Search Results (58)

Objectives: Previous studies have suggested differences in vasculitic and eosinophilic phenotypes based on anti-neutrophil cytoplasmic antibody (ANCA) positivity in eosinophilic granulomatosis with polyangiitis (EGPA). However, their relevance under the 2022 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria remains unclear. We aimed to evaluate the clinical features and outcomes of EGPA according to myeloperoxidase (MPO)-ANCA status in a Korean cohort. Methods: We conducted a retrospective cohort study that included 57 patients with EGPA without proteinase 3-ANCA positivity who fulfilled the 2022 ACR/EULAR classification criteria. Patients were classified into MPO-ANCA-positive (n = 25) and MPO-ANCA-negative (n = 32) groups. Clinical manifestations, laboratory findings, and outcomes, including all-cause mortality, relapse, end-stage kidney disease (ESKD), cerebrovascular accident (CVA), and acute coronary syndrome (ACS), were compared between the two groups. Results: MPO-ANCA-positive patients exhibited higher Five-Factor Scores (1.0 [0.0–1.0] vs. 0.0 [0.0–1.0], p = 0.038), lower Short Form 36 Physical Component Summary scores (35.0 [19.7–56.3] vs. 52.5 [43.5–69.7], p = 0.048), and elevated systemic inflammation markers (higher erythrocyte sedimentation rate: 58.0 [16.0–97.5] mm/hr vs. 25.5 [7.0–63.8] mm/hr, p = 0.026). Constitutional symptoms were more frequent among MPO-ANCA-positive patients (n = 14 [56.0%] vs. n = 3 [9.4%], p < 0.001), whereas no significant differences were found in vasculitic or eosinophilic manifestations. Kaplan–Meier analysis revealed no differences in the overall (p = 0.36), relapse-free (p = 0.80), ESKD-free (p = 0.87), CVA-free (p = 0.26), or ACS-free (p = 0.94) survival rates between the two groups. Conclusions: In Korean patients with EGPA classified under the 2022 ACR/EULAR classification criteria, MPO-ANCA positivity, as compared to ANCA-negative status, was associated with a higher disease burden and poorer quality of life but not with distinct vasculitic or eosinophilic manifestations and adverse outcomes. Full article

Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibroinflammatory condition marked by tumefactive lesions, IgG4+ plasma cell-rich infiltrates, storiform fibrosis, and obliterative phlebitis. Its multisystem involvement and overlap with malignancies, infections, and immune disorders complicate diagnosis despite recent classification advances. This study summarizes diagnostic challenges, highlights the role of histopathology as per the 2019 classification criteria established by the American College of Rheumatology and the European League Against Rheumatism (ACR/EULAR), and explores emerging tools to improve diagnostic accuracy. ACR/EULAR classification emphasizes three cardinal histopathological features (storiform fibrosis, obliterative phlebitis, or dense lymphoplasmacytic infiltrates) combined with an IgG4+/IgG+ plasma cell ratio >40% and organ-specific IgG4+ thresholds. While serum IgG4 levels are often elevated, their poor specificity necessitates confirmatory biopsy. Diagnostic limitations include sampling variability due to patchy fibrosis, interobserver discrepancies in immunohistochemical interpretation, and differentiation from mimics like lymphoma. Emerging solutions incorporate novel biomarkers (plasmablasts, anti-annexin A11) and advanced techniques (flow cytometry, digital pathology). Future research directions should focus on AI-assisted pattern recognition, multi-omics profiling, and organ-specific criteria refinement. While histopathology remains the diagnostic cornerstone, a multidisciplinary approach integrating clinical, radiological, and laboratory data is vital. Innovations in biomarkers promise improved diagnostic accuracy and personalized care, balancing novel advancements with foundational pathological evaluation. Full article

