Integrating pretest probability for rheumatoid arthritis with likelihood ratios of RF and ACPA to improve clinical utility of rheumatoid arthritis autoantibody testing.

BACKGROUND AND AIMS: Rheumatoid arthritis (RA) manifests through various symptoms and systemic manifestations. Diagnosis involves serological markers like rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). Past studies have shown the added value of likelihood ratios (LRs) in result interpretation. LRs can be combined with pretest probability to estimate posttest probability for RA. There is a lack of information on pretest probability. This study aimed to estimate pretest probabilities for RA. MATERIALS AND METHODS: This retrospective study included 133 consecutive RA patients and 651 consecutive disease controls presenting at a rheumatology outpatient clinic. Disease characteristics, risk factors associated with RA and laboratory parameters were documented for calculating pretest probabilities and LRs. RESULTS: Joint involvement, erosions, morning stiffness, and positive CRP, ESR tests significantly correlated with RA. Based on these factors, probabilities for RA were estimated. Besides, LRs for RA were established for RF and ACPA and combinations thereof. LRs increased with antibody levels and were highest for double high positivity. Posttest probabilities were estimated based on pretest probability and LR. CONCLUSION: By utilizing pretest probabilities for RA and LRs for RF and ACPA, posttest probabilities were estimated. Such approach enhances diagnostic accuracy, offering laboratory professionals and clinicians insights in the value of serological testing during the diagnostic process.

Bowel and Small Joint Involvement in Granulomatosis With Polyangiitis: A Case Report.

We discuss the case of a 45-year-old male with complaints of abdominal pain, loose stools with on and off melena, and multiple joint pains bilaterally. The patient reported having similar episodes in the past, with slight variations in the symptoms and relief with short courses of steroids. Initially, a workup was done to identify an infectious etiology of the diarrhea. However, no such cause was identified. Similarly, an autoimmune profile was ordered to investigate the patient's joint complaints, albeit with no conclusive findings. His renal function tests and urinalysis showed findings indicative of an acute kidney injury. This prompted an antineutrophil cytoplasmic antibody (ANCA) profile, which was positive for c-ANCA. A diagnosis of granulomatosis with polyangiitis (GPA) was made, and the patient was started on pulse steroid and immunomodulator therapy with improvement in the patient's condition. This case is atypical due to its involvement of the gastrointestinal system, which is relatively rare, as well as polyarthritis of the small joints.

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

Introduction: 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). Material and methods: 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. Results: 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. Conclusions: 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.

Potential prognostic value of rheumatoid factor in anti-aquaporin 4-immunoglobin G-positive neuromyelitis optica spectrum disorders.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is the central nervous system demyelinating disease differentiated from multiple sclerosis by the presence of anti-aquaporin 4-antibody (AQP4-ab), which is sometimes accompanied by non-organ-specific autoantibodies. METHODS: We prospectively collected clinical information and profiles of non-organ-specific autoantibodies such as fluorescent antinuclear (FANA), anti-Sjögren's syndrome A (SSA)/Ro, anti-SS B (SSB)/La, anti-neutrophil cytoplasmatic (ANCA), lupus anticoagulant (LA), anti-cardiolipin (ACA), anti-double-stranded DNA (dsDNA), rheumatoid factor (RF), anti-thyroperoxidase, and anti-thyroglobulin antibodies in patients with NMOSD. Clinical characteristics and laboratory findings of patients with NMOSD with or without autoantibodies were analyzed. Cox proportional hazard models were used to identify independent risk factors predicting high disability in patients with NMOSD. RESULTS: A total of 158 patients with NMOSD (Female: Male = 146:12; age, 36.11 ± 14.7) were included. FANA was observed most frequently (33.3 %), followed by anti-SSA (28.6 %), anti-SSB (10.0 %), RF (8.5 %), anti-dsDNA (7.0 %), LA (4.7 %), ACA (4.8 %), and ANCA (2.4 %). High disability (Expanded Disability Status Scale (EDSS) score ≥ 6) was observed more frequently in patients with RF (45.5 %) than in those without RF (14.5 %) (p = 0.02). RF was a significant predictive factor for the high disability (hazard ratio [HR], 3.763; 95 % confidence interval [CI], 1.086-13.038; p = 0.037), age at onset (HR, 1.093; 95 % CI, 1.05-1.14; p ≤0.001), and annual relapse rate (ARR) (HR, 4.212; 95 % CI, 1.867-9.503; p = 0.001). CONCLUSION: Organ-specific and non-organ-specific autoantibodies are frequently observed in Korean patients with AQP4-ab-positive NMOSD. RF may be an independent predictor of high disability, along with age at onset and ARR.

