Anti-cyclic Citrullinated Peptide Antibodies Research Articles

Rapid Microfluidic Biosensor for Point-of-Care Determination of Rheumatoid Arthritis via Anti-Cyclic Citrullinated Peptide Antibody Detection

Rheumatoid arthritis (RA) is a chronic autoimmune disorder that causes extensive damage to multiple organs and tissues and has no known cure. This study introduces a microfluidic detection platform that combines a microfluidic reaction chip with a micro-spectrometer to accurately detect the anti-cyclic citrullinated peptide antibody (anti-CCP Ab) biomarker, commonly associated with arthritis. The surface of the microfluidic reaction chip is functionalized using streptavidin to enable the subsequent immobilization of biotinylated-labeled cyclic citrullinated peptide (biotin–CCP) molecules through a streptavidin–biotin reaction. The modified chip is then exposed to anti-CCP Ab, second antibody conjugated with horseradish peroxidase (HRP) (2nd Ab-HRP), 3,3′,5,5′-tetramethylbenzidine (TMB), and a stop solution. Finally, the concentration of the anti-CCP Ab biomarker is determined by analyzing the optical density (OD) of the colorimetric reaction product at 450 nm using a micro-spectrometer. The detection platform demonstrated a strong correlation (R2 = 0.9966) between OD and anti-CCP Ab concentration. This was based on seven control samples with anti-CCP Ab concentrations ranging from 0.625 to 100 ng/mL. Moreover, for 30 artificial serum samples with unknown anti-CCP Ab concentrations, the biosensor achieves a correlation coefficient of (R2 = 0.9650). The proposed microfluidic detection platform offers a fast and effective method for accurately identifying and quantifying the anti-CCP Ab biomarker. Thus, it offers a valuable tool for the early diagnosis and monitoring of RA and its progression in point-of-care settings.

Evaluation of the clinical performance of anti-mutated citrullinated vimentin antibody and 14-3-3 eta testing in rheumatoid arthritis.

Early rheumatoid arthritis (RA) detection is crucial for improving patient prognosis. Anticyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factors (RF) support RA diagnosis but are undetectable in ∼20 % of cases. Recently, antibodies against mutated citrullinated vimentin (anti-MCV) and detection of 14-3-3 eta have emerged with implications for preclinical RA diagnosis and monitoring treatment. The objective of this study was to assess the clinical performance of anti-MCV antibodies and 14-3-3 eta in RA and to compare it to current RA criteria anti-CCP and RF markers, individually and in combination. A retrospective chart review of 326 subjects submitted for RA serology testing identified 134 RA positive and 192 RA negative disease control individuals. Fifty healthy controls specimens were also included. Performance of anti-MCV and 14-3-3 eta, alone and combined with CCP3.1 and RF, was assessed. Anti-MCV had a sensitivity of 71 % and a specificity of 92 %. 14-3-3 eta had a sensitivity of 43 % and a specificity of 90 %. In comparison, CCP3.1 and RF displayed a sensitivity of 79 % and 84 % and a specificity of 92 % and 61 %, respectively. ROC curve analysis demonstrated CCP3.1 and anti-MCV had superior diagnostic performance compared to RF and 14-3-3 eta. In our cohort, anti-MCV and 14-3-3 eta failed to identify seronegative RA patients. Different combinations of double antibody positivity increased specificity at the cost of lost sensitivity. Individually, 14-3-3 eta, anti-MCV and CCP3.1 assays had≥90 % specificity in diagnosed RA patients, with better sensitivities for anti-MCV and CCP3.1 than 14-3-3 eta. Overall diagnostic performance of anti-MCV was similar to CCP3.1 and RF, all of which outperformed 14-3-3 eta in our cohort.

Pathogenic Mechanisms of Collagen TypeⅦA1 (COL7A1) and Transporter Protein Transport and Golgi Organization 1 (TANGO1) in Rheumatoid Arthritis: A New Therapeutic Target

