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1.
Ann Rheum Dis ; 83(4): 475-487, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38129117

RESUMEN

OBJECTIVES: This phase 2b, randomised, double-blind, placebo-controlled trial evaluated the efficacy and safety of telitacicept, a novel fusion protein that neutralises signals of B lymphocyte stimulator and a proliferation-inducing ligand, in active systemic lupus erythematosus (SLE). METHODS: Adult patients with active SLE (n=249) were recruited from 29 hospitals in China and randomised 1:1:1:1 to receive subcutaneous telitacicept at 80 mg (n=62), 160 mg (n=63), 240 mg (n=62) or placebo (n=62) once weekly in addition to standard therapy. The primary endpoint was the proportion of patients achieving an SLE Responder Index 4 (SRI-4) response at week 48. Missing data were imputed using the last observation carried forward method. RESULTS: At week 48, the proportion of patients achieving an SRI-4 response was 75.8% in the 240 mg telitacicept group, 68.3% in the 160 mg group, 71.0% in the 80 mg group and 33.9% in the placebo group (all p<0.001). Significant treatment responses were observed in secondary endpoints, including a ≥4-point reduction on the Systemic Lupus Erythematosus Disease Activity Index, a lack of Physician's Global Assessment score worsening and a glucocorticoid dose reduction in the 240 mg group. Telitacicept was well tolerated, and the incidence of adverse events and serious adverse events was similar between the telitacicept and placebo groups. CONCLUSIONS: This phase 2b clinical trial met the primary endpoint. All telitacicept groups showed a significantly higher proportion of patients achieving an SRI-4 response than the placebo group at week 48, and all doses were well tolerated. These results support further investigations of telitacicept in clinical trials involving more diverse populations and larger sample sizes. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT02885610).


Asunto(s)
Lupus Eritematoso Sistémico , Proteínas Recombinantes de Fusión , Adulto , Humanos , Método Doble Ciego , Glucocorticoides/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
2.
Scand J Immunol ; 98(1): e13285, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38441210

RESUMEN

Autoimmunity is reported involving in reproductive failures, and antinuclear antibody (ANA) positivity has been regarded as a typical feature of autoimmunity. Published studies on the association of ANA with reproductive failures including infertility are controversial. The aim of this meta-analysis was to analyse whether the presence of ANA positivity increases the risk of infertility in women. We searched the PubMed and Embase databases for relevant literature without any restrictions prior to April 28, 2021. All analyses were performed using the RevMan 5.3 software. Twelve studies with 2734 participants, including 1482 patients with infertility, met the inclusion and exclusion criteria. The total positivity rate of ANA was 23.8% (353/1482) in all infertile patients and 8.5% (107/1252) in the control group. Infertile females had a significantly higher ANA positivity rate than the control group (odds ratio [OR] = 2.90, 95% confidence interval [CI]: 1.72-4.87, I2 = 65%, P < .0001). Several subgroup analyses were performed to reduce the heterogeneity. ANA positivity was associated with female infertility in studies either performed by indirect immunofluorescence (OR = 2.26, 95% CI:1.67-3.06, P < .00001) or by ELISA (OR = 10.76, 95% CI:1.82-63.64, P < .00001). ANA was significantly associated with increased risk of women infertility either after the definite exclusion of individuals with autoimmune diseases (AID) or without exclusion [(OR = 1.99, 95% CI:1.29-3.06, P = .002), (OR = 2.76, 95% CI:1.56-4.88, P = .0005), respectively]. This meta-analysis provides a comprehensive overview of the prevalence of antinuclear antibodies (ANA) in infertile women and suggests that ANA positivity increases the risk of infertility.


Asunto(s)
Enfermedades Autoinmunes , Infertilidad Femenina , Femenino , Humanos , Anticuerpos Antinucleares , Autoinmunidad , Ensayo de Inmunoadsorción Enzimática
3.
Lupus ; 32(14): 1598-1609, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37903189