Impact of high rheumatoid factor levels on treatment outcomes with certolizumab pegol and adalimumab in patients with rheumatoid arthritis.

OBJECTIVE: To assess the impact of baseline rheumatoid factor (RF) level on drug concentrations and efficacy of certolizumab pegol (CZP; tumour necrosis factor inhibitor [TNFi] without a crystallisable fragment [Fc]) and adalimumab (ADA; Fc-containing TNFi) in patients with rheumatoid arthritis (RA). METHODS: The phase 4 EXXELERATE study (NCT01500278) was a 104-week, randomised, single-blind (double-blind until week 12; investigator-blind thereafter), head-to-head study of CZP vs ADA in patients with RA. In this post hoc analysis, we report drug concentration and efficacy outcomes stratified by baseline RF quartile (≤Q3 or >Q3). RESULTS: Baseline data by RF quartiles were available for 453 CZP-randomised and 454 ADA-randomised patients (≤Q3: ≤204 IU/ml; >Q3: >204 IU/ml). From week 12, the area under the curve (AUC) of ADA concentration was lower in patients with RF > 204 IU/ml vs patients with RF ≤ 204 IU/ml; the AUC of CZP concentration was similar in patients with RF ≤ 204 IU/ml and >204 IU/ml. For patients with RF ≤ 204 IU/ml, disease activity score (DAS28)-C-reactive protein (CRP) was similar between CZP- and ADA-treated patients through week 104. For patients with RF > 204 IU/ml, mean DAS28-CRP was lower in CZP- vs ADA-treated patients at week 104. The proportion of patients with RF > 204 IU/ml achieving DAS28-CRP low disease activity at week 104 was greater in CZP- vs ADA-treated patients. CONCLUSION: CZP was associated with maintained drug concentration and efficacy in patients with RA and high RF and may therefore be a more suitable therapeutic option than TNFis with an Fc fragment in these patients.

Influence of rheumatoid factor levels and TNF inhibitor structure on secondary nonresponse in rheumatoid arthritis patients.

Background: The EXXELERATE study revealed poorer clinical outcomes in patients treated with adalimumab (ADL) and baseline rheumatoid factor (RF) above 203 IU/mL. However, responses were similar in patients treated with certolizumab pegol (CZP) regardless of RF levels. Objectives: This study investigated the impact of RF levels >203 IU/mL on TNF inhibitors (TNFi) serum levels and the association with secondary nonresponse in RA patients treated with TNFi. Methods: We performed an observational ambispective study with RA patients treated with infliximab (IFX), ADL, or CZP. Patients were stratified according to baseline RF levels: ≤ or >203 IU/mL. After 6 months, serum drug levels and antidrug antibodies were measured, and reasons for discontinuation were collected. Results: We included 170 RA patients: 90 (53%) received IFX, 48 (28%) ADL, and 32 (19%) CZP. While CZP serum levels did not differ between RF groups at 6 months (p = 0.6), RF levels >203 IU/mL were linked to lower serum drug levels in patients treated with IFX (p = 0.09) or ADL (p = 0.02). Secondary nonresponse was 3.6 times higher in patients with high versus low RF levels in patients under IFX or ADL. However, the reasons for withdrawal were not affected by RF levels in patients treated with CZP. Conclusion: Baseline RF above 203 IU/mL is associated with lower serum drug levels and an increased risk of discontinuation due to secondary nonresponse in patients treated with IFX or ADL. In contrast, drug levels and clinical outcomes are not significantly impacted by baseline RF levels in patients under CZP.