Rheumatoid arthritis (RA) is an autoimmune disorder causing chronic inflammation primarily due to collagen regulation and transport imbalances. Collagen VII A1(COL7A1), a major component of anchoring fibrils, regulates inflammation via interacting with its transporter protein Transport and Golgi organization 2 homologs (TANGO1). The study revealed a significant increase in COL7A1 levels in both the plasma and PBMCs of RA patients. Additionally, a positive correlation between COL7A1 and ACCPA (anti-cyclic citrullinated peptide antibody) levels was observed among RA patients. TANGO1 mRNA expression was also found to be elevated in PBMCs. The knockdown of COL7A1 in RA synoviocytes using siRNA affected the expression of TANGO1 and inflammatory genes. Western blot analysis showed that COL7A1 si-RNA in TNF-α-induced SW982 cells reduced the expression of COL7A1, TANGO1, and NF-kBp65. The mRNA expression of inflammatory genes TNF-α, NF-kB p65, and IL-6 simultaneously decreased after the knockdown of COL7A1, as measured by qRT-PCR. An in silico analysis found 20 common interacting proteins of COL7A1 and TANGO1, with pathway enrichment analysis linking them to antigen presentation, class I and II MHC, and adaptive immunity pathways in RA. Among the common proteins, The DisGeNET database depicted that COL1A1, MIA3, SERPINH1, and GORASP1 are directly linked to RA. The molecular docking analysis of COL7A1 and TANGO1 revealed strong interaction with a −1013.4 energy-weighted score. Common RA-used drugs such as Adalimumab, Golimumab, and Infliximab were found to inhibit the interaction between COL7A1 and TANGO1, which can further impede the transport of COL7A1 from ER exit sites, indicating COL7A1 and TANGO1 as potential therapeutic targets to diminish RA progression.

Anti TNF-Alpha Treatment Improves Microvascular Endothelial Dysfunction in Rheumatoid Arthritis Patients.

Nailfold capillaroscopy is a non-invasive investigation, which allows for the study of the microvasculature (anatomical and functional). Rheumatoid arthritis (RA) is associated with a high risk of cardiovascular atherosclerotic diseases, with endothelial dysfunction (macrovascular and microvascular) representing the first step in atherosclerosis development. The aim of this study is represented by the assessment of microvascular endothelial dysfunction in RA patients by means of nailfold capillaroscopy and to assess its evolution after a period of 12 months of anti TNF-alpha treatment. The study included 70 consecutive patients with RA and 70 healthy subjects, matched for age and gender, as the control group. Rheumatoid factor, anti-cyclic citrullinated peptide antibodies, serum TNF-α, C reactive protein, and erythrocytes sedimentation rate were evaluated in all patients, but in controls, only rheumatoid factor, serum TNF-α, C reactive protein, and erythrocytes sedimentation rate were measured. The RA activity was measured by DAS28. Nailfold capillaroscopy was carried out in all patients and controls, determining the baseline nailfold capillary density (Db), nailfold capillary density during reactive hyperemia (Dh), and nailfold capillary density after venous congestion (Dc). Data were presented as mean ± standard deviation. Statistical analysis was performed using ANOVA and Pearson's correlation, with p < 0.05 being statistically significant. Db, Dh, and Dc were lower in RA patients than in controls (p < 0.0001), correlating with RA activity and TNF-α (p < 0.05). After 12 months of anti TNF-α treatment, microvascular endothelial dysfunction improved (p < 0.0001). Microvascular endothelial dysfunction can be assessed by nailfold capillaroscopy, with anti TNF-α medication contributing to its improvement.

Prevalence of Subclinical Peripheral Neuropathy in Patients With Autoimmune Connective Tissue Disorders: An Observational Cross-Sectional Study.

Background Autoimmune connective tissue disorders (AICTDs) are a group of chronic inflammatory diseases characterized by immune responses targeting the body's own tissues. Peripheral neuropathy, which can be symmetrical or asymmetrical, is a common complication in AICTD patients. Early detection of subclinical peripheral neuropathy remains challenging, as nerve conduction studies are not routinely performed. This study aimed to determine the prevalence of subclinical peripheral neuropathy among patients with AICTD and to assess its association with potential predictor variables, including laboratory parameters and autoimmune markers. Materials and methods This observational cross-sectional study included 100 patients undergoing treatment for AICTDs for over three years, conducted over 15 months. Ethical approval and informed consent were obtained before detecting subclinical peripheral neuropathy through nerve conduction studies on bilateral ulnar, radial, sural, peroneal, and tibial nerves at a tertiary-level medical college hospital. Inclusion criteria encompassed patients treated at the tertiary hospital, not on immunosuppressants other than steroids, with at least three years of treatment, while exclusions were made for established peripheral neuropathy and other specified conditions. Descriptive statistics, Chi-square/Fisher's exact tests, independent samples t-tests, and logistic regression were used for data analysis at a 0.05 significance level, with IBM SPSS Statistics for Windows, Version 20 (Released 2011; IBM Corp., Armonk, NY, USA). Results Subclinical peripheral neuropathy was present in 18% (n = 18) of the study participants, while 82% (n = 82) did not exhibit neuropathy. Patients with subclinical neuropathy had a significantly higher mean age (49.66 ± 4.77 years) compared to those without neuropathy (46.02 ± 12.7 years, p = 0.047). The majority of the study population was female, 79 (79%), and there was no significant gender difference between the groups (p = 0.513). There was no significant association between inflammatory markers (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)) and neuropathy. However, patients with subclinical neuropathy were more likely to test positive for rheumatoid factor (RF) (8 (66.7%) vs. 71 (58.5%), p = 0.011) and anti-cyclic citrullinated peptide (Anti-CCP) antibodies (11 (78.5%) vs. 32 (47%), p = 0.032). Steroid use did not significantly affect the presence of neuropathy (p = 0.769). Conclusion The study found a high prevalence of subclinical peripheral neuropathy in AICTD patients, detectable only by nerve conduction studies. RF and Anti-CCP antibodies were associated with subclinical neuropathy, suggesting these markers could guide early detection, and inform treatment intensification to reduce neuropathy prevalence among AICTD patients.

