OBJECTIVE:To investigate longitudinal serum IgG dynamics in IgG4-related disease (IgG4-RD) after treatment and assess their prognostic value for relapse. METHODS:A retrospective cohort of 274 newly treated patients with IgG4-RD was stratified into elevated IgG (n = 186) and normal IgG (n = 88) groups. Treatment responses were evaluated by covariance analysis adjusted for baseline IgG. Longitudinal IgG trends and relapse risk were analyzed using Kaplan-Meier curves and Cox regression. RESULTS:Elevated baseline IgG level was associated with more severe phenotypes, including male predominance, older age, higher responder index scores, more internal organ involvement, hypocomplementemia, and elevated erythrocyte sedimentation rate/C-reactive protein level. IgG1 and IgG4 mainly contributed to IgG elevation. After treatment, 79.6% of patients with elevated IgG levels achieved normalization, with the greatest decline in the first year. Glucocorticoid (GC)-based regimens reduced IgG levels more effectively than GC-sparing therapies and achieved higher normalization rates (85.2% vs 66.7%). Twelve-month IgG normalization strongly predicted reduced relapse risk. Patients achieving IgG normalization had lower relapse rates (17.9% vs 44.1%; P = 0.001) and superior relapse-free survival (mean 33.20 [95% CI 32.21-34.19] vs 27.71 [95% CI 24.29-31.13] months; log-rank P < 0.001). Multivariate Cox regression confirmed failure of 12-month IgG normalization (hazard ratio [HR] 2.67 [95% CI 1.43-4.99], P = 0.002) and treatment intensity (GCs + weak immunosuppressants [IMs]: HR 0.36, P = 0.012; GCs + potent IMs: HR 0.40, P = 0.020, vs GC-sparing) as independent relapse determinants. CONCLUSION:Baseline IgG elevation marks more severe IgG4-RD phenotypes. The first treatment year achieving IgG normalization represents a critical prognostic biomarker. Failure to normalize IgG within 12 months markedly increases relapse risk. Longitudinal IgG monitoring supports risk stratification and treatment optimization.

Background: Immunoglobulin G4-related disease (IgG4-RD) is a multisystem immune disorder characterized by fibroinflammatory lesions involving multiple organs. B cells play a pivotal role in IgG4-RD pathogenesis, and autophagy substantially influences their functional capacity. This study aimed to evaluate the role of B-cell autophagy in IgG4-RD. Methods: Single-cell sequencing data were analyzed. Autophagy was assessed by flow cytometry with CYTO-ID (R) Autophagy Detection Kit 2.0 (CytoID) and by measuring autophagy-related proteins in peripheral blood mononuclear cell (PBMC) B cells from IgG4-RD patients and healthy controls (HCs) via polymerase chain reaction (PCR) and western blotting. Autophagy in B cells from IgG4-RD patients and HCs was inhibited, and B-cell activity was evaluated using Enzyme-linked immunoassay (ELISA) and flow cytometry. Results: Altered autophagy levels and extracellular signal-regulated kinase (ERK) pathway activity were observed in total B cells, as well as in na & iuml;ve B cells and plasmablasts. Autophagy in B cells was enhanced, as indicated by greater autophagosome formation and higher levels of autophagy-related proteins (p < 0.05). ERK phosphorylation was markedly reduced in IgG4-RD compared to HCs (p < 0.05). Following autophagy inhibition, B-cell metabolism, proliferation, antibody production, and cytokine secretion were significantly decreased in IgG4-RD (p < 0.05). Cell differentiation was similarly affected, with reduced memory B-cell and plasma cell proportions but elevated regulatory B-cell proportions (p < 0.05), whereas the reduction of memory B cells in HCs was not significant. Conclusion: IgG4-RD patients exhibited defective B-cell autophagy and elevated autophagy levels associated with multiple serological and hematological markers, alongside impaired autophagy flux. Significantly reduced ERK1/2 phosphorylation was uniquely observed among signaling pathways, suggesting potential autophagy-apoptosis interactions. Upon autophagy inhibition, B cells exhibited a broad functional decline and anti-inflammatory features, highlighting an autophagy-B-cell activity relationship that may be valuable for disease monitoring.