RESUMEN

BACKGROUND: Cuproptosis is a novel mode of cell death, which is strongly related to energy metabolism in mitochondria and regulated by protein lipoylation. Currently, the molecular mechanisms of cuproptosis-related genes (CRGs) involved in systemic lupus erythematosus (SLE) largely remained unclear, our study is aimed to explore the mechanisms of cuproptosis and CRGs involved in SLE. METHODS: Bulk RNA-seq datasets were collected to display the expressions of CRGs in peripheral blood mononuclear cells (PBMCs) of SLE and healthy individuals, and then ROC analysis was used to establish the diagnostic models of CRGs. Next, the immune infiltration analyses were applied to reveal the difference of immune cells infiltration in LIAS-low and LIAS-high group. Additionally, WGCNA analysis was performed to find the gene modules significantly correlated with the LIAS expression level. We also performed the functional enrichment analyses for LIAS-related gene modules to determine the potential pathways involved in the development of SLE. Finally, scRNA-seq dataset was used to cluster immune cell subsets, reveal the activated pathways, and study cell-cell interactions in LIAS-low and LIAS-high cells. RESULT: We found CDKN2A was significantly increased and LIAS was significantly decreased in SLE patients compared with healthy individuals. The AUC score showed that LIAS had a great diagnostic value than other CRGs. Additionally, the results of immune infiltration analyses showed that immune cells proportion were diverse in LIAS-low and LIAS-high samples. The gene sets related to LIAS expression level were involved in dephosphorylation of JAK1 by SHP1, phosphorylation of STAT2, cytokine signaling in immune system, expression of interferon-alpha and beta, inhibition of JAK kinase activity by SOCS1/3, and so on. Finally, the results of cell-cell communication showed that CCL- (CCL5 + CCR1) and ANNEXIN- (ANXA1 + FPR1) might play an essential role in the communication network between LIAS-low and LIAS-high cells. CONCLUSION: Above findings inferred that LIAS-mediated cuproptosis might involve in a comprehensive cellular and molecular mechanism to cause the occurrence and development of SLE.


Asunto(s)
Apoptosis , Leucocitos Mononucleares , Lupus Eritematoso Sistémico , Sulfurtransferasas , Humanos , Comunicación Celular , Cobre , Redes Reguladoras de Genes , Lupus Eritematoso Sistémico/genética , Fosforilación , Sulfurtransferasas/genética
4.
Lupus ; 31(4): 407-414, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35246003

RESUMEN

PURPOSE: To investigate meibomian gland (MG) alteration in patients with systemic lupus erythematosus (SLE). METHODS: This study included 23 SLE patients evaluated with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and 21 healthy controls (HCs). All the subjects were evaluated with Ocular Surface Disease Index (OSDI) questionnaire, and the eyes were performed examinations of tear meniscus height (TMH), non-invasive keratographic tear film break-up time (NIKBUT), Schirmer I Test, MG eyelid score, meibography score, and in vivo confocal microscopy (IVCM) on the meibomian gland. RESULTS: There was no significant difference between the SLE patients and the HCs in the TMH, NIKBUT, and Schirmer I Test. However, the SLE patients had higher MG eyelid scores and meibography scores on both upper eyelid and lower eyelid than the HCs. Through meibography observation, 34.8% of the SLE patients presented MG deficiency in Grade 3, whereas that of all the HCs were less than Grade 3. The SLE patients were found to have significant MG atrophy and vascular enrichment around the meibomian glands (MGs). The SLE patients were also found to have excessive inflammatory cell infiltration around the MGs, especially the typical lymph node-like foci of inflammatory cell infiltration. CONCLUSIONS: MG alteration can be found in the SLE patients. Examinations of the MGs can help diagnose or infer ocular diseases at an early stage of SLE.


Asunto(s)
Síndromes de Ojo Seco , Enfermedades de los Párpados , Lupus Eritematoso Sistémico , Síndromes de Ojo Seco/diagnóstico , Enfermedades de los Párpados/diagnóstico , Enfermedades de los Párpados/etiología , Humanos , Lupus Eritematoso Sistémico/complicaciones , Glándulas Tarsales , Lágrimas
5.
BMC Musculoskelet Disord ; 23(1): 717, 2022 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-35897055

RESUMEN

OBJECTIVES: To investigate longitudinal relationship between serum uric acid (SUA) and disease activity among Chinese males with axial spondyloarthritis (axSpA). METHODS: Two-year data from the NASA study cohort of male patients with axial spondyloarthritis were analyzed. Patients global assessment of disease activity (PtGA), BASDAI, ASDAS-CRP, BASFI, and SF-36 were used as the outcomes. The autoregressive Generalized Estimation Equation (GEE) model was used to investigate the longitudinal relationship between SUA and the above outcomes. Age and gender and symptom duration were tested as effect modifiers or confounders. RESULTS: In total, 102 male axSpA patients were included, 33.3% of who were hyperuricemia at baseline. Over time,serum uric acid levels associated with the global assessment of patient global assessment of disease activity (PtGA)[P=0.041, ß=-2.059,95%CI(-4.032, -0.086)], SF-36: Vitality (VT) [P=0.01, ß=1.751, 95%CI (0.415,3.087)], SF-36: Social Functioning (SF)[P=0.002, ß= 2.968,95%CI (1.067,4.869)]). And these relationgships were independent of age, symptom duration, baseline uric acid levels, and medication use. CONCLUSIONS: In summary, SUA levels is longitudinally related to PtGA and mental health assessment. Age, gender and symptom duration do not have an impact on the relationships.


