Even though immune checkpoint inhibitors (ICI) remain effective treatments for an increasing number of cancers, they are also liable to cause immune-related adverse events (irAE). Rheumatologic manifestations occur in 5-10 % of patients. The most common rheumatologic irAEs are immune checkpoint-induced inflammatory arthritis (ICI-IA) and immune checkpoint-induced polymyalgia rheumatica (ICI-PMR). While ICI-IA can mimic rheumatoid arthritis (RA), it is predominantly immuno-negative (absence of rheumatoid factor and anti-citrullinated peptide antibodies) and can persist subsequent to r ICI cessation. ICI-PMR is usually reversible. First-line treatments consist of corticosteroids at the lowest effective doses and are given for short periods. They are aimed at reducing symptoms such as joint swelling, with minimal (if any) disruption of ICI therapy. In patients with corticoid dependence at a dose > 10 mg/day, second-line treatments include methotrexate and biologic therapy: anti-IL6 and TNF inhibitors (TNFi). Management of these manifestations requires balancing the opposed perspectives of effective arthritis control and possible cancer progression. When possible, ICI cessation should be avoided, and immunomodulating therapies are to be applied cautiously. Co-management by patients, oncologists, and rheumatologists is of crucial importance when balancing the risks and benefits of treatment.

Rationale:Rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) are distinct inflammatory rheumatic diseases with different clinical, serological, and genetic profiles. RA is typically characterized by symmetric peripheral polyarthritis and autoantibody positivity, particularly anti-cyclic citrullinated peptide (anti-CCP), whereas axSpA primarily involves the axial skeleton and sacroiliac joints and is often associated with human leukocyte antigen-B27 (HLA-B27). The coexistence of seropositive RA and axSpA is uncommon and presents diagnostic and therapeutic challenges, particularly when axial symptoms are under-recognized in young patients. This case highlights a rare overlap phenotype and emphasizes the role of advanced imaging and individualized management.Patient concerns:An 18-year-old Saudi woman presented with inflammatory peripheral joint pain, associated with chronic axial symptoms suggestive of sacroiliac involvement.Diagnoses:Laboratory investigations revealed markedly elevated anti-cyclic citrullinated peptide (anti-CCP) antibodies (373 U/mL), supporting the diagnosis of seropositive RA based on the 2010 American College of Rheumatology/European Alliance of Associations for Rheumatology criteria. Magnetic resonance imaging of the sacroiliac joints demonstrated bilateral sacroiliitis with active inflammatory changes, fulfilling the Assessment of SpondyloArthritis International Society (ASAS) criteria for axial spondyloarthritis, despite negative HLA-B27 and absence of other typical spondyloarthritis features.Interventions:The patient was initially managed with methotrexate (15 mg/wk) and low-dose prednisone (5 mg/d). Due to persistent axial symptoms, treatment was escalated to adalimumab following appropriate screening and counseling.Outcomes:At 3-month follow-up, the patient demonstrated significant clinical improvement (>70%) in both peripheral and axial symptoms, with normalization of inflammatory markers C-reactive protein (CRP) and erythrocyte sedimentation rate.Lessons:This case underscores the importance of considering overlapping rheumatologic conditions in patients with atypical presentations. Magnetic resonance imaging plays a critical role in detecting axial involvement, particularly in HLA-B27–negative patients. Early recognition of such overlap syndromes is essential to guide appropriate targeted therapy and improve long-term outcomes, especially in young populations.