Background/Objectives: The overlap syndrome of primary Sjögren syndrome (pSS) with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) (OvSD/pSS/AAV) has been reported in other studies. This study applied the new criteria for AAV proposed by the American College of Rheumatology/European Alliance of Associations for Rheumatology in 2022 (the ACR/EULAR criteria) to patients with pSS presenting signs and symptoms suggestive of small- and medium-vessel vasculitis. It also investigated the overall frequency of OvSD/pSS/AAV and the major contributing factors to its reclassification. Methods: This study included 116 patients with pSS from March 2005 to December 2020, according to the inclusion criteria, and defined signs and symptoms suggestive of small- or medium-vessel vasculitides as lung parenchymal lesions supporting AAV, peripheral neuropathy, and suspected renal vasculitis. The classification could be made when the total scores for microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are ≥5 points and the eosinophilic GPA (EGPA) score is ≥6 points. Results: The median age of the patients was 56.0 years, and 101 patients (87.1%) were women. In total, 95, 12, and 37 patients had lung parenchymal lesions supporting AAV, peripheral neuropathy, and suspected renal vasculitis, respectively. According to the ACR/EULAR criteria for AAV, 35 of 116 (30.2%) patients were reclassified as having OvSD/pSS/AAV. Among these 35 patients, 4 were reclassified as having both OvSD/pSS/MPA and OvSD/pSS/GPA and 1 as having both OvSD/pSS/MPA and OvSD/pSS/EGPA simultaneously. The major contributing factor to the reclassification of OvSD/pSS/AAV was ANCA positivity. Conclusions: The overall frequency of the reclassification of OvSD/pSS/AAV was 30.2% in pSS patients presenting signs and symptoms suggestive of small- and medium-vessel vasculitis. Its likelihood increased according to ANCA positivity. Full article

Background. Fibromyalgia Syndrome (FMS) is characterized by chronic widespread pain, sleep disturbances, fatigue and cognitive impairment. Methods. In this retrospective study, we analyzed data collected between 2017 and 2022 regarding Acetyl-L-Carnitine (ALC) as an add-on treatment in 183 adult patients with FMS according to the 2016 ACR (American College of Rheumatology) criteria and patients’ pain lasting for over three months. Patients with prior exposure to ALC or without informed consent were excluded. Results. Regarding efficacy, in the 137 analyzed patients, the change from baseline to the end of observation in Visual Analogue Scale score (VAS) was statistically significant, ranging from 75.9 ± 1.56 to 51.9 ± 1.99 (p < 0.001). Patients without FMS concomitant drug treatments achieved better VAS reduction than patients who were not drug-free at baseline. Regarding quality of life, a significant improvement in the Revised Fibromyalgia Impact Questionnaire (FIQ-R) score was evidenced, ranging from 75.1 ± 1.13 to 53.5 ± 1.34 (p < 0.001). The Short Form 12 Health Survey (SF12) scores showed a statistically significant improvement in both physical and mental components. Finally, the Pittsburgh Sleep Quality Index (PSQI) did not show a statistically significant difference from baseline. In the whole population, 23 patients (16.7%) reported Adverse Events (AEs), predominantly insomnia, shivering, headaches, and nausea. Only six patients reporting AEs discontinued the ALC treatment. Conclusions. This retrospective study evidenced the efficacy and safety of ALC in FMS patients. This may represent a useful approach, particularly for long-term treatments. Methodologically stronger studies will be necessary to validate our observations. Full article

Systemic lupus erythematosus (SLE) is a complex autoimmune disease that poses serious long-term patient burdens. (1) Background: SLE patient classification and care are often complicated by case heterogeneity (diverse variations in symptoms and severity). Large language models (LLMs) and generative artificial intelligence (genAI) may mitigate this challenge by profiling medical records to assess key medical criteria. (2) Methods: To demonstrate genAI-based profiling, ACR (American College of Rheumatology) 1997 SLE classification criteria were used to define medically relevant LLM prompts. Records from 78 previously studied patients (45 classified as having SLE; 33 indeterminate or negative) were computationally profiled, via five genAI replicate runs. (3) Results: GenAI determinations of the “Discoid Rash” and “Pleuritis or Pericarditis” classification criteria yielded perfect concurrence with clinical classification, while some factors such as “Immunologic Disorder” (56% accuracy) were statistically unreliable. Compared to clinical classification, our genAI approach achieved a 72% predictive success rate. (4) Conclusions: GenAI classifications may prove sufficiently predictive to aid medical professionals in evaluating SLE patients and structuring care strategies. For individual criteria, accuracy seems to correlate inversely with complexities in clinical determination, implying that improvements in AI patient profiling tools may emerge from continued advances in clinical classification efficacy. Full article

