OBJECTIVE:Although Takayasu arteritis (TAK) is not a prototypical autoantibody-mediated disease, accumulating evidence suggests that B cells are involved. This study aimed to investigate the pathway of B cell activation and its contributions to TAK pathogenesis. METHODS:Histologic analysis of paravascular lymph nodes and affected arteries was conducted to investigate B cell activation pathways in TAK. Bulk RNA-seq, single-cell RNA-seq (scRNA-seq), flow cytometry, and in vitro experiments were performed to characterize the composition, transcriptomic features, and functional profiles of B cells. The numeric and phenotypic alterations induced by tumor necrosis factor (TNF) and JAK inhibition were assessed both in vitro and in four patients with TAK. RESULTS:Histologic (n = 5), flow cytometric (n = 125), and bulk RNA-seq (n = 12) analyses indicated the presence of extrafollicular response and up-regulated age-associated B cell (ABC) production in TAK, along with cross-data set transcriptomic differences between B cells from patients with TAK and systemic lupus erythematosus (SLE). Cross-data set scRNA-seq analysis and in vitro experiments (n = 5) demonstrated that ABC differentiation in TAK was largely uncoupled from antibody-secreting cell (ASC) generation, unlike that in SLE. Functional experiments showed that ABCs exhibited proinflammatory properties, including proinflammatory cytokine production, and that CD11c+ B cells, which contain the ABC compartment, promoted Th17 cell differentiation (n = 6). In vitro, tofacitinib was more effective than adalimumab at reducing ABC proportions and attenuating their proinflammatory phenotype (n = 15), consistent with trends in the exploratory clinical follow-up (n = 4). CONCLUSION:ABCs promote inflammation through proinflammatory functions independent of ASC differentiation in TAK. JAK inhibition exerts distinct suppressive effects on ABCs compared with anti-TNF therapy.

OBJECTIVES:Study the efficacy and safety of mycophenolate mofetil (MMF) combined with methotrexate (MTX) compared to cyclophosphamide (CYC) followed by azathioprine (AZA) to treat active Takayasu arteritis (TAK). METHODS:Adults with active TAK were randomised in a 2:1 ratio to receive oral MMF plus MTX or intravenous CYC followed by oral AZA. All subjects also received high-dose oral glucocorticoids with a predefined taper. The primary endpoint was overall response rate at week 52, defined as achieving a complete response (CR) or partial response (PR). Secondary endpoints included rates of CR and PR at weeks 28 and 52. RESULTS:A total of 111 patients with TAK were enrolled: 74 in the MMF+MTX group and 37 in the CYC/AZA group, with comparable baseline demographic and clinical features. The overall response rates at 28 and 52 weeks were 58.1% and 55.4% in the MMF+MTX group, respectively, higher than 32.4% at both time points in the CYC/AZA group (P = .011 and .022). CR and PR rates at 28 and 52 weeks were also higher in the MMF+MTX group. Relapse occurred in 4 patients in the MMF+MTX group and 2 in the CYC/AZA group. One serious adverse event, neutropenia with fever, occurred in 1 patient in the CYC/AZA group. CONCLUSIONS:Treatment of active TAK with MMF+MTX has more favourable efficacy compared to CYC/AZA. These findings provide evidence to use the combination of MTX and MMF, 2 generally well-tolerated and inexpensive therapies, to treat TAK.