This study aimed to assess the prevalence of comorbidities among patients with rheumatoid arthritis (RA) and identify factors associated with it. A cross-sectional study was conducted at 2 tertiary care hospitals among 653 patients with RA. Data on demographics, poor prognostic factors (high erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], rheumatoid factor, anticyclic citrullinated peptide antibody titers, and Disease Activity Score in 28 joints [DAS28] > 5.1), and comorbidities were collected through a structured questionnaire and medical record review. Comorbidities were quantified by the Charlson Comorbidity Index (CCI). Logistic regression analyses were used to identify associated factors. A total of 646 (98.9%) patients had ≥ 1 comorbidity. The most prevalent were dyslipidemia (75.8%), obesity (58.7%), hypertension (42.7%), type 2 diabetes mellitus (30.3%), and osteoporosis (OP; 15.6%). Age ≥ 45 years was independently associated with coronary artery disease (odds ratio [OR] 9.71, 95% CI 1.91-178.00), OP (OR 19.60, 95% CI 5.96-121.00) and infectious diseases (OR 1.60, 95% CI 1.03-2.54). Female sex was associated with lower cardiovascular risk (OR 0.27, 95% CI 0.11-0.62), whereas female sex was associated with increased odds of OP (OR 3.55, 95% CI 1.71-8.37) and gastrointestinal (GI) disorders (OR 2.18, 95% CI 1.37-3.56). The use of targeted synthetic and biologic disease-modifying antirheumatic drugs increased the risk of infection (OR 14.80 and 4.11, respectively). High DAS28-CRP and ESR values were linked to GI comorbidities. The CCI survival index was significantly lower in older patients (≥ 45 years; mean 68.7 [SD 26.7]) than in younger patients (mean 93.3 [SD 6.7], P < 0.001). The prevalence of multimorbidity is high among patients with RA in Bangladesh, particularly early cardiovascular disease risk.

A substantial proportion of individuals with palindromic rheumatism develop rheumatoid arthritis (RA). This randomized, open-label, multicenter trial aimed to assess whether 2 years of treatment with abatacept (n = 34; 125 mg subcutaneous injections weekly during the first year and every 2 weeks during the second year) compared with oral hydroxychloroquine (n = 36; 5 mg kg-1 per day) could reduce the frequency of RA development in individuals with palindromic rheumatism positive for rheumatoid factor and/or anticitrullinated protein antibody. The primary outcome was the development of persistent arthritis that fulfilled the 2010 RA classification criteria of the American College of Rheumatology and the European Alliance of Associations for Rheumatology, as evaluated by the participant clinicians during the 24 months of follow-up. Secondary outcomes included the frequency, intensity and duration of joint attacks, the proportion of patients in remission and the frequency of adverse events. In the primary analysis, in the modified full analysis set with failure imputation, 7 (20.6%) of the 34 participants treated with abatacept and 18 (50.0%) of the 36 participants treated with hydroxychloroquine developed RA during the 24 months of follow-up (P = 0.010; risk difference 29.4%, 95% confidence interval 8.2 to 50.7), meeting the primary endpoint. Using the available-data-only approach, the corresponding figures were 3 (10.0%) of 30 individuals and 10 (35.7%) of 28 individuals, respectively (P = 0.019). Compared with participants treated with hydroxychloroquine, participants treated with abatacept had a significantly longer time to progression to RA (hazard ratio 0.27, 95% confidence interval 0.07 to 0.96; log-rank test P = 0.0299). Abatacept was also associated with a reduced intensity of joint attacks and a higher frequency of symptom remission; however, there were no differences in the frequency of attacks between the two study drugs. No relevant differences in the evolution of antimodified peptide and/or protein antibody titers were observed between the two treatment arms. Both drugs were well tolerated. In patients with seropositive palindromic rheumatism, compared with hydroxychloroquine, abatacept given for 2 years reduced the risk of progression to RA and improved symptoms. ClinicalTrials.gov identifier NCT03669367 and EudraCT no. 2017-004543-20.

Zika virus (ZIKV) is a key member of the Flavivirus genus that has emerged as a major global public health concern. The fusion loop region (residues 98-110), located within domain II of the envelope protein, is highly conserved among flaviviruses, including ZIKV and Japanese encephalitis virus (JEV). However, the functional consequences of such conservation for cross-reactive immunity remains unclear. Here, we integrated bioinformatic analyses, functional assays in vitro and mouse models in vivo to systematically determine the effects of antibodies directed against the JEV fusion loop (FL) region on ZIKV infection. Sequence alignment and structural analysis revealed complete amino acid identity and almost identical three-dimensional conformations between the FL regions of the two viruses, providing a molecular basis for cross-reactivity. Antisera generated against the JEV FL region recognized ZIKV particles and displayed concentration-dependent bidirectional effects. Increased and decreased antibody levels respectively neutralized viral entry and replication, and facilitated infection via antibody-dependent enhancement (ADE). These effects were confirmed in vivo, in which high and low antibody doses reduced tissue pathology and improved survival, and increased viremia and exacerbated inflammatory responses, respectively. These findings highlight the importance of antibody concentration in determining whether cross-reactive responses to conserved structural elements engender neutralization or enhancement response. Our findings provide experimental evidence for assessing ZIKV susceptibility in JEV-vaccinated populations and offer structural insights for designing flavivirus vaccines that maximize protection while minimizing ADE risk. These findings further highlight potential pathogenic and clinical considerations for optimizing vaccine formulations to reduce cross-reactive enhancement risks.

