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1.
Immun Inflamm Dis ; 12(5): e1276, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38780036

RESUMO

OBJECTIVES: The dysregulated immune response is one of the cardinal features of severe coronavirus disease 2019 (COVID-19). This study was conducted to clarify the occurrence of autoantibodies (AABs) associated with systemic autoimmune rheumatic diseases (SARDs) in hospitalized patients with a moderate, severe, and critical form of COVID-19. METHODS: The serum samples obtained from 176 hospitalized COVID-19 patients were investigated in this study, including patients with moderate (N = 90), severe (N = 50), and critical (N = 36) forms of COVID-19. Also, the serum samples collected from healthy subjects before the COVID-19 pandemic were used as controls (N = 176). The antinuclear antibodies (ANAs), antidouble-stranded DNA (anti-dsDNA), cytoplasmic-anti neutrophil cytoplasmic antibody (c-ANCA), perinuclear ANCA (p-ANCA), antiphospholipid antibodies (aPLs), and anticyclic citrullinated peptide (anti-CCP) occurrence was evaluated using a solid-phase enzyme-linked immunosorbent assay (ELISA). RESULTS: The results showed that the occurrence of ANAs, anti-dsDNA, anti-CCP, c-ANCA, and p-ANCA was significantly higher in the COVID-19 patients compared to serum obtained from healthy subjects (p < .0001, p < .0001, p < .0001, p < .05, and p < .001, respectively). The positive number of anti-CCP tests increased significantly in severe COVID-19 compared to the moderate group (p < .01). CONCLUSION: Our study further supports the development of autoantibodies related to systemic autoimmune rheumatologic diseases. To the best of our knowledge, this is the first study with a large sample size that reported the occurrence of anti-CCP in a severe form of COVID-19.


Assuntos
Anticorpos Antiproteína Citrulinada , COVID-19 , SARS-CoV-2 , Humanos , COVID-19/imunologia , COVID-19/sangue , Masculino , Feminino , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Adulto , Idoso , Anticorpos Antiproteína Citrulinada/sangue , Anticorpos Antiproteína Citrulinada/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Índice de Gravidade de Doença , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologia , Doenças Reumáticas/imunologia , Doenças Reumáticas/sangue , Doenças Autoimunes/imunologia , Doenças Autoimunes/sangue
2.
Clin Exp Med ; 24(1): 96, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38717644

RESUMO

Primary Sjögren's Syndrome (pSS) falls within the category of connective tissue diseases, characterized by the presence of autoantibodies such as antinuclear antibodies (ANA). However, according to the classification criteria for pSS, some patients may exhibit a negative result for autoantibodies. Patients with a negative result for autoantibodies may lack typical features of connective tissue diseases, and the immunological state as well as the extent of organ involvement and damage may differ from those with positive autoantibodies. This study aims to compare the clinical phenotypes of patients with positive and negative autoantibodies, providing insights for disease classification and treatment selection for clinicians. Patients with pSS were grouped based on the presence and titers of their autoantibodies. Subsequently, differences in organ damage and laboratory indicators were compared between these groups, aiming to analyze the value of autoantibody titers in assessing the condition of pSS. (1) Patients with positive ANA exhibited elevated levels of inflammatory indicators, including ESR, IgG levels, lip gland biopsy pathology grade, and overall organ involvement, in comparison with patients with negative ANA (P < 0.05). Furthermore, ANA-positivity correlated with a higher occurrence of multi-organ damage, particularly affecting the skin, mucous membranes, and the hematological system (P < 0.05). (2) As ANA titers increased, patients demonstrated elevated levels of IgG and an escalation in organ involvement (P < 0.05). (3) Patients in the positive autoantibody group (positive for antinuclear antibodies, anti-SSA, or anti-SSB antibodies) had higher IgG levels compared to the negative group (P < 0.05). (4) Patients with positive anti-SSA and anti-SSB antibodies exhibited higher levels of inflammatory indicators and IgG compared to other patients (P < 0.05); however, no significant differences were observed in terms of organ involvement and organ damage. Patients with positive ANA in pSS typically exhibit higher levels of inflammation and an increased likelihood of experiencing multi-organ damage. Furthermore, as the ANA titers increase, both inflammation levels and the risk of multi-organ damage also escalate. Additionally, the presence of anti-SSA and anti-SSB antibodies may contribute to an elevated risk of increased inflammation levels, but does not increase the risk of organ damage.