Utility of common investigations for suspected inflammatory arthritis in adults.

Inflammatory arthritis may be the principal feature or one component of an inflammatory rheumatological disease. It is a clinical diagnosis, principally made based on the patient's history and examination. Specific investigations, such as rheumatoid factor and human leucocyte antigen B27 gene, may support the diagnosis in the context of a suggestive clinical presentation, but a diagnosis cannot be made based on these tests alone because positive results may also be seen in healthy individuals. To reduce the likelihood of false positive results, laboratory and radiological investigations should be tailored to the suspected diagnosis based on pretest probability. While musculoskeletal symptoms are a common presentation in general practice, specific features that increase suspicion of an inflammatory arthritis include prolonged morning stiffness (more than 1 hour) that is improved by exercise or movement. A broad 'rheumatological panel' increases the likelihood of false positive results and should be avoided to prevent unnecessary further investigations and treatment, and unwarranted anxiety in both the patient and the doctor.

Next-generation rheumatoid factor assay provides improved predictive power for the development of arthritis in patients at risk.

OBJECTIVE: Rheumatoid arthritis (RA) is characterised by the presence of autoantibodies, among which those targeting the constant region of immunoglobulin G (IgG), called rheumatoid factors (RF). Despite this link, RFs can also be found in other disorders and the healthy population, which hampers its use as a diagnostic tool. We recently showed that a subset of RA-derived RFs target a distinct epitope on the IgG-Fc, a feature that is currently not used in the clinic. METHODS: We determined immunoglobulin M (IgM)-RF levels specific against an RA-associated epitope (using our engineered next-generation RF antigen 'T3-17') in a prospective cohort of 475 patients with seropositive (for IgM-RF or aCCP) arthralgia that were followed for 5 years or until the development of arthritis. RESULTS: The presence of RFs targeting T3-17 was more strongly associated with progression to arthritis in comparison to traditional RF measurements. Within the group of patients positive for T3-17 RF the risk of arthritis development was increased as compared with wild-type RF, HR=3.2 (95% CI 2.4 to 4.3) vs HR=2.2 (95% CI 1.7 to 3.0). Predictive power of T3-17 RF was improved in combination with aCCP titres, HR=6.4 (4.7-8.7) vs HR=5.1 (3.9-6.8). This combination performed better than aCCP detection on its own. CONCLUSION: The detection of disease-specific RF is feasible and seems to improve the diagnostic power of RF and should be considered to be implemented in the clinic.

Complete Description of the Three Pathways of the Complement System in a Series of 430 Patients with Rheumatoid Arthritis.

The complement (C) system is implicated in the etiopathogenesis of rheumatoid arthritis (RA). However, there is a lack of studies characterizing all three C pathways in RA patients. This study aimed to evaluate the association between an in-depth examination of the C system and RA patient characteristics, focusing on disease activity and the presence of rheumatoid factor and anti-citrullinated protein autoantibodies (ACPA). In a cohort of 430 RA patients, functional assays of the three C pathways (classical, alternative, and lectin) and serum levels of their components were assessed. Components included C1q (classical); factor D and properdin (alternative); lectin (lectin); C1-inhibitor; C2, C4, and C4b (classical and lectin); C3, C3a, and C4b (common); and C5, C5a, and C9 (terminal). A multivariable linear regression analysis showed significant positive correlations between C-reactive protein and C system proteins and functional assays, especially in the terminal and common pathways. Disease activity, measured by scores with or without acute phase reactants, positively correlated with the classical pathway functional test and terminal pathway products. Conversely, rheumatoid factor or ACPA presence was associated with lower classical pathway values and decreased C3a and C4b levels, suggesting complement depletion. In conclusion, RA disease activity increases C molecules and functional complement assays, while rheumatoid factor or ACPA positivity is linked to C consumption. Our study offers a detailed analysis of the complement system's role in RA, potentially guiding the development of more targeted and effective treatment strategies.