To investigate longitudinal trends in the proportion of seronegative rheumatoid arthritis (RA) and to compare clinical outcomes between seronegative and seropositive patients in a Japanese single-centre cohort. We included 4,354 RA patients with a disease duration < 4years from the Institute of Rheumatology, Rheumatoid Arthritis cohort. Seronegativity was defined as the absence of both rheumatoid factor (RF) and anti-citrullinated peptide (CCP) antibody. We assessed the association between enrolment period and seronegativity using multivariable logistic regression. A mixed-effects model was used to compare 3-year trends in Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR), clinical disease activity index (CDAI), and the Japanese version of the Health Assessment Questionnaire (J-HAQ) scores between serostatus groups. The proportion of seronegative RA increased from 14.4% in 2000-2010 to 17.9% in 2011-2021. The later period was associated with seronegativity (adjusted odds ratio [95% confidence interval]: 1.32 [1.08-1.61]), negative RF (1.23 [1.05-1.45]), and negative anti-CCP antibody (1.31 [1.11-1.56]). At 3years, seronegative patients had better mean (95% confidence interval) CDAI (4.50 [3.48-5.53] vs. 5.57 [4.66-6.48]), DAS28-ESR (2.13 [1.93-2.32] vs. 2.54 [2.37-2.71]), and J-HAQ (0.43 [0.33-0.54] vs. 0.52 [0.42-0.61]) compared with seropositive patients. The proportions of patients achieving J-HAQ remission were comparable between the groups. The proportion of seronegative RA has increased significantly over time. Seronegative patients demonstrate a favourable disease course with a higher rate of remission compared with seropositive patients, thus identifying them as a distinct RA subgroup. Key Points • The proportion of seronegative rheumatoid arthritis increased over time in a large Japanese cohort. • Patients with seronegative rheumatoid arthritis had significantly higher rates of clinical remission over 3years. • The increasing proportion and distinct prognosis of seronegative rheumatoid arthritis may require specific management strategies.

To develop and validate a risk assessment model for interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). A retrospective study analyzed clinical data from 312 patients with RA treated at Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine between January 1, 2021 and June 30, 2024. Patients were divided into an RA-only group and an RA-ILD group based on the presence of ILD. Demographic characteristics, laboratory test results, clinical manifestations, disease activity scores, medication history, joint X-ray findings, and traditional Chinese medicine (TCM) syndrome types were collected as potential predictors. Variables were screened using univariable analysis and LASSO regression, and binary logistic regression was used to build the model and construct a nomogram using the rms package in R software. The discrimination and clinical utility of this model were assessed via receiver operating characteristic (ROC) and decision curves, and calibration was evaluated using Bootstrap-resampled (1000 iterations) calibration curves. A LightGBM machine learning model was also developed based on the selected predictors, and its performance was evaluated using ROC and precision-recall (PR) curves. Five-fold cross-validation was employed to further assess the robustness of the predictors. Multivariate logistic regression identified sex, age, anti-cyclic citrullinated peptide (CCP) antibody, disease activity score in 28 joints (DAS28) based on erythrocyte sedimentation rate (ESR), Krebs von den Lungen-6 (KL-6), international normalized ratio (INR), activated partial thromboplastin time (APTT), and methotrexate use as independent predictors of RA-ILD (all P<0.05). The model showed excellent discrimination with an area under the curve (AUC) of 0.976. Calibration curves showed strong agreement between predicted and observed probabilities, with an optimism-corrected slope approaching unity (0.9973). Decision curve analysis demonstrated a high net clinical benefit. The LightGBM model yielded an ROC AUC of 0.8464 and a PR AUC of 0.9417. In five-fold cross-validation, all ROC AUC values were greater than 0.65. The developed risk assessment model for ILD in patients with RA indicates high predictive ability and clinical utility.

