatoid arthritis (RA). RF positivity is widely observed in patients with advanced age, infectious, autoimmune, and lymphoproliferative diseases. In this context, the objective of this study is to investigate the demographic characteristics, frequency of antinuclear antibody (ANA) and anti-cyclic citrullinated peptide (anti-CCP) positivity, hemogram parameters and distribution of the diagnoses in RF-positive patients followed at the rheumatology clinic. The population of this retrospective study consisted of patients above 18 years of age who were referred to have RF positivity by nephelometric method at Kahramanmaraş Necip Fazıl City Hospital Rheumatology Clinic between January 2020 and June 2022. The mean age of the 230 patients with a positive RF test result, 155 (76%) male and 55 (24%) female, was 52.7 ± 15.5 years. There were 81 (35.2%), 54 (23.5%), 73 (31.7%) and 22 (9.6%) patients with RF levels between 20 and 50 IU/mL, 50 and 100 IU/mL, 100 and 500 IU/mL, and above 500 IU/mL, respectively. There was no significant difference detected between the groups that were created based on the RF titers regarding demographic characteristics (P > 0.05). The rate of being diagnosed with any rheumatic disease was significantly lower in the group with RF levels between 20 and 50 IU/mL compared to other groups (P = 0.001). The distribution of rheumatic and non-rheumatic disease diagnoses according to RF levels did not reveal any significant difference between the groups (P = 0.369 and P = 0.147, respectively). RA was the most common (62.2%) rheumatic disease diagnosis among the patients included in the study. The leukocyte count was significantly higher in the group with RF levels above 500 IU/mL compared to the group with RF levels between 20 and 50 IU/mL (P = 0.024). There was no significant difference between the groups in other laboratory results, that is, hemogram, sedimentation, C-reactive protein, platelet, and lymphocyte/monocyte ratio (P > 0.05). The study findings indicate that RF positivity can be seen in the context of different rheumatological diseases; hence RF levels alone may not predict rheumatological disease. There was also no significant relationship between RF levels and ANA and anti-CCP positivity. The most common diagnosis in patients presenting with elevated RF levels was RA. Nevertheless, it should be noted that RF can be found asymptomatically in the general population.

Rheumatoid factor is associated with severe COVID-19.

Coronavirus disease 2019 (COVID-19) has been proposed as triggering autoimmunity. The aim of this study was to evaluate the presence and clinical significance of autoantibodies in patients with COVID-19. We retrospectively collected data from 245 patients who were hospitalized for COVID-19. All patients were tested for the presence of antinuclear antibody (ANA), rheumatoid factor (RF), anti-citrullinated peptide antibody (ACPA), and anti-cytoplasmic neutrophil antibody (ANCA). Risk factors for death and critical COVID-19, defined as the need for invasive mechanical ventilation or extracorporeal membrane oxygenation, were analyzed. Ninety (36.7%) patients tested positive for ANA, and 51 (20.8%) patients tested positive for RF. Three patients each (1.2%) tested positive for ACPA and ANCA. RF-positive patients had higher rates of invasive mechanical ventilation and death than RF-negative patients (70.6% vs 28.4%, P < 0.001 and 45.1% vs 18.6%, P < 0.001, respectively). Underlying lung disease, kidney disease, heart disease, quick COVID severity index (qCSI), and lactate dehydrogenase (LDH) were associated with in-hospital death. RF (odds ratio [OR] 7.31, 95% CI 2.50-21.37, P < 0.001), qCSI (OR 1.42, 95% CI 1.19-1.69, P < 0.001), and LDH (OR 1.004, 95% CI 1.002-1.005, P < 0.001) were associated with critical COVID-19. Combination of RF, qCSI, and LDH showed good prognostic value (area under the curve=0.903, P < 0.001) for critical COVID-19. ANA and RF were frequently detected in COVID-19 patients. RF could be a risk factor for critical COVID-19. The results of this study suggest immune dysfunction contributes to the complications of COVID-19.

VEGF Profile in Early Undifferentiated Arthritis Cohort.

Background and Objectives: Early undifferentiated arthritis (UA) is a group of inflammatory joint diseases that are not classified under any specific rheumatic or connective tissue disorder and might evolve into chronic inflammatory arthritis or may be a self-limiting condition. Early recognition and treatment are crucial for the future course of the disease. Vascular endothelial growth factor (VEGF) is an angiogenic regulator that induces the growth of new capillary blood vessels, which are important in joint invasion and destruction during the progression of chronic inflammatory arthritis. The aim of this study was to assess VEGF levels associated with sociodemographic, clinical, laboratory, and ultrasound findings in the early UA patient cohort as well as to evaluate VEGF as a potential prognostic marker for arthritis outcomes. Materials and Methods: Seventy-six patients with inflammatory arthritis in at least one joint, with a duration of arthritis <12 months at the study entry that did not meet any rheumatic disease classification criteria, were enrolled after informed consent was obtained. Patient’s sociodemographic, laboratory data, and clinical disease characteristics were recorded, VEGF levels were measured, and ultrasound (US) of tender and swollen joints was performed. Results: VEGF levels had positive correlation with conventional rheumatic disease activity and diagnostic markers: erythrocyte sedimentation rate (ESR), C–reactive protein (CRP), and rheumatoid factor (RF) (p < 0.05). RF-positive patients had higher VEGF values (p = 0.024). A statistically higher number of patients whose VEGF levels were below the median value presented with active infection (p = 0.046). In patients with a higher number of swollen joints, and a higher score of synovitis and power doppler (PD) seen on US, VEGF levels were statistically significantly higher. Patients who after 12-month follow-up developed rheumatoid arthritis (RA) had statistically higher VEGF levels at baseline compared with those who developed spondyloarthropathies (p = 0.028). Conclusions: This study demonstrated that VEGF levels significantly represented inflammatory processes that were present in the joints (number of swollen joints, synovitis, and PD changes) of the early UA cohort.