Risk factors for interstitial lung disease in rheumatoid arthritis: a cohort study from the KOBIO registry.

Background: Interstitial lung disease (ILD) is a critical extra-articular manifestation of rheumatoid arthritis (RA). However, little is known about the risk factors of RA-ILD. Objectives: Here, we examined the effect of demographic, clinical, therapeutic, and environmental factors on the incidence of ILD in RA patients using the Korean College of Rheumatology Biologics and Targeted Therapy (KOBIO) registry. Design: We used data from the KOBIO registry, a multi-center, prospective, observational cohort that included RA patients in South Korea. Methods: RA patients who used biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) or conventional synthetic (cs)DMARDs, and were enrolled in the KOBIO registry, were examined. Demographic, clinical, and radiographic characteristics, as well as medications, were recorded at baseline and annually thereafter. Kaplan-Meier curves and the log-rank test were used to compare the incidence of ILD between RA patients taking different b/tsDMARDs. Hazard ratios (HRs) were calculated by Cox regression analyses. Results: In total, 2492 patients (1967 in the b/tsDMARDs group and 525 in the csDMARDs group) were analyzed. The b/tsDMARDs group showed longer disease duration, higher erythrocyte sedimentation rate/C-reactive protein, and higher disease activity score-28 (DAS28) than the csDMARDs group. The incidence of ILD was significantly higher in those taking tumor necrosis factor inhibitors and abatacept than in those taking csDMARDs (log ranked p < 0.001). Multivariate Cox regression analysis identified older age (HR = 1.057, p = 0.001), male sex (HR = 2.824, p = 0.007), time-averaged DAS28 (HR = 2.241, p < 0.001), and rheumatoid factor titer (HR = 1.009, p = 0.007) as having a significantly increased HR for ILD occurrence. Conclusion: ILD is a rare but critical extra-articular symptom of RA patients. Therefore, RA patients with the above risk factors should be monitored carefully for ILD development.

Autoantibodies Serum Level and 10-Year Risk of Fractures Evaluated by FRAX® Tool in Rheumatoid Arthritis Patients.

Purpose: FRAX® is a tool used for evaluation of risk of fracture in RA and non-RA patients and to identify those eligible for intervention. One of the limitations of FRAX in RA settings is that it does not consider factors known to contribute to osteoporosis such as autoantibodies. This study analysed the association of anti-mutated citrullinated vimentin antibody (anti-MCV), anti-cyclic citrullinated peptide antibody (anti-CCP), IgM rheumatoid factor (RF), IgA RF with 10-year risk of major osteoporosis and hip fracture. Methods: FRAX® tool was used to estimate 10-year risk of major osteoporosis fracture and hip fracture in 189 RA patients over 40 years of age. Anti-MCV, anti-CCP, IgM RF and IgA RF were tested using enzyme immunoassay and analysed at different levels. Results were adjusted for various confounders including disease activity. Results: Fifty-one (26.9%) RA patients had high (≥20%) 10-year risk of major osteoporosis fracture and 67 (35.4%) had high (>3%) 10-year risk of hip fracture. Among all the tested autoantibodies, only IgM RF at elevated levels was associated with high 10-year risk of major osteoporosis fracture (adjusted OR = 4.1, 95% CI = 1.5-11.3, p = 0.006) and of hip fracture (adjusted OR = 17.4, 95% CI = 3.7-81.3, p < 0.0001). There was no agreement between FRAX and femoral neck (FN) BMD. None of the autoantibodies tested were associated with FN osteopenia or osteoporosis including IgM RF at high levels. Conclusion: Our study highlights the importance of quantitative measurement of autoantibodies in assessment of risk for fractures among RA patients. Our preliminary findings need to be assessed in prospective studies to determine the actual predictive value of high IgM RF levels among patients with RA.