Estimation of interleukin-6 level and atherogenic indices as predictors of severity of rheumatoid arthritis in Iraqi patients

Background &amp; Objective: Rheumatoid Arthritis (RA) is an inflammatory illness that causes joint degeneration and inflammation of the synovial membrane, leading to significant disability over time. Interleukin-6 (IL-6) is a widely distributed pro-inflammatory cytokine that has a variety of roles in several pathophysiologic systems, most notably in the RA development. The purpose of this study was to assess the blood levels of IL-6 and the severity and activity of RA in patients, and to assess the association of atherogenic indices with IL-6 as a predictor of severity in RA disease. Methodology: This study was a case control observational study involving 300 participants diagnosed with RA by the rheumatologists in accordance with American College of Rheumatologists (ACR)/ European League Against Rheumatism (EULAR) 2010 criteria. Serum levels of IL-6, CRP, RF and ACPA were measured by using ELISA technique. While, lipid profile was determined with spectrophotometry. Receiver operating curve (ROC) was used to study the opportunity of using atherogenic indices and IL-6 as diagnostic tools for RA. Results: The results indicated a higher IL-6 level in RA patients in comparison to the control group, e.g., 28.55 (18.76-41.07) pg/mLvs 10.19 (6.11-12.50) pg/ml. High atherogenic index of plasma (AIP) risk &gt; 0.24 in RA patients parameters (GDF-15, IL-6), the lipid profile parameters and atherogenic indices (TC, TG, VLDL-C, LDL-C, CRI-I, CRI-II, AIP, and AC) were compared with moderate atherogenic risk (AIP &lt; 0.24) in RA patients. While a significant decrease was recorded in the HDL-C and BMI levels, it had significantly high atherogenic risk (AIP &gt; 0.24) compared with moderate atherogenic risk (AIP &lt; 0.24) in RA patients. The ROC results analysis showed that the top 5 highly sensitive predictors for RA, e.g., CRI-I, AC, AIP, CRI-II followed by IL-6, have a relatively good sensitivity and specificities for predictors for RA. Conclusion: Increase in interleukin-6 may indicate the activity and severity of the disease. This biomarker could be helpful for early disease detection. The results showed a higher IL-6 in RA patients as well as increased dyslipidemia and atherogenicity in RA patients. Elevation of serum IL-6 and atherogenic indices are the best predictors for RA patients with a higher risk of atherosclerosis than other biomarkers. There is an important correlation between atherogenic indices parameters and the immunological biomarkers IL-6 indicating a significant role of the inflammation in the incidence of atherogenic indices in RA. Abbreviations: AUC- Area Under Curve; ACPA - Anti Cyclic Citrullinated Peptide Antibodies; CRP- C-Reactive Protein; ESR- Erythrocyte Sedimentation Rate; RF- Rheumatoid Factor; BMI- Body Mass Index; GDF-15 -Growth Differentiation Factor-15; DAS28-CRP- Disease Activity Score-28-C-Reactive Protein; TC- Total Cholesterol; TG- Triglyceride; HDL-C -High Density Lipoprotein Cholesterol; LDL-C -Low Density Lipoprotein Cholesterol; VLDL-C-Very Low Density Lipoprotein Cholesterol; AC-Atherogenic Coefficient; AIP-Atherogenic Index of Plasma; CR-I, CR-II- Castelli’s Risk Indexes. Keywords: Rheumatoid Arthritis, Interleukin-6, Atherogenic Indices. Citation: Abdulridha GAO, Hussein MA, Majeed SR. Estimation of interleukin-6 level and atherogenic indices as predictors of severity of rheumatoid arthritis in Iraqi patients. Anaesth. pain intensive care 2024;28(4):700−705; DOI: 10.35975/apic.v28i4.2400. Received: February 26, 2024; Reviewed: April 16, 2024; Accepted: July 09, 2024