International Journal of Rheumatic DiseasesVolume 27, Issue 6 e15213 LETTER TO THE EDITOR Case report of legionnaire's disease mimicking idiopathic inflammatory myopathy Xiaochuan Sun, Xiaochuan Sun orcid.org/0000-0003-3697-6737 Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, ChinaSearch for more papers by this authorYutie Wang, Yutie Wang Department of Rheumatology and Immunology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, ChinaSearch for more papers by this authorLi Wang, Corresponding Author Li Wang [email protected] Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, China Correspondence Li Wang, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, China. Email: [email protected]Search for more papers by this authorZuojun Xu, Zuojun Xu Department of Pulmonary and Critical Care, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, ChinaSearch for more papers by this authorFulin Tang, Fulin Tang Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, ChinaSearch for more papers by this authorXiaofeng Zeng, Xiaofeng Zeng Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, ChinaSearch for more papers by this authorFengchun Zhang, Fengchun Zhang Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, ChinaSearch for more papers by this author Xiaochuan Sun, Xiaochuan Sun orcid.org/0000-0003-3697-6737 Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, ChinaSearch for more papers by this authorYutie Wang, Yutie Wang Department of Rheumatology and Immunology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, ChinaSearch for more papers by this authorLi Wang, Corresponding Author Li Wang [email protected] Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, China Correspondence Li Wang, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, China. Email: [email protected]Search for more papers by this authorZuojun Xu, Zuojun Xu Department of Pulmonary and Critical Care, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, ChinaSearch for more papers by this authorFulin Tang, Fulin Tang Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, ChinaSearch for more papers by this authorXiaofeng Zeng, Xiaofeng Zeng Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, ChinaSearch for more papers by this authorFengchun Zhang, Fengchun Zhang Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, ChinaSearch for more papers by this author First published: 17 June 2024 https://doi.org/10.1111/1756-185X.15213 Xiaochuan Sun and Yutie Wang contributed equally to this work. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. REFERENCES 1Malik A, Hayat G, Kalia JS, Guzman MA. Idiopathic inflammatory myopathies: clinical approach and management. Front Neurol. 2016; 7:64. 10.3389/fneur.2016.00064 PubMedWeb of Science®Google Scholar 2Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med. 1975; 292(7): 344-347. 10.1056/NEJM197502132920706 CASPubMedWeb of Science®Google Scholar 3Bohan A, Peter JB. 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Aim: To explore the value of serial monitoring of serum interleukin-6 (IL-6) levels for predicting treatment response and occurrence of adverse events during tocilizumab (TCZ) treatment in refractory Takayasu arteritis (TAK). Methods: TAK patients receiving TCZ treatment were prospectively recruited and followed up at 1 month, 3 months and then every 3-6 months. Serum IL-6 levels were measured at each visit. Overall response was the combination of complete and partial response, requiring resolution of signs and symptoms, hsCRP and ESR level decreased at least by half, no progression on imaging and dose of glucocorticoid <15 mg/d. Results: Thirty-five patients with a median follow up duration of 17 [9-44] months were included. The change of IL-6 after TCZ treatment for 6 months compared to the baseline was significantly lower in patients achieved overall response at 6, 12, 18 and 24 months. The ratio of IL-6 at 6 months to baseline could predict overall response at 12 and 24 months after TCZ treatment. With a cutoff value of 1.6, the sensitivity and specificity were 83.3 % and 87.5 % for 12 months, while 100 % and 88.9 % for 24 months. Patients with the ratio less than 1.6 were also 9 times more likely to achieve sustained improvement without treatment intensification. No correlation between IL-6 dynamics and occurrence of adverse events was found. Conclusions: The change of IL-6 levels after TCZ treatment for 6 months compared to the baseline can predict the overall treatment response at 12 months, 24 months and sustained improvement.

Objectives Both burdens of tuberculosis (TB) and systemic lupus erythematosus (SLE) in China are ranked as top three in the world. SLE patients are at high risk for TB, but so far, there are no guidelines for TB prevention and management targeting this population in China. This study aims to investigate the incidence of active tuberculosis (ATB) and to explore the risk factors for developing ATB in SLE patients, and to provide evidence for TB prevention and management for SLE patients in China. Methods A multi-center prospective cohort study was conducted. SLE patients were enrolled from clinics and wards of 13 tertiary hospitals in Eastern, Middle, and Western China from September 2014 to March 2016. Baseline demographic features, TB infection status, clinical information, and laboratory data were collected. ATB development was examined during follow-up visits. Kaplan-Meier method was applied to plot survival curves, and Log-rank test was used to evaluate differences. Cox proportional-hazards model was used to explore the risk factors for ATB development. Results With a median follow-up time of 58 months [interquartile range (IQR): 55-62], 16 out of 1361 SLE patients developed ATB. The 1-year incidence of ATB was 368 [95% confidence interval (CI): 46-691] per 100,000. Over a 5-year period, the cumulative incidence of ATB was 1141 [95% CI: 564-1718] per 100,000, and the incidence density was 245 per 100,000 person-years. Cox regression models were constructed with maximum daily dose of glucocorticoids (GCs) as a continuous variable and a categorical variable, respectively. In model 1, maximum daily dose of GCs (pills per day) [adjusted hazard ratio (aHR)=1.16, 95%CI: 1.04-1.30, p=0.010] and TB infection (aHR=8.52, 95%CI: 3.17-22.92, p<0.001) were independent risk factors for ATB development. In model 2, maximum daily dose of GCs≥30 mg/d (aHR =4.81, 95%CI: 1.09-22.21, P=0.038) and TB infection (aHR=8.55, 95%CI: 3.18-23.00, p<0.001] were independent risk factors for ATB development. Conclusions SLE patients had a higher incidence of ATB compared to the general population. The risk of developing ATB was even higher with increased daily dose of GCs or in a status of TB infection, in which case TB preventive treatment should be considered.

