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1.
Artigo em Inglês | MEDLINE | ID: mdl-34559215

RESUMO

OBJECTIVES: Thrombosis occurring in the central nerve system is common in antiphospholipid syndrome (APS) patients, leading to neuropsychiatric symptoms. We investigated the prevalence of silent brain abnormalities on magnetic resonance imaging (MRI) in primary antiphospholipid syndrome (PAPS) patients and antiphospholipid antibodies (aPL) carriers and assessed the association between the vascular risk factors, aPL profile, clinical manifestations, and MRI abnormalities. METHODS: We consecutively included 44 PAPS patients, 24 aPL carriers and 23 healthy controls with comparable age and gender in a single-center, observational cross-sectional study. None of the patients had a history of stroke, TIA, migraine, dementia, epilepsy and bipolar disorders. On cerebral MRI, we assessed the imaging features and location of abnormality. Multivariate analysis was performed to identify the risk factors contributing to the MRI abnormalities. RESULTS: 38 (55.88%) patients persisted abnormal MRI findings, while only one healthy control showed some abnormalities in the MR findings. Lacunes were the most frequent MRI abnormality in aPL (+) group (31/68, 45.59%), which were followed by white matter hyperintensities (20/68, 29.41%). In all study population, age (OR = 1.086, p= 0.016) and LA positivity (OR = 5.191, p= 0.002) were the independent associated factors with the brain MRI abnormalities. When analyzed only in the aPL (+) group, age (OR = 1.116, p= 0.007), female gender (OR = 7.519, p= 0.025) and thrombocytopenia (OR = 8.336, p= 0.047) were the significant independent risk factors with abnormal MRI. CONCLUSIONS: PAPS patients and aPL carriers showed a high prevalence of brain MRI abnormalities, indicating an increased cerebrovascular risk, which emphasized attention to silent cerebral lesions in persistently aPL positive patients.

2.
Rheumatol Int ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34499196

RESUMO

In view of the possible involvement of vascular endothelial growth factor-C (VEGF-C) in pathogenesis of adult-onset Still's disease (AOSD) based on our previous genome-wide association study (GWAS) results, the primary objective of this study, therefore, was to investigate the correlations between the content of VEGF-C in serum and clinical and biochemical markers of AOSD. Blood samples were collected from 80 patients with AOSD, 26 with rheumatoid arthritis (RA), 30 with systemic lupus erythematosus (SLE) and 31 healthy control subjects. The serum VEGF-C levels were determined using an enzyme-linked immunosorbent assay (ELISA). Statistical analysis and comparisons were conducted. A significantly higher serum VEGF-C level was observed in patients with AOSD than in HC. Serum VEGF-C levels had high AUC value of 0.8145 for distinguishing AOSD group from healthy group with sensitivity of 0.7097 and specificity of 0.8250. It also showed good diagnostic value to differentiate AOSD from other autoinflammatory diseases with sensitivity of 0.7500 and specificity of 0.5500. AOSD patients with fever, arthralgia, skin rash, sore throat, lymphadenopathy, splenomegaly hepatomegaly and pleuritis, had a higher level than those who did not have these symptoms (p = 0.0012, p = 0.0092, p = 0.0056, p = 0.0123, p = 0.0068, p = 0.0030, p = 0.0020, and p = 0.0018, respectively). The serum VEGF-C levels were also positively correlated with laboratory features and several cytokines related to AOSD disease activity. In conclusion, our study unveiled a close association between serum VEGF-C levels and AOSD including disease activity and clinical hematological manifestations, suggesting the potential utility of VEGF-C as a candidate biomarker to assess disease activity in AOSD.