Asunto(s)
Espondiloartritis Axial , Espondiloartritis , Espondilitis Anquilosante , Estudios de Cohortes , Humanos , Masculino , Índice de Severidad de la Enfermedad , Espondiloartritis/diagnóstico , Espondilitis Anquilosante/diagnóstico , Ácido Úrico
6.
J Autoimmun ; 117: 102590, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33310686

RESUMEN

There are some challenges and unmet needs in the early diagnosis and management of Sjögren's syndrome (SjS) such as prominent glandular dysfunction at diagnosis and long diagnostic delay. Those challenges are partly attributed to the lack of a good knowledge of the early stages of SjS, which is a major obstacle to delivering appropriate care to SjS patients. Findings from both clinical and experimental studies suggest the plausibility of a redefined SjS course consisting of 4 stages, which includes initiation stage, preclinical stage, asymptomatic SjS stage and overt SjS stage. More studies focusing on the pathological processes and changes during the early stages of SjS are needed. To enable early diagnosis and treatment for SjS, more useful biomarkers of the early stages of SjS need to be identified, and individuals at high risk of SjS development need to be identified. Appropriate screening can be performed to facilitate the early diagnosis of SjS among those high-risk individuals.


Asunto(s)
Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/terapia , Animales , Enfermedades Asintomáticas , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Autoinmunidad , Biomarcadores , Terapia Combinada , Manejo de la Enfermedad , Progresión de la Enfermedad , Susceptibilidad a Enfermedades/inmunología , Diagnóstico Precoz , Humanos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Síndrome de Sjögren/etiología , Síndrome de Sjögren/metabolismo
7.
J Clin Rheumatol ; 27(2): 50-55, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33617165

RESUMEN

BACKGROUND/OBJECTIVE: The neurological involvement associated with primary Sjögren's syndrome (pSS) can be life threatening. However, the specific characteristics of pSS-related neurological involvement remain obscure. This study aimed at determining the clinical characteristics of this neurological involvement in patients with pSS. METHODS: The clinical data of 205 patients with pSS who were admitted to our department between January 2015 and June 2017 were studied. Characteristics and laboratory findings of pSS patients with neurological abnormalities were compared with pSS patients without. RESULTS: Forty of the 205 patients with pSS exhibited neurological abnormalities (19.51%); of these, 13 patients exhibited central nervous system (CNS) involvement only, 20 patients exhibited peripheral nervous system (PNS) involvement only, and 7 patients exhibited both, yielding a total of 20 (9.76%) patients with CNS involvement and 27 (13.17%) patients with PNS involvement. The titers of anti-Sjögren's syndrome type A (SSA) antibodies were significant higher while the presence of anti-Sjögren's syndrome type B (SSB) antibodies was significant lower in patients with vs. without neurological involvement. Similar results were found in patients with CNS involvement. No significant differences between patients with and without neurological involvement were found for the other clinical parameters examined. CONCLUSIONS: Neurological involvement in patients with pSS is common and needs to be carefully evaluated. Patients with pSS with a high titer of anti-SSA and low presence of anti-SSB antibodies might have a relatively high risk of developing neurological involvement. Future studies should focus on identifying biomarkers that may aid in the early diagnosis of neurological involvement in patients with pSS.


Asunto(s)
Anticuerpos Antinucleares/sangre , Enfermedades del Sistema Nervioso/inmunología , Síndrome de Sjögren , Adulto , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/sangre , Enfermedades del Sistema Nervioso/etiología , Síndrome de Sjögren/sangre , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/inmunología
8.
Hum Reprod ; 35(11): 2439-2453, 2020 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-33047116

