There is limited evidence on the recommended voriconazole (VCZ) concentration ranges for prophylactic versus therapeutic use, and the factors influencing individualized dosing in young children remain insufficiently characterized. This retrospective study analyzed the clinical data from pediatric patients (2-17 years) at Peking University People's Hospital from September 2020 to December 2024. The aim was to define optimal concentration thresholds for prophylaxis and treatment and identify sources of pharmacokinetic variability across age groups to support individualized dosing in children. In the exposure-effect study, VCZ trough concentration (Cmin) was significantly correlated with clinical efficacy. VCZ Cmin ≥0.41 mg/L and Cmin ≥1.115 mg/L were proven to be significant predictors of prophylactic and therapeutic dosing success, respectively. For pharmacokinetic analysis, patients were stratified into three age groups: Group 1 (2 to <6 years), Group 2 (6 to <12 years), and Group 3 (≥12 years). The final multiple regression analysis showed that affecting factors, including sex, moderate-to-severe inflammation, cytochrome P450 2C19 (CYP2C19) metabolic phenotype, and coadministration, explained 34.5%, 23.4%, and 47.6% of the variability in VCZ exposure in three groups, respectively. This study investigated pediatric patients with hematologic malignancies to define exposure-response differences between therapeutic and prophylactic VCZ regimens and identify age-related determinants of exposure variability. Overall, the findings support the use of individualized, age-appropriate dosing strategies to optimize VCZ exposure in children.

The aim of this study is to investigate the effect of arthroscopic synovectomy (AS) on disease status in patients with rheumatoid arthritis (RA). A prospective study was conducted among patients with RA who underwent AS of the elbow or knee joints due to persistent swelling following conventional treatment, as well as control individuals who only received conventional treatment. All patients were evaluated at baseline and 4, 12, 24, 48, 96 weeks after AS. The coprimary outcomes were week 96 disease activity score (DAS)-28 remission and American College of Rheumatology improvement criteria (ACR20/50/70) remission. Key secondary outcomes were changes from baseline to week 96 in Mayo score, Lysoholm score, Health Assessment questionnaire (HAQ), patient’s visual analogue scale, Magnetic Resonance Imaging in AS group. The correlation between synovial tissue biology and clinical response was analyzed. A total of 51 patients were included, with 17 accepted AS and conventional treatment, 34 only accepted conventional treatment. At week 96, more patients in AS group achieved DAS-28 remission [52.9

Anti-citrullinated peptide/protein antibodies (ACPAs) are specific serological markers for rheumatoid arthritis (RA), but their direct role in promoting osteoclastogenesis remains controversial. This study aims to determine whether polyclonal ACPAs purified from RA patients can directly drive osteoclastogenesis in vitro. Polyclonal ACPAs were purified from pooled sera of 37 ACPA positive RA patients using Protein G and multi-citrullinated-epitope peptide (MCEP) conjugated affinity chromatography, with control IgG from 10 ACPA negative RA patients and a healthy donor. The purity and specific binding capability to citrullinated vimentin were verified by Coomassie Blue staining and western blot. CD14 + monocytes from healthy donors and RA patients were induced to differentiate into osteoclasts with M-CSF and RANKL, in the presence or absence of ACPAs. Osteoclast formation was evaluated by tartrate resistant acid phosphatase (TRAP) staining, gene expression of osteoclast-specific markers (TRAP, cathepsin K, MMP9) by quantitative PCR, and bone resorption activity by scanning electron microscopy. The purified ACPAs showed intact IgG structure of heavy and light chains, and specific binding to citrullinated vimentin, but not to native vimentin. However, ACPAs treatment did not significantly increase the number of TRAP-positive multinucleated cells, the expression of osteoclast-related genes, or bone resorption pit area compared to controls. Our findings demonstrate that pooled polyclonal ACPAs from RA patients, purified by MCEP affinity chromatography, do not directly promote osteoclastogenesis in vitro, suggesting that their osteoclastogenic effects may require a more complex microenvironment or depend on specific antibody properties not captured in this experimental setting.