3.
Front Immunol ; 12: 702425, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489952

RESUMO

Antiphospholipid syndrome (APS) is a multisystem disorder characterized by thrombosis and/or recurrent fetal loss. This clinical phenotype heterogeneity may result in differences in response to treatment and prognosis. In this study, we aimed to identify primary thrombotic APS (TAPS) from primary obstetric APS (OAPS) using urine proteomics as a non-invasive method. Only patients with primary APS were enrolled in this study from 2016 to 2018 at a single clinical center in Shanghai. Urine samples from 15 patients with TAPS, 9 patients with OAPS, and 15 healthy controls (HCs) were collected and analyzed using isobaric tags for relative and absolute quantification (iTRAQ) labeling combined with liquid chromatography-tandem mass spectrometry analysis to identify differentially expressed proteins. Cluster analysis of urine proteomics identified differentiated proteins among the TAPS, OAPS, and HC groups. Urinary proteins were enriched in cytokine and cytokine receptor pathways. Representative secreted cytokines screened out (fold change >1.20, or <0.83, p<0.05) in these differentiated proteins were measured by enzyme-linked immunosorbent assay in a validation cohort. The results showed that the levels of C-X-C motif chemokine ligand 12 (CXCL12) were higher in the urine of patients with TAPS than in those with OAPS (p=0.035), while the levels of platelet-derived growth factor subunit B (PDGFB) were lower in patients with TAPS than in those with OAPS (p=0.041). In addition, correlation analysis showed that CXCL12 levels were positively correlated with immunoglobulin G anti-ß2-glycoprotein I antibody (r=0.617, p=0.016). Our results demonstrated that urinary CXCL12 and PDGFB might serve as potential non-invasive markers to differentiate primary TAPS from primary OAPS.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34508561

RESUMO

OBJECTIVES: To explore the efficacy of plasma exchange (PE) therapy in refractory idiopathic inflammatory myopathy (IIM) patients with positive anti-signal recognition particle (SRP) antibody. METHODS: Nine refractory IIM patients with positive anti-SRP antibody were enrolled, who received PE therapy at Ruijin Hospital from Octobor 2017 to December 2020. The clinical manifestations, laboratory tests, chest CT and lower extremity MRI images before and after PE therapy were compared. The treatment response was evaluated by the 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) myositis response criteria. RESULTS: 88.9% (8/9) subjects had achieved improvement by 3 weeks after PE therapy, with 55.6% (5/9) minimal improvement and 33.3% (3/9) moderate improvement. There were statistically significant improvements between baseline and after PE therapy at 3 weeks on the core set measures: physician global activity, patient global activity, Health Assessment Questionnaire (HAQ), manual muscle testing (MMT), extramuscular disease activity, and muscle enzymes activity including creatine kinase (CK), lactate dehydrogenase (LDH), aspartate transaminase (AST), except for alanine transaminase (ALT). Moreover, the chest CT showed regression of ground glass opacities and irregular linear opacities after PE therapy in four patients with interstitial lung disease. The MRI images of lower extremity in four patients showed reduction of muscle oedema after the therapy. CONCLUSION: PE therapy is effective for refractory IIM patients with positive anti-SRP antibody. It should be considered as an alternative treatment for those patients who are resistant to the combined therapy of glucocorticoids and immunosuppressive agents.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34015111

RESUMO

OBJECTIVE: Anti-ß-2 glycoprotein I (anti-ß2GPI) antibodies, defined as primary pathogenic antibody in antiphospholipid syndrome (APS). It has been reported that IgG Fc N-glycosylation affects IgG effector, we aim to investigate the association of Fc glycosylation profiles of purified anti-ß2GP1 IgG with clinical features of APS. METHODS: We purify anti-ß2GPI IgG and total IgG from 82 APS patients including 9 catastrophic antiphospholipid syndrome (CAPS) patients, as well as total IgG from 103 healthy controls to quantitatively analyze all detectable Fc N-glycanforms of all IgG subclasses with Multiple Reaction Monitoring (MRM) method based on UPLC-ESI-QqQ mass spectrometry. RESULTS: Both purified anti-ß2GPI IgG and APS total IgG showed altered N-glycan profiles when compared with HC IgG. Anti-ß2GPI IgG presented with lower galactosylation, increased bisection and core fucosylation compared with APS total IgG and HC IgG. We found higher galactosylation of aß2GPI IgG2 in thrombotic APS compared with the obstetric APS, and lower galactosylation of aß2GPI IgG2 associated with late pregnancy morbidity. Moreover, low galactosylation of all anti-ß2GPI IgG subclasses, increased bisection and core fucosylation of anti-ß2GPI IgG1/2 were strongly associated with CAPS and triple positivity of antiphospholipid antibodies (aPLs). CONCLUSION: We comprehensively characterize the N-Glycans landscape of both anti-ß2GP1 and total IgG in APS. Altered N-glycan profiles of anti-ß2GPI IgG enables enabled the antibodies with proinflammatory properties. Furthermore, we associated levels of IgG Fc-glycosylation with clinical features antiphospholipid syndrome. These findings could increase our understanding of anti-ß2GPI antibody mediated mechanisms in APS and be used to develop diagnostics and new target treatments.