Objective: to study clinical and imaging characteristics in patients with rheumatoid arthritis (RA) with atlantoaxial joint involvement. Material and methods. A total of 60 patients with RA were examined; mean age was 53.6±12.4 years. Median DAS28-CRP was 5.1 [4.8; 5.3], and median disease duration was 120 [66; 300] months. Extended clinical assessment included evaluation of neurological status, components of neuropathic pain and central sensitization, quality of life, and the degree of functional impairment. Magnetic resonance imaging (MRI) of the craniovertebral junction (CVJ) was performed with assessment of structural changes and measurement of five craniometric parameters to detect displacement of the CII odontoid process. Results and discussion. Clinical signs of cervical spine (C-spine) involvement were present in 91.7% of patients: neck and head pain, varying degrees of activity limitation due to neck pain, and neurological manifestations. MRI revealed CVJ changes in 90% (n=54) of patients: structural abnormalities in 81.7% and displacement of the CII odontoid process in 68.3%. The strongest correlations of structural changes were found with the presence of neck pain, low quality-of-life scores (EQ-5D), high RA activity, peripheral joint erosions on radiographs, arterial hypertension, high body mass index, and the absence of systemic manifestations of the disease. Craniometric abnormalities were associated (p&lt;0.05) with older age, concomitant osteoporosis, poorer quality of life, neuropathic pain, features of the RA course (duration, positivity for anti-cyclic citrullinated peptide antibodies, small joint involvement at onset, functional limitations, fewer systemic manifestations), elevated CRP, more advanced radiographic stage, and glucocorticoid use. Long-term therapy with nonsteroidal anti-inflammatory drugs and biologic agents was associated with less pronounced MRI changes (p&lt;0.05). Conclusion. Based on the study, the risk factors for C-spine involvement in RA patients are neck pain, certain features of the RA course, comorbidity, functional limitations (HAQ), and low quality of life (EQ-5D).

Introduction Early-phase arthritis can manifest with significant clinical aggression despite minimal symptomatic inflammation. Intervention at an early stage is critical to prevent irreversible structural damage and preserve longterm joint function. Case description We present the case of a 41-year-old male referred to the Rheumatologic Outpatient Clinic with a one-month history of bilateral hand and feet arthralgia. Patient reported significant morning stiffness (lasting 3060 minutes), although nocturnal pain was absent. Physical examination revealed tenderness in several metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints; joint swelling was not present at the time of the examination. A family history revealed an aggressive form of rheumatoid arthritis (RA) in the patient’s mother. The laboratory tests indicated slightly elevated values of inflammatory markers and highly elevated anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor. The ultrasonographic examination showed no synovial hypertrophy but identified swelling of the extensor tendon of the right second MCP joint (Fig. 1), bilateral tenosynovitis of the second finger flexors and the right hallux flexor. Based on the American College of Rheumatology/European Alliance of Associations for Rheumatology criteria, the patient was diagnosed with RA. The initial treatment was methotrexate (MTX) and prednisone. Due to the patients’ intolerance, MTX was changed to hydroxychloroquine. The patient remained non-compliant due to reported malaise; therefore, remained on low-dose prednisone monotherapy. Arthralgia in the hands and feet persisted. With disease progression, clinically evident inflammatory changes developed in the hands, characterised by erythema and soft tissue swelling in the metacarpophalangeal joint region (Fig. 2). After three months of ineffective therapy, an ultrasound identified erosive changes in the right second MCP joint (Fig. 3) and left second proximal interphalangeal joint. Given the aggressive clinical course and objective evidence of joint destruction, initiation of biological therapy was indicated. Conclusions Patients presenting with high anti-CCP titers (ACPA-positive) require prompt and intensive treatment, along with frequent rheumatologic monitoring. This case indicates the importance of musculoskeletal ultrasonography in detecting early structural changes and monitoring subclinical activity that may be overlooked by conventional laboratory tests or physical assessments.