Background and Objectives: This study aimed to evaluate serum asprosin levels in female patients with fibromyalgia syndrome (FM), investigate their associations with clinical parameters such as disease severity, anxiety, and depression, and evaluate the potential of serum asprosin levels as a biomarker for fibromyalgia diagnosis. Materials and Methods: A total of 80 participants were included in the study, 40 women aged 18–60 years who were diagnosed with FM according to the American College of Rheumatology (ACR) 2016 criteria and 40 healthy women with similar sociodemographic characteristics to the patient group. All participants were measured for hemograms, biochemistry tests, and serum asprosin levels. Additionally, the Fibromyalgia Impact Questionnaire (FIQ), Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI) were administered to the patient group. Results: The median asprosin level in the case group was 15.01 (SD = 10.08–31.42), while in the control group it was 31.03 (SD = 25.14–35.7). The asprosin levels in the case group were significantly lower than those in the control group (p = 0.001). In contrast, AST, vitamin B12, and folic acid levels were significantly higher in the case group than in the control group. When all participants were evaluated, asprosin levels showed a significant positive correlation with systolic arterial blood pressure (Rho = 0.337, p = 0.002) and diastolic arterial blood pressure (Rho = 0.238, p = 0.033). A cut-off value of 17.72 ng/mL for asprosin levels in the diagnosis of fibromyalgia demonstrated a sensitivity of 60% and a specificity of 90%. Conclusions: Low asprosin levels may serve as a potential biomarker for the diagnosis of fibromyalgia in women. Full article

Background and Objectives: The heterogeneous clinical manifestations of fibromyalgia syndrome have led to the revision of diagnostic criteria in the last decade. The aim of this study was to determine the capability of clinical, psychological, and cognitive patient-related outcome measures (PROMs) to differentiate women with fibromyalgia syndrome (FMS) from women with localized or regional pain conditions. Materials and Methods: A diagnostic accuracy study was conducted. Clinical (pain intensity—NPRS; related disability—FIQ), psychological (anxiety/depressive levels—HADS-A/HADS-D), and cognitive (sleep quality—PSQI; pain hypervigilance—PVAQ-9) PROMs were collected in 129 women with FMS and 65 women with localized/regional chronic pain conditions. The area under the receiver operating characteristic (ROC) curve, cut-off point, sensitivity/specificity values, and positive and negative likelihood (LR) ratios of each variable were calculated. Results: Women with FMS showed higher levels of pain, related disability, and anxiety/depressive levels, worse sleep quality, and higher levels of hypervigilance (all, p < 0.001) than women without FMS. All PROMs showed excellent discriminatory power and good sensitivity (pain intensity: ROC 0.987, sensitivity 91.5%; related disability: ROC 0.980, sensitivity 93.8%; HADS-A: ROC 0.901, sensitivity 81.4%; HADS-D: ROC 0.906, sensitivity 85.3%; PSQI: ROC 0.909, sensitivity 79.1%; PVAQ-9: ROC 0.798, sensitivity 80.6%). Specificity was extremely small for all variables (<18%) except for pain hypervigilance (specificity: 34%). Conclusions: Women with FMS exhibited worse clinical, psychological, and cognitive variables than women with localized/regional chronic pain. Although all PROMs had good discriminatory power, related disability and pain hypervigilance were those showing the best models. These PROMs could be combined with the American College of Rheumatology (ACR) diagnostic criteria to better discriminate between women with and without FMS. Studies investigating the relevance of combining these PROMs with the ACR diagnostic criteria in clinical settings are needed. Full article

Autoimmune diseases represent a severe personal and healthcare problem that seeks novel therapeutic solutions. Mesenchymal stem cells (MSCs) are multipotent cells with interesting cell biology and promising therapeutic potential. The immunoregulatory effects of secretory factors produced by umbilical cord mesenchymal stem cells (UC-MSCs) were assessed on B lymphocytes from 17 patients with systemic lupus erythematosus (SLE), as defined by the 2019 European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE, and 10 healthy volunteers (HVs). Peripheral blood mononuclear cells (PBMCs) from patients and HVs were cultured in a UC-MSC-conditioned medium (UC-MSCcm) and a control medium. Flow cytometry was used to detect the surface expression of CD80, CD86, BR3, CD40, PD-1, and HLA-DR on CD19+ B cells and assess the percentage of B cells in early and late apoptosis. An enzyme-linked immunosorbent assay (ELISA) quantified the production of BAFF, IDO, and PGE2 in PBMCs and UC-MSCs. Under UC-MSCcm influence, the percentage and mean fluorescence intensity (MFI) of CD19+BR3+ cells were reduced in both SLE patients and HVs. Regarding the effects of the MSC secretome on B cells in lupus patients, we observed a decrease in CD40 MFI and a reduced percentage of CD19+PD-1+ and CD19+HLA-DR+ cells. In contrast, in the B cells of healthy participants, we found an increased percentage of CD19+CD80+ cells and decreased CD80 MFI, along with a decrease in CD40 MFI and the percentage of CD19+PD-1+ cells. The UC-MSCcm had a minimal effect on B-cell apoptosis. The incubation of patients’ PBMCs with the UC-MSCcm increased PGE2 levels compared to the control medium. This study provides new insights into the impact of the MSC secretome on the key molecules involved in B-cell activation and antigen presentation and survival, potentially guiding the development of future SLE treatments. Full article