7.
Aging (Albany NY) ; 13(8): 12143-12159, 2021 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-33902006

RESUMO

Increased accumulation of advanced glycation end products (AGEs) in diabetic skin is closely related to delayed wound healing. Studies have shown that the concentration of AGEs is elevated in the skin tissues and not subcutaneous tissues in refractory diabetic wounds, which suggests there may be a causal relationship between the two. In the present study, in vitro experiments revealed that AGEs activated neutrophils, and the migratory and adhesive functions of neutrophils decreased once AGE levels reached a certain threshold. Different levels of AGE expression differentially affected the function of neutrophils. Messenger RNA (mRNA) sequencing analysis combined with real-time polymerase chain reaction (PCR) showed that poliovirus receptor (PVR/CD155) and CTNND1, which play a role in migration- and adhesion-related signaling pathways, were decreased following AGE stimulation. Consequently, neutrophils cannot effectively stimulate the formation of the inflammatory belt needed to remove necrotic tissues and defend against foreign microorganisms within diabetic chronic wounds. In addition, this phenomenon may be related to the differential accumulation of AGEs in different layers of the skin.


Assuntos
Complicações do Diabetes/imunologia , Diabetes Mellitus Experimental/complicações , Produtos Finais de Glicação Avançada/metabolismo , Neutrófilos/imunologia , Pele/patologia , Animais , Cateninas/metabolismo , Agregação Celular/imunologia , Linhagem Celular Tumoral , Movimento Celular/imunologia , Complicações do Diabetes/patologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/imunologia , Diabetes Mellitus Experimental/patologia , Humanos , Masculino , Ratos , Receptores Virais/metabolismo , Pele/citologia , Pele/imunologia , Estreptozocina/administração & dosagem , Estreptozocina/toxicidade , Cicatrização/imunologia
8.
Arthritis Res Ther ; 23(1): 97, 2021 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-33785060

RESUMO

BACKGROUND: To investigate the potential utility of quantitative parameters obtained by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the assessment of disease severity and the occurrence of macrophage activation syndrome (MAS) in adult-onset Still's disease (AOSD). METHODS: Fifty-seven patients with AOSD who underwent pre-treatment 18F-FDG PET/CT were recruited in this study and compared with 60 age- and sex-matched healthy controls. Clinical features and laboratory data were recorded. The systemic score was assessed to determine the disease severity. The maximal standardized uptake value (SUVmax), metabolic lesion volume (MLV), and total lesion glycolysis (TLG) were used to evaluate the involved organs and tissues that abnormally accumulated 18F-FDG. Multivariate analysis was performed to identify the PET/CT-derived risk factors contributing to the AOSD-related MAS, and their diagnostic efficiency was evaluated. RESULTS: High 18F-FDG accumulation was observed in the bone marrow (SUVmax median, 5.10), spleen (SUVmax median, 3.70), and lymph nodes (LNs, SUVmax median, 5.55). The SUVmax of the bone marrow (rho = 0.376, p = 0.004), SUVmax of the spleen (rho = 0.450, p < 0.001), TLGtotal of LNs (rho = 0.386, p = 0.017), and MLVtotal of LNs (rho = 0.391, p = 0.015) were correlated with the systemic score. The SUVmax of the spleen (p = 0.017), TLGtotal of LNs (p = 0.045), and MLVtotal of LNs (p = 0.012) were higher in patients with MAS than in those without MAS. A MLVtotal of LNs > 62.2 (OR 27.375, p = 0.042) was an independent predictive factor for MAS with a sensitivity of 80.0% and a specificity of 93.9%. CONCLUSIONS: The glucose metabolic level of the spleen could be an effective and easy-to-use imaging indicator of disease severity, and MLVtotal of LNs > 62.2 was a strong predictor of MAS occurrence in patients with AOSD.