Immunological markers of rheumatoid arthritis in the Moroccan population

Aim: few studies exist on HLA-DRB1 alleles and their association with RA in North Africa. We aimed to provide an evaluation of the distribution of the HLA-DRB1* and -DQB1* genes in Moroccan patients with early RA. Additionally, we sought to analyze the relationship between HLA molecules and the production of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP) in these patients. Methods: 65 patients with rheumatoid arthritis benefited from HLA class II typing (DRB1* and DQB1*) and testing for anti-CCP and RF antibodies. The frequency of HLA alleles was compared to that of 180 healthy controls. Logistic regression analysis was used to investigate the association of HLA-DR and -DQ molecules in the different subgroups according to anti-CCP and RF status. Results: The frequency of HLA-DRB1*04 and *11 alleles is increased in patients compared to controls (OR = 1.9; 95% CI (1.06-3.30), P=0.029; OR=2, 95% CI (1-3.83, P=0.047, respectively). 56 patients (86.1%) were RF positive, and 67.7% were anti-CCP positive. A significant increase in the frequency of DRB1*04 alleles was also noted in seropositive patients. Conclusion: Our results suggest the predisposition of the HLA-DRB1*04 allele and the seropositive status of patients with RA. This could be useful in predicting the evolution of RA and establishing a diagnosis in some patients at an early stage of disease use.

Contribution of Musculoskeletal Ultrasound in the Diagnosis of Seronegative Rheumatoid Arthritis.

This is a study to investigate the value of musculoskeletal ultrasound for the early diagnosis of seronegative rheumatoid arthritis (SNRA); and to study the relationship between anti-cyclic citrullinated peptide antibody (anti-CCP) and the occurrence of bone erosion in rheumatoid arthritis (RA) detected by ultrasound. A total of 101 patients with RA or osteoarthritis (OA) admitted to the First Affiliated Hospital of Anhui Medical University from July 2022 to December 2023 were selected and divided into the SNRA group, the SPRA group, and the OA group. The patients' metacarpophalangeal joints, proximal interphalangeal joints, distal interphalangeal joints, and wrist joints of both hands were ultrasonically examined separately, and the extensor tendon, flexor tendon, synovium, joint surface, joint cavity, and bone surface were observed. The differences in the detection of joint effusion, bone erosion, and joint space narrowing were not statistically significant between SNRA group and OA group (P > .05), the differences in the detection of synovitis and tenosynovitis were statistically significant (P < .05). The mean levels of synovial hyperplasia grade and synovial blood flow grade between SNRA group and OA group were significantly different (P < .05). The differences in synovitis, tenosynovitis, joint effusion, and joint space narrowing were not statistically significant between SNRA and SPRA groups (P > .05), and the differences in bone erosion were statistically significant (P < .05). The mean levels of synovial hyperplasia grade and synovial blood flow grade between SNRA group and SPRA group were significantly different (P < .05). Logistic regression analysis showed that anti-CCP antibody was an influential factor for bone erosion in RA patients (P < .05). The ROC curve was plotted, and the optimal cut-off value of anti-CCP antibody was 356.5U/mL, at which time the AUC was 0.716, the sensitivity of diagnosing bone erosion was 0.714, the specificity was 0.694, and the Yoden index was 0.408. In summary, ultrasound is helpful for the early diagnosis of SNRA by evaluating the condition of joints, synovium, and tendon sheath, and when anti-CCP antibodies are positive, ultrasound is more likely to detect bone erosion. Ultrasound examination combined with anti-CCP antibody can further observe the joint lesions.

Upregulated miR-146b-3p predicted rheumatoid arthritis development and regulated TNF-α-induced excessive proliferation, motility, and inflammation in MH7A cells