Assuntos
Anticorpos Antinucleares , Síndrome de Sjogren , Humanos , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologia , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/patologia , Síndrome de Sjogren/sangue , Feminino , Pessoa de Meia-Idade , Masculino , Adulto , Idoso , Inflamação/imunologia , Inflamação/patologia , Imunoglobulina G/sangue
3.
Lupus Sci Med ; 11(1)2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724181

RESUMO

OBJECTIVE: To identify new genetic variants associated with SLE in Taiwan and establish polygenic risk score (PRS) models to improve the early diagnostic accuracy of SLE. METHODS: The study enrolled 2429 patients with SLE and 48 580 controls from China Medical University Hospital in Taiwan. A genome-wide association study (GWAS) and PRS analyses of SLE and other three SLE markers, namely ANA, anti-double-stranded DNA antibody (dsDNA) and anti-Smith antibody (Sm), were conducted. RESULTS: Genetic variants associated with SLE were identified through GWAS. Some novel genes, which have been previously reported, such as RCC1L and EGLN3, were revealed to be associated with SLE in Taiwan. Multiple PRS models were established, and optimal cut-off points for each PRS were determined using the Youden Index. Combining the PRSs for SLE, ANA, dsDNA and Sm yielded an area under the curve of 0.64 for the optimal cut-off points. An analysis of human leucocyte antigen (HLA) haplotypes in SLE indicated that individuals with HLA-DQA1*01:01 and HLA-DQB1*05:01 were at a higher risk of being classified into the SLE group. CONCLUSIONS: The use of PRSs to predict SLE enables the identification of high-risk patients before abnormal laboratory data were obtained or symptoms were manifested. Our findings underscore the potential of using PRSs and GWAS in identifying SLE markers, offering promise for early diagnosis and prediction of SLE.


Assuntos
Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Lúpus Eritematoso Sistêmico , Herança Multifatorial , Humanos , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia , Taiwan/epidemiologia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Cadeias alfa de HLA-DQ/genética , Estudos de Casos e Controles , Anticorpos Antinucleares/sangue , Cadeias beta de HLA-DQ/genética , Fatores de Risco , Haplótipos , Polimorfismo de Nucleotídeo Único , Estratificação de Risco Genético
4.
Lupus Sci Med ; 11(1)2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38724183

RESUMO

OBJECTIVE: This study aimed to evaluate the prevalence of sarcopenia and its clinical significance in Turkish women with SLE, exploring the association between muscle mass, muscle strength and SLE disease activity. METHODS: A cross-sectional study was conducted at Gazi University Hospital's Department of Rheumatology from January to December 2020. It involved 82 patients with SLE, diagnosed according to the 2019 American College of Rheumatology/European Alliance of Associations for Rheumatology criteria, and 69 healthy controls. Sarcopenia was assessed using hand grip dynamometry (hand grip strength (HGS)) and bioelectrical impedance analysis for muscle mass, with sarcopenia defined according to the 2018 European Working Group on Sarcopenia in Older People criteria and specific cut-offs for the Turkish population. The main outcomes measured were the presence of sarcopenia and probable sarcopenia, HGS values, skeletal muscle mass index and SLE Disease Activity Index 2000 (SLEDAI-2K). RESULTS: Among the patients with SLE, 51.2% met the criteria for probable sarcopenia and 12.9% were diagnosed with sarcopenia. The mean HGS was significantly lower in the SLE group (21.7±4.9 kg) compared with controls, indicating reduced muscle strength. The prevalence of anti-double-stranded DNA (anti-dsDNA) antibodies was 82.9%. Multivariate regression analysis identified height and levels of anti-dsDNA antibodies as independent predictors for developing probable sarcopenia. No significant association was found between clinical parameters, including SLEDAI-2K scores, and sarcopenia status. CONCLUSIONS: Sarcopenia is prevalent among Turkish women with SLE, with a significant proportion showing reduced muscle strength. The study found no direct association between sarcopenia and SLE disease activity or clinical parameters. These findings underscore the importance of including muscle strength assessments in the routine clinical evaluation of patients with SLE to potentially improve management and quality of life.