RESUMEN

STUDY QUESTION: Does osteoprotegerin (OPG) promote human endometrial stromal decidualization? SUMMARY ANSWER: OPG is essential for human endometrial stromal decidualization through its interaction with syndecan-1 to decrease Akt phosphorylation. WHAT IS KNOWN ALREADY: OPG (a cytokine receptor) levels are significantly increased in the circulation of pregnant women. However, the role and mechanism of OPG in human endometrial stromal cell (ESC) decidualization remain elusive. STUDY DESIGN, SIZE, DURATION: We analyzed the endometrial expression of OPG in endometrial tissue samples collected from women with regular menstrual cycles (ranging from 25 to 35 days), and decidual tissue samples collected from woman with normal early pregnancy or recurrent pregnancy loss (RPL) who visited the Department of Gynecology and Obstetrics at a tertiary care center from January to October 2018. None of the subjects had hormonal treatment for at least 3 months prior to the procedure. In total, 16 women with normal early pregnancy and 15 with RPL were selected as subjects for this study. The function of OPG in decidualization was explored in a human endometrial stromal cell (HESC) line and primary cultures of HESCs. PARTICIPANTS/MATERIALS, SETTING, METHODS: We collected endometrial tissues (by biopsy) from the subjects during their menstrual cycle and decidual tissues from subjects with a normal early pregnancy and those with RPL at the time of dilation and curettage. The control group comprised randomly selected women who underwent termination of an apparently normal early pregnancy. The endometrial OPG expression was analyzed using immunohistochemical staining and quantitative RT-PCR (qRT-PCR). Immunofluorescence staining and western blot, and qRT-PCR were used to explore the mRNA and protein expression, respectively, of OPG in an immortalized HESC line and in primary cultures of HESC during proliferation and decidualization. siRNA-mediated knockdown experiments were performed to examine the function of OPG in HESC proliferation and decidualization. Flow cytometry and the cell proliferation MTS assay were performed to further examine the role of OPG in HESC proliferation. We also analyzed decidual marker gene expression by qRT-PCR to assess the consequences of OPG loss for HESC decidualization. A co-immunoprecipitation (IP) assay was used to determine the potential interaction between the OPG and Syndecan-1. Western blot analysis of the rescue experiments performed using the phosphatidylinositol 3-kinase (PI3K) signaling-specific inhibitor LY294002 was used to investigate the downstream signaling pathways through which OPG could mediate HESC decidualization. MAIN RESULTS AND THE ROLE OF CHANCE: OPG was expressed in both the human endometrium and in vitro decidualized ESCs. Knockdown experiments revealed that OPG loss impaired the expression of IGF-binding protein-1 (IGFBP-1) (P < 0.05) and prolactin (PRL) (P < 0.05), two specific markers of decidualization, in HESC undergoing decidualization. We also uncovered that OPG knockdown induced the aberrant activation of Akt (protein kinase B) during HESC decidualization (P < 0.05). The inhibition of Akt activation could rescue the impaired expression of the decidual markers PRL (P < 0.05) and IGFBP-1 (P < 0.05) in response to OPG knockdown. Syndecan-1 was considered a potential receptor candidate, as it was expressed in both the endometrium and in vitro cultured stromal cells. Subsequent co-IP experiments demonstrated the interaction between OPG and Syndecan-1 during decidualization. In addition, Syndecan-1 knockdown not only clearly attenuated the decidualization markers PRL (P < 0.05) and IGFBP-1 (P < 0.05) but also induced the aberrant enhancement of Akt phosphorylation in decidualized cells, consistent with the phenotype of OPG knockdown cells. Finally, we revealed that the transcript and protein expression of both OPG and Syndecan-1 was significantly lower in the decidual samples of women with RPL than in those of women with normal pregnancy (P < 0.05). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: In this study, based on a number of approaches, it was demonstrated that OPG mediated the repression of Akt that occurs during human stromal cell decidualization, however, the molecular link between OPG and Akt signaling was not determined, and still requires further exploration. WIDER IMPLICATIONS OF THE FINDINGS: OPG is required for decidualization, and a decrease in OPG levels is associated with RPL. These findings provide a new candidate molecule for the diagnosis and potential treatment of RPL. STUDY FUNDING/COMPETING INTEREST(S): This work was supported in part by the National Natural Science Foundation of China U1605223 (to G.S.), 81701457 (to Y.J.) and 81601349 (to Y.J.). The authors have no conflicts of interest to disclose.


Asunto(s)
Decidua , Proteínas Proto-Oncogénicas c-akt , Células Cultivadas , China , Decidua/metabolismo , Endometrio/metabolismo , Femenino , Humanos , Osteoprotegerina/genética , Osteoprotegerina/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Embarazo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Células del Estroma/metabolismo , Sindecano-1/genética , Sindecano-1/metabolismo
9.
Lupus ; 29(11): 1346-1352, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32703115

RESUMEN

OBJECTIVES: Lupus fundus abnormalities are a sight-threatening complication of systemic lupus erythematosus (SLE) and its pathogenesis remains to be studied. The aim of this study was to assess the clinical characteristics associated with the presence of anti-recoverin antibodies in patients with SLE, especially those with fundus abnormalities. METHODS: Seventy-six participants were enrolled, including 21 patients with fundus abnormalities (fundus group), 30 patients without fundus abnormalities (non-fundus group) and 25 healthy individuals. Serum anti-recoverin antibody levels were measured using enzyme-linked immunosorbent assay, and clinical and laboratory data were obtained from medical records. RESULTS: Compared with the non-fundus group, the fundus group had a higher incidence of hematuria (p < 0.05). The Systemic Erythematosus Disease Activity Index (SLEDAI) score in the fundus group was significantly higher than the non-fundus group (21.48 ± 8.06 versus 10.80 ± 5.74, p < 0.001). The levels of serum anti-recoverin antibodies in the fundus group were significantly higher than the non-fundus group (p = 0.029) or the healthy control group (p = 0.011). Anti-recoverin-negative and -positive patients differed on a number of clinical parameters, including incidence of fever, rash, antinuclear antibody, anti-dsDNA antibody, erythrocyte sedimentation rate, immunoglobulin G, complement C3 and complement C4. The average SLEDAI score of anti-recoverin-positive patients was significantly higher than anti-recoverin-negative patients (17.73 ± 8.11 versus 12.56 ± 8.37, p < 0.05). CONCLUSIONS: Anti-recoverin antibodies were related to higher disease activities in SLE, especially those with fundus abnormalities, suggesting that anti-recoverin antibodies may play an important role in the pathogenesis of fundus abnormalities in SLE.