OBJECTIVES:Orelabrutinib is an oral, highly selective, irreversible inhibitor of Bruton's tyrosine kinase (BTK). Preclinical mechanistic studies have demonstrated its therapeutic potential in systemic lupus erythematosus (SLE). METHODS:A multicentre, double-blind, randomised, placebo-controlled, parallel-group, phase Ib/IIa study was conducted in 11 centres in China. Patients diagnosed with SLE were randomised 1:1:1:1 to receive oral orelabrutinib at 50 mg, 80 mg, and 100 mg or placebo once daily for 12 weeks, respectively. This trial is registered with ClinicalTrials.gov, NCT04305197. RESULTS:Between July 9, 2020 and September 29, 2021, 60 patients were randomised, with 55 patients who completed 12 weeks of treatment. Adverse events (AEs) were mostly mild or moderate. In all evaluable patients, the SLE Response Index (SRI)-4 rates at week 12 were 50%, 62%, and 64% for orelabrutinib at 50 mg, 80 mg, and 100 mg, respectively, compared with 36% for placebo, indicating dose-dependent improvement. Among patients with baseline SLEDAI-2K > 8, significantly higher SRI-4 responses were noted with orelabrutinib at 50 mg (80%, p = 0·048), 80 mg (83%, p = 0·048), and 100 mg (100%, p = 0·029) compared to placebo (0%). SRI-6 responses at week 12 were 36%, 39%, and 21% for orelabrutinib at 50 mg, 80 mg, and 100 mg, respectively, compared with 7% for placebo. Reduced proteinuria, anti-dsDNA, IgG, and IgM and increased C4 were observed with orelabrutinib treatment. CONCLUSIONS:Orelabrutinib was well tolerated and potentially efficacious in patients with SLE.

OBJECTIVE:Idiopathic retroperitoneal fibrosis (RPF) is considered a 'silent disease' due to the lack of distinct disease biomarker. Our purpose was to study characteristic changes in circulating lymphocytes in RPF patients and explore their roles in etiopathogenesis. METHODS:Twenty-three RPF patients were enrolled and followed up for 48 weeks of treatment. Changes of T and B lymphocyte subsets in their peripheral blood were measured, and their associations with disease activity and severity were evaluated. The proliferation, secretion and chemotactic functions of circulating follicular helper T (cTFH) cells were assessed by flow cytometry and RNA sequencing following CD4+ T cell sorting. RESULTS:Among the changed lymphocytes, cTFH cells present a distinct pattern compared with other autoimmune conditions. They were significantly reduced in RPF patients but positively correlated with disease severity and TFH expansion in fibrotic tissues. Remarkably, they were further declined upon disease amelioration, indicating their potential as a disease marker. Further investigation revealed unchanged proliferation and low cytokine secretion in these cTFH cells. Instead, chemokine CXCL13 expression was markedly elevated in CD4+ T cells isolated from both fibrotic tissues and peripheral blood of RPF patients, whereas key cytokines IL-21, IL-6 and Bcl were elevated only in the fibrotic tissues. CONCLUSION:Our findings suggest that cTFH cells in the circulating blood of RPF do not expand but may undergo chemotactic migration to fibrotic tissues, marking a distinct feature of RPF and may serve as a potential biomarker.

BackgroundIgG4-related disease (Immunoglobulin G4-related disease) is an immune-mediated condition characterized by elevated serum IgG4 levels, clinically presenting as multi-organ enlargement. However, only case reports exist of IgG4-related disease presenting initially with peripheral neuropathy. This study aims to elucidate the clinical features of IgG4-related disease with prominent peripheral neuropathy manifestations.MethodsWe reviewed 16 cases of IgG4-related disease with peripheral neuropathy as the initial presentation, including 15 cases from the literature and one case from our institution. Patient data were extracted and analyzed, encompassing clinical characteristics, pathological features, electrophysiological findings, and treatment information.ResultsThe median age of onset was 64.5 years, with 3 female and 13 male patients. Initially, 15 patients presented with limb numbness and weakness, while 1 exhibited hoarseness. All 16 patients demonstrated organ enlargement in addition to peripheral nerve damage. Peripheral nerve electrophysiology revealed demyelination and/or axonal lesions. All cases received oral corticosteroids, with immunosuppressants added in 3 cases. All patients responded well to corticosteroid therapy.ConclusionPeripheral neuropathy may present as the initial manifestation of IgG4-related disease. Such neuropathy demonstrates favorable response to corticosteroid therapy, and the indication for adding immunosuppressive agents should be evaluated based on individual circumstances.