Assuntos
Síndrome de Ativação Macrofágica , Doença de Still de Início Tardio , Adulto , Fluordesoxiglucose F18 , Humanos , Linfonodos/diagnóstico por imagem , Síndrome de Ativação Macrofágica/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Doença de Still de Início Tardio/diagnóstico por imagem
9.
Rheumatology (Oxford) ; 60(10): 4520-4529, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33493278

RESUMO

OBJECTIVES: To describe the detailed characteristics and explore the potential risk factors of relapses in patients with adult-onset Still's disease (AOSD). METHODS: We enrolled patients with AOSD admitted to the Department of Rheumatology and Immunology, Ruijin Hospital from August 2016 to September 2019. Kaplan-Meier curves and the log rank test were used to estimate the cumulative relapse probability and persistent remission rate before the first occurrence of relapse. The multivariate Cox proportional hazard method was utilized to identify risk factors associated with relapses of AOSD. RESULTS: A total of 122 patients with AOSD were enrolled with a median follow-up of 12.6 months. Among them, 26 (21.3%) patients had at least one relapse. The cumulative relapse rates of AOSD patients were 14.42%, 21.79%, 24.81% and 28.57% at 6, 12, 18 and 36 months, respectively. According to the multivariate analysis, intensive treatment (odds ratio: 6.848; 95% CI: 2.441, 19.211) and macrophage activation syndrome (odds ratio: 4.020, 95% CI: 1.564, 10.322) were associated with increased risk of relapse. CONCLUSION: Our study indicated that relapses occurred in at least one-fifth of patients with AOSD, and patients with high disease severity at initial attack may have an increased risk of relapse, which needs more intensive therapy and close follow-up.

12.
J Autoimmun ; 116: 102562, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33168359

RESUMO

Adult-onset Still's disease (AOSD) is a rare autoinflammatory disease with systemic involvement, and its pathophysiology remains unclear. Genome-wide association studies (GWAS) in the Chinese population have revealed an association between AOSD and the major histocompatibility complex (MHC) locus; however, causal variants in the MHC remain undetermined. In the present study, we identified independent amino-acid polymorphisms in human leukocyte antigen (HLA) molecules that are associated with Han Chinese patients with AOSD by fine-mapping the MHC locus. Through conditional analyses, we identified position 34 in HLA-DQα1 (p = 1.44 × 10-14) and Asn in HLA-DRß1 position 37 (p = 5.12 × 10-11) as the major determinants for AOSD. Moreover, we identified the associations for three main HLA class II alleles: HLA-DQB1*06:02 (OR = 2.70, p = 3.02 × 10-14), HLA-DRB1*15:01 (OR = 2.44, p = 3.66 × 10-13), and HLA-DQA1*01:02 (OR = 1.97, p = 1.09 × 10-9). This study reveals the relationship between functional variations in the class II HLA region and AOSD, implicating the MHC locus in the pathogenesis of AOSD.