Early identification of rheumatoid arthritis: does it induce treatment-related cost savings?

OBJECTIVE: Early diagnosis and treatment-start is key for rheumatoid arthritis (RA), but the economic effect of an early versus a later diagnosis has never been investigated. We aimed to investigate whether early diagnosis of RA is associated with lower treatment-related costs compared with later diagnosis. METHODS: Patients with RA consecutively included in the Leiden Early Arthritis Clinic between 2011 and 2017 were studied (n=431). Symptom duration was defined as the time between symptom onset and first presentation at the outpatient clinic; early treatment start was defined as symptom duration <12 weeks. Information on disease-modifying anti-rheumatic drug use per patient over 5 years was obtained from prescription data from patient records. Prices were used from 2022 and 2012 (proxy of time of prescription) to study the impact of changes in drug costs. Autoantibody-positive and autoantibody-negative RA were studied separately because differences in disease severity may influence costs. RESULTS: Within autoantibody-negative RA, costs were 316% higher in the late compared with the early group (ß=4.16 (95% CI 1.57 to 11.1); €4856 vs €1159). When using 2012 prices, results were similar. For autoantibody-positive RA, costs were 19% higher in the late group (€9418 vs €7934, ß=1.19, 0.57 to 2.47). This effect was present but smaller when using 2012 prices. Within patients with autoantibody-positive RA using biologicals, late treatment start was associated with 46% higher costs (ß=1.46 (0.91 to 2.33)); higher costs were also seen when using 2012 prices. CONCLUSION: When RA is detected within 12 weeks after symptom onset, treatment-related costs were lower in both autoantibody-negative and autoantibody-positive RA. This study is the first to report how early diagnosis and treatment start impact treatment-related costs.

Association of rheumatoid factor, anti-citrullinated protein antibodies and shared epitope with clinical response to initial treatment in patients with early rheumatoid arthritis: data from a randomised controlled trial.

OBJECTIVES: To investigate whether rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPAs) and shared epitope (SE) allele-related genetic markers associate with treatment response to abatacept, certolizumab pegol or tocilizumab versus active conventional treatment (ACT). METHODS: Patients with treatment-naïve early rheumatoid arthritis were randomised in the NORD-STAR trial to ACT, certolizumab pegol, abatacept or tocilizumab, all with methotrexate. Centralised laboratory analyses for ACPA, RF and SE were performed. Clinical Disease Activity Index remission was analysed longitudinally with logistic generalised estimating equations. Differences in treatment effect across RF, ACPA and SE subgroups were assessed with interaction terms at 24 and 48 weeks, adjusted for sex, country, age, body mass index, Disease Activity Score of 28 joints based on C-reactive protein and smoking. RESULTS: In total, 778 patients were included. At 24 weeks, abatacept treatment showed a better response than ACT in the RF and/or ACPA-positive subgroups, but this effect was not significantly different from the negative subgroups. By 48 weeks, abatacept treatment showed better response regardless of RF/ACPA status. No differences were found across RF, ACPA, SE allele, valine at amino acid position 11 or valine-arginine-alanine haplotype subgroups for any biological treatment at 48 weeks. CONCLUSIONS: Based on this randomised controlled trial, abatacept treatment was associated with a better response than ACT in the RF and/or ACPA-positive subgroup at 24 weeks, but this was no longer seen at 48 weeks; adding SE allele-related genetic markers did not strengthen the association. Moreover, ACPA, RF and SE allele-related genotypes were not, alone or in combination, associated with clinical responses of importance sufficiently strongly to warrant implementation in clinical practice. TRIAL REGISTRATION NUMBER: EudraCT 2011-004720-35; ClinicalTrials.gov NCT01491815.