OBJECTIVES:This study aims to evaluate the efficacy and safety of IM19, an autologous anti-CD19 chimeric antigen receptor (CAR) T cell, in patients with refractory systemic lupus erythematosus (SLE), with a particular focus on lupus nephritis (LN). METHODS:This is an open-label, single-arm clinical trial. IM19 was administered following lymphodepletion. Repeated renal biopsies were performed at day 180. Single-cell RNA sequencing on peripheral blood mononuclear cells was performed pre- and 180-day post-CAR-T infusion. A literature search on the efficacy of CAR T-cell therapy in LN in PubMed database was conducted. RESULTS:Six patients with refractory SLE and renal involvement were enrolled. IM19 therapy was well tolerant, with mild cytokine release syndrome occurring in 4 patients. The median Systemic Lupus Erythematosus Disease Activity Index-2000 score decreased from 12 (range, 10-24) to 4 (range, 2-8) at day 90, and remained stable at 5 (range, 2-6) at day 180. The renal responses were heterogeneous with 2 complete responders, 2 partial responders, and 2 nonresponders. Repeated renal biopsies showed no B-cell infiltration, but dominant chronic changes and podocytopathies post-CAR-T therapy. A mini-review demonstrated that the renal complete response rate of CAR-T therapy was 72.4%, and advanced age was associated with suboptimal response. Single-cell analysis confirmed B-cell reconstitution in 3/6 patients. CONCLUSIONS:IM19 CAR T-cell therapy demonstrated a favourable safety profile and clinically meaningful systemic improvement. Responses to CAR-T therapy in LN were variable. Chronic renal manifestations, podocytopathy, and ageing were associated with suboptimal therapeutic outcome.

Objective: This study aimed to investigate the effect of hydroxychloroquine (HCQ) application during pregnancy on perinatal outcomes in cases of combined non-specific auto-antibodies. Methods: A retrospective cohort study was carried out. Cases of pregnancy combined with isolated auto-antibody positivity at Peking University Third Hospital from 2016 to 2020 were included. HCQ use during pregnancy was defined as the primary exposure. The impact of HCQ on perinatal outcomes was explored through univariate and multivariate analyses, and stratified analyses of its effects were conducted according to prophylactic anticoagulation use and medication duration. Results: A total of 338 cases were included, accounting for 39.62% (338/853) of pregnancies with autoimmune abnormalities during the same period. Univariate analysis of the overall population showed that HCQ use during pregnancy was associated with a significantly lower incidence of pre-eclampsia (9.13% vs. 25.53%), early-onset pre-eclampsia (1.37% vs. 10.08%), and small for gestational age (SGA) (12.07% vs. 22.88%). In the subgroup without anticoagulation, both multivariate and univariate analyses revealed that HCQ was associated with markedly lower rates of pre-eclampsia (0% vs. 36.67%, p = 0.004), early-onset pre-eclampsia (0% vs. 15.00%, p = 0.046), and SGA (0% vs. 28.33%, p = 0.006), and a significantly longer pregnancy gestational age with a higher birth weight. The timing of HCQ initiation showed no significant impact on adverse pregnancy outcomes. Conclusions: HCQ use during pregnancy is associated with favorable perinatal outcomes among women with isolated non-specific auto-antibody positivity, especially in those not receiving anticoagulation. Strengthened clinical evaluation and careful risk-benefit assessment are warranted to avoid unnecessary interventions.