Objectives. Our study aimed to investigate the distinct clinical patterns of seronegative IgG4-related disease (IgG4-RD) patients. Methods. We retrospectively enrolled 698 treatment-na & iuml;ve IgG4-RD patients in this study. Patients were divided into four different subgroups according to their baseline serum IgG4 levels. The distinct clinical patterns of seronegative IgG4-RD patients were revealed through the comparison of baseline clinical data and disease prognosis among the different subgroups. COX regression analyses were used to investigate the risk factors for disease relapse and to construct the nomogram model. Results. Seronegative IgG4-RD patients account for a minority of IgG4-RD patients (49/698, 7.02%). The proportions of seronegative IgG-RD patients in our study and several Asian cohorts were significantly lower than those of the European and American cohorts. Seronegative IgG4-RD patients got lower serum IgG levels (p < 0.0001), lower eosinophil count (p < 0.0001), lower serum IgE levels (p < 0.0001)), lower IgG4-RD responder index (RI) scores (p < 0.0001), and fewer affected organ numbers (p < 0.0001) compared with other subgroups, whereas they were more likely to manifest fibrotic type with some special organ involvement. Younger age at onset, GCs monotherapy, elevated C-reactive protein level, and elevated erythrocyte sedimentation rate level are the risk factors for the disease relapse of seronegative IgG4-RD patients. An effective nomogram model predicting disease relapse of seronegative IgG4-RD patients was constructed. Seronegative IgG4-RD patients with scores >84.65 at baseline were susceptible to suffering from disease relapse. Conclusions. Distinct clinical features and multiple risk factors for disease relapse of seronegative IgG4-RD patients have been revealed in this study. A nomogram model was constructed to effectively predict disease relapse during the follow-up period.

Our study aimed to investigate the distinct clinical patterns of seronegative IgG4-related disease (IgG4-RD) patients. We retrospectively enrolled 698 treatment-naïve IgG4-RD patients in this study. Patients were divided into four different subgroups according to their baseline serum IgG4 levels. The distinct clinical patterns of seronegative IgG4-RD patients were revealed through the comparison of baseline clinical data and disease prognosis among the different subgroups. COX regression analyses were used to investigate the risk factors for disease relapse and to construct the nomogram model. Seronegative IgG4-RD patients account for a minority of IgG4-RD patients (49/698, 7.02%). The proportions of seronegative IgG-RD patients in our study and several Asian cohorts were significantly lower than those of the European and American cohorts. Seronegative IgG4-RD patients got lower serum IgG levels ( p < 0.0001), lower eosinophil count ( p < 0.0001), lower serum IgE levels ( p < 0.0001)), lower IgG4-RD responder index (RI) scores ( p < 0.0001), and fewer affected organ numbers ( p < 0.0001) compared with other subgroups, whereas they were more likely to manifest fibrotic type with some special organ involvement. Younger age at onset, GCs monotherapy, elevated C-reactive protein level, and elevated erythrocyte sedimentation rate level are the risk factors for the disease relapse of seronegative IgG4-RD patients. An effective nomogram model predicting disease relapse of seronegative IgG4-RD patients was constructed. Seronegative IgG4-RD patients with scores >84.65 at baseline were susceptible to suffering from disease relapse. Distinct clinical features and multiple risk factors for disease relapse of seronegative IgG4-RD patients have been revealed in this study. A nomogram model was constructed to effectively predict disease relapse during the follow-up period.

Objective: To externally validate the performance of the 2019 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for IgG4-related disease (IgG4-RD) within a cohort from China and to compare the criteria with the 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD. Methods: This study included 875 IgG4-RD and 302 non-IgG4-RD cases (213 mimickers and 89 patients with other diseases). Using expert clinical judgment as the gold standard for diagnosis of IgG4-RD, the performance (sensitivity, specificity, area under the curve (AUC) of the 2019 ACR/EULAR criteria for IgG4-RD was evaluated. We also compared it with the 2020 RCD criteria. Results: The 2019 ACR/EULAR classification criteria had a sensitivity of 76.6% (95% CI: 73.8% to 79.4%) and a specificity of 98.0% (96.0%-99.4%), an AUC of 0.873 (0.857-0.889) in the overall cohort. Those false negative cases under the 2019 ACR/EULAR classification criteria had significantly lower levels of serum IgG4, and fewer had pathological information, with a higher frequency in the involvement of those uncommon organs compared with the true positive cases. The cases judged as negative by the 2019 ACR/EULAR classification criteria yet judged as "definite" by the 2020 RCD criteria had more involvement of uncommon organs. Conclusions: The 2019 ACR/EULAR classification criteria for IgG4-RD show outstanding specificity and good sensitivity in real-world clinical practice. The 2020 RCD criteria are helpful for the diagnosis of IgG4-RD in clinical scenarios where IgG4-RD presents as involving an isolated organ, especially the unusual sites.