The Impact of Autoantibodies on Outcomes in Patients with Idiopathic Pulmonary Fibrosis: Post-Hoc Analyses of the Phase III ASCEND Trial.

INTRODUCTION: Clinical practice guidelines recommend autoimmune serological testing in patients newly diagnosed with interstitial lung disease of apparently unknown cause who may have idiopathic pulmonary fibrosis (IPF), in order to exclude connective tissue disease (CTD). Autoantibody positivity has been associated with unique patient profiles and prognosis in patients with IPF who otherwise lack a CTD diagnosis. METHODS: This post-hoc analysis of patients with IPF from the Phase III ASCEND trial (NCT01366209) evaluated the association of antinuclear antibodies (ANA), rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) status with baseline disease characteristics, disease progression [percent predicted forced vital capacity (%FVC), forced vital capacity (FVC) volume and progression-free survival (PFS)], and treatment outcomes with pirfenidone and placebo (%FVC, FVC and PFS). RESULTS: Of 555 participants, 244/514 (47.5%) were ANA positive (ANA+), 83/514 (16.1%) had high ANA+ (ANA titre ≥ 1:160 or positive nucleolar- or centromere-staining patterns), 60/555 (10.8%) were RF positive (RF+) and/or anti-CCP positive (anti-CCP+) and 270/514 (52.5%) were autoantibody negative (AAb-). Baseline demographics and characteristics were generally comparable between autoantibody subgroups. Although not statistically significant, more placebo-treated participants with ANA+ or high ANA+ had a decline from baseline to Week 52 of ≥ 10% in %FVC or death (48.7% and 55.9%, respectively) or in FVC volume or death (48.7% and 47.1%, respectively) compared with the AAb- group (%FVC or death: 42.0%; FVC volume or death: 42.0%). The RF+ and/or anti-CCP+ group was similar to AAb-. No differences were observed in PFS. A treatment benefit for pirfenidone versus placebo was observed regardless of autoantibody status [PFS: ANA+ HR (95% CI): 0.56 (0.37 to 0.86), P = 0.007; AAb- HR (95% CI): 0.50 (0.32 to 0.78), P = 0.002]. CONCLUSION: IPF disease course did not differ by autoantibody status in ASCEND. Pirfenidone had a treatment benefit regardless of the presence of ANA. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01366209.

People with idiopathic pulmonary fibrosis sometimes have abnormal antibodies, called autoantibodies, in their blood. Uncommonly, autoantibodies may mistakenly target the person's own tissues, including the lungs. It is unknown whether these autoantibodies cause idiopathic pulmonary fibrosis or make it worse. This analysis looked at data from the ASCEND clinical trial in people with idiopathic pulmonary fibrosis, who were split randomly into two groups to receive tablets of either a medicine called pirfenidone or a placebo for 52 weeks. One goal was to see whether people with certain autoantibodies called antinuclear antibodies ('ANA' for short), rheumatoid factor ('RF') and anti-cyclic citrullinated peptide ('anti-CCP') had different traits from people without autoantibodies, such as age, race or smoking history. Other goals were to see if autoantibodies affected (1) how well people's lungs worked during the trial, (2) how quickly people's idiopathic pulmonary fibrosis got worse or they died and (3) how well pirfenidone worked. The analysis showed that most traits were similar in people with and without autoantibodies. In people who received placebo, the change in lung function during the trial was not different for people with ANA, RF or anti-CCP compared with people with no autoantibodies. People who received pirfenidone were less likely to have worsening lung function, or die, than people who received placebo, regardless of whether or not they had autoantibodies. Doctors evaluating patients with idiopathic pulmonary fibrosis should consider the impact of autoantibodies and feel confident that pirfenidone is effective regardless of whether or not autoantibodies are present.