Syndecan-4 is correlated with disease activity and serological characteristic of rheumatoid arthritis

ObjectivesTo describe the feature of expression of syndecan-4 in serum, synovial fluid (SF) and synovium in rheumatoid arthritis (RA) patients, and to analyze the correlation of syndecan-4 with disease activity and serological characteristic of RA.MethodsSyndecan-4 in sera of 60 RA patients, 20 osteoarthritis (OA) patients, 20 healthy controls, and in SF of 25 RA patients and 25 OA patients were tested by enzyme linked immunosorbant assay. The expressions of syndecan-4 in synovium of RA and OA patients were detected by immunohistochemistry. The expression of syndecan-4 on synovial fibroblasts from RA and OA patients were detected by immunofluorescence. The correlation between serum syndecan-4 concentration and disease activity were analyzed in RA patients.ResultsThe serum syndedcan-4 concentration was significantly higher in RA patients than in OA patients and healthy controls, and was higher in rheumatoid factor (RF)-positive RA patients than in RF-negative ones. Syndecan-4 concentration in SF of RA patients was comparable with OA patients. Syndecan-4 expression in synovial tissue was similar between RA and OA patients. The syndecan-4 concentration was significantly lower in SF than in serum of RA and OA patients. Syndecan-4 concentration in both serum and SF was positively correlated with disease activity of RA patients.ConclusionThe serum syndecan-4 concentration was higher in RA patients than in OA patients, and significantly higher in RF-positive RA patients than in RF-negative ones. Syndecan-4 concentration in both serum and SF was positively correlated with disease activity of RA patients.

C-reactive protein as a disease activity marker in rheumatoid arthritis

Introduction: CRP is a valuable marker and regulator of systemic inflammation in RA that also appears to play a direct role in bone destruction and radiographic progression. CRP has also been implicated in the etiology of common comorbidities associated with RA. Decreasing CRP levels with RA treatment may contribute to reductions in disease activity, although beneficial effects of RA treatment seem to occur irrespective of CRP values. Aim: The purpose of this study was to examine whether levels of C-reactive protein (CRP), a sensitive marker of disease activity in rheumatoid arthritis (RA). Materials &amp; methods: This study was carried out on 39 RF Positive patients from both sexes male and female from different age group at NIMS Super-Specialty Hospital, Sobha Nagar, Jaipur, Rajasthan. Inflammatory markers were performed in the laboratory. Results: In the current study, the majority of Rheumatoid Arthritis patients belong to the age group of 41 to 60 (58.97%) and male to female ration were 1:2. C - reactive protein found highly significant positive correlation. Out of total Rheumatoid Arthritis patients, 7.69% patients have normal C - reactive protein level and 92.30% have highly increased CRP level. T

Rheumatoid Factor, Anti-cyclic Citrullinated Peptide and HLA-B Locus Antigens in Psoriatic Arthritis Patients in Bangladesh

Introduction: Psoriatic arthritis (PsA) is established as a multifactorial disease resulting from a complex interplay between genetic, environmental and immunological factors. It is a seronegative arthritis but rheumatoid factor may be present in up to 15% of PsA patients Antibodies recognizing a cyclic citrullinated peptide are highly speciûc for rheumatoid arthritis (RA) but their role in PsA remains unclear. An increased prevalence of anti-CCP antibody in PsA is also reported. Study shows that HLA-DRB1 shared epitope is signiûcantly associated with the presence of anti-CCP antibody in PsA patients but this type of association is not found with other human leukocyte antigens. Objectives: The aim of this study was to investigate the frequency of anti-CCP and RF in PsA patients and their associations with HLA-B locus antigens. Methods: In this cross sectional study, we selected 50 unrelated consecutive patients with PsA according to CASPAR criteria for PsA. 6 ml of blood was collected from each patient for HLAB locus typing, RA test and test for anti-CCP. Patient’s serum samples were tested for RF by Nephelometric system and tests for anti-CCP were done by ELISA. HLA-B locus typing was done by PCR with sequence specific primer. Results: Among 50 PsA patients, 27 (54%) are female and 23 (46%) are male. RA test is positive in 10 (20%) patients and anti-CCP is positive in 7 (14%) patients. Significant association was found between HLA-B*37 and RF (p value= &lt; 0.001). Conclusion: RF is present in 10 (20%) and anti-CCP is present in 7 (14%) PsA patients. HLAB* 37 was significantly found in RF positive patients. J Shaheed Suhrawardy Med Coll 2020; 12(2): 109-114