Assuntos
Força da Mão , Lúpus Eritematoso Sistêmico , Força Muscular , Sarcopenia , Humanos , Sarcopenia/epidemiologia , Sarcopenia/fisiopatologia , Sarcopenia/diagnóstico , Feminino , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Estudos Transversais , Turquia/epidemiologia , Adulto , Pessoa de Meia-Idade , Prevalência , Estudos de Casos e Controles , Anticorpos Antinucleares/sangue , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Índice de Gravidade de Doença
5.
J Assoc Physicians India ; 72(3): 32-35, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38736114

RESUMO

OBJECTIVE: Systemic lupus erythematosus (SLE) is a chronic inflammatory disease with a wide range of clinical manifestations having considerable variation in clinical features that are influenced by ethnic, sociocultural, and geographical factors. This disease primarily affects young women aged between 18 and 35 years. The aim of this present study was to delineate the clinical manifestations and immunological patterns of SLE patients from the Northeastern (NE) region of India. MATERIALS AND METHODS: The study was carried out in a tertiary care hospital from January 2016 to January 2021. Adult patients of age >18 years fulfilling systemic lupus international collaborating clinic criteria (SLICC) for classification of SLE were included in this study. Immunology such as antinuclear antibodies (ANA) and double-stranded deoxyribonucleic acid (dsDNA) were also performed followed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Over a period of 5 years, 142 patients were recruited for the study, with an overall female-to-male ratio was 9.9:1, a median age at onset of 25 years (interquartile range age 21-32 years) and a mean disease duration was 15.25 months (range 2-60 months). Our study revealed that ANA was positive in 97.18% of patients while anti-dsDNA was positive in 78.68%, indicating that women from this region have higher positivity rates. CONCLUSION: Our findings support the notion that SLE is a multisystem disorder that predominantly affects young females, especially during the second and third decades of life. Hematological, mucocutaneous, and renal manifestations are common in our patients. Moreover, pulmonary, cardiovascular, and gastrointestinal (GI) manifestations were understudied in other cohorts, which is one of our study's strengths.


Assuntos
Anticorpos Antinucleares , Lúpus Eritematoso Sistêmico , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Adulto , Feminino , Índia/epidemiologia , Masculino , Estudos Retrospectivos , Anticorpos Antinucleares/sangue , Adulto Jovem
6.
Arthritis Res Ther ; 26(1): 93, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702799

RESUMO

BACKGROUND: Anti-SS-A/Ro antibody (anti-SSA), the diagnostic marker of Sjögren's syndrome (SS), is often detected in systemic sclerosis (SSc). Some patients are diagnosed with SSc/SS overlap syndromes, while there are anti-SSA-positive SSc cases without SS. In this study, we investigated the clinical characteristics of SSc with anti-SSA and clarified the clinical impact of this antibody in SSc. METHODS: A retrospective chart review was conducted of 156 patients with SSc at Yokohama City University Hospital from 2018 to 2021. Clinical data, laboratory data, imaging, and autoantibody positivity status were collected and analysed to assess the association between these variables and anti-SSA using multivariable logistic regression analysis. RESULTS: This cohort included 18 men and 138 women with SSc (median age, 69.0 years). Thirty-nine patients had diffuse cutaneous SSc (dcSSc) (25%), and 117 patients had limited cutaneous SSc (75%). Forty-four patients were anti-SSA-positive. Among them, 24 fulfilled the SS criteria. Multivariable logistic regression revealed that anti-SSA was statistically associated with interstitial lung disease (ILD; odds ratio [OR] = 2.67; 95% confidence interval [CI], 1.14-6.3; P = 0.024). Meanwhile, anti-SSA positivity tended to increase the development of digital ulcer (OR = 2.18; 95% CI, 0.99-4.82, P = 0.054). In the comparative analysis of the autoantibody single-positive and anti-SSA/SSc-specific autoantibody double-positive groups, the anti-SSA single-positive group showed a significantly increased risk of ILD (OR = 12.1; 95% CI, 2.13-140.57; P = 0.003). Furthermore, patients with SSc and anti-SSA indicated that anti-SSA-positive SSc without SS was strongly associated with dcSSc when compared to that in patients with SS (OR = 6.45; 95% CI, 1.23-32.60; P = 0.024). CONCLUSIONS: Anti-SSA positivity increases the risk of organ involvement, such as ILD, in patients with SSc. Additionally, the anti-SSA-positive SSc without SS population may have more severe skin fibrosis than others. Anti-SSA may be a potential marker of ILD and skin severity in SSc.