Introduction: We conducted a comprehensive comparative analysis of the Okazaki, Umehara, and American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for diagnosing immunoglobulin G4-related disease (IgG4-RD). Materials and Methods: A retrospective study was conducted in a single tertiary hospital, using expert clinical judgment as the gold standard. We compared the diagnostic accuracy of the Okazaki, Umehara, and ACR/EULAR criteria in a cohort of 41 patients with suspected IgG4-RD. We assessed sensitivity, specificity, and positive and negative predictive values for each criterion, and conducted a separate analysis based on four IgG4-RD subtypes. Results: A total of 30 patients were confirmed to have IgG4-RD and 11 were identified as mimickers. The Umehara criteria demonstrated the highest sensitivity (83.33%), followed by the ACR/EULAR 2019 (66.67%) and Okazaki (60.0%) criteria. All three criteria exhibited 100% specificity, with overall diagnostic accuracy ranging from 70% to 88%. The areas under the curve (AUC) were 0.917 (Umehara), 0.800 (Okazaki), and 0.833 (ACR/EULAR 2019), indicating significant diagnostic effectiveness (p < 0.000). Subtype analysis revealed that the Umehara and ACR/EULAR 2019 criteria were more effective in diagnosing pancreato-hepato-biliary involvement (subtype 1), while the Okazaki and ACR/EULAR 2019 criteria were more effective in diagnosing retroperitoneal fibrosis and/or aortitis (subtype 2). Conclusions: Our study provides valuable insights into the diagnostic performance of the Okazaki, Umehara, and ACR/EULAR criteria for a cohort of patients with suspected IgG4-RD. The Umehara criterion demonstrated the highest sensitivity, suggesting its potential utility for screening purposes, while all three criteria showed consistent specificity. Full article

The effectiveness of monocyte chemotactic protein-1 (MCP-1) and Disease Activity Score 28 (DAS28)-MCP-1 (DAS28-MCP-1) in assessing rheumatoid arthritis (RA) disease activity is unclear, although some studies have demonstrated their potential usefulness. The present study investigated relationships between MCP-1 and different DAS28 measures, the occurrence of residual swollen joints in different DAS28 remission statuses, changes in medication dosage in relation to the 2005 modified American Rheumatism Association and 2011 American College of Rheumatology/European League against Rheumatism (ACR/EULAR) remission definitions, and the correlations between different DAS28-related scores and Health Assessment Questionnaire Disability Index (HAQ-DI) scores in two RA patient cohorts. The results revealed that the MCP-1 level was correlated with five disease activity measures (DAS28-erythrocyte sedimentation rate [DAS28-ESR], DAS28-C-reactive protein [CRP], Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), and DAS28-MCP-1) in multivariable regression analysis (all p < 0.05; ESR, CRP, and MCP-1 as independent variables). However, ESR was not significantly associated with SDAI and CDAI scores (p = 0.343 and 0.323, respectively). Residual swollen joints were more frequently observed in patients who met the DAS28-ESR remission criteria (<2.6) compared with those meeting the other four remission criteria, with a difference ranging from 71% to 94%. Among patients meeting the DAS28-ESR remission criteria (<2.6), medication changes (dose increase by ≥30% or new medications prescribed) were less frequent in those who also met the 2011 ACR/EULAR remission criteria than in those who did not meet them (p = 0.006). Moreover, the correlation coefficients for the relationship between DAS28-ESR and HAQ-DI scores were the lowest among the five disease activity measures. In conclusion, MCP-1 and DAS28-MCP-1 are effective in assessing RA disease activity, with less residual joint swelling and less frequent medication increases observed in the DAS28-MCP-1 remission < 2.2 subgroup. Full article