Immune dysfunction in rheumatoid arthritis (RA) is a contributing factor to the development of peripheral neuropathy (PN). The objective of our study was to investigate the biological and clinical factors associated with PN in patients with RA. We conducted a retro-prospective cross-sectional study. A total of 63 patients with RA were included. They were divided into two groups, 18 with PN and 45 without PN. Participants with PN were those with a pathological electroneuromyogram (ENMG) with or without signs and symptoms of PN. Blood samples were taken for the measurement of rheumatoid factor (RF) and C-reactive protein (CRP). The concentration of anti-citrullinated peptide antibodies (ACPA) were collected from patient records. The significance threshold was set at a p-value <0.05. The majority of participants, 82.5% were female. The mean age was 51.86 ± 13.07 years. PN was present in 28.6% of the participants. RF and ACPA were positive in 71.4 and 77.8% of the participants, respectively. Severely active RA was significantly associated with the presence of PN (p < 0.001, OR = 55.13). RF concentrations were significantly higher in patients with PN. The area under the ROC curve for RF concentration in predicting PN in patients with RA was 0.7 (AUC = 0.7), patients with an RF > 169.10 IU/mL had a significant risk of presenting PN (p = 0.003, OR = 8.20). Severe rheumatoid arthritis is associated with PN. Inflammatory markers may play a key role in the pathogenesis and may provide valuable guidance for the early diagnosis of PN in RA.

Introduction Rheumatoid arthritis (RA) is a type of autoimmune disorder that can manifest itself by affecting various organs, predominantly joints. Pulmonary involvement is being defined as highly associated with substantial morbidity and mortality, with male sex, late onset, smoking history and high cyclic citrullinated peptide antibodies count being the main risk factors. Respiratory manifestations are usually present in patients already diagnosed with RA; however, they can also be the presenting feature. The spectrum of lung involvement is vast, with the most common being interstitial lung disease (ILD), especially usual interstitial pneumonia, pleuritis, rheumatoid nodules and airway disease. It is estimated that 10% of RA patients will suffer from significant ILD, and up to 60% will develop subclinical lung disease. Notably, patients with RA have an increased risk of lung cancer, which poses a significant diagnostic challenge. Case report A 70-year-old male with a 30-pack-year smoking history, arterial hypertension and rheumatoid arthritis was referred to the Institute of Tuberculosis and Lung Disease after multiple pulmonary nodules were detected on a chest computed tomography (CT) before initiation of immunosuppressive therapy with leflunomide. The most prominent nodule containing necrosis and measuring 13 × 21 mm was biopsied and diagnosed as a RA-nodule. The patient subsequently underwent follow-up CTs at least once a year. In which multiple scattered nodules, intermittent pleural effusions mainly on the left and ground-glass opacities (GGOs) predominantly in the right lower lobe (RLL) were identified. After 3 years of observation, in 2018, a progressive increase in the volume of GGO in RLL was noticed, with a growing solid component of the lesion reaching 64 × 27 mm by 2019, raising suspicion of cancerous growth, which was later confirmed in 2020. After the diagnosis, the patient underwent a wedge resection of the right lower lobe and was lost to follow-up in 2022. Conclusions Cancer is one of the leading causes of death in rheumatoid patients. The hazard ratio of lung cancer in RA patients revolves around 1.5 compared with the non-RA population. Thus, RA patients with risk factors such as male sex and a history of smoking should be screened for lung cancer. The guidelines of the American College of Rheumatology indicate that high-resolution chest CT may be used for screening patients for lung cancer, besides other pulmonary involvement, with the frequency being guided by individual clinical symptoms.