The objective of this study was to provide an updated review on the active warming effects on major adverse cardiac events, 30-day all-cause mortality, and myocardial injury after noncardiac surgery. We systematically searched MEDLINE, EMBASE, CINAHL, Cochrane CENTRAL, Web of Science, and Chinese BioMedical Literature Database. We included randomized controlled trials of adult population undergoing noncardiac surgeries that concentrate on the comparison of active warming methods and passive thermal management. Cochrane Collaboration’s tool was applied for risk-of-bias assessment. We used trial sequential analysis to evaluate the possibility of false positive or negative results. A total of 13,316 unique records were identified, of which only 19 with reported perioperative cardiovascular outcomes were included in the systematic review and nine of them were included in final meta-analysis. No statistically significant difference between active warming methods and routine care was found in major adverse cardiac events (RR 0.56, 95

Dear Editor, Activated Phosphoinositide 3-kinase δ syndrome (APDS) is a cluster of autosomal dominant primary immunodeficiency diseases with significant autoimmune manifestations, and can be classified into APDS1 and APDS2 according to the types of gene mutations [1]. APDS2 is caused by the loss of function (LOF) mutation in the Phosphoinositide-3-Kinase Regulatory Subunit 1 (PIK3R1) gene which encodes the p85α regulatory subunit. Continuously activated Phosphoinositide 3-kinase δ (PI3Kδ) due to monoallelic LOF mutation of PIK3R1 can cause the abnormally activated signal pathway, which leads to abnormal development of immune cells and production of antibodies, specifically the B and T cells [2]. Here we report a case of APDS2 with arthritis, as well as the treatment options and outcome of the patient. A 19-year-old male was admitted to Peking Union Medical College Hospital (PUMCH) in 2019 with recurrent respiratory tract infections—several episodes per year following birth. Since 2017, he has gradually developed multiple peripheral joint pain and swelling and was admitted to another hospital previously. Laboratory tests identified a significant reduction of serum immunoglobulin levels (IgG 4.38 g/l, IgA 0.07 g/l and IgM 0.245 g/l) and elevated inflammatory markers (ESR 25 mm/h and CRP 13.8 mg/l), and lymphocyte subset analysis showed significant decrease of B cell counts (2/μl). He was tested negative for RF, ACPA and ANA. US examinations showed splenomegaly and bilateral axillary lymph nodes enlargement, and biopsy showed hyperplasia of lymph nodes with predominantly T cells. Whole-exome sequencing indicated a splicing mutation (c.1425 + 1G>T) in PIK3R1 (monoallelic LOF), and APDS2 was diagnosed.

Background Neuropsychiatric involvement is one of the major concerns in systemic lupus erythematosus (SLE). The therapeutic effect of intrathecal treatment of methotrexate and dexamethasone has been investigated in some exploratory studies, but its influence on the long-term prognosis of neuropsychiatric SLE (NPSLE) remains unknown. Methods This was a propensity score-matched retrospective study. Outcomes at discharge and time free from NPSLE relapse or death were evaluated by multivariate logistic regression, survival analysis, and Cox regression as appropriate. Results Among 386 hospitalized patients with NPSLE, the median [IQR] age was 30.0 [23.0–40.0] years, and 342 patients (88.4%) were female. Of those, 194 patients received intrathecal treatment. Patients in the intrathecal treatment group had higher Systemic Lupus Erythematosus Disease Activity Index 2000 scores (median 17 vs. 14 points, IQR 12–22 vs. 10–19 points, P <0 .001) and were more likely to receive methylprednisolone pulse therapy (71.6% vs. 49.5%, P < 0.001) than those who did not receive intrathecal therapy. Intrathecal treatment was associated with a higher probability of survival and being free from NPSLE relapse than control treatment among the 386 unmatched patients ( P =0.042 by log-rank test) and within 147 propensity score-matched pairs ( P =0.032 by log-rank test). In the subgroup of NPSLE patients with increased levels of protein in cerebrospinal fluid, intrathecal treatment had a positive influence on their prognosis ( P < 0.001). Conclusions Intrathecal treatment of methotrexate and dexamethasone was associated with a more favorable prognosis of NPSLE and may serve as a valuable additional therapy for NPSLE patients, especially for those with elevated levels of protein in cerebrospinal fluid.