BackgroundRheumatoid arthritis (RA) is a chronic immune system disease with a high disability rate threatening the living quality of patients. Identifying potential biomarkers for RA is of necessity to improve the prevention and management of RA.ObjectivesThis study focused on miR-146b-3p evaluating its clinical significance and revealing the underlying regulatory mechanisms.Materials and methodsA total of 107 RA patients were enrolled, and both serum and synovial tissues were collected. Another 78 osteoarthritis patients (OA, providing synovial tissues), and 72 healthy individuals (providing serum samples) were enrolled as the control group. The expression of miR-146b-3p was analyzed by PCR and analyzed with ROC and Pearson correlation analyses evaluating its significance in diagnosis and development prediction of RA patients. In vitro, MH7A cells were treated with TNF-α. The regulation of cell proliferation, motility, and inflammation by miR-146b-3p was assessed by CCK8, Transwell, and ELISA assays.ResultsSignificant upregulation of miR-146b-3p was observed in serum and synovial tissues of RA patients, which distinguished RA patients and were positively correlated with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-cyclic citrullinated peptide antibodies (anti-CCP), and rheumatoid factor (RF) of RA patients. TNF-α promoted the proliferation and motility of MH7A cells and induced significant inflammation in cells. Silencing miR-146b-3p alleviated the effect of TNF-α and negatively regulated the expression of HMGCR. The knockdown of HMGCR reversed the protective effect of miR-146b-3p silencing on TNF-α-stimulated MH7A cells.ConclusionsIncreased miR-146b-3p served as a biomarker for the diagnosis and severity of RA. Silencing miR-146b-3p could suppress TNF-α-induced excessive proliferation, motility, and inflammation via regulating HMGCR in MH7A cells.

Autoantibody-positivity before and seroconversion during treatment with anti-PD-1 is associated with immune-related adverse events in patients with melanoma

IntroductionTreatment with the immune checkpoint inhibitor anti-programmed cell death protein-1 (PD-1) often causes immune-related adverse events (irAEs). Since irAEs resemble autoimmune diseases, autoantibodies might play a role and could potentially...

Diabetic cheiroarthropathy in uncontrolled type 2 diabetes with positive anti-nuclear antibodies: a case report from Sudan

Background: Diabetic cheiroarthropathy, also known as limited joint mobility, is one of the long-standing complications of type 2 diabetes mellitus (DM). It affects 8–50% of patients with type 1 diabetes and is also seen in type 2 diabetic patients. Consequently, it can mimic many rheumatological diseases and is often underdiagnosed. The authors present a case of a long-standing poorly controlled diabetes with diabetic cheiroarthropathy and diabetic neuropathy, along with positive ANA in the absence of any correlated autoimmune or rheumatological diseases. Case presentation: A 52-year-old female patient with poorly controlled diabetes (her last HbA1c reading was 9.5%) presented to the Rheumatology clinic with flexion deformities of the fingers. The patient has impaired vibration, two-point discrimination, and pinprick sensation in gloves and stock distribution, indicating peripheral neuropathy, entrapment neuropathy in the forms of bilateral carpal tunnel syndrome, and the diagnosis of diabetic cheiroarthropathy was made. Additionally, she has a positive prayer sign and a tabletop sign. Despite the absence of symptoms and signs of autoimmune disorders, this patient has positive anti-nuclear antibodies global (ANA positive by indirect immuno-fluorescence (IIF) 1\320 nucleolar pattern) with a negative: ANA profile, rheumatoid factor (RF) and anticyclic citrullinated peptide antibody (ACPA). Conclusion: Regular and careful hand examination should be part of clinical assessment for diabetic patients as it could be a very simple and useful screening tool for diabetic cheiroarthropathy. Physicians can use this condition as a mirror for microvascular complications of diabetes. This allows for early detection and appropriate interventions to prevent further progression of diabetes-related complications. It is also essential to consider the presence of positive ANA in diabetic cheiroarthropathy despite the absence of any rheumatological and autoimmune diseases.

Combination of scavenger receptor-A with anti-cyclic citrullinated peptide antibody for the diagnosis of rheumatoid arthritis.

The routine biomarkers for rheumatoid arthritis (RA), including anticyclic citrullinated peptide antibody (anti-CCP), rheumatoid factor (RF), immunoglobulin M (IgM), erythrocyte sedimentation rate (ESR), and C-reaction protein (CRP) have limited sensitivity and specificity. Scavenger receptor-A (SR-A) is a novel RA biomarker identified by our group recently, especially for seronegative RA. Here, we performed a large-scale multicentre study to further assess the diagnostic value of SR-A in combination with other biomarkers for RA. The performance of SR-A in combination with other biomarkers for RA diagnosis was first revealed by a pilot study, and was further elucidated by a large-scale multicentre study. A total of 1129 individuals from 3 cohorts were recruited in the study, including RA patients, healthy controls, and patients with other common rheumatic diseases. Diagnostic properties were evaluated by the covariate-adjusted receiver-operating characteristic (AROC) curve, sensitivity, specificity and clinical association, respectively. Large-scale multicentre analysis showed that SR-A and anti-CCP dual combination was the optimal method for RA diagnosis, increasing the sensitivity of anti-CCP by 13% (87% vs 74%) while maintaining a specificity of 90%. In early RA patients, SR-A and anti-CCP dual combination also showed promising diagnostic value, increasing the sensitivity of anti-CCP by 7% (79% vs 72%) while maintaining a specificity of 94%. Moreover, SR-A and anti-CCP dual combination was correlated with ESR, IgM, and autoantibodies of RA patients, further revealing its clinical significance. SR-A and anti-CCP dual combination could potentially improve early diagnosis of RA, thus improving the prognosis and reducing mortality.