Introduction Ocrelizumab is a humanised anti-CD20 monoclonal antibody used in the treatment of multiple sclerosis (MS) by targeting B-cells to reduce autoimmune demyelination. It is generally well tolerated, although rare pulmonary toxicities, including interstitial lung disease and organising pneumonia (OP) have been reported. Migratory ground-glass opacities and consolidations are common radiological features in OP, with systemic symptoms such as fever. Drug-induced OP should be suspected when infectious and autoimmune causes are excluded, and radiological abnormalities improve after drug withdrawal. Case description A 51-year-old man with MS treated with ocrelizumab presented with recurrent fever up to 39°C since 8 weeks and night sweats, without cough nor dyspnea. Chest computed tomography scan revealed diffuse ground-glass opacities mainly in the upper lobes. Fever recurred despite antibiotic treatment and low-dose glucocorticosteroids. Laboratory investigations revealed elevated C-reactive protein with procalcitonin level with in normal range, normocytic anaemia, and elevated liver enzymes. High-resolution computed tomography (HRCT) demonstrated migratory peripheral ground-glass opacities with consolidations, reverse halo sign, and air bronchograms, which may be compatible with OP. Auto- immune serology (antinuclear antibodies, anti-neutrophilic cytoplasmic autoantibodies, anti-cyclic citrullinated peptide antibodies) and viral tests (cytomegalovirus, Epstein-Barr virus) were negative. Pulmonary function tests found normal lung volumes and low diffusing capacity of lung for carbon monoxide (DLCO, 55% predicted). Bron choalveolar lavage cultures excluded bacterial, viral, and fungal infections. Ocrelizumab therapy was stopped. Three months after cessation on ocrelizumab, HRCT confirmed almost complete resolution of pulmonary infiltrates and improvement in DLCO (67% predicted). No different etiological mechanism was detected, and MS remained clinically stable. Conclusions This case highlights the importance of maintaining a high index of suspicion for drug-induced pulmonary toxicity in patients receiving anti-CD20. Although ocrelizumab is generally well tolerated, awareness of rare but potentially reversible complications such as OP is essential to ensure prompt diagnosis, appropriate management, and favourable clinical outcomes.

Arthralgia, an early manifestation preceding definite rheumatoid arthritis (RA), represents a critical window to identify high-risk individuals and implement timely interventions. However, the immunopathologic mechanisms underlying the transition from arthralgia to established RA remain incompletely defined. We employed a multiomics strategy integrating peripheral immune cell phenotyping, serum proteomics, and autoantibody profiling to investigate the immunopathologic continuum from preclinical to established RA. A prospective cohort of 346 patients with recent-onset arthralgia was enrolled. Participants included healthy controls, self-limiting arthralgia (SLA), arthralgia at risk of RA (at-risk individuals, ARI), early RA, and established RA. RA development in ARI was ascertained through 24-month follow-up. Compared with SLA, ARI showed immune dysregulation, including reduced Treg cells and a lower Treg/Th17 cell ratio, with related changes persisting into early RA. Serum proteomics revealed upregulation of C5, α-1-B glycoprotein, RPUSD4, WDR87, and FUBP2, which showed inverse associations with Treg cells. Autoantibody profiling identified stage-specific reactivity, with ARI showing elevated antibodies against stress-related proteins. Within 24 months, 18.4% of ARI progressed to RA (converters). Baseline immunophenotypic differences between converters and nonconverters were comparable, whereas longitudinal paired analyses revealed a reduction in Treg cells and Treg/Th17 cell ratio. Treg/Th17 cell ratio (area under the curve [AUC] 0.734) outperformed anti-cyclic citrullinated peptide (CCP; AUC 0.611) in discriminating ARI from SLA, particularly in patients who are anticitrullinated peptide antibodies negative (AUC 0.729). Combining Treg cells, anti-CCP and Treg/Th17 cell ratio improved classification performance (AUC 0.783). These findings delineate a critical transition from reversible immune dysregulation to established autoimmunity along the arthralgia-RA continuum, suggesting that Treg cell-related dysregulation may be associated with progression toward persistent inflammatory arthritis.

Chronic myeloid leukemia (CML) is a hematologic malignancy originating from hematopoietic stem cells with the fusion oncogene BCR-ABL1 on the Philadelphia chromosome, which drives the abnormal proliferation of leukemic blast cells within the bone marrow microenvironment. While previous research has primarily focused on the hematopoietic compartment, the functional contribution of the bone marrow microenvironment to the CML pathology remains understudied. We investigated the changes in the peripheral nervous system in the bone marrow with myeloid leukemia via immunofluorescence staining of tyrosine hydroxylase (TH) and calcitonin gene-related peptide (CGRP) antibodies in mouse with NUP98-HOXA9- and BCR-ABL1-expressing myeloid leukemia. We found that the TH-positive fibers were significantly reduced, while no overt changes were observed in CGRP-positive nerves in the bone marrow. The reduction in TH-positive nerve cells was also evident in the spleen. Human patient gene expression data suggested that the levels of sympathetic nerve receptor expression change during the blastic transformation of human CML. Our findings indicate that the sympathetic nervous system regulates the pathogenesis of myeloid leukemia and could play a crucial role in the disease progression of myeloid leukemia.