13.
Rheumatology (Oxford) ; 60(1): 304-315, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-32766690

RESUMO

OBJECTIVE: Liver damage is a common manifestation and can be life-threatening in adult-onset Still's disease (AOSD), an autoinflammatory disease. The hallmark of AOSD is activation of neutrophils, whose infiltration in liver is suspected to promote tissue injury. Here we aimed to identify a candidate biomarker and to validate its association with liver damage in AOSD. METHODS: Transcriptome analysis of neutrophils from treatment-naïve active AOSD patients and healthy donors was performed. Lipocalin-2 (LCN2) expression was assessed in neutrophils, plasma and liver biopsies of AOSD. The correlations of LCN2 with different variables and its ability to identify liver damage from AOSD patients were analysed. RESULTS: LCN2, a novel biomarker in hepatic inflammation, was found to be upregulated in AOSD neutrophils by RNA sequencing and confirmed at the mRNA and protein levels. Plasma levels of LCN2 were significantly higher in AOSD patients than healthy controls, RA and SLE patients. Plasma LCN2 levels were closely correlated with inflammatory markers, systemic score, HScore and cytokines. Moreover, LCN2 levels were increased in active AOSD with liver involvement and independently associated with liver dysfunction. Enhanced expression of LCN2 was detected in liver biopsies from three patients with ongoing liver injury. Furthermore, the area under the curve value of LCN2 for identifying AOSD with liver injury from other liver diseases was 0.9694. CONCLUSION: Our results reveal that neutrophils-derived LCN2 is higher in plasma and liver tissue in AOSD patients than in healthy controls, and it could serve as a potent biomarker for identifying AOSD with systemic inflammation, especially liver damage caused by hyperinflammation.


Assuntos
Lipocalina-2/metabolismo , Fígado/metabolismo , Doença de Still de Início Tardio/metabolismo , Adulto , Biomarcadores/metabolismo , Feminino , Humanos , Inflamação/metabolismo , Inflamação/patologia , Lipocalina-2/sangue , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Índice de Gravidade de Doença , Doença de Still de Início Tardio/sangue , Doença de Still de Início Tardio/diagnóstico , Doença de Still de Início Tardio/patologia
15.
Arthritis Rheumatol ; 73(6): 1033-1043, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33381895

RESUMO

OBJECTIVE: Adult-onset Still's disease (AOSD) is a severe autoinflammatory disease. Neutrophil activation with enhanced neutrophil extracellular trap (NET) formation is involved in the pathogenesis of AOSD. Functional leukocyte immunoglobulin-like receptor A3 (LIR-A3; gene name LILRA3) has been reported to be associated with many autoimmune diseases. We aimed to investigate the association of LILRA3 with disease susceptibility and neutrophil activation in AOSD. METHODS: The LILRA3 deletion polymorphism and its tagging single-nucleotide polymorphism rs103294 were genotyped in 164 patients with AOSD and 305 healthy controls. The impact of LILRA3 on clinical features and messenger RNA expression was evaluated. Plasma levels of LIR-A3 were detected using enzyme-linked immunosorbent assay (ELISA), and the correlation between LIR-A3 plasma levels and disease activity and levels of circulating NET-DNA was investigated. LIR-A3-induced NETs were determined using PicoGreen double-stranded DNA dye and immunofluorescence analysis in human neutrophils and a neutrophil-like differentiated NB4 cell line transfected with LIR-B2 small interfering RNA. RESULTS: The findings from genotyping demonstrated that functional LILRA3 was a risk factor for AOSD (11% in AOSD patients versus 5.6% in healthy controls; odds ratio 2.089 [95% confidence interval 1.030-4.291], P = 0.034), and associated with leukocytosis (P = 0.039) and increased levels of circulating neutrophils (P = 0.027). Functional LILRA3 messenger RNA expression was higher in the peripheral blood mononuclear cells (P < 0.0001) and neutrophils (P < 0.001) of LILRA3+/+ patients. Plasma levels of LIR-A3 were elevated in patients with AOSD (P < 0.0001) and correlated with disease activity indicators and levels of circulating NET-DNA complexes. Finally, enhanced NET formation was identified in neutrophils from healthy controls and patients with inactive AOSD after stimulation of the neutrophils with LIR-A3. Moreover, NET formation was impaired in NB4 cells after knockdown of LILRB2 gene expression. CONCLUSION: Our study provides the first evidence that functional LILRA3 is a novel genetic risk factor for the development of AOSD and that functional LIR-A3 may play a pathogenic role by inducing formation of NETs.