Assuntos
Anticorpos Antinucleares , Escleroderma Sistêmico , Humanos , Masculino , Feminino , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/sangue , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Anticorpos Antinucleares/imunologia , Anticorpos Antinucleares/sangue , Estudos de Coortes , Adulto , Autoanticorpos/sangue , Autoanticorpos/imunologia , Doenças Pulmonares Intersticiais/imunologia , Doenças Pulmonares Intersticiais/diagnóstico , Idoso de 80 Anos ou mais
7.
Respir Res ; 25(1): 222, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811943

RESUMO

OBJECTIVE: To investigate the association of serum anti-Jo-1 antibody levels with the disease activity and prognosis in anti-Jo-1-positive patients with antisynthetase syndrome (ASS). METHODS: This study included 115 anti-Jo-1-positive patients with ASS who were admitted to China-Japan Friendship Hospital between 2009 and 2019. Anti-Jo-1 antibody serum levels at initial admission and follow-up were determined by enzyme-linked immunosorbent assay (ELISA). Global and organ disease activity was assessed at baseline and follow-up according to the International Myositis Assessment and Clinical Studies guidelines. RESULTS: Among enrolled patients, 70 (60.9%) patients initially presented with interstitial lung disease (ILD), and 46 (40%) patients presented with with muscle weakness at initial admission. At baseline, patients with ILD had lower levels of anti-Jo-1 antibodies than those without ILD (p = 0.012). Baseline anti-Jo-1 antibody levels were higher in patients with muscle weakness, skin involvement, and arthritis (all p < 0.05) compared to those without these manifestations. Baseline anti-Jo-1 antibody levels were positively correlated with skin visual analogue scale (VAS) scores (r = 0.25, p = 0.006), but not with disease activity in other organs. However, changes in anti-Jo-1 antibody levels were significantly positively correlated with the changes in PGA (ß = 0.002, p = 0.001), muscle (ß = 0.003, p < 0.0001), and pulmonary (ß = 0.002, p = 0.013) VAS scores, but not with skin and joint VAS scores. Older age of onset (hazard ratio [HR] 1.069, 95% confidence interval [CI]:1.010-1.133, p = 0.022) and higher C-reactive protein (CRP) levels (HR 1.333, 95% CI: 1.035-1.717, p = 0.026) were risk factors for death. CONCLUSION: Anti-Jo-1 titers appear to correlate more with disease activity changes over time rather than with organ involvement at baseline, which provides better clinical guidance for assessing the disease course using anti-Jo-1 levels.


Assuntos
Anticorpos Antinucleares , Miosite , Humanos , Miosite/sangue , Miosite/imunologia , Miosite/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Adulto , Anticorpos Antinucleares/sangue , Seguimentos , Idoso , Estudos Retrospectivos , Biomarcadores/sangue , Doenças Pulmonares Intersticiais/imunologia , Doenças Pulmonares Intersticiais/sangue , Doenças Pulmonares Intersticiais/diagnóstico
8.
Lupus Sci Med ; 11(1)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806217