Dynamic salivary gland scintigraphy in rheumatoid arthritis: Association with disease activity.

Elderly-Onset Seronegative Inflammatory Arthritis: A Narrative Review and Practical Approach.

Anti-cyclic citrullinated peptide antibodies (ACPAs) are associated with more aggressive rheumatoid arthritis disease. We aimed to determine the effect of ACPA serostatus on survival free from revision, all-cause reoperation, and recurrence of coronal plane deformity in patients with rheumatoid arthritis (RA) undergoing silicone metacarpophalangeal (MCP) arthroplasty. We retrospectively identified silicone MCP arthroplasties performed in patients with RA with known ACPA serostatus from 2000 to 2022. Kaplan-Meier estimates were used to report survival free from revision, all-cause reoperation, and recurrence of coronal plane deviation >10° on postoperative radiographs. We analyzed ACPA serostatus as a risk factor for these endpoints using cluster-robust Cox proportional hazard models, adjusting for patient sex. We included 133 joints in 39 ACPA seropositive patients (9.0 years mean follow-up) and 63 joints in 21 ACPA seronegative patients (5.7 years mean follow-up). Survival free from revision, all-cause reoperation, and recurrent coronal deformity was higher in seropositive patients than in seronegative patients. Anti-cyclic citrullinated peptide antibody seropositivity was significantly associated with lower risk for revision (hazard ratio [HR] = 0.16), all-cause reoperation (HR = 0.20), and recurrent coronal plane deviation >10° (HR = 0.28). Seropositive patients had longer average time to recurrent coronal deviation >10° (3.5 years vs 1.3 years) and less coronal deviation at final radiographic follow-up (15.9° vs 21.5°). Anti-cyclic citrullinated peptide antibody seropositivity is associated with improved silicone MCP implant survivorship and lower risk of recurrent coronal plane deformity in patients with rheumatoid arthritis. More work is needed to better understand the biologic basis of these findings.

Objectives: Parkinson’s disease (PD) is a heterogeneous neurodegenerative condition characterized by both motor and systemic non-motor features. Engaging peripheral immune signatures in pathophysiology has recently gained attention; however, their prognostic and diagnostic roles remain to be better defined. This study investigatedlongitudinal behavioral and cognitive performance in PD alongside neuroinflammatory plasma signatures, with an emphasis on differentiating PD from Stiff-person syndrome (SPS) based on immune and clinical parameters. Material and Methods: One hundred and thirty-three PD participants were prospectively enrolled from Guru Gobind Singh Medical College, Faridkot. Standardized evaluations, including unified PD rating scale (UPDRS) motor and non-motor subscales and the PD-cognitive functional rating scale, were administered at baseline and on routine clinic follow-up. Plasma concentrations of Clusterin (CLU), glutamic acid decarboxylase (anti-GAD) antibody, and cyclic citrullinated peptide (anti-CCP) antibody were quantified by enzyme-linked immunosorbent assay. Relationships among biomarkers and clinical indices were examined through Pearson’s correlation coefficients, while hierarchical regression modeling served to elucidate independent prognostic trajectories. Distinction from SPS relied on stratigraphy of anti-GAD antibody titers in conjunction with divergent clinical and demographic features. Results: Follow-up assessments revealed marked reductions across all evaluated clinical domains (UPDRS-I: P &lt; 0.001; UPDRS-II: P &lt; 0.001; UPDRS-CF: P &lt; 0.001; and PD cognition functional rating scale [PD-CFRS]: P &lt; 0.001). Biomarker profiling demonstrated reliable declines in CLU concentration (from 125.68 ± 7.32 to 115.16 ± 7.69 µg/mL; P &lt; 0.001) and anti-CCP antibody titers (from 36.47 ± 9.91 to 30.64 ± 9.66 EU/mL; P &lt; 0.001). In contrast, anti-GAD antibody levels remained unchanged. Correlation analysis indicated a moderate positive relationship between anti-CCP concentrations and UPDRS-CF scores (r = 0.30). Hierarchical multiple regression revealed that baseline UPDRS-I (β = 0.256, P = 0.003) and UPDRS-II (β = 0.190, P = 0.029) independently predicted post-treatment with standard anti-Parkinson’s therapy UPDRS-CF levels. None of the enrolled subjects fulfilled clinical or serological criteria for SPS. Conclusion: These findings extend the current understanding of the interplay between plasma CLU, anti-CCP antibodies, and cognitive-behavioral deterioration in PD. The degree of motor and non-motor symptomatology at baseline emerges as a robust determinant of subsequent cognitive decline. Anti-GAD antibody screening retains its diagnostic value in differentiating Parkinson’s disease from SPS in ambiguous presentations. Cumulative use of plasma markers alongside clinical scoring systems strengthens both diagnostic accuracy and prognostic stratification in PD.