Asunto(s)
Anticuerpos Antinucleares , Fondo de Ojo , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/patología , Recoverina/inmunología , Adolescente , Adulto , Biomarcadores , Estudios de Casos y Controles , Niño , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/inmunología , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Adulto Joven
10.
Biochem Biophys Res Commun ; 508(2): 392-397, 2019 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-30502083

RESUMEN

OBJECTIVE: The purpose of this study is to provide a further theoretical basis for the role of Suberoyllanilide hyroxamic acid (SAHA) affect on Dendritic cells (DCs). METHODS: We first downloaded the GSE74306 microarray data, which was about the effect of SAHA act on DCs, from the Gene Expression Omnibus database. Then we analyzed the differential expression genes (DEGs) between SAHA-treated DCs and SAHA-untreated DCs by limma package of R software; The Database for Annotation, Visualization and Integrated Discovery was used to analyze the Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for these DEGs. The protein protein interaction (PPI) network was constructed by using STRING database, Cytoscape 3.6.1 software was used to dispose the PPI network for visualization. Finally, we determine the Hub genes in the PPI network according by the degree centrality and betweenness centrality, which were calculated by the CentScaPe 2.2 plug-in of Cytoscape 3.6.1 software. RESULT: There were 551 DEGs between SAHA-treated DC cells and SAHA-untreated DC cells, including 357 upregulated genes and 194 downregulated genes. These DEGs genes were enriched in 115 Go terms (Biological Process, 51; Cellular Component, 35 and Molecular Function, 29) and a total of 16 pathways. Glutathione metabolic process, Glutathione metabolism pathway, Rheumatoid arthritis pathway and Systemic lupus erythematosus pathway were most significant function clusters. In the PPI network, Rad51, Src, and Eno2 were Hub genes. CONCLUSION: The biological function and KEGG pathway enriched by DEGs may reveal the molecular mechanism of SAHA acting on DC cells. Its Hub genes, Src, Rad51 and Eno2, were expected to be new targets for SAHA therapeutic effects. However, it still need to be confirmed by the next more rigorous molecular biological experiments research.


Asunto(s)
Células Dendríticas/efectos de los fármacos , Células Dendríticas/metabolismo , Vorinostat/farmacología , Animales , Biología Computacional , Células Dendríticas/inmunología , Expresión Génica/efectos de los fármacos , Perfilación de la Expresión Génica , Ontología de Genes , Redes Reguladoras de Genes/efectos de los fármacos , Redes Reguladoras de Genes/inmunología , Inhibidores de Histona Desacetilasas/farmacología , Humanos , Ratones , Análisis de Secuencia por Matrices de Oligonucleótidos , Mapas de Interacción de Proteínas/efectos de los fármacos , Mapas de Interacción de Proteínas/genética , Mapas de Interacción de Proteínas/inmunología , Programas Informáticos
11.
Clin Immunol ; 188: 58-63, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29292085

RESUMEN

In order to evaluate autoantibody to SP-1 as an early biomarker in pSS, we investigated autoantibody to SP-1 in Chinese patients with primary Sjögren's syndrome (pSS). Autoantibodies to SP-1 are significantly increased in pSS patients compared to RA patients, SLE patients, and healthy people without secondary SS. The presence of anti SP-1 antibodies was negatively correlated with the focus score (FS), RF, and salivary gland function. It was positively correlated with FS=0, RF≤20, and normal salivary gland function. In further studies, the autoantigen SP-1 was identified in ductal epithelia of salivary glands in il14α TG mice by IIF. SP-1 mRNAs expression increased with growing age in il14α TG mice. SP-1 mRNA was also identified in labial biopsies of patients with pSS. In conclusion, autoantibody to SP-1 is an early marker in pSS. It is useful to diagnose pSS patients who lack RF or antibodies to Ro/La.