AIM:To verify the role of CX3C chemokine ligand 1 - CX3C chemokine receptor 1 (CX3CL1-CX3CR1) pathway in the pathogenesis of primary biliary cholangitis (PBC). To explore whether CCL26, a novel functional ligand to CX3CR1, participates in the immunological mechanism of PBC.METHODS:Fifty-nine PBC patients and 54 healthy controls were recruited. Enzyme-linked immunosorbent assay and flow cytometry were used to measure CX3CL1 and CCL26 concentrations in plasma and CX3CR1 expression on peripheral lymphocytes, respectively. Chemotactic effects of CX3CL1 and CCL26 toward lymphocytes were detected by Transwell cell migration assays. CX3CL1 and CCL26 expressions in liver were assessed by immunohistochemical staining. Effects of CX3CL1 and CCL26 on stimulating cytokine production from lymphocytes were evaluated using intracellular flow cytometry.RESULTS:Significantly elevated CX3CL1 and CCL26 plasma concentration and CX3CR1 expression on CD4+ and CD8+ T cells were noted in PBC patients. CX3CL1 exhibited chemotactic activity toward CD8+ T, natural killer (NK) and NKT cells in a dose-dependent manner while such chemotactic effects were not detected for CCL26. In PBC patients, CX3CL1 and CCL26 were both increasingly expressed in biliary tracts and a concentration gradient of CCL26 in hepatocytes around portal areas was observed. Immobilized CX3CL1 could enhance interferon-γ production from T and NK cells while such effect was not exhibited by soluble CX3CL1 or CCL26.CONCLUSIONS:CCL26 expression is significantly elevated in plasma and biliary duct of PBC patients, yet does not appear to attract CX3CR1-expressing immune cells. CX3CL1-CX3CR1 pathway promotes the infiltration of T, NK and NKT cells into bile ducts and forms a positive feedback loop with T-helper 1 type cytokines in PBC.

BACKGROUND:Nontuberculous mycobacteria (NTM) usually invades vulnerable hosts. Disseminated NTM (dNTM) infection can affect nearly all organs and be easily misdiagnosed as metastatic carcinoma or other systemic diseases, especially in seemingly immunocompetent hosts. Identification of underlying immunodeficiency is critical for the diagnosis and treatment of dNTM. Adult-onset immunodeficiency (AOID) with anti-IFN-γ autoantibodies has recently been recognized as a crucial but frequently neglected risk factor for dNTM infection. Frequent relapses of infection are common in AOID patients despite appropriate anti-infective treatment and B-cell-depleting therapy has shown some promising results. Herein, we report a case of dNTM infection mimicking malignancy in an AOID patient who was successfully treated with rituximab.CASE PRESENTATION:A middle-aged male presented with fever, productive cough, multifocal skin abscesses and multiple osteolytic lesions with pathological fractures. Chest CT revealed consolidation of the lingula while bronchoscopy showed a mass completely blocking the airway opening of the inferior lingual segment. Metagenomic next-generation sequencing and mycobacterial culture of skin pus and bronchoalveolar lavage fluid reported Mycobacterium Colombiense, confirming the diagnosis of dNTM infection. However, anti-NTM antibiotics alone failed to prevent disease relapse and progression. Further evaluation indicated undetectable serum IFN-γ concentration and high-titer autoantibodies against IFN-γ, suggesting that AOID was the underlying reason for dNTM. Rituximab was added to treatment and successfully controlled the infection without relapse at one-year follow-up.CONCLUSION:We reported a rare case of disseminated Mycobacterium Colombiense infection manifested with pulmonary mass, pathological fracture and dermapostasis in a host with AOID. Our case demonstrated that AOID should be screened when patients get the episode of disseminated NTM infection particularly when other risk factors are excluded. Besides prolonged anti-NTM therapy, AOID-associated NTM infection should be treated with B-cell-depleting therapy to prevent recurrence.