IgA rheumatoid factor is associated with bone mineral density preservation in rheumatoid arthritis

Autoantibodies such as IgM rheumatoid factor (RF) and anti-citrullinated proteins/peptides antibodies (ACPA) have previously been incriminated in systemic bone loss in rheumatoid arthritis (RA). There are, however, no data describing association of IgA RF and IgG RF with systemic bone loss. This study was aimed to investigate the association of RF isotypes with systemic bone loss among patients with RA. RF isotypes and ACPA were measured by enzyme-linked immunosorbent assay among 153 patients with RA. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry. Ninety-four (61.4%) patients had positive IgA RF, 89 (58.2%) had positive IgG RF, 109 (71.2%) had positive IgM RF, whereas 122 (80.3%) RA patients tested positive for ACPA. Compared to the IgA RF-negative patients, IgA RF-positive patients exhibited higher disease activity and had higher RF titers. Seven (4.6%) patients had low BMD at femoral neck, 12 (7.8%) at total femur, and 47 (30.7%) at lumbar spine. IgA RF was found to be associated with protection against low BMD at spine (OR = 0.47, 95% CI = 0.23-0.95, p = 0.034). This association was further confirmed in the multivariate regression analysis taking into account several potential confounding factors(OR = 0.21, 95% CI = 0.06-0.65, p = 0.039). No association between low BMD and the presence of IgG RF or IgM RF or ACPA was found. IgA RF for the first time ever was shown to be associated with BMD preservation at spine in RA. Key points • IgA RF was associated with protection against low spinal BMD. • No association between low BMD and the presence of IgG RF or IgM RF was found.

Rheumatoid factor and falsely elevated results in commercial immunoassays: data from an early arthritis cohort

The aim of the study was to assess RF cross-reactivity to animal antibodies used in immunoassays, and to test if selected commercial immunoassays are vulnerable to interference from RF, causing false test results. Our study included samples from patients with RF-positive rheumatoid arthritis (RA) and controls (patients with RF-negative RA and psoriatic arthritis), included in an early arthritis-cohort. Reactivity to mouse IgG1, mouse IgG2a, rabbit IgG, bovine IgG, sheep/goat IgG and human IgG was analysed using in-house interference assays. RF-positive sera with strong reactivity to mouse IgG1 were analysed in three commercial immunoassays. To reveal interference, results before and after addition of blocking aggregated murine IgG1 were compared. Samples from 124 RF-positive RA patients and 66 controls were tested. We found considerably stronger reactivity toward animal antibodies, particularly mouse IgG1 (73% vs. 12%) and rabbit IgG (81% vs. 6%), in sera from RF-positive RA-patients compared to controls (p < 0.001). After selecting samples for testing in commercial assays, interference was revealed in 6/30 sera in the Architect β-hCG assay, 7/10 sera in the 27-plex cytokine assays, and in 2/33 samples in the Elecsys Soluble Transferrin Receptor assay. Our study revealed considerable RF reactivity to animal antibodies used in immunoassays and RF was associated with falsely elevated results in immunoassays used in clinical care and research. Clinicians, laboratorians, researchers and assay manufacturers must be alert to the risk of falsely elevated test results in RF-positive RA patients.

14-3-3η Protein as a Potential Biomarker in Juvenile Idiopathic Arthritis.

The 14-3-3η (eta) protein was evaluated as a biomarker in a cohort of patients with juvenile idiopathic arthritis (JIA), as well as disease- and healthy-controls, to determine its potential clinical utility. In this case-control study, levels of 14-3-3η protein were evaluated in archival specimens from patients with JIA, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA), as well as healthy pediatric controls. Just over 200 patients were evaluated, using specimens banked between 1990 and 2011. Comparisons were made to complete blood cell count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, and anti-nuclear antibody (ANA) positivity. 14-3-3η at levels 0.2 ng/mL or higher was considered positive. Fisher’s exact tests, odds ratios, 95% confidence intervals, and p-values were reported. 14-3-3η positivity was seen in all included JIA subtypes. The rate of positivity was the highest in RF-positive (pos) polyarticular JIA. In the disease and healthy controls, lower rates of positivity were observed. The frequency of 14-3-3η positivity among RF-positive and RF-negative (neg) polyarticular JIA patients, especially at values ≥0.5 ng/mL (associated with poor outcomes in adults), was also highest. Several JIA patients with 14-3-3η positivity developed RF and anti-CCP positivity later in their disease. Significant levels of 14-3-3η can be found in approximately 30% of RF-pos and RF-neg patients with polyarticular JIA. This protein may represent a new biomarker for polyarticular JIA, particularly RF-neg polyarticular JIA.