Asunto(s)
Autoanticuerpos/inmunología , Autoantígenos/inmunología , Proteínas y Péptidos Salivales/inmunología , Síndrome de Sjögren/inmunología , Adulto , Animales , Pueblo Asiatico , Línea Celular Tumoral , China , Femenino , Expresión Génica/inmunología , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Persona de Mediana Edad , Glándulas Salivales/inmunología , Glándulas Salivales/metabolismo , Proteínas y Péptidos Salivales/genética , Proteínas y Péptidos Salivales/metabolismo , Síndrome de Sjögren/etnología , Síndrome de Sjögren/genética , Adulto Joven
13.
Mediators Inflamm ; 2017: 4639081, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28197018

RESUMEN

The Gαq-containing G protein, an important member of Gq/11 class, is ubiquitously expressed in mammalian cells. Gαq has been found to play an important role in immune regulation and development of autoimmune disease such as rheumatoid arthritis (RA). However, how Gαq participates in the pathogenesis of RA is still not fully understood. In the present study, we aimed to find out whether Gαq controls RA via regulation of Th1 differentiation. We observed that the expression of Gαq was negatively correlated with the expression of signature Th1 cytokine (IFN-γ) in RA patients, which suggests a negative role of Gαq in differentiation of Th1 cells. By using Gαq knockout (Gnaq-/-) mice, we demonstrated that loss of Gαq led to enhanced Th1 cell differentiation. Gαq negative regulated the differentiation of Th1 cell by modulating the expression of T-bet and the activity of STAT4. Furthermore, we detected the increased ratio of Th1 cells in Gnaq-/- bone marrow (BM) chimeras spontaneously developing inflammatory arthritis. In conclusion, results presented in the study demonstrate that loss of Gαq promotes the differentiation of Th1 cells and contributes to the pathogenesis of RA.


Asunto(s)
Artritis Reumatoide/sangre , Artritis/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/metabolismo , Inflamación/metabolismo , Células TH1/citología , Adulto , Anciano , Animales , Diferenciación Celular , Citocinas/metabolismo , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Persona de Mediana Edad , Factor de Transcripción STAT4/genética , Factor de Transcripción STAT4/metabolismo , Células TH1/metabolismo
15.
Mediators Inflamm ; 2016: 4927530, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27738386

RESUMEN

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by aberrant T cell immune response. Diffuse proliferative lupus nephritis (LN-IV) is the most common, severe, and active form of lupus nephritis. In this study, we investigated the production of Th1, Th2, and Th17 cytokines in prediction of active form of LN-IV. ProcartaPlex multiplex immunoassays panels were used for detection of serum Th1, Th2, and Th17 cytokines profiling. Th1 and Th17 cytokines (IL-18, IFN-γ, IL-12p70, IL-6, and IL-17A) were considerably expressed in the serum of lupus nephritis IV patients in comparison to the healthy control. However, only IL18 and IL6 were higher in class IV versus class III lupus nephritis. Importantly, the ratios of Th1/Th2 (IL-18/IL-4) and Th17/Th2 (IL-17A/IL-4) were significantly elevated in LN-IV when compared with LN-III, LN-V, and healthy controls. Consistently, the serum cytokines IL-18, IL-17A, and IFN-γ were markedly expressed in LN-IV patient glomeruli and interstitial tissue compared to other classes of LN by IHC. ROC further suggests that IL-18 was a potential marker for LN-IV. The data from our study suggests that the early detection and quantification of these cytokines may help in prediction of active form of LN-IV.


Asunto(s)
Citocinas/sangre , Células TH1/metabolismo , Células Th17/metabolismo , Células Th2/metabolismo , Adulto , Pueblo Asiatico , Complemento C3/metabolismo , Complemento C4/metabolismo , Femenino , Humanos , Interferón gamma/sangre , Interleucina-12/sangre , Interleucina-13/sangre , Interleucina-18/sangre , Interleucina-4/sangre , Interleucina-6/sangre , Lipocalina 2/sangre , Nefritis Lúpica/sangre , Masculino , Persona de Mediana Edad , Factor de Necrosis Tumoral alfa/sangre
16.
Immunol Cell Biol ; 93(7): 616-24, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25732870

RESUMEN

Gαq, the α-subunit of Gq protein, is ubiquitously expressed in mammalian cells. It initially attracted attention for its physiological significance in cardiovascular system. In recent years, studies have also indicated the important roles of Gαq in regulating immunity, supplying us a new insight into the mechanism of immune regulation. T helper type 17 (Th17) cells are potent inducers of tissue inflammation. Many studies have shown that Th17 cells are major effector cells in the pathogenesis of many experimental autoimmune diseases and human inflammatory conditions such as rheumatoid arthritis (RA). One of our previous studies has shown that Gαq negatively controls the disease activity of RA. However, how Gαq controls the pathogenesis of autoimmune disease is not clear. Whether this effect is via the regulation of Th17 differentiation is still not known. We aimed to find out the role of Gαq in control of Th17 differentiation. We investigated the relationship between Gαq and Th17 in RA patients. We then investigated the mechanism of how Gαq regulated Th17 differentiation by using Gnaq(-/-) mice. We observed that the expression of Gαq was negatively associated with interleukin-17A expression in RA patients, indicating that Gαq negatively controlled the differentiation of Th17 cells. By using Gnaq(-/-) mice, we demonstrated that Gαq inhibited the differentiation of Th17 cell via regulating the activity of extracellular signal-regulated kinase-1/2 to control the expression of STAT3 (signal transducer and activator of transcription 3) and RORα (RAR-related orphan receptor-α). These data suggest the possibility of targeting Gαq to develop a novel therapeutic regimen for autoimmune disease.