Pro-inflammatory cytokine IL-21 correlates with the reactive oxygen species and 25-hydroxy vitamin D in rheumatoid arthritis patients.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disorder and its characteristics include the immune system's invasion of the healthy lining of the joints and the articular structures degeneration. The IL-21 pro-inflammatory cytokine, and the reactive oxygen species (ROS) might have a role in the RA etiopathogenesis. The present study assessed the correlation of IL-21 with vitamin 25(OH)D and the ROS. METHODS: The study included 120 RA patients and 60 healthy group. The RA patients were categorized based on rheumatoid factor (RF) seropositivity or seronegativity and the RA severity. Chemiluminescent immunoassay and 10% hematocrit were used to check levels of vitamin 25(OH)D and ROS, respectively. ELISA was used for the detection of IL-21 in the plasma. RESULTS: The RA patients had a significantly reduced vitamin 25(OH)D level compared to the healthy controls. The IL-21 and ROS were however significantly increased in the RA patients compared to the controls. Further, the seropositive RF and the high RA severity patients had significant IL-21 and ROS increase in comparison with the seronegative RF and the low severity RA patients. Finally, IL-21 negatively correlated with vitamin 25(OH)D, but positively correlated with the ROS. CONCLUSION: This is the first investigation to confirm the relationship between IL-21 with vitamin 25(OH)D and the ROS among the RA patients. The findings indicate that vitamin 25(OH)D is reduced in the RA patients' serum. ROS and IL-21 are also associated with increased RA severity.

Granulomatosis With Polyangiitis and Concomitant Superinfection: A Defying Diagnosis and Management Approach.

Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis mainly involving the ear, nose, and upper and lower airways. Diagnosis is based on clinical manifestations, positive antineutrophil cytoplasmic antibodies (ANCA) serology, and histopathological findings. We report a case of inflammatory polyarthralgia with a high titer of rheumatoid factor (RF), which was revealed to be GPA after extensive diagnosis workup. However, the disease was complicated by superinfections, which delayed and limited immunosuppressive treatment. Methotrexate was at last initiated with antibiotic prophylaxis, and there was significant clinical improvement. This case underlines the importance of an adequate diagnosis workup and the difficulties that often arise when other entities are present.

The Serological Evidence of Positive Rheumatoid Factor in Morphea Patients and Its Relation to Disease Severity.

Background and objective Morphea, or localized scleroderma (LS), is an autoimmune skin disorder characterized by inflammation and sclerosis. Its potential causes include infections, genetic predisposition, and trauma. The disease involves cycles of inflammation and fibrosis, leading to skin hardening and scarring, which can cause deformities if untreated. Research exploring the link between morphea and rheumatoid factor (RF), a marker associated with other autoimmune conditions, is ongoing. This study aimed to examine the less-explored role of RF, a marker typically linked to rheumatoid arthritis (RA), in the severity of morphea. It focused on assessing the levels of RF among morphea patients and its correlation with disease severity, intending to provide deeper insights into the condition and its management. Methods This study involved a simple randomized cross-sectional analysis to evaluate the role of the RF in measuring morphea severity among patients at the Dermatology and Venereology Department of Al-Sader Teaching Hospital from October 2022 to December 2023. We included participants with clinically and laboratory-confirmed morphea while excluding those with other autoimmune dermatological diseases, recent systemic steroid or immunosuppressive therapy, and pregnant women. The assessment of disease severity was done by utilizing the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT). Statistical analyses were performed using SPSS Statistics version 27 (IBM Corp., Armonk, NY), with a significance threshold of p<0.05. Results Elevated RF levels were significantly associated with increased morphea severity, with severe cases showing higher RF levels (mean: 30.34 U/mL) compared to moderate (25.83 U/mL) and mild cases (21.56 U/mL) (p = 0.028). However, no significant correlation was found between RF levels and demographic factors such as age, gender, or occupation. Patients with high RF levels had a longer disease duration (mean: 57.15 years) compared to those with normal levels (25.83 years, p = 0.020). Significant differences were observed in lesion distribution on the back (p = 0.002). Logistic regression indicated that severe morphea patients were more likely to have elevated RF levels [odds ratio (OR): 1.158, p = 0.014]. Conclusions This study enriches our understanding of RF's role in morphea, revealing no significant correlation with demographic factors but suggesting its potential role in disease chronicity and severity.