Objective.Individuals with serum elevations of anti–cyclic citrullinated peptide (anti-CCP) antibodies are at increased risk for future rheumatoid arthritis (RA). No pharmacologic interventions have been approved for the prevention of RA in such at-risk individuals. However, hydroxychloroquine (HCQ) is used without supporting clinical trial evidence.Methods.In this phase 2 randomized trial, individuals at risk for RA with anti-CCP3 ≥2 times the upper limit of normal (ULN) were assigned to receive HCQ or placebo for 12 months, with up to 24 months of postdrug follow-up. The primary outcome was the development of clinical RA, as defined in the protocol, at 36 months. Secondary outcomes included safety, development of inflammatory arthritis (IA), and participant-reported joint symptoms.Results.Of 144 randomized participants, 71 were assigned to HCQ and 73 to placebo. In the modified intent-to-treat population, clinical RA occurred in 21 of 69 (30.4%) participants in the HCQ group and 24 of 73 (32.9%) in the placebo group. The risk of clinical RA at 36 months was 0.336 with HCQ and 0.394 with placebo (difference −0.058; 95% confidence interval −0.336 to 0.220; P = 0.52). Results for IA were similar. The occurrence and severity of joint symptoms were not observed to differ between groups. Adverse event incidence was similar between groups.Conclusion.In this trial involving individuals with anti-CCP3 levels ≥2 times the ULN, 12 months of HCQ did not prevent the development of clinical RA at 36 months.

The purpose of this study was to determine the cumulative incidence of diagnosis switching, drug-free remission, and initiation of a biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) in individuals with seronegative rheumatoid arthritis (RA). Adult residents of Olmsted County, Minnesota, with incident seronegative (rheumatoid factor negative/anti-cyclic citrullinated peptide antibody negative) RA meeting the 1987 and/or 2010 American College of Rheumatology classification criteria were included. Data were collected from January 1, 2005, to December 31, 2023, through manual chart review. Drug-free remission was defined as a period of at least six months where the individual was no longer taking treatment for RA and did not have evidence of active inflammatory arthritis upon evaluation by a rheumatologist. We calculated the 10-year cumulative incidence of a change in diagnosis, adjusting for the competing risk of death, and of drug-free remission and initiation of a b/tsDMARD, adjusting for the competing risks of death or change in diagnosis. A total of 176 individuals with seronegative RA (68% women) were included. The 10-year cumulative incidence of a change in diagnosis was 12.8% (95% confidence interval [CI] 8.7%-18.9%). The most common change in diagnosis was to spondyloarthritis (4%). The 10-year cumulative incidence of drug-free remission and initiation of a b/tsDMARD was 26.6% (95% CI 20.7%-34.2%) and 19.9% (95% CI 14.7%-26.9%), respectively. Over a median follow-up of 11.8 years, 49 individuals entered drug-free remission. After initial diagnosis of seronegative RA, about 13% of individuals had a change in diagnosis and a quarter experienced drug-free remission within 10 years.