OBJECTIVE:To analyze the related factors of rheumatoid arthritis (RA) patients with anemia of chronic disease (ACD) and to guide the clinical diagnosis and treatment. METHODS:A retrospective study was used to analyze the patients admitted to Department of Rheumatology and Immunology in Peking University Third Hospital from January 2013 to December 2018. Clinical data (including general conditions, joint lesions, extra-articular manifestations, and comorbidities), laboratory examinations, and treatment were collected to analyze the differences in clinical characteristics between group RA with ACD (RA-A) and group RA without ACD (RA-nA). Univariate and multivariate Logistic regression analysis was conducted to screen for relevant factors of RA with ACD. RESULTS:A total of 468 RA patients were included, including 194 cases (41.5%) in RA-A group and 274 cases (58.5%) in RA-nA group. There were no significant differences in age, gender, onset age, or course of disease between the two groups (P>0.05). The RA-A group had more joint swelling [13 (2, 14) vs. 10 (2, 11)], more tenderness [10 (2, 12) vs. 7 (2, 10)], and higher 28 joint disease activity scores (DAS28) [DAS28-CRP (C-reactive protein): 5.2±1.4 vs. 4.6±1.5; DAS28-ESR (erythrocyte sedimentation rate): 5.9±1.5 vs. 5.1±1.8] compared with the RA-nA group (P < 0.05). The incidence of pleural effusion (4.6% vs. 1.1%) and venous thrombosis (5.7% vs. 1.5%) were higher in RA-A group (P < 0.05). The platelet count, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, ESR, CRP, immunoglobulin G (IgG) in RA-A group were significantly higher than those in RA-nA group (P < 0.05). Elevated ESR and CRP levels, DAS28 > 5.1 were relevant factors for anemia in the RA patients. CONCLUSION:RA patients with ACD had more severe joint involvement, higher inflammatory indicators, and more active conditions, making them more prone to pleural effusion and venous thrombosis. High disease activity, high inflammatory status, and venous thrombosis were risk factors for RA with ACD.

OBJECTIVES:We aimed to find a diagnostic indicator that contributed to differential diagnosis and activity assessment of retroperitoneal fibrosis (RPF). METHODS:We analysed the expression of MMP-12 in pathological tissues and peripheral blood, and explored their correlations with clinical, laboratory, radical and pathological parameters. RESULTS:The positive rate of MMP-12 in pathological tissues was significantly higher than that in the healthy controls. It was positively correlated with the positive rates of mTOR, CXCR5, IL-13 in the germinal centres (GCs) and MMP-12, IL-13 in the periphery. The parametric estimate of the area under the ROC curve of the positive rate and its 95% confidence interval were 0.875 and 0.673 ~1.000. The cut-off value and sensitivity and specificity were 16.395%, 0.938 and 0.750. Thickness of RPF mass was more severe in MMP-12 positive group based on this cut-off value. Although the concentration of MMP-12 in peripheral blood did not increase significantly, it was positively correlated with time before treatment and the positive rate of CXCR5 in the GCs. CONCLUSIONS:The positive rate of MMP-12 in the GCs of pathological tissues is a potential marker that contributes to the differential diagnosis of RPF and might be associated with the degree of fibrosis, although MMP-12 in the peripheral blood was not very helpful for disease diagnosis and monitoring of treatment effects. MMP-12 had the potential to become an indicator for the differential diagnosis RPF and monitoring the disease process.

Interstitial lung disease (ILD) is a significant extra-articular complication of rheumatoid arthritis (RA), characterized by high prevalence and mortality rates. Although advancements have been made in understanding its potential mechanisms, the pathogenesis of RA-associated ILD remains incompletely understood. Recent research has shed light on roles of various disease-related signaling pathways, including TGF-β/SMAD, JAK/STAT, PI3K–Akt, Wnt/β-catenin, and NF-κB, which are implicated in development of both RA and lung fibrosis. These shared pathways, which drive inflammatory cytokine production and fibroblast proliferation, offer promising opportunities for therapeutic intervention, including pathway-specific inhibition and drug repurposing. Furthermore, the growing identification of potential biomarkers for early detection and severity assessment in RA-ILD patients holds promise for improving clinical management and guiding treatment strategies. Current treatments fall short in effectively halting the progression of lung fibrosis. This highlights the potential of advancements in signaling pathways and targeted therapies as promising alternatives with significant opportunities for improvement.