RESUMO

OBJECTIVES: To investigate the effectiveness of belimumab on active lupus nephritis (LN) and explore the predictors, including serological biomarkers, of renal response to belimumab in a real-world setting. METHODS: This multicentre, real-world observational study enrolled patients with active LN receiving intravenous belimumab as an add-on therapy with 24-hour urine protein≥1 g and estimated glomerular filtration rate≥30 mL/min/1.73 m2 at baseline. Complete renal response (CRR), partial renal response (PRR), no renal response (NRR) and primary efficacy renal response (PERR) were evaluated. Multivariable logistic regression was used to identify risk factors for NRR to belimumab at 6 months. RESULTS: Among the 122 patients enrolled, the proportions of patients achieving CRR, PRR, NRR and PERR were 35.9%, 17.1%, 47.0% and 44.4% at 6 months (n=117) and 55.6%, 19.4%, 26.4% and 58.3% at 12 months (n=72), respectively. Proteinuria, daily prednisone dosage and Systemic Lupus Erythematosus Disease Activity Index 2000 scores significantly decreased at 6 and 12 months (p<0.0001). NRR at 6 months (NRR6) was the strongest negative predictor of CRR at 12 months. Baseline anti-dsDNA positivity inversely predicted NRR6 (OR=0.32,95% CI=0.10 to 0.98, p=0.049), while anti-SSA/Ro60 positively predicted NRR6 (OR=3.16, 95% CI=1.14 to 8.74, p=0.027). The combination of anti-SSA/Ro60 and anti-dsDNA serotype quantitatively predicted belimumab renal response. CONCLUSION: The effectiveness of belimumab was reproducible in Chinese patients with active LN. The simple yet interesting serotype predictive model needs further validation and its possible underlying mechanistic relevance deserves further exploration.


Assuntos
Anticorpos Antinucleares , Anticorpos Monoclonais Humanizados , Taxa de Filtração Glomerular , Imunossupressores , Nefrite Lúpica , Humanos , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/imunologia , Feminino , Masculino , Anticorpos Monoclonais Humanizados/uso terapêutico , Adulto , Anticorpos Antinucleares/sangue , Imunossupressores/uso terapêutico , Pessoa de Meia-Idade , Taxa de Filtração Glomerular/efeitos dos fármacos , Resultado do Tratamento , Rim/fisiopatologia , Rim/efeitos dos fármacos , Rim/imunologia , Biomarcadores/sangue , Adulto Jovem , Proteinúria/tratamento farmacológico , DNA
9.
Front Immunol ; 15: 1358114, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38711518

RESUMO

Background: The relationship between serum antinuclear antibody (ANA) and rheumatoid arthritis (RA) remains unknown. Therefore, we aimed to evaluate whether serum ANA was associated with an increased risk of RA in a case-control study. Methods: Patients with rheumatoid arthritis hospitalized at Shandong Provincial Hospital from January 2018 to December 2022 were recruited as the case group, and patients with other types of arthritis and healthy people at the same time were taken as the control group. Antinuclear antibody (ANA) was detected by indirect immunofluorescence assays. Propensity score matching was employed to construct a cohort of patients exhibiting comparable baseline characteristics. The relationship between serum ANA and the risk of rheumatoid arthritis was analyzed by logistic regression analysis. Results: A total of 1,175 patients with RA and 1,662 control subjects were included in this study. After adjusting for potential confounding factors in the propensity-score matched cohort, the risk of RA gradually increased with rising of ANA titers. When ANA titers were divided into three groups (1:100, 1:320, and 1:1,000), the OR (95% CI) for ANA titers from low to high was 3.95 (3.01, 5.18), 16.63 (9.44, 29.30), and 17.34 (9.53, 31.54), respectively, compared to those when ANA was negative. The ANA patterns closely related to the occurrence of RA include nuclear homogeneous, nuclear speckled, and cytoplasmic speckled. Among them, the positive rate of nuclear homogeneous was the highest, which accounted for 42.64%. The OR (95% CI) of ANA patterns including nuclear homogeneous, nuclear speckled, and cytoplasmic speckled was 16.81 (11.46, 24.65), 3.40 (2.49, 4.63), and 3.09 (1.77, 5.40), respectively. Conclusion: There was a curve relation between ANA titer and RA, and the higher the ANA titer, the higher the probability of RA. However, there was no statistical difference in probability of RA for 1:320 versus 1:1,000 ANA titers. The most important kind of ANA pattern in the blood of RA patients was nuclear homogeneous. These findings suggest that ANA may be a novel risk marker for RA.