Asunto(s)
Artritis Reumatoide/patología , Subunidades alfa de la Proteína de Unión al GTP/fisiología , Células Th17/patología , Animales , Artritis Reumatoide/genética , Artritis Reumatoide/inmunología , Artritis Reumatoide/metabolismo , Linfocitos T CD4-Positivos/metabolismo , Células Dendríticas/metabolismo , Flavonoides/farmacología , Subunidades alfa de la Proteína de Unión al GTP/biosíntesis , Subunidades alfa de la Proteína de Unión al GTP/deficiencia , Subunidades alfa de la Proteína de Unión al GTP/genética , Subunidades alfa de la Proteína de Unión al GTP Gq-G11 , Regulación de la Expresión Génica , Humanos , Interleucina-17/biosíntesis , Interleucina-17/genética , Interleucina-6/biosíntesis , Interleucina-6/genética , Linfopoyesis/genética , Linfopoyesis/fisiología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Miembro 1 del Grupo F de la Subfamilia 1 de Receptores Nucleares/fisiología , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Quimera por Radiación , Factor de Transcripción STAT3/fisiología , Espondilitis Anquilosante/genética , Espondilitis Anquilosante/metabolismo , Células Th17/inmunología
17.
Immunol Cell Biol ; 92(9): 781-90, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24957218

RESUMEN

We have previously reported that Gαq, the α subunit of the Gq protein, had important roles in dendritic cell migration, B-cell survival and autoimmunity. In this study, we showed that the deficiency of Gαq led to enhanced T-cell survival. Cultured Gnaq(-/-) T cells exhibited survival advantages both in medium alone and in the presence of anti-CD3 stimulation. Gnaq(-/-) T cells still exhibited a survival advantage when they were cultured in the presence of interleukin (IL)-2 or IL-7. Gnaq(-/-) T cells were more resistant to activation-induced cell death (AICD) in vitro. The survival advantage of Gnaq(-/-) T cells was further confirmed by transferring T cells into syngeneic hosts in vivo. Gαq deficiency might promote T-cell survival by upregulated Bcl-xL expression and downregulated Fas and FasL expressions. Furthermore, upon T-cell receptor (TCR) ligation, Akt activity was increased in Gnaq(-/-) T cells in comparison with wild-type (WT) T cells. The survival advantage of Gnaq(-/-) T cells was significantly attenuated after adding Akt inhibitor. Taken together, our data demonstrated a negative role of Gαq in regulating T-cell survival.


Asunto(s)
Supervivencia Celular/genética , Supervivencia Celular/inmunología , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/genética , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/inmunología , Linfocitos T/inmunología , Animales , Muerte Celular/genética , Muerte Celular/inmunología , Regulación hacia Abajo/genética , Regulación hacia Abajo/inmunología , Proteína Ligando Fas/genética , Proteína Ligando Fas/inmunología , Interleucina-2/genética , Interleucina-2/inmunología , Interleucina-7/genética , Interleucina-7/inmunología , Ratones , Ratones Endogámicos C57BL , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/inmunología , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/inmunología , Regulación hacia Arriba/genética , Regulación hacia Arriba/inmunología
18.
J Clin Rheumatol ; 20(5): 275-7, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25036559

RESUMEN

Limb-girdle muscular dystrophy type 2B,a type of dysferlinopathy, is caused by mutations in the dysferlin gene (DYSE). It is characterized by predominant weakness and atrophy of muscles of the pelvic and shoulder girdles, massive elevation of serum CK concentration, slow progression, and onset usually within the second or third decade of life. We present a Chinese patient whose disease onset was at the age of 50 years with persistent elevation of transaminases for 3 years before weakness appeared. She had been considered as having liver disease for a long time and then polymyositis. Finally, biceps brachii biopsy revealed dystrophic morphology and depletion of dysferlin in immunohistochemistry. This case should remind readers that late-age onset of dysferlinopathy can be misdiagnosed as liver disease or polymyositis.