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.

Serum levels of tumour necrosis factor (TNF-α) and interleukin-17 (IL-17) in patients with nail psoriasis: A cross-sectional study.

Background Psoriasis is a common chronic inflammatory disorder affecting all aspects of a patient's life. Nail involvement is frequent, but little is known about its associated inflammatory biomarker profile, including similarities or differences from cutaneous disease. Aims We conducted this cross-sectional study to evaluate serum levels of inflammatory cytokines [tumour necrosis factor-alpha (TNF-α) and interleukin -17 (IL-17)] in patients with nail psoriasis and compared these to psoriasis patients without nail involvement, as well as in non-psoriatic healthy controls. Methods Adult psoriasis patients with (Group I, n = 30) and without nail involvement (Group-II, n = 30) were sequentially recruited. In addition, non-psoriatic healthy controls (Group-III, n = 20) were recruited. The nail disease severity by NAPSI score was determined for patients in Group I. Cutaneous disease severity (by PASI score) and presence of psoriatic arthritis (through CASPAR criteria) were evaluated for patients in Groups I and II. Serum levels of TNF-α, IL-17, erythrocyte sedimentation rate (ESR), rheumatoid factor (RA factor), and anti-cyclic citrullinated peptide antibody (Anti-CCP) were evaluated for all three groups. Results The median age was significantly higher for Group I as compared to Group II patients (41 ± 12.6 years vs 30 ± 12.4 years, p = 0.017). Group I patients also had higher median PASI score than Group II patients, although the difference was not statistically significant (10 ± 11.41 vs 6.50 ± 5.46, p = 0.275). The mean serum IL-17 levels were significantly higher for Group-I (113.39 ± 251.30 pg/mL) than Group II (27.91 ± 18.22 pg/mL, p = 0.002) and Group III (25.67 ± 12.08 pg/mL, p = 0.005). A weak positive correlation was found between NAPSI and serum IL-17 levels (Spearman's Rho = 0.355) though not statistically significant (p = 0.054). Correlation between serum IL-17 and PASI was poor for Group-I patients (Spearman's Rho = 0.13, p = 0.944) and strongly negative for Group-II patients (Spearman's Rho = -0.368, statistically significant with p = 0.045). The mean serum levels of TNF-α were below the detection threshold of the assay kit, hence no meaningful comparison could be made. Limitations A small sample size and low sensitivity of TNF-α assay kit. Conclusion Our study showed that nail psoriasis could be independently associated with an elevation of IL-17. This can help choose appropriate drugs and estimate drug response in patients with nail psoriasis.