To investigate the value of repeated bone scintigraphy in the follow-up of patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome and to characterize the changing pattern of osteoarticular lesions revealed by bone scintigraphy. Twenty-four patients with SAPHO syndrome who had repetitively undergone bone scintigraphy and tests of inflammatory markers (erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP)) were included in this retrospective study. The change in accumulation number was recorded as the difference in the number of accumulation sites between consecutive bone scintigraphy. The visual analog scale (VAS) for pain and medications prescribed were also reviewed. The relationships of the change in accumulation number with medication prescribed and change in ESR or CRP were analyzed. Twenty-four and 23 patients had follow-up tests of ESR and CRP, from which 30 and 28 follow-up data were obtained, containing the corresponding changes in ESR and CRP, respectively. A decrease in total accumulation number observed by bone scintigraphy was rarely observed, while decreases in ESR, CRP, and VAS were predominant. The accumulation number had significantly increased over time (follow-up with ESR: r = 0.389, p = 0.034; follow-up with CRP: r = 0.438, p = 0.020), in accordance with an “imprinting” pattern, while the inflammatory markers and VAS for pain predominantly decreased. There was no significant association between the change in accumulation number (local/total) and the change in ESR or CRP values (p > 0.05) or medications used for SAPHO (p > 0.05). This retrospective cohort study of 24 SAPHO patients demonstrated an “imprinting” pattern on bone scintigraphy, without a correlation to the decrease in inflammatory markers, patient disease assessment, or treatment type. Thus, repeated bone scintigraphy did not contribute an additional clinical value for the follow-up of patients with SAPHO.

目的 探究CX3CL1/CCL26-CX3CR1通路在原发性胆汁性胆管炎(primary biliary cholangitis,PBC)免疫机制中的作用.方法 收集PBC患者和健康对照者外周血及肝脏病理标本,采用ELISA检测血浆CX3CL1及CCL26水平,流式细胞术检测外周血单个核细胞各亚群中CX3CR1+细胞比例.使用免疫组化分析肝活检组织中CX3CL1和CCL26表达情况.采用ELISA和流式细胞术检测不同细胞因子及LPS刺激下,体外培养的人肝内胆管上皮细胞中CX3CL1/CCL26-CX3CR1通路表达水平变化.结果 共纳入PBC患者40例、 健康对照者18例.PBC患者血浆CX3CL1水平[(0.690±0.271)ng/mL]较健康对照者[(0.540±0.101)ng/ml]显著升高(P=0.044).PBC患者血浆CCL26浓度[(8.94±4.09)pg/mL]较健康对照者[(6.75±1.86)pg/mL]有升高趋势,但无统计学差异(P=0.104).与健康对照者相比,PBC患者CX3CR1表达水平在NKT-like细胞[(63.5±25.4)％vs.(78.6±18.0)％,P=0.026]和CD4+T细胞[(5.5±5.4)％vs.(13.7±9.0)％,P=0.003]中显著增高,且后者这一差异在其CD28+和CD28-亚群中均显著.PBC患者肝脏胆管上皮细胞同时高表达CX3CL1和CCL26,健康对照者则弱表达CX3CL1,无CCL26表达.人肝内胆管上皮细胞CX3CL1表达水平在IFN-γ刺激下显著增加,CCL26表达在IL-4、IL-13刺激下显著增加;在IFN-γ刺激下,CX3CR1表达显著升高.结论 PBC患者肝内胆管上皮细胞可能在IFN-γ刺激下CX3CL1表达增加,在IL-4和IL-13刺激下CCL26表达增加,其受体CX3CR1在外周血NKT-like细胞和CD4+T细胞中表达上调.CX3CL1和CCL26可能通过CX3CR1协同介导PBC胆管上皮损伤.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome encompasses heterogeneous dermatological manifestations, mainly palmoplantar pustulosis (PPP) and severe acne (SA). This study aims to explore the necessity of stratified management according to skin lesions. In a cohort of SAPHO patients, we compared the demographic, clinical, and scintigraphic characteristics of the SAPHO patients whose skin lesion was PPP or SA. A total of 249 patients were included (227 affected by PPP and 22 affected by SA). Patients with SA were younger at onset (20, interquartile ranges (IQR) 15–30 vs. 37, IQR 30–46 years old; p < 0.001) and enrollment (35, IQR 25–38 vs. 41, IQR 33–50 years old; p = 0.001), and they had a prolonged disease duration (88.5 months, IQR 18.7–216.0 vs. 16.0, IQR 7.0–48.0 months; p < 0.001) and time needed for diagnosis (7.5, IQR 2.0–19.0 vs. 1.0, IQR 1.0–4.0 years; p < 0.001). Adjusted by age, sex, and disease duration, SA was significantly associated with more disease-modifying anti-rheumatic drug (DMARD) use (adjusted odds ratio (OR) 3.72; 95% confidence interval (CI) 1.23, 12.62; p = 0.019) and more sternoclavicular joint involvement (adjusted OR 5.91; 95% CI 1.17, 61.3; p = 0.030) in two separate Firth's logistic regression models. SAPHO patients affected by PPP or SA as the only skin lesion may have different epidemiologic features, osteoarticular manifestations, and treatment history.