Assuntos
Anticorpos Antinucleares , Artrite Reumatoide , Humanos , Artrite Reumatoide/sangue , Artrite Reumatoide/imunologia , Artrite Reumatoide/diagnóstico , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos de Casos e Controles , Adulto , Idoso , Biomarcadores/sangue , Fatores de Risco
10.
Front Immunol ; 15: 1327255, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38562920

RESUMO

Background: Lupus pathogenesis is mainly ascribed to increased production and/or impaired clearance of dead cell debris. Although self-reactive T and B lymphocytes are critically linked to lupus development, neutrophils, monocytes, and natural killer (NK) cells have also been implicated. This study assessed apoptosis-related protein expressions in NK cells of patients with juvenile-onset systemic lupus erythematosus (jSLE) and relations to disease activity parameters, nephritis, and neuropsychiatric involvement. Methods: Thirty-six patients with jSLE, 13 juvenile dermatomyositis (JDM) inflammatory controls, and nine healthy controls had Fas, FasL, TRAIL, TNFR1, Bcl-2, Bax, Bim, and caspase-3 expressions in NK cells (CD3-CD16+CD56+) simultaneously determined by flow cytometry. Disease activity parameters included Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, erythrocyte sedimentation rate, C-reactive protein level, anti-double strain DNA antibody level, complement fractions C3 and C4 levels. Results: Patients with jSLE had a profile of significantly reduced expression of TRAIL, Bcl-2, and TNFR1 proteins in NK cells when compared to healthy controls. Similar profile was observed in patients with jSLE with active disease, positive anti-dsDNA, nephritis, and without neuropsychiatric involvement. Patients with jSLE with positive anti-dsDNA also had reduced expression of Bax in NK cells when compared healthy controls and to those with negative anti-dsDNA. Yet, patients with jSLE with negative anti-dsDNA had reduced mean fluorescence intensity (MFI) of Bim in NK cells compared to healthy controls. Patients with jSLE with nephritis also had reduced MFI of Fas in NK cells when compared to those without nephritis. In addition, in patients with jSLE, the proportion of FasL-expressing NK cells directly correlated with the SLEDAI-2K score (rs = 0.6, p = 0.002) and inversely correlated with the C3 levels (rs = -0.5, p = 0.007). Moreover, patients with jSLE had increased NK cell percentage and caspase-3 protein expression in NK cells when compared to JDM controls. Conclusion: This study extends to NK cells an altered profile of TRAIL, Bcl-2, TNFR1, Fas, FasL, Bax, Bim, and caspase-3 proteins in patients with jSLE, particularly in those with active disease, positive anti-dsDNA, nephritis, and without neuropsychiatric involvement. This change in apoptosis-related protein expressions may contribute to the defective functions of NK cells and, consequently, to lupus development. The full clarification of the role of NK cells in jSLE pathogenesis may pave the way for new therapies like those of NK cell-based.


Assuntos
Dermatomiosite , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Anticorpos Antinucleares , Apoptose , Proteína X Associada a bcl-2 , Caspase 3 , Dermatomiosite/complicações , Células Matadoras Naturais , Receptores Tipo I de Fatores de Necrose Tumoral
11.
Front Immunol ; 15: 1384229, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38571954