Rare complication of rheumatoid arthritis: Charcot Neuro-osteoarthropathy

BackgroundRheumatoid arthritis (RA) is an autoimmune disease.However, there are few cases of Charcot Neuro-osteoarthropathy (CN) caused by rheumatoid diseases in clinical reports. It is not easy to pay attention to the diagnosis of CN in the complications of rheumatoid disease, which greatly increases the probability of misdiagnosis and missed diagnosis. This case reported a rare complication of rheumatoid arthritis, Charcot arthritis, and the molecular mechanism and diagnosis and treatment of CN caused by RA were systematically discussed.Case presentationThe patient, a 79-year-old woman, was hospitalized due to bilateral shoulder pain, limited activity for half a year, aggravated for 4 months to the hospital. During this period, the symptoms did not improve after treatment with acupuncture and Chinese medicine. The patient was previously diagnosed with rheumatoid arthritis for more than 3 years and intermittent irregular use of methylprednisolone and methotrexate for 2 years. She had a history of osteoporosis. Physical examination: symmetrical malformed swelling of the finger joints of both hands; Bilateral supraspinatus and deltoid muscle atrophy, tenderness at the acromion, and attachment of the long head tendon of the biceps brachii were observed. The left Dugas test and the right Dugas test were positive.Blood test: anti-cyclic citrullinated peptide antibody (A-CCP) 33.10U/ml (normal range: 0-5RU/ml); antinuclear antibody quantification (ANA) 47.40AU/ml (normal range: Negative or < 32); anti-double stranded DNA IgG antibody quantification (dsDNA) 31.00 IU/ml (normal range: 0-100 IU/ml); D-Dimer 6.43 µg/ml (normal range: 0–0.5 mg/L); erythrocyte sedimentation rate (ESR) was 27 mm/h (normal range: < 20 mm/60 min). C-reactive protein (CRP) 39.06 mg/L(0.068-8 mg/L).MRI 3.0 T enhancement of bilateral shoulder joints, cervical spine and thoracic spine showed: 1.Large bone destruction, cartilage injury, multiple effusion, synovitis, obvious on the right side. 2.Intervertebral disc degeneration, cervical 3/4, 4/5, 5/6, 6/7 disc herniation, with cervical 3/4 obvious, posterior central herniation;ConclusionsRheumatoid arthritis complicated with Charcot's joint is rare. Clinically, patients with rheumatoid diseases should not ignore Charcot's joint complications because of rareness. Early blood inflammatory markers, neuro electrophysiology, and imaging MRI of rheumatoid CN are of great significance for the diagnosis of this mild or early neurovascular inflammation. Early diagnosis and treatment are helpful to prevent further joint injury. The clinical diagnosis, treatment, and molecular mechanism of osteolysis in RA and peripheral sensory nerve injury remain to be further revealed.

CCR9+CD4+ T cells are associated with disease activity in patients with rheumatoid arthritis.

An increase in CD4+ T cells in the synovium is closely linked to the pathogenesis of rheumatoid arthritis (RA). We aimed to identify the possible causes of the elevated CD4+ T cell levels and to explore the factors influencing disease activity in RA. Fifty-five RA patients, including 28 with active RA (ARA), 27 with inactive RA, and 22 healthy controls, were recruited for this study. The proportion of CCR9+CD4+ T cells and the expression of chemokine receptor 9 (CCR9) on CD4+ T cells were analyzed by flow cytometry. Enzyme-linked immunosorbent assay and chemiluminescent immunoassay were used to evaluate interleukin (IL)-17A and IL-6 levels, respectively. The proportion of CCR9+CD4+ T cells and the expression of CCR9 on CD4+ T cells increased significantly in peripheral blood (PB) and synovial fluid (SF) in ARA compared to those in inactive RA. Furthermore, SF contained more CCR9+CD4+ T cells, IL-6, and IL-17A than PB in RA patients. Moreover, CD4+ T cells in the PB of patients with RA, especially ARA, expressed more CCR9 and secreted more IL-6 and IL-17A after activation. Here, we also demonstrated that both the percentage of CCR9+ cells in CD4+ T cells and the expression of CCR9 on circulating CD4+ T cells were positively correlated with erythrocyte sedimentation rate, hypersensitive C-reactive protein, rheumatoid factor, and anti-cyclic citrullinated peptide antibody. CCR9+CD4+ T cells are elevated in PB and SF, and are associated with disease activity in patients with RA.

Serum PYCARD may become a new diagnostic marker for rheumatoid arthritis patients

BackgroundThe objective of this investigation is to analyze the levels and clinical relevance of serum PYCARD (Pyrin and CARD domain-containing protein, commonly known as ASC—apoptosis-associated speck-like protein containing a caspase activation and recruitment domain), interleukin-38 (IL-38), and interleukin-6 (IL-6) in individuals afflicted with rheumatoid arthritis (RA).MethodsOur study comprised 88 individuals diagnosed with RA who sought medical attention at the Affiliated Hospital of Chengde Medical University during the period spanning November 2021 to June 2023, constituting the test group. Additionally, a control group of 88 individuals who underwent health assessments at the same hospital during the aforementioned timeframe was included for comparative purposes. The study involved the assessment of IL-38, IL-6, PYCARD, anti-cyclic citrullinated peptide antibody (anti-CCP), and erythrocyte sedimentation rate (ESR) levels in both groups. The research aimed to explore the correlations and diagnostic efficacy of these markers, employing pertinent statistical analyses for comprehensive evaluation.ResultsThe test group had higher expression levels of PYCARD, IL-6, and IL-38 than the control group (P < 0.05). Based on the correlation analysis, there was a strong relationship between PYCARD and IL-38 (P < 0.01). The receiver operating characteristic (ROC) curve analysis revealed area under the curve (AUC) values of 0.97, 0.96, and 0.96 when using combinations of PYCARD and anti-CCP, IL-38 and anti-CCP, and IL-6 and anti-CCP for predicting RA, respectively. Importantly, all three of these pairs demonstrated superior AUC values compared to PYCARD, IL-38, IL-6, ESR, or anti-CCP used as standalone diagnostic indicators.ConclusionPYCARD, IL-6, and IL-38 exhibit promising potential as novel diagnostic markers and may constitute valuable tools for supporting the diagnosis of RA.

