Juvenile Dermatomyositis (JDM) is the most common inflammatory myopathy in pediatrics. This study evaluates the role of Natural Killer (NK) cells in Juvenile Dermatomyositis (JDM) pathophysiology. The study included 133 untreated JDM children with an NK cell count evaluation before treatment. NK cell subsets (CD56low/dim vs. CD 56bright) were examined in 9 untreated children. CD56 and perforin were evaluated in situ in six untreated JDM and three orthopedic, pediatric controls. 56% of treatment-naive JDM had reduced circulating NK cell counts, designated \"low NK cell\". This low NK group had more active muscle disease compared to the normal NK cell group. The percentage of circulating CD56low/dim NK cells was significantly lower in the NK low group than in controls (0.55% vs. 4.6% p < 0.001). Examination of the untreated JDM diagnostic muscle biopsy documented an increased infiltration of CD56 and perforin-positive cells (p = 0.023, p = 0.038, respectively). Treatment-naive JDM with reduced circulating NK cell counts exhibited more muscle weakness and higher levels of serum muscle enzymes. Muscle biopsies from treatment-naive JDM displayed increased NK cell infiltration, with increased CD56 and perforin-positive cells.

BACKGROUND: Patients with ankylosing spondylitis (AS) frequently suffer from comorbid sleep disorders, exacerbating the burden of the disease and affecting their quality of life.
OBJECTIVE: To investigate the clinical significance of serum inflammatory factors, health index and disease activity scores in patients with AS complicated by sleep disorders.
METHODS: A total of 106 AS patients with comorbid sleep disorders were included in the study. The patients were grouped into the desirable and undesirable prognosis groups in accordance with their clinical outcomes. The serum levels of inflammatory factors, including C-reactive protein, erythrocyte sedimentation rate, interleukin (IL)-6, tumour necrosis factor-α and IL-1β, were measured. Disease activity scores, such as the Bath AS functional index, Bath AS disease activity index, Bath AS metrology index and AS disease activity score, were assessed. The health index was obtained through the Short Form-36 questionnaire.
RESULTS: The study found significant associations amongst serum inflammatory factors, health index and disease activity scores in AS patients with comorbid sleep disorders. Positive correlations were found between serum inflammatory factors and disease activity scores, indicating the influence of heightened systemic inflammation on disease severity and functional impairment. Conversely, negative correlations were found between disease activity scores and health index parameters, highlighting the effect of disease activity on various aspects of health-related quality of life. Logistic regression analysis further confirmed the predictive value of these factors on patient outcomes, underscoring their potential utility in risk assessment and prognostication.
CONCLUSIONS: The findings demonstrate the intricate interplay amongst disease activity, systemic inflammation and patient-reported health outcomes in AS patients complicated by sleep disorders. The results emphasise the need for comprehensive care strategies that address the diverse needs and challenges faced by these patients and underscore the potential relevance of serum inflammatory factors, health index and disease activity scores as prognostic markers in this patient population.

BACKGROUND: Juvenile Dermatomyositis (JDM) is a rare autoimmune disease characterized by skin and muscle inflammation. The loss of nail fold capillary end row loops (ERL) is evidence of small vessel involvement in JDM. This study aimed to examine the specific association of ERL over the disease course with evidence of JDM disease damage.
METHODS: We analyzed data from 68 initially treatment-naïve JDM children who had been observed for at least five years with multiple ERL density assessments. The JDM disease course were categorized into monocyclic short, monocyclic long, polycyclic, and chronic. The ERL capillary count was cumulatively evaluated using the area under the curve (AUC) method.
RESULTS: The mean ERL density for the treatment-naive JDM was significantly lower than that of their healthy age-matched controls (4.8 ± 1.6 /mm vs. 7.9 ± 0.9 /mm; p < 0.0001). The ERL AUC was significantly lower in children with a chronic disease course compared to those with a monocyclic short (p = 0.001) or monocyclic long disease course (p = 0.013). JDM patients with lipodystrophy had lower ERL AUC than those without lipodystrophy (p = 0.04). There was no association between ERL AUC and calcifications or fractures.
CONCLUSIONS: Persistently decreased ERL capillary density, reflected by low ERL AUC, is associated with a chronic disease course and lipodystrophy in JDM. Despite medical therapy, the mean ERL count remained below normal even after five years, particularly in polycyclic and chronic cases. It is not clear that restoring normal capillary density is currently feasible in children with JDM.