The microbiome has been implicated in small-, medium-, large-, and variable-vessel vasculitis. Dysbiosis can frequently be found in vasculitis patients with altered microbial diversity and abundance, compared with those with other diseases and healthy controls. Dominant bacteria discovered in different studies vary greatly, but in general, the intestinal microbiome in vasculitis patients tends to contain more pathogenic and less beneficial bacteria. Improvement or resolution of dysbiosis has been observed after treatment in a few longitudinal studies. In addition, some molecular changes in intestinal permeability and immune response have been found in animal models of vasculitis diseases.

Immunoglobulin G4 (IgG4)-related autoimmune pancreatitis (AIP), also known as “type 1 AIP,” is a rare, chronic, and fibroinflammatory disease manifested as obstructive jaundice and enlargement of the pancreas, usually accompanied by extra-pancreatic organ involvement. The understanding of IgG4-related AIP is gradually deepening. In this review, we summarized the basic concepts, common clinical manifestations, and new progress of the disease including diagnostic, therapeutic strategies, and prognosis mainly based on published case reports, cohort studies, meta-analyses, and guidelines in the past 5 years. Issues such as diagnostic markers, risk factors for relapse, and more effective treatment still need to be further studied.

SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome is a rare chronic inflammatory disease involving bone, joints, and skin1. No consensus has been reached on the treatment of SAPHO syndrome and the current options may lead to variable outcomes2. Secukinumab, an antiinterleukin (IL)-17A monoclonal antibody, is a promising novel biologic approved for plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis (AS)3. Only a few cases on the use of secukinumab in SAPHO syndrome were reported and have not yielded a unified conclusion4. To further clarify the efficacy of secukinumab in SAPHO syndrome, we report here a case series of 4 patients from our single-center dynamic cohort of SAPHO syndrome (a permanently open cohort continuously accumulating patients)5. All 4 patients were treated with 24-week secukinumab (150 mg subcutaneous once weekly for 4 wks and every 4 wks thereafter), without concomitant nonsteroidal antiinflammatory drugs (NSAIDs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), or other biologics. Their clinical conditions, skin lesions, and the whole-body magnetic resonance imaging (MRI) before and after treatment were prospectively collected and evaluated as the preliminary result of a clinical trial, which prematurely ceased due to the outbreak of the coronavirus disease 2019 (COVID-19; caused by SARS-CoV-2). The original clinical trial was registered in the Chinese Clinical Trial Register (ChiCTR1900028064; Supplementary Data 1, available with the online version of this article). …

目的 评估SAPHO综合征全脊柱病变的MRI表现,探索其影像学规律.材料与方法 分析22例SAPHO综合征全脊柱病变MRI图像,对活动性病变和结构性病变及椎旁、椎间隙病变的特征进行评估、统计与分析.结果 SAPHO综合征脊柱受累病变主要在胸段(占脊柱病变的45.4％)(P<0.05),其中活动性病变骨髓水肿(bone marrow edema,BME)和结构性病变脂质沉积最为常见,且均以胸段前侧椎角为主,跳跃分布和对吻分布分别为:BME 53.3％、46.7％,脂质沉积41.3％、58.7％.其他病变包括骨桥(3.9％)、骨质破坏(19.2％)、骨质硬化(3.0％)、椎间隙狭窄(4.3％)、压缩性骨折(3.5％)和椎旁软组织水肿(4.6％).结论 SAPHO综合征全脊柱病变以胸椎前侧椎角的BME和脂质沉积为主,呈跳跃和对吻分布,具有一定的特征性.

Successful treatment of refractory mandibular lesions in SAPHO syndrome with secukinumab Boyuan Sun, Boyuan Sun Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Search for other works by this author on: Oxford Academic PubMed Google Scholar Yihan Cao, Yihan Cao Department of Radiology, Peking Union Medical College Hospital https://orcid.org/0000-0001-9486-3365 Search for other works by this author on: Oxford Academic PubMed Google Scholar Lun Wang, Lun Wang Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Search for other works by this author on: Oxford Academic PubMed Google Scholar Mu Wang, Mu Wang Department of Stomatology, Peking Union Medical College Hospital and Search for other works by this author on: Oxford Academic PubMed Google Scholar Chen Li Chen Li Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Beijing, China Correspondence to: Chen Li, Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, No1. Shuaifuyuan, 100730 Beijing, China. E-mail: casio1981@163.com https://orcid.org/0000-0002-8527-1680 Search for other works by this author on: Oxford Academic PubMed Google Scholar Rheumatology, Volume 60, Issue 1, January 2021, Pages 473–474, https://doi.org/10.1093/rheumatology/keaa352 Published: 26 July 2020 Article history Received: 04 May 2020 Accepted: 28 May 2020 Published: 26 July 2020