Asunto(s)
Hepatopatías/diagnóstico , Proteínas de la Membrana/sangre , Proteínas Musculares/sangre , Distrofia Muscular de Cinturas/diagnóstico , Polimiositis/diagnóstico , Alanina Transaminasa/sangre , Biopsia con Aguja , Diagnóstico Tardío , Diagnóstico Diferencial , Progresión de la Enfermedad , Disferlina , Electromiografía/métodos , Femenino , Humanos , Inmunohistoquímica , Hepatopatías/sangre , Pruebas de Función Hepática , Proteínas de la Membrana/genética , Persona de Mediana Edad , Proteínas Musculares/análisis , Proteínas Musculares/genética , Distrofia Muscular de Cinturas/patología , Distrofia Muscular de Cinturas/rehabilitación , Medición de Riesgo
19.
Eur Cytokine Netw ; 35(1): 1-12, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38909355

RESUMEN

Primary Sjögren syndrome (pSS) is a systemic autoimmune disorder that affects various systems in the body, resulting in symptoms such as dry eyes and mouth, pain, and fatigue. Inflammation plays a critical role in pSS and its associated complications, with chronic inflammation being a common occurrence in patients with pSS. This review of the literature highlights inflammatory markers that could serve as indicators to predict disease progression in pSS. Laboratory markers are frequently and significantly increased in pSS patients, including erythrocyte sedimentation rate, C-reactive protein, complement proteins, S100 proteins, cytokines (IFNs, CD40 ligand, soluble CD25, rheumatoid factors, interleukins, and TNF-α), and chemokines (CXCL13, CXCL10, CCL2, CXCL11, and CCL25). These inflammatory markers can be used as prognostic indicators for disease progression in pSS. In conclusion, the results from the studies reported in this review indicate that high levels of inflammatory markers may serve as markers for disease progression of pSS, which, in turn, may be valuable in predicting disease outcome.


Asunto(s)
Biomarcadores , Progresión de la Enfermedad , Inflamación , Síndrome de Sjögren , Humanos , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/sangre , Biomarcadores/sangre , Inflamación/sangre , Citocinas/sangre , Citocinas/metabolismo , Pronóstico , Proteína C-Reactiva/metabolismo , Proteína C-Reactiva/análisis , Sedimentación Sanguínea
20.
Semin Arthritis Rheum ; 68: 152488, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38896912

RESUMEN

BACKGROUND: Primary Sjögren syndrome (pSjS) is one of the most prevalent systemic autoimmune diseases and characterized with hyperactivation of B cell and the abundant presence of autoantibodies in sera. The salivary gland epithelial cells (SGECs) release autoantigens to evoke autoimmunity through releasing elevated apoptosis or secreting autoantigen-containing exosomes, thus identifying autoantibodies directly to SGECs might provide insights into disease related biomarkers as well as further elucidating pathogenesis mechanisms. The present study was undertaken to identify autoantibodies to SGECs and to evaluate its clinical values in Chinese pSjS. METHODS: Cell-based indirect immunofluorescence and immunostaining, two-dimensional electrophoresis and liquid chromatograph-tandem mass spectrometry were conducted to identify the autoantibodies to human salivary gland cell line A253 in pSjS sera. Enzyme-linked immunosorbent assay (ELISA) was applied to identify autoantibody titer in pSjS cohort and healthy controls. The prevalence and clinical significance of the identified autoantibodies was further assessed in pSjS population. RESULTS: Anti-calreticulin (CALR) antibody was identified as a new autoantibody directly to SGECs in sera from pSjS patients. Anti-CALR antibody were detected in 37 of 120 pSjS patients (30.83 %) and 1 of 54 healthy controls (1.85 %). It was found in 40.85 % pSjS with anti-SSA positive, 53.85 % with anti-SSB positive, and 14.7 % in sero-negative pSjS. Anti-CALR antibody was associated with clinical manifestations including weight loss(p = 0.045), vasculitis (p = 0.031), and laboratory parameters including erythrocyte sedimentation rate (ESR) (r = 0.056, p = 0.021), Krebs von den Lungen-6 (KL-6) (r = 0.121, p = 0.035), IgG (r = 0.097, p < 0.001), IgG2 (r = 0.142, p = 0.022), IgG3 (r = 0.287, p < 0.001), fibrinogen (r = 0.084, p = 0.016), D-Dimer (r = 0.086, p = 0.012) and fibrinogen degradation production (r = 0.150, p = 0.002). The expression of CALR in salivary glands was related to lymphocytes infiltration into salivary glands in pSjS patients (r = 0.7076, p = 0.0034). CONCLUSION: To our knowledge, this was the first study to investigate the prevalence and clinical significance of anti-CALR antibody in Chinses pSjS patients. The present study identified an autoimmune antibody, anti-CALR antibody, as a good autoimmune biomarker for sero-negative pSjS.

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