Rheumatoid arthritis (RA) with anti-citrullinated protein/peptide antibodies (ACPA + RA) demonstrates more significant radiographic damage compared to ACPA-negative RA (ACPA- RA). Chemokine-activated signaling pathways contribute to the regulation of the bone formation and resorption. The potential role of C-X-C motif chemokine ligand 7 (CXCL7) in bone erosion and its viability as a therapeutic target for RA merit further investigation. Plasma CXCL7 concentration was quantified using enzyme-linked immunosorbent assay (ELISA). The effect of CXCL7 on receptor activator of NF-κB ligand (RANKL)-induced osteoclastogeneis was assessed through tartrate-resistant acid phosphates (TRAP) staining and F-actin ring immunofluorescence. Western blotting analysis was used to identify the signaling pathways activated by CXCL7. To investigate the potential therapeutic effect by targeting Cxcl7, Cxcl7 neutralizing antibodies were administrated intraperitoneally to mice with collagen-induced arthritis (CIA). Histopathology and micro-computed tomography (micro-CT) scanning were utilized to assess joint inflammation and bone destruction in CIA mice. The plasma CXCL7 concentration was significantly higher in ACPA + RA compared with ACPA- RA and healthy controls. The level of CXCL7 was positively correlated with disease activity and bone erosion in RA patients. It was discovered that CXCL7 promoted RANKL-induced osteoclastogenesis in CD14 + monocytes derived from RA patients. Mechanistically, the addition of Cxcl7 significantly enhanced RANKL-induced phosphorylation of ERK1/2 and NFATc1 expresssion. Cxcl7 neutralizing antibody alleviated arthritis severity in CIA by reducing the inflammatory response, osteoclasts numbers, and bone destruction in CIA mice joints. CXCL7 contributes to the bone erosion in RA by enhancing RANKL-induced osteoclastogenesis via the activation of ERK/NFATc1 signaling pathways. CXCL7 could potentially be targeted for therapeutic interventions in RA.

Sjogren syndrome (SS) is a chronic systemic autoimmune disease and its pathogenesis often involves the participation of numerous immune cells and inflammatory factors. Despite increased researches and studies recently focusing on this area, it remains to be fully elucidated. We decide to incorporate genetic insight into investigation of the causal link between various immune cells, inflammatory factors and pathogenesis of Sjogren syndrome (SS). Our study leveraged the genetic variants of multi-omics statistics extracted from genome-wide association study (GWAS), the University of Bristol and the FinnGen study. We performed a bidirectional Mendelian randomization and mediation study based on randomly allocated instrumental variables to infer causality, followed by external validation with UK Biobank data and Bayesian colocalization. We demonstrated that an elevated level of CD27 on IgD + CD24 + B cell, a subset of B cells expressing both IgD and CD24, was associated with a higher risk of SS (OR = 1.119, 95

Charcot neuroarthropathy (CN) is a rare but severely disabling complication most commonly seen in patients with longstanding diabetic peripheral neuropathy. CN is characterized by progressive destruction, dislocation, and deformity of the foot and ankle joints, often accompanied by altered biomechanics, chronic ulceration, secondary infection, and, in advanced cases, a high risk of amputation or even mortality. The early clinical presentation of CN is frequently atypical, with mild or painless swelling, warmth, and erythema due to underlying sensory deficits, which can easily lead to misdiagnosis as other rheumatic or autoimmune joint disorders such as rheumatoid arthritis and gout. In this report, we present the case of a 60-year-old woman with a 12-year history of type 2 diabetes mellitus who developed persistent swelling and pain in her left ankle for eight months, along with progressive numbness in her left foot for six months. Her initial laboratory and imaging findings suggested a diagnosis of rheumatoid arthritis combined with gout, resulting in the administration of anti-rheumatic and uric acid-lowering therapies, which proved ineffective. Further diagnostic workup, including advanced imaging modalities, neuroelec-trophysiological testing, and synovial biopsy, ultimately confirmed the diagnosis of diabetic Charcot neuroarthropathy, revealing severe joint dislocation, bone fragmentation, and extensive osteolysis. The patient received comprehensive management, including strict glycemic control, anti-osteoporosis treatment, neurotrophic support, and ultimately underwent left ankle multi-joint fusion surgery. During postoperative follow-up, the patient demonstrated significant improvement in limb function, with no recurrence of ulcers or infection. This case highlights the importance of considering CN in diabetic patients with unilateral, painless joint swelling, deformity, and sensory disturbance. Accurate differential diagnosis from rheu-matic and autoimmune diseases, early recognition, and standardized intervention are crucial to prevent irreversible deformity and reduce the risk of amputation, ultimately improving patient outcomes. Early multidisciplinary management and individualized treatment strategies play a key role in optimizing prognosis for patients with diabetic CN.