Currently available Interferon-gamma release assay cannot reliably differentiate active TB (ATB) from non-active TB (non-ATB). This study aimed to evaluate the diagnostic accuracy of the IFN-gamma/IL-2 FluoroSpot assay, which can simultaneously detect IFN-gamma and IL-2 secretion, for differentiating ATB from non-ATB. 191 suspected ATB patients with positive T-SPOT. TB results were consecutively recruited. 64 (33.5%) participants had ATB, including 22 (34.4%) microbiologically or histologically confirmed TB and 42 (65.6%) clinically diagnosed TB. 119 (62.3%) cases were non-ATB and 8 (4.2%) were clinically indeterminate. After being stimulated with ESAT-6 and CFP-10 antigens, the median frequency and proportion of IFN-gamma +IL-2(-) T cells were significantly higher in the ATB group than the non-ATB group (P < .001). The areas under the ROC curves of IFN-gamma +IL-2(-) T cells were larger than those of total IFN-gamma(+) T cells (0.788 vs. 0.739, p = .323). With a cutoff value of 25 SFCs/250,000 PBMCs for frequency, sensitivity and specificity of this assay were 73.4% and 69.8% respectively. When combining the frequency and proportions of IFN-gamma +IL-2(-) T cells, the sensitivity and specificity were increased to 95.3% in parallel testing and 83.2% in serial testing respectively. In conclusion, IFN-gamma/IL-2 FluoroSpot assay is conducive for the diagnosis of ATB in patients with positive T-SPOT. TB results.

Objective SAPHO syndrome is a rare inflammatory disorder with multiple phenotypes, including synovitis, acne, pustulosis, hyperostosis, and osteitis. IgG4 is a subclass of immunoglobulin G, and the elevation of IgG4 has been found in different autoimmune diseases. In the present study, we explored the clinical significance of serum IgG4 levels in patients with SAPHO syndrome. Methods Fifty-two patients who met the classification criteria of SAPHO syndrome were included in this study. Clinical data and disease activity markers were collected including erythrocyte sedimentation rate (ESR), high sensitivity C-reactive protein (hsCRP), pain visual analogue scale (VAS), Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Ankylosing Spondylitis Disease Activity Score (ASDAS). Serum immunoglobin (IgA, IgM, and IgG) and IgG subclass (IgG1, IgG2, IgG3, and IgG4) levels were determined using the immunonephelometric assay. Results Raised serum IgG4 levels (>1400 mg/dL) were detected in 23% (12/52) of patients. Patients with elevated sIgG4 levels had significantly higher pain VAS (5.42 +/- 2.76 vs. 3.08 +/- 1.78, p=0.02), BASMI (1.80 +/- 1.64 vs. 0.38 +/- 0.94, p=0.03) and ASDAS (3.20 +/- 0.65 vs. 1.74 +/- 0.58, p<0.001) levels compared with patients with normal sIgG4 levels. This difference was also observed for ESR (38.2 vs. 22.2 mm/h, p=0.01) and serum CRP (21.0 vs. 2.2 mg/L, p=0.04) levels, which also positively correlated with sIgG4 levels. We also included 4 patients whose IgG4 levels decreased and correlated with the decrease in hsCRP and ESR levels after treatment. Conclusion Elevated sIgG4 levels are common in patients with SAPHO syndrome and are associated with high disease activity. Further investigations are needed for this phenomenon.