Assuntos
Armadilhas Extracelulares/genética , Ativação de Neutrófilo/genética , Receptores Imunológicos/genética , Doença de Still de Início Tardio/genética , Adulto , Estudos de Casos e Controles , Armadilhas Extracelulares/metabolismo , Feminino , Predisposição Genética para Doença , Humanos , Leucocitose , Masculino , Neutrófilos , Polimorfismo de Nucleotídeo Único , RNA Mensageiro/metabolismo , Receptores Imunológicos/metabolismo , Doença de Still de Início Tardio/metabolismo
16.
Front Immunol ; 11: 563335, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33240258

RESUMO

Adult-onset Still's disease (AOSD) is an autoinflammatory disease with multisystem involvement. Early identification of patients with severe complications and those refractory to glucocorticoid is crucial to improve therapeutic strategy in AOSD. Exaggerated neutrophil activation and enhanced formation of neutrophil extracellular traps (NETs) in patients with AOSD were found to be closely associated with etiopathogenesis. In this study, we aim to investigate, to our knowledge for the first time, the clinical value of circulating NETs by machine learning to distinguish AOSD patients with organ involvement and refractory to glucocorticoid. Plasma samples were used to measure cell-free DNA, NE-DNA, MPO-DNA, and citH3-DNA complexes from training and validation sets. The training set included 40 AOSD patients and 24 healthy controls (HCs), and the validation set included 26 AOSD patients and 16 HCs. Support vector machines (SVM) were used for modeling and validation of circulating NETs signature for the diagnosis of AOSD and identifying patients refractory to low-dose glucocorticoid treatment. The training set was used to build a model, and the validation set was used to test the predictive capacity of the model. A total of four circulating NETs showed similar trends in different individuals and could distinguish patients with AOSD from HCs by SVM (AUC value: 0.88). Circulating NETs in plasma were closely correlated with systemic score, laboratory tests, and cytokines. Moreover, circulating NETs had the potential to distinguish patients with liver and cardiopulmonary system involvement. Furthermore, the AUC value of combined NETs to identify patients who were refractory to low-dose glucocorticoid was 0.917. In conclusion, circulating NETs signature provide added clinical value in monitoring AOSD patients. It may provide evidence to predict who is prone to be refractory to low-dose glucocorticoid and help to make efficient therapeutic strategy.


Assuntos
Armadilhas Extracelulares/metabolismo , Glucocorticoides/administração & dosagem , Doença de Still de Início Tardio/diagnóstico , Doença de Still de Início Tardio/tratamento farmacológico , Máquina de Vetores de Suporte , Adulto , Estudos de Casos e Controles , Ácidos Nucleicos Livres , Citocinas/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Doença de Still de Início Tardio/sangue , Doença de Still de Início Tardio/imunologia , Resultado do Tratamento , Adulto Jovem
17.
J Immunol Res ; 2020: 2180708, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33224991

RESUMO

Background: Systemic lupus erythematosus (SLE) is a disease characterized by the production of a large number of autoantibodies. Defected phagocytosis of macrophage plays an important role in innate immunity in the pathogenesis of SLE. Tyro3 is a receptor responsible for the recognition of apoptotic cells during efferocytosis by macrophages. To investigate the role of Tyro3 receptor in macrophages' efferocytosis of apoptotic cells in SLE, we aimed to reveal the clinical relevance and impact of Tyro3 autoantibody on SLE. Methods: The serum levels of IgG-type autoantibody against Tyro3 receptor were detected in new-onset, treatment-naïve SLE patients (n = 70), rheumatoid arthritis (RA) (n = 24), primary Sjögren's Syndrome (pSS) (n = 21), and healthy controls (HCs) (n = 70) using enzyme-linked immunosorbent assay (ELISA). The effects of purified Tyro3 autoantibody from SLE patients on the efferocytosis of human monocyte-derived macrophages were measured by flow cytometry and immunofluorescence. Results: The serum levels of IgG-type autoantibody against Tyro3 receptor were significantly elevated in patients with SLE compared to RA, pSS, and HCs (all p < 0.0001). The levels of anti-Tyro3 IgG were positively associated with the SLE disease activity index (SLEDAI) score (r = 0.254, p = 0.034), erythrocyte sedimentation rate (ESR) (r = 0.430, p < 0.001), C-reactive protein (CRP) (r = 0.246, p = 0.049), and immunoglobulin G (IgG) (r = 0.408, p = 0.001) and negatively associated with haemoglobin (Hb) (r = -0.294, p = 0.014). ROC curves illustrated that the anti-Tyro3 antibody could differentiate patients with SLE from HCs. Furthermore, flow cytometry and immunofluorescence demonstrated that purified anti-Tyro3 IgG inhibited the efferocytosis of macrophages (p = 0.004 and 0.044, respectively) compared with unconjugated human IgG. Conclusions: These observations indicated that autoantibody against Tyro3 was associated with disease activity and could impair efferocytosis of macrophages. It might be a potential novel disease biomarker and might be involved in the pathogenesis of SLE.