Alterations in intestinal microbiota have been identified as a key risk factor in rheumatoid arthritis (RA). This study presents a multidimensional gut microbiota profile from a large cohort of RA patients, stratified by disease stage and treatment regimens, and compared to healthy controls. Our dataset comprises gut microbiota profiles from 2,238 individuals, including 1,034 RA patients (Ascia Pacific RA cohort, APRAC) and 1,204 healthy controls. This dataset is enriched with detailed clinical metadata, including patient profiles, treatment histories, and environmental factors, providing a comprehensive “disease exposome” for RA. By integrating 16S rRNA gene sequencing with demographic, clinical, and environmental data, we offer a valuable resource to explore the complex relationships between gut microbiota and RA progression. This large-scale dataset is expected to be a foundation for collaborative research, advancing our understanding of the microbiome’s systemic effects in RA and other autoimmune diseases and potentially guiding new therapeutic approaches.

OBJECTIVE:To evaluate the use of aspirin during pregnancy in patients with systemic lupus erythematosus (SLE) and to assess its effects on pregnancy outcomes. METHODS:We consecutively enrolled SLE patients discharged from the Department of Obstetrics at Peking University Third Hospital between 2010 and 2024. Collected data included general patient characteristics, such as age, histories of adverse pregnancy, thrombosis, hypertension and renal disease. SLE related organ involvement, antiphospholipid antibodies (aPLs), SLE disease activity index (SLEDAI) score, medication regimens during pregnancy, and pregnancy outcomes were all documented. Differences in clinical characteristics between the aspirin user group and the non-user group were compared. Logistic regression analysis was used to assess the impact of aspirin on pregnancy outcomes. RESULTS:A total of 171 SLE patients were included in this study. The mean age was (31±4) years, and 46 patients had a history of adverse pregnancy. The most commonly involved organs were skin and joints, accounting for 68.4% and 45.6% respectively. In the study, 52 cases had renal involvement, accounting for 30.4%. SLEDAI scores during pregnancy of the 87.1% patients were less than 4 scores. Aspirin use during pregnancy accounted for 48.5%. Among them, 19 patients (11.1%) used between 2010 and 2017, while 64 patients (37.4%) used after 2017, demonstrating an increasing trend. Regarding pregnancy outcomes, the rates of fetal loss, preterm birth, preeclampsia/eclampsia, and early-onset preeclampsia were 14.0%, 23.4%, 22.8%, and 10.5%, respectively. After adjusting for covariates such as age, adverse pregnancy history, SLEDAI score, and aPLs, aspirin use was a protective factor for live birth (OR=2.34, 95%CI: 1.18－4.65, P=0.015) and reduced the incidence of preeclampsia/eclampsia and early-onset preeclampsia (OR=0.42, 95%CI: 0.19－0.91, P=0.028; OR=0.31, 95%CI: 0.11－0.89, P=0.029, respectively) for the total 171 SLE patients. Among the SLE pregnant patients without high-risk factors for preeclampsia/eclampsia, aspirin use was a protective factor for live birth (OR=8.22, 95%CI: 1.61－42.16, P=0.012) and might help reduce the incidence of early-onset preeclampsia/eclampsia (OR=0.26, 95%CI: 0.06－1.10, P=0.067). CONCLUSION:Aspirin can reduce the incidence of preeclampsia/eclampsia, early-onset preeclampsia, and stillbirth in pregnant SLE patients. Even for those without high-risk factors for preeclampsia/eclampsia, aspirin should be taken under physician evaluation and recommendation. Current clinical practice in managing SLE during pregnancy deviates from guideline recommendations, underscoring the need for greater standardization.