Background/Objectives: Our aim was to validate the performance of the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for antiphospholipid syndrome (APS), published in 2023, in an APS cohort. Methods: A total of 193 patients, 83 with APS (secondary APS, n = 45; primary APS, n = 38) and 110 without APS (systemic lupus erythematosus (SLE), n = 100; others, n = 10), were included in this study. The performance (sensitivity, specificity and area under the curve (AUC)) of the 2023 ACR/EULAR classification criteria for APS was evaluated and the agreement with the revised Sapporo criteria was compared using the kappa test. Results: In our cohort, the sensitivity and specificity of the 2023 ACR/EULAR classification criteria for APS were 73% and 94%, respectively (AUC: 0.836, 95% CI: 0.772–0.899), while the sensitivity and specificity of the revised Sapporo criteria were 66% and 98%, respectively (95% CI: 0.756–0.888). The performance of the two sets of criteria in our cohort was significantly consistent and significant (p < 0.001). When the sensitivity, specificity and ROC curve analysis were performed again by excluding livedo racemosa, the sensitivity of the new criteria in our cohort was 62% and the specificity was 100% (AUC: 0.813, 95% CI: 0.746–0.881). Conclusions: Although the newly published criteria broaden the scope of APS classification by including clinical findings other than thrombosis and obstetric criteria, their sensitivity in our cohort was low. On the other hand, we found that the specificity of the criteria in our cohort reached 100% when livedo findings were excluded. Full article

Objectives: We applied the 2022 American College of Rheumatology/ European Alliance of Association for Rheumatology (ACR/EULAR) criteria for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) to patients histologically diagnosed with lupus nephritis (LN) to investigate the overall rate of and initial contributing factors to the reclassification of overlap syndrome of LN with AAV (OS-LN-AAV). Methods: We retrospectively reviewed the medical records of 1292 patients with systemic lupus erythematosus (SLE) and included 164 patients with LN in this study. Patient demographics, SLE manifestations, LN classes, and laboratory data, including ANCA levels, were recorded. All-cause mortality and end-stage kidney disease (ESKD) were evaluated as poor outcomes. Results: The median age of the 164 patients was 37.0 years, and 12.2% were men. The overall reclassification rate was 37.8%, of which 34.1% and 3.7% of the patients were reclassified as having OS-LN-microscopic polyangiitis and OS-LN-granulomatosis with polyangiitis (GPA), respectively, but none as having eosinophilic GPA. ANCA positivity and AAV-suggesting lung lesions were major contributors to OS-LN-AAV reclassification. When patients were compared based on OS-LN AAV reclassification, ANCA positivity and myeloperoxidase-ANCA (or P-ANCA) positivity favoured for OS-LN-AAV reclassification, whereas oral ulcers did not. However, OS-LN-AAV reclassification did not affect all-cause mortality or ESKD. Conclusions: This is the first study demonstrating a 37.8% reclassification rate in patients histologically diagnosed with LN using the 2022 ACR/EULAR criteria for AAV. Furthermore, it was also the first to reveal ANCA positivity and AAV-suggesting lung lesions as major contributors to OS-LN-AAV reclassification. Full article

New-onset chronic musculoskeletal (MSK) pain (>3 months duration) is a common symptom of post-COVID-19 syndrome (PCS). This study aimed to characterise new-onset chronic MSK pain in patients with PCS and its overlap with Fibromyalgia Syndrome (FMS). We enrolled patients with new-onset chronic MSK pain post-COVID-19 and assessed the nature of the pain and associated symptoms using the C19-YRS (Yorkshire Rehabilitation Scale). The FMS assessment was conducted as part of a standard clinical examination using the American College of Rheumatology (ACR) 2010 criteria: (1) Widespread Pain Index (WPI) ≥ 7 and symptoms severity (SS) score ≥ 5, or WPI between 3 and 6 and SS score ≥ 9, (2) symptoms consistent for at least 3 months, and (3) no alternative diagnosis. Of the eighteen patients (average age 49.6 (SD 11.8) years; BMI 31.7 (SD 8.6)), twelve were female. The average symptom duration was 27.9 (SD 6.97) months post-infection. Thirteen patients (72.2%) met the FMS criteria, with an average WPI score of 8.8 and an average SS score of 8.2, indicating a high level of pain and significant quality of life impacts. These findings support the hypothesis that FMS may develop as a long-term sequela of a viral infection, underscoring the need for further research into post-viral long-term conditions. Full article