OBJECTIVE: This study aims to assess the association of obesity and CRP concentrations in adult patients with rheumatoid arthritis (RA), and its influence on measures of disease activity.
METHODS: A comprehensive search was performed using Scopus, Web of Science, MEDLINE, and EMBASE, from the time of their inception to November 2021. Observational studies that evaluated the association between CRP concentrations and obesity or overweight in patients with RA were considered eligible. Correlation coefficients were pooled using the inverse variance method, while effect sizes were pre-calculated for adjusted standardized regression coefficients (β).
RESULTS: A total of 10 studies, which comprised 4024 patients, were included in this systematic review. Individually, most studies report a significant association between CRP concentrations and a higher body mass index or other adiposity measures, but the statistical significance was not sustained when pooling their data together. Through the estimates provided in the present review, it is noted that CRP tends to be more elevated in female patients with RA that have a higher BMI. However, this association is not present in men.
CONCLUSIONS: CRP tends to be elevated in female patients with RA that have a higher BMI. Further research is required to assess this possible sex-related difference and to aid shared decision-making in order to avoid over-treatment and increased burden in patients with obesity and RA. PROSPERO registration number: CRD42022314580.

UNASSIGNED: Juvenile Dermatomyositis (JDM) is a rare autoimmune disease characterized by skin and muscle inflammation. The loss of nail fold capillary end row loops (ERL) is evidence of small vessel involvement in JDM. This study aimed to examine the association of ERL over the disease course and evidence of disease damage.
UNASSIGNED: We analyzed data from 68 initially treatment-naïve JDM children who had been observed for at least five years with multiple ERL density assessments. The JDM disease courses were categorized into monocyclic short, monocyclic long, polycyclic, and chronic. The ERL capillary count was cumulatively evaluated using the area under the curve (AUC) method.
UNASSIGNED: The mean ERL density for the treatment-naive JDM was significantly lower than that of their healthy controls (4.8±1.6 /mm vs. 7.9±0.9 /mm; p <0.0001). The ERL AUC was significantly lower in children with chronic disease course compared to those with monocyclic short (p =0.001) or monocyclic long disease course (p =0.013). JDM patients with lipodystrophy had lower ERL AUC than those without lipodystrophy (p =0.04). There was no association between ERL AUC and calcifications or fractures.
UNASSIGNED: Persistently decreased ERL capillary density, evident by low ERL AUC, is associated with chronic disease course and lipodystrophy in JDM. Despite medical therapy, the mean ERL count remained below normal even after five years, particularly in polycyclic and chronic cases. Therefore, the goal of restoring normal capillary density in children with JDM might be challenging and require novel therapeutic strategies targeting their underlying endothelial dysfunction.