OBJECTIVE:To comprehensively assess the occurrence of residual symptoms in patients with axial spondyloarthritis who have successfully attained the treatment goal of low disease activity, and to conduct a thorough analysis of the related factors. METHODS:An analysis was performed on axial spondyloarthritis patients who achieved low disease activity for the first time during their visits at the Rheumatology and Immunology Department of Peking University Third Hospital, spanning from May 1, 2021, to February 29, 2024. Based on the ankylosing spondylitis disease activity score-C-reactive protein (ASDAS-CRP), the patients who achieved low disease activity were divided into a non-remission low disease activity group and a remission group. The occurrence of residual fatigue and pain symptoms in both groups was assessed, and binary Logistic regression analysis was used to evaluate the related factors. RESULTS:In the study, 201 patients achieved low disease activity during treatment. The gender distribution was skewed towards males, with 151 male patients (75.1%) and 50 female patients (24.9%). The median age of the patients who achieved low disease activity was 32.0 (28.0, 37.0) years, and the median disease duration was 6.7 (3.8, 11.5) years. Notably, 140 patients (69.7%) achieved low disease activity but did not experience complete remission, while 61 patients (30.3%) attained remission. A substantial proportion of the patients, 45.8%, reported residual fatigue visual analogue scale (VAS) ≥4, with a marked difference between the non-remission low disease activity group and the remission group (53.6% vs. 27.9%, P=0.001). Similarly, 24.4% of the patients had residual pain VAS ≥4, with a significant disparity between the non-remission low disease activity group and the remission group (30.0% vs. 11.5%, P=0.005). Binary Logistic regression analysis revealed that C-reactive protein levels had a notable negative influence on residual fatigue symptom (B=-0.142, P=0.008, OR=0.868), whereas ASAS-HI had a positive effect on residual fatigue (B=0.288, P < 0.001, OR=1.334). Gender was found to have a significant impact on residual pain symptoms, with females exhibiting a higher risk (B=1.135, P=0.002, OR=3.112). CONCLUSION:The residual fatigue and pain symptoms are common in axial spondyloarthritis patients who have achieved low disease activity, particularly among female patients. More assessment and recognition of the residual disease burden in these patients will be needed to optimize the treatment strategies.

Aims: The aim of this study was to explore the influence and possible mechanisms of pharmacokinetics-related gene polymorphisms, especially CYP2C19 polymorphisms, and non-genetic factors combined with the inflammatory status on the voriconazole (VRC) metabolism of the Chinese population.Methods: Clinical studies were performed by collecting more than one VRC trough concentration and C-reactive protein (CRP) level. A total of 265 blood samples were collected from 120 patients.Results: Results of multiple regression analyses demonstrated that CYP2C19 genotypes and albumin (Alb) level remained predictors of C(min)ss/D in patients with no to mild inflammation (R-2 = 0.12, P < .001). In addition, in patients with moderate to severe inflammation, it resulted in a significant model containing factors of CRP and total bilirubin (T-Bil) levels (R-2 = 0.19, P < .001). In non-clinical studies, 32 rats were divided into control and inflammatory groups, and it was found that the mean residence time (MRT(0-t)) of VRC in the inflammatory group was significantly longer than that in the control group (P < .001), which may be due to down-regulation of mRNA and protein expression of CYP2C19 (CYP2C6 in rats) through interleukin (IL)-6/signal transducer and activator of transcription (STAT) 3 pathway.Conclusions: Therefore, the effect of CYP2C19 polymorphisms on VRC metabolism may be masked by inflammatory status, which should be of more concern than CYP2C19 polymorphisms in patients with moderate to severe inflammation. Additionally, the impact of Alb and T-Bil on VRC metabolism should not be disregarded.

IgG4-related disease (IgG4-RD) is a recently described autoimmune disorder characterized by elevated serum IgG4 levels and tissue infiltration of IgG4+ plasma cells in multiple organ systems. Recent advancements have significantly enhanced our understanding of the pathological mechanism underlying this immune-mediated disease. T cell immunity plays a crucial role in the pathogenesis of IgG4-RD, and follicular helper T cells (Tfh) are particularly important in germinal center (GC) formation, plasmablast differentiation, and IgG4 class-switching. Apart from serum IgG4 concentrations, the expansion of circulating Tfh2 cells and plasmablasts may also serve as novel biomarkers for disease diagnosis and activity monitoring in IgG4-RD. Further exploration into the pathogenic roles of Tfh in IgG4-RD could potentially lead to identifying new therapeutic targets that offer more effective alternatives for treating this condition. In this review, we will focus on the current knowledge regarding the pathogenic roles Tfh cells play in IgG4-RD and outline potential therapeutic targets for future clinical intervention.