Utility of testing for third-generation anticyclic citrullinated peptide (anti-CCP3) antibodies in individuals who present with new musculoskeletal symptoms but have a negative second-generation anticyclic citrullinated peptide (anti-CCP2) antibody test

ObjectivesTo investigate the role of third-generation anticyclic citrullinated peptide (anti-CCP3) antibodies in predicting progression to inflammatory arthritis (IA) in individuals with new musculoskeletal (MSK) symptoms and a negative second-generation anti-CCP...

Simplified vs modified (reduced) ultrasound 6 joint score in assessing disease activity in rheumatoid arthritis patients

Introduction and aim. With increasing ultrasound US assessment opportunities for tight rheumatoid arthritis (RA) management, more simplified accurate US-assessment is desired in clinical practice. Aim of the work is assessing modified vs simplified ultrasound 6-joint scores relevance in assessing rheumatoid arthritis disease activity. Material and methods. Fifty-five RA patients were subjected to detailed history, clinical, and musculoskeletal examination with disease activity assessment by clinical disease activity index, simple disease activity index and disease activity score in 28 joints. Com plete blood count, erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, anti-cyclic citrullinated peptide antibodies were done. Patients underwent US examination (gray-scale and power Doppler) for wrist, 2nd and 3rd metacarpophalangeal and knee joints bilaterally. Synovitis composite score was added. Two US indices were constructed: simplified S6 and modified M6 joint scores. Results. Statistical significant positive correlations were high between S6/M6 score parameters (total, grey-scale (GS), power doppler (PD), Composite) and disease activity markers. Both M6 and S6 scores differentiated mild-moderate and moderate-severe disease activity patients. However, only S6 score differentiated remission from mild disease activity patients. Conclusion. Ultrasound 6-joint scores (especially simplified S6) were rapid, easy and sensitive ultrasound tools assessing rheu matoid arthritis disease activity in clinical practice.

Effect of Docetaxel on Matrix Metalloproteinase 1 Expression in Freund’s Adjuvant Induced Arthritis

Rheumatoid arthritis is an autoimmune disorder that affects the synovial joints. It lead to inflammatory changes occur in synovial tissue, cartilage, bone, and, less frequently, extra-articular structures. Docetaxel, is an anti-neoplastic drug. Methotrexate is a treatment for early-stage rheumatoid arthritis but have 30% failure in treatment within the first year due to resistance or side effects. Matrix metalloproteinase 1 is the proteinase primarily in charge of the irreversible degradation of cartilage, bone, and tendons in the joints, which are induced by cytokines. This study aims to evaluate the effects of docetaxel and methotrexate on Matrix metalloproteinase 1 in the structure of the induced arthritis joints. Methods: To induce the disease, complete Freund's adjuvant is injected subcutaneously into rats. From the 40 male Wister rats, five groups of eight were formed. The control group is composed of non-diseased rats. The second group is induced by complete Freund's adjuvant and 0.5 ml of normal saline was administered intraperitoneally to both the control and induction groups. After being induced by complete Freund's adjuvant, the third group is administered 1 mg/kg/ on alternate day of Docetaxel based on a preliminary experiment. The fourth group is induced and given 1 mg/kg/week of Methotrexate intraperitoneally. The fifth group receives a half dose of Methotrexate and Docetaxel simultaneously. Serum level of Anti Cyclical citrullinated Peptide Antibody, tissue homogenate level of tumor necrosis factor-alpha, knee joint circumference and Immunohistochemical of Matrix metalloproteinase 1 measurements were applied. Results: Significant decreased in the Serum level of Anti-Cyclic citrullinated Peptide Antibody, tissue homogenate level of tumor necrosis factor-alpha &amp; Knee joint circumference in the Docetaxel group. significant lowering in the expression of Matrix metalloproteinase 1 immunoreactivities in Docetaxel and Methotrexate groups with almost absent spots of positive reaction with the matrix of synovial tissue, hyaline cartilage &amp; articular surface. Conclusion: This study showed that Docetaxel may have anti-arthritic effect through their significant lowering expression of Matrix metalloproteinase 1 immunoreactivities.&#x0D; &#x0D;