Otoferlin mRNA expression is increased in JDM patients\' PBMCs and muscle compared to healthy controls. This study aims to evaluate the role of otoferlin in JDM disease pathophysiology and its association with disease activity in untreated children with JDM. A total of 26 untreated JDM (88.5% female, 92.3% white, non-Hispanic) and 15 healthy controls were included in this study. Otoferlin mRNA expression was determined by qRT-PCR before and a few months after therapy. Detailed flow cytometry of various cell surface markers and cytoplasmic otoferlin was performed to identify cells expressing otoferlin. In addition, muscle otoferlin expression was evaluated in situ in six untreated JDM patients and three healthy controls. There was a significant increase in otoferlin expression in JDM children compared to controls (Median 67.5 vs. 2.1; p = 0.001). There was a positive correlation between mRNA otoferlin expression and the following disease activity markers: disease activity scores (DAS)-total (rs = 0.62, p < 0.001); childhood myositis assessment scale (CMAS) (rs = -0.61, p = 0.002); neopterin (rs = 0.57, p = 0.004) and von Willebrand factor antigen (vWF: Ag) (rs = 0.60, p = 0.004). Most of the otoferlin-positive cells were unswitched B cells (63-99.4%), with 65-75% of them expressing plasmablast markers (CD19+, IgM+, CD38hi, CD24-). The findings of this pilot study suggest that otoferlin expression is associated with muscle weakness, making it a possible biomarker of disease activity. Additionally, B cells and plasmablasts were the primary cells expressing otoferlin.

OBJECTIVE: This study determined if an accessible, serologic indicator of vascular disease activity, the von Willebrand factor antigen (vWF:Ag), was useful to assess disease activity in children with juvenile dermatomyositis (JDM), a rare disease, but the most common of the pediatric inflammatory myopathies.
METHODS: A total of 305 children, median age 10 years, 72.5% female, 76.5% white, with definite/probable JDM at diagnosis, were enrolled in the Ann & Robert H. Lurie Cure JM Juvenile Myositis Repository, a longitudinal database. Disease Activity Score (DAS) and vWF:Ag data were obtained at each visit. These data were analyzed using generalized estimating equation (GEE) models (both linear and logistic) to determine if vWF:Ag reflects disease severity in children with JDM. A secondary analysis was performed for untreated active JDM to exclude the effect of medications on vWF:Ag.
RESULTS: The vWF:Ag test was elevated in 25% of untreated JDM. We found that patients with elevated vWF:Ag had a 2.55-fold higher DAS total (CI95: 1.83-3.27, p < 0.001). Patients with difficulty swallowing had 2.57 higher odds of elevated vWF:Ag (CI95: 1.5-4.38, p < 0.001); those with more generalized skin involvement had 2.58-fold higher odds of elevated vWF:Ag (CI95: 1.27-5.23, p = 0.006); and those with eyelid peripheral blood vessel dilation had 1.32-fold higher odds of elevated vWF:Ag (CI95: 1.01-1.72, p = 0.036). Untreated JDM with elevated vWF:Ag had more muscle weakness and higher muscle enzymes, neopterin and erythrocyte sedimentation rate compared to JDM patients with a normal vWF:Ag.
CONCLUSIONS: vWF:Ag elevation is a widely accessible concomitant of active disease in 25% of JDM.

Easily accessible biomarkers are urgently needed to evaluate immune activation in Juvenile Dermatomyositis (JDM). The goal of this retrospective study is to define immunological and clinical differences between untreated JDM patients with either normal or elevated (>10 mmol/L) levels of neopterin, a biomarker of macrophage activation. We included all JDM with neopterin data obtained before initiating medical therapy. We assessed T, B, NK cell populations, muscle enzymes, and disease activity scores for skin (sDAS), muscle (mDAS), total (tDAS), the duration of untreated disease, disease course, and myositis-specific antibody (MSA). Seventy-nine percent of 139 untreated JDM patients had elevated serum neopterin. The group with elevated neopterin had significantly more active disease: tDAS 11.9 vs. 8.1 (p < 0.0001), mDAS 5.8 vs. 3.1 (p < 0.0001), sDAS 6.1 vs. 4.9 (p = 0.0002), aldolase 24.0 vs. 7.6 U/L (p < 0.0001), von Willebrand factor antigen (p < 0.0001), and ESR 19.8 vs. 11.5 mm/hr (p = 0.01). The flow cytometry documented both reduced T cells (1494 vs. 2278/mm3, p = 0.008) and NK cells (145 vs. 240/mm3, p = 0.003). TNFα-308AA/AG polymorphism was more common in children with elevated neopterin than TNFα-308GG (p 0.05). We conclude that the availability of neopterin data will contribute to the rapid assessment of untreated JDM disease activity.