18.
Front Immunol ; 11: 2112, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013889

RESUMO

Adult-onset Still's disease (AOSD) is a systemic, multigenic autoinflammatory disease, and the diagnosis of AOSD must rule out neoplasms, infections, and other autoimmune diseases. Development of a rapid and efficient but non-invasive diagnosis method is urgently needed for improving AOSD therapy. In this study, we first performed a urinary proteomic study using isobaric tags for relative and absolute quantification (iTRAQ) labeling combined with liquid chromatography-tandem mass spectrometry analysis in patients with AOSD and healthy control (HC) subjects. The urinary proteins were enriched in pathways of the innate immune system and neutrophil degranulation, and we identified that the α-1-acid glycoprotein 1 (LRG1), orosomucoid 1 (ORM1), and ORM2 proteins were highly expressed in patients with AOSD. The elevated urine levels of LRG1, ORM1, and ORM2 were further validated by enzyme-linked immunosorbent assay in active patients with AOSD, disease controls, and HC subjects. Receiver operating characteristic curves showed that the areas under the curve of LRG1, ORM1, and ORM2 were 0.700, 0.837, and 0.736, respectively (all p < 0.05). Furthermore, we found that the urine levels of LRG1, ORM1, and ORM2 were positively correlated with the systemic score and erythrocyte sedimentation rate and that the urine levels of LRG1 were positively correlated with interleukin 1ß (IL-1ß), IL-6, and IL-18 levels, whereas the urine levels of ORM1 were positively correlated with the IL-1ß level. Together, our study identified novel urinary markers for non-invasive and simple screening of AOSD.


Assuntos
Imunidade Inata , Proteômica , Doença de Still de Início Tardio/urina , Adulto , Idoso , Biomarcadores/urina , Cromatografia Líquida , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Still de Início Tardio/imunologia , Espectrometria de Massas em Tandem
20.
Exp Ther Med ; 20(5): 91, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32973940

RESUMO

Gilbert syndrome (GS) is a hereditary unconjugated hyperbilirubinemia that results from mutations in the bilirubin uridine diphosphate-glucuronosyltransferase (UGT1A1) gene. To the best of our knowledge, there are currently no reports that focus on patients with systemic lupus erythematosus (SLE) coexisting with GS. The present study aimed to evaluate the clinical characteristics and genotype of UGT1A1 in a Chinese patient with SLE and GS. Complete medical records and laboratory data were reviewed for a patient with SLE referred to Ruijin Hospital (Shanghai, China) for treatment between March 2016 and January 2020. Genetic analysis of the UGT1A1 gene was performed by PCR amplification and Sanger sequencing. The serum total bilirubin and unconjugated bilirubin concentrations on admission were 96.2 and 86.8 µmol/l, respectively. The homozygous mutation c.1456T>G (p.Y486D) in exon 5 was detected in this patient. The patient had a good response to phenobarbital orally at a dose of 30 mg/day and a decrease in serum bilirubin was observed. Elevated unconjugated hyperbilirubinemia in SLE needs to be differentiated from other diseases, such as GS, which can be diagnosed by UGT1A1 genetic sequencing.

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