Background and Objectives: Fibromyalgia (FM) is a chronic musculoskeletal pain syndrome characterized by widespread pain and a variety of other symptoms, including fatigue, cognitive dysfunction, and sleep disturbances. Recent research has highlighted the potential role of pro-inflammatory cytokines and neurotransmitters in the pathophysiology of FM. This study aimed to investigate the relationship between serum levels of interleukin-6 (IL-6) and serotonin with the clinical parameters observed in patients with fibromyalgia. Additionally, it sought to analyze the similarities and differences among the different groups classified by symptom severity. Materials and Methods: This cross-sectional study included 26 female patients aged 20–70 diagnosed with FM according to the American College of Rheumatology (ACR) 2016 criteria and 14 healthy controls (HCs). Serum levels of IL-6 and serotonin were measured using electrochemiluminescence and high-performance liquid chromatography (HPLC), respectively. Results: FM patients exhibited significantly higher pain scores (VAS), anxiety, and depression levels compared to HCs. FIQ-R scores were significantly elevated in FM patients, with stratification showing 3.8% mild, 65.4% moderate, 23.1% severe, and 7.7% very severe cases. While no significant difference in IL-6 levels was observed between the FM patients and HCs, a trend towards increased IL-6 levels in patients with higher FIQ-R scores was noted. Serum serotonin levels were significantly lower in the FM patients than in the HCs, with moderate patients having lower levels than those classified as severe and very severe. Conclusions: The study underscores the potential role of IL-6 and serotonin in the pathophysiology of FM, suggesting that these biomarkers could be relevant in assessing the severity and impact of FM. Further research is needed to elucidate these relationships and their implications for developing personalized treatment strategies. Full article

It is not clear whether immunoregulatory cytokines and cells are associated with Disease Activity Score 28 (DAS28) scores and ultrasound grades/scores. Here, we investigated the relationships between immunoregulatory cytokines or cells and different DAS28 scores or ultrasound grades/scores in patients with rheumatoid arthritis (RA). This study enrolled 50 RA patients (with 147 visits) who had remission/low/moderate DAS28-ESR scores (92% in remission and low disease activity) at baseline. Blood was collected and an ultrasound was performed three times in a year. Percentages of regulatory B cells and T regulatory type 1 cells and M2 macrophage numbers in the blood were examined. Plasma levels of 10 immunoregulatory cytokines IL-4, IL-5, IL-9, IL-10, IL-13, IL-27, IL-35, TGF-β1, sTNF-R1, and sTNF-R2 and monocyte chemotactic protein-1 (MCP-1) were assessed using ELISA assay. The correlations of cytokines and cells with different DAS28 scores and ultrasound grades were investigated, and cytokines and cells were compared between different categories of DAS28 scores and ultrasound grades. Plasma TGF-β1 levels were higher in the DAS28-ESR < 2.6 (remission) subgroup than in the DAS28-ESR ≥ 2.6 (nonremission) subgroup (p = 0.037). However, plasma TGF-β1 levels were higher in the high ultrasound grade subgroup than those in the low ultrasound grade subgroup (p = 0.007). The number of M2 macrophages was lower in the DAS28-MCP-1 < 2.2 subgroup than in the DAS28-MCP-1 ≥ 2.2 subgroup (p = 0.036). The levels of TGF-β1, sTNF-R2, IL-10, and IL-27 were higher in patients with high ultrasound grades than in those with low ultrasound grades. IL-27 was also higher in the nonremission DAS28-ESR subgroup than the remission one (p = 0.025). Moreover, sTNF-R1 levels in the 2011 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) remission subgroup were significantly lower than in the 2011 ACR/EULAR nonremission subgroup (p = 0.007). This trend was reflected in that lower sTNF-R1 levels correlated with low DAS28-MCP-1 scores (rho = 0.222, p = 0.007). We conclude that high plasma TGF-β1 levels indicate the DAS28-ESR remission (<2.6) subgroup and the high ultrasound grade subgroup. IL-27 probably connects the nonremission DAS28-ESR to high ultrasound grades. Low sTNF-R1 levels probably link low DAS28-MCP-1 scores with the 2011 ACR/EULAR remission subgroup. It suggests that incongruent immuno-inflammatory abnormalities exist between DAS28 scores and ultrasound grades, and are also dissimilar among various DAS28-formula categories. Therefore, this study may provide a basis for further research into individual cytokines and immunoregulatory cells behind each DAS28 formula and ultrasound grades/scores. Full article