BackgroundCX3CL1-CX3CR1 pathway has been found to be critically involved in the pathogenesis of primary biliary cholangitis (PBC)1. As a novel ligand to CX3CR1, CCL26 can promote chemotaxis of CX3CR1+ immune cells but its role in PBC remains elusive2.ObjectivesThis study aimed to explore the role of CCL26, together with CX3CL1-CX3CR1 pathway, in the pathogenesis of PBC.MethodsWe recruited 40 patients diagnosed with PBC in the Peking Union Medical College Hospital from Jan 2018 to May 2018 and 18 age and sex-matched healthy controls (HCs). Peripheral blood and liver tissue samples were collected. The plasma level of CX3CL1 and CCL26 were determined by ELISA. Flow cytometry was used to measure the percentage of CX3CR1+ cells in various subsets of PBMCs. The expression of CX3CL1 and CCL26 in liver tissues was revealed by immunohistochemical staining. Using ELISA and flow cytometry, the change of CX3CL1/CCL26-CX3CR1 pathway expression in human intrahepatic biliary epithelial cells (HIBECs) upon stimulation of various cytokines was studied.ResultsThe plasma level of CX3CL1 and CCL26 was higher in patients with PBC than HCs with a P value of 0.044 and 0.104 respectively. The increased level of CCL26 was positively correlated with peripheral eosinophils, basophils and CRP level. In comparison with HCs, the expression of CX3CR1 was significantly higher in NKT-like and CD4+ T cells in PBC patients. In liver samples from PBC patients, CX3CL1 and CCL26 were significantly over-expressed in intrahepatic bile ducts and CCL26 also tended to be abundant in hepatocytes near portal areas and gradually weakened in distant regions. This distribution pattern was not observed in HCs. Upon stimulation of IFN-γ, the expression of CX3CR1 on HIBEC surface and CX3CL1 in culture supernatant was significantly up-regulated, while the expression of CCL26 was increased upon IL-4 and IL-13 stimulation.ConclusionCCL26 may cooperate with CX3CL1 to mediate the immune injury of intrahepatic bile ducts via CX3CR1 in PBC.References[1] Isse K, Harada K, Zen Y, et al. Fractalkine and CX3CR1 are involved in the recruitment of intraepithelial lymphocytes of intrahepatic bile ducts. Hepatology. 2005;41(3):506-16. [2] Nakayama T, Watanabe Y, Oiso N, et al. Eotaxin-3/CC chemokine ligand 26 is a functional ligand for CX3CR1. J Immunol. 2010;185(11):6472-9.Disclosure of InterestsNone declared

OBJECTIVES:To evaluate the clinical efficacy of bisphosphonates treatment for spinal bone marrow oedema (BME) in patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome.METHODS:SAPHO syndrome patients presenting to Peking Union Medical College Hospital from 2015 to 2016 were recruited. Patients were administered pamidronate disodium 1 mg/kg/d intravenously, for 3 days, at baseline and 3 months later. The symptoms were evaluated using the Visual Analog Score (VAS) for pain, and other clinical measures including, spinal BME scores, β-crosslaps, osteocalcin, and inflammatory factors, were collected.RESULTS:A total of 30 patients (20 women and 10 men) with a median age of 47.2 (interquartile range 8.8) years were recruited. In a short time, the patients showed a significant decrease in VAS (before vs. after; first treatment: 5.70±1.62 vs. 2.30±1.29 cm, second treatment: 4.03±1.88 vs. 2.17±1.23 cm) and β-crosslaps (first treatment: 0.4441±0.1923 vs. 0.0859±0.0374 pg/ml, second treatment: 0.2891±0.1983 vs. 0.0962±0.0324 pg/ml) (all p<0.05). At 12-month follow-up, compared with the baseline, we noticed a significant drop in the VAS (5.70±1.62 vs. 2.43±1.25 cm), erythrocyte sedimentation rate (28.87±25.26 vs. 18.00±18.65 mm/h), high-sensitivity C-reactive protein level (11.76±10.19 vs. 5.84±5.88 mg/L), osteocalcin (2.30±1.27 vs. 1.65±0.80 ng/ml), and BME (30.50±24.09 vs. 22.13±27.79) (all p<0.05). No one had serious adverse events.CONCLUSIONS:Bisphosphonates can significantly and rapidly relieve symptoms in patients with SAPHO syndrome and have a long-term effect on inflammation and spinal BME. We suggest that bisphosphonates could be used as the first-line therapeutic drug for SAPHO syndrome, especially in patients with spinal BME.