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.

Nipocalimab, an anti-FcRn monoclonal antibody, in participants with moderate to severe active rheumatoid arthritis and inadequate response or intolerance to anti-TNF therapy: results from the phase 2a IRIS-RA study.

OBJECTIVES: To investigate the efficacy, safety, pharmacokinetics and pharmacodynamics of nipocalimab in participants with moderate to severe active rheumatoid arthritis (RA) and inadequate response or intolerance to ≥1 antitumour necrosis factor agent. METHODS: In this phase 2a study, participants with RA seropositive for anticitrullinated protein antibodies (ACPA) or rheumatoid factors were randomised 3:2 to nipocalimab (15 mg/kg intravenously every 2 weeks) or placebo from Weeks 0 to 10. Efficacy endpoints (primary endpoint: change from baseline in Disease Activity Score 28 using C reactive protein (DAS28-CRP) at Week 12) and patient-reported outcomes (PROs) were assessed through Week 12. Safety, pharmacokinetics and pharmacodynamics were assessed through Week 18. RESULTS: 53 participants were enrolled (nipocalimab/placebo, n=33/20). Although the primary endpoint did not reach statistical significance for nipocalimab versus placebo, a numerically higher change from baseline in DAS28-CRP at Week 12 was observed (least squares mean (95% CI): -1.03 (-1.66 to -0.40) vs -0.58 (-1.24 to 0.07)), with numerically higher improvements in all secondary efficacy outcomes and PROs. Serious adverse events were reported in three participants (burn infection, infusion-related reaction and deep vein thrombosis). Nipocalimab significantly and reversibly reduced serum immunoglobulin G, ACPA and circulating immune complex levels but not serum inflammatory markers, including CRP. ACPA reduction was associated with DAS28-CRP remission and 50% response rate in American College of Rheumatology (ACR) criteria; participants with a higher baseline ACPA had greater clinical improvement. CONCLUSIONS: Despite not achieving statistical significance in the primary endpoint, nipocalimab showed consistent, numerical efficacy benefits in participants with moderate to severe active RA, with greater benefit observed for participants with a higher baseline ACPA. TRIAL REGISTRATION NUMBER: NCT04991753.

Zinc oxide nanoparticles-doped curcumin-assisted recovery of rheumatoid arthritis and antioxidant status in experimental rabbits.

Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and synovial joint destruction. Aims: The current study investigated the possible beneficial effect of zinc oxide nanoparticles doped curcumin (ZnONPs-DC) on the recovery of RA and antioxidant status of experimental rabbits. Methods: RA was induced in experimental rabbits by injecting complete Freund's adjuvant and collagen type-II emulsion (100 µL/kg body weight) in the base of their tail. Arthritic rabbits were orally treated with ZnONPs, curcumin, and ZnONPs-DC(250 µL/kg bodyweight). Serumsamples fromthe control and study groupswere collected before and afterRAinduction and after treatment. The sera were subjected to analysis of biological markers of RA and antioxidant status. Results: The complete Freund's adjuvant and collagen type II treatment resulted in positive rheumatoid factor and C-reactive protein elevated oxidative stress and decreased antioxidant potential. Each treatment showed the absence of rheumatoid factor and C-reactive protein decreased oxidative stress and improved antioxidant potential compared to the control. However, ZnONPs-DC treatment showed a comparatively higher decline in serum malondialdehyde MDA content and an elevation in the antioxidant activity of RA animals. Conclusions: In conclusion, using zinc oxide nanoparticles-doped curcumin may be an effective anti-arthritic and anti-inflammatory drug in controlling RA.