Sustained DMARD-free remission (SDFR) is increasingly achievable. The pathogenesis underlying SDFR development is unknown and patient characteristics at diagnosis poorly explain whether SDFR will be achieved. To increase the understanding, we studied the course of disease activity scores (DAS) over time in relation to SDFR development. Subsequently, we explored whether DAS course could be helpful identifying RA patients likely to achieve SDFR.
772 consecutive RA patients, promptly treated with csDMARDs (mostly methotrexate and treat-to-target treatment adjustments), were studied for SDFR development (absence of synovitis, persisting minimally 12 months after DMARD stop). The course of disease activity scores (DAS) was compared between RA patients with and without SDFR development within 7 years, using linear mixed models, stratified for ACPA. The relation between 4-month DAS and the probability of SDFR development was studied with logistic regression. Cumulative incidence of SDFR within DAS categories (< 1.6, 1.6-2.4, 2.4-3.6, ≥ 3.6) at 4 months was visualized using Kaplan-Meier curves.
In ACPA-negative RA patients, those achieving SDFR showed a remarkably stronger DAS decline within the first 4 months, compared to RA patients without SDFR; - 1.73 units (95%CI, 1.28-2.18) versus - 1.07 units (95%CI, 0.90-1.23) (p < 0.001). In APCA-positive RA patients, such an effect was not observed, yet SDFR prevalence in this group was low. In ACPA-negative RA, DAS decline in the first 4 months and absolute DAS levels at 4 months (DAS4 months) were equally predictive for SDFR development. Incidence of SDFR in ACPA-negative RA patients was high (70.2%) when DAS4 months was < 1.6, whilst SDFR was rare (7.1%) when DAS4 months was ≥ 3.6.
In ACPA-negative RA, an early response to treatment, i.e., a strong DAS decline within the first 4 months, is associated with a higher probability of SDFR development. DAS values at 4 months could be useful for later decisions to stop DMARDs.

OBJECTIVE: To define the most appropriate imaging parameters in combined Fluorodeoxyglucose (FDG) PET/CT reflecting the inflammatory burden in large vessel vasculitis.
METHODS: Two readers retrospectively graded disease extent and activity in 17 LVV patients using visual and quantitative scores in FDG PET and contrast enhanced CT. Visual PET scores were assessed corresponding to FDG-uptake vs. liver uptake (score 0-3). CT visual scoring referred to the affected vessel extent (score 1-5). Quantitative PET scores relied on normalized SUV ratios. For quantitative CT evaluation vessel wall thickness was correlated with FDG- uptake. Imaging scores were correlated with Erythrocyte Sedimentation Rate (ESR) and C-reactive protein (CRP). Intraclass correlation coefficients (ICC) were measured for interreader reliability.
RESULTS: Visual PET scores showed stronger correlation with CRP (ρ 0.640, 0.541 for reader I and II, respectively) than with ESR levels (ρ 0.477, 0.447). Quantitative PET showed strongest correlation with CRP using liver as reference tissue. Visual CT scores did neither correlate with ESR nor with CRP levels (ESR: ρ 0.085, 0.294 with p 0.743, 0.252; CRP: ρ 0.322, 0.395 with p 0.208, 0.116). Quantitative CT evaluation correlated with ESR levels in one reader (ρ 0.505, -0.026), however no correlation between quantitative CT measures and quantitative PET scores was found. Best ICC between readers was 0.994 for highest SUVavg vessel/highest SUVavg liver.
CONCLUSIONS: Visual and quantitative PET scores were superior to CT scores with best ICC and strongest correlations between quantitative PET score and inflammation markers especially when using vessel to liver ratios.