目的 评价非诺贝特用于治疗难治型原发性胆汁性胆管炎/肝硬化(primary biliary cholangitis/cirrhosis,PBC)患者的有效性和安全性.方法 入组19例熊去氧胆酸(UDCA)应答不良的患者,在维持原有熊去氧胆酸治疗基础上予非诺贝特200 mg/d,在开始非诺贝特前、 使用非诺贝特3、6、12个月等不同时间点监测患者血生化等指标变化,评价其安全性和有效性.结果 使用非诺贝特治疗的难治型PBC患者,1例血清胆红素上升,其他无严重不良反应;使用非诺贝特治疗后患者的ALP、GGT及AST较用药前下降,其中ALP由(210.2±113.2)U/L降为(110.1±75.8)U/L,GGT由(258.5±201.2)U/L降为(128.2±103.4)U/L,AST由(58.3±30.6)U/L降为(39.2±16.0)U/L,差异有统计学意义(P<0.05).结论 对熊去氧胆酸应答不良的难治型PBC患者,加用非诺贝特有助于血ALP、GGT和AST水平的下降,且相对安全,不良反应较少.

BACKGROUNDS:Whole-body bone scintigraphy (WBBS) and MRI are widely used in assessment of patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. However, the value of F-18 fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) in SAPHO syndrome was unclear. The aim of this study was to characterize the manifestation of SAPHO syndrome on 18F-FDG PET/CT and explore its relationship with clinical symptoms and WBBS.METHODS:Twenty-six patients who suffered from SAPHO syndrome and had undergone whole-body 18F-FDG PET/CT were recruited in Peking Union Medical College Hospital from 2004 to 2016. Clinical manifestations and laboratory findings were recorded for all patients. Imaging data on 18F-FDG PET/CT and WBBS were collected and analyzed retrospectively.RESULTS:All the 26 patients (20 females and 6 males) exhibited skeletal abnormalities on 18F-FDG PET/CT. Multiple skeletal lesions affecting the anterior chest wall or spine with low to moderate 18F-FDG uptake and coexistence of osteolysis and osteosclerosis presented as the typical features of SAPHO syndrome. Sixteen (61.5%) patients had abnormal 18F-FDG uptake outside the osteoarticular system. PET scan had moderate to substantial agreement with CT and WBBS in revealing lesions in the anterior chest wall and axial skeleton. Nonetheless, the correlation between increased 18F-FDG uptake and clinical symptoms was weak.CONCLUSIONS:SAPHO syndrome exhibits characteristic features on 18F-FDG PET/CT. It showed comparable capacity in revealing skeletal lesions with bone scintigraphy.

目的 探讨1例糖原累积症Ⅰa型(GSDⅠa)患者的临床特点及治疗方法.方法 详细收集患者病史、体格检查和实验室检查结果等临床资料.提取患者及父母外周血DNA,采用PCR-序列测定法,检测葡萄糖-6-磷酸催化亚基(G6PC)基因的外显子1至外显子5.结果 患者为23岁男性,有低血糖、肝肿大、高乳酸血症、高尿酸血症和高脂血症的典型临床表现,并同时存在罕见的严重骨骼畸形.在患者G6PC基因外显子5中检测到纯合c.648G>T(p.Leu216Leu)剪切致病突变,母亲和父亲均在该位点为杂合突变.该基因突变为GSDⅠa型中最常见的基因突变类型,但极少出现明显骨骼畸形.结论 GSDⅠa型可出现罕见的骨骼畸形,早期诊断和治疗有助于提高生活质量和减轻器官损害.