RESUMO

Objective: Positive antinuclear antibodies (ANAs) cause diagnostic dilemmas for clinicians. Currently, no tools exist to help clinicians interpret the significance of a positive ANA in individuals without diagnosed autoimmune diseases. We developed and validated a risk model to predict risk of developing autoimmune disease in positive ANA individuals. Methods: Using a de-identified electronic health record (EHR), we randomly chart reviewed 2,000 positive ANA individuals to determine if a systemic autoimmune disease was diagnosed by a rheumatologist. A priori, we considered demographics, billing codes for autoimmune disease-related symptoms, and laboratory values as variables for the risk model. We performed logistic regression and machine learning models using training and validation samples. Results: We assembled training (n = 1030) and validation (n = 449) sets. Positive ANA individuals who were younger, female, had a higher titer ANA, higher platelet count, disease-specific autoantibodies, and more billing codes related to symptoms of autoimmune diseases were all more likely to develop autoimmune diseases. The most important variables included having a disease-specific autoantibody, number of billing codes for autoimmune disease-related symptoms, and platelet count. In the logistic regression model, AUC was 0.83 (95% CI 0.79-0.86) in the training set and 0.75 (95% CI 0.68-0.81) in the validation set. Conclusion: We developed and validated a risk model that predicts risk for developing systemic autoimmune diseases and can be deployed easily within the EHR. The model can risk stratify positive ANA individuals to ensure high-risk individuals receive urgent rheumatology referrals while reassuring low-risk individuals and reducing unnecessary referrals.


Assuntos
Doenças Autoimunes , Reumatologia , Feminino , Humanos , Anticorpos Antinucleares , Autoanticorpos , Doenças Autoimunes/diagnóstico , Registros Eletrônicos de Saúde , Masculino
12.
Front Immunol ; 15: 1320880, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38633257

RESUMO

Objectives: Nephritis is a life-threatening complication of primary Sjögren's syndrome (pSS), with membranous nephropathy (MN) being prevalent. Renal biopsy is the gold standard for MN diagnosis, but it is invasive and cannot be repeatedly performed. This study aimed to develop a nomogram for the prediction of MN in patients with pSS. Methods: This retrospective study included patients with pSS admitted to the Rheumatology and Immunology Department of the First Affiliated Hospital of China Medical University between January 2015 and January 2021. A nomogram was developed using multivariable logistic regression analysis and evaluated using receiver operating characteristic (ROC) curve analysis. Bootstrap resampling analysis (1,000 times) was performed to evaluate the nomogram for discrimination and the calibration curve for consistency. Results: A total of 237 patients with pSS [aged 53.00 (44.00, 61.00) years] were included, with 35 pSS-MN patients. Based on clinical practice and multivariable logistic regression analysis, seven variables associated with pSS-MN were selected, including white blood cells, creatine, complement 3, rheumatoid factor, antinuclear antibodies, anti-SSA antibody, and interstitial lung disease. The area under the ROC curve was 0.860 (95% confidence interval: 0.796-0.919), indicating good predictive power. In addition, the nomogram exhibited excellent performance, as demonstrated by the calibration curve and decision curve analysis. Conclusion: This study developed a risk prediction nomogram for MN in patients with pSS, with high predictive power. It may be used to improve the management of patients with pSS.


Assuntos
Glomerulonefrite Membranosa , Síndrome de Sjogren , Humanos , Estudos Retrospectivos , Glomerulonefrite Membranosa/complicações , Nomogramas , Anticorpos Antinucleares
13.
Int J Mol Sci ; 25(8)2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38673811

RESUMO

Despite conventional therapy, lupus nephritis (LN) remains a significant contributor to short- and long-term morbidity and mortality. B cell abnormalities and the production of autoantibodies against nuclear complexes like anti-dsDNA are recognised as key players in the pathogenesis of LN. To address the challenges of chronic immunosuppression associated with current therapies, we have engineered T cells to express chimeric autoantibody receptors (DNA-CAART) for the precise targeting of B cells expressing anti-dsDNA autoantibodies. T cells from LN patients were transduced using six different CAAR vectors based on their antigen specificity, including alpha-actinin, histone-1, heparan sulphate, or C1q. The cytotoxicity, cytokine production, and cell-cell contact of DNA-CAART were thoroughly investigated in co-culture experiments with B cells isolated from patients, both with and without anti-dsDNA positivity. The therapeutic effects were further evaluated using an in vitro immune kidney LN organoid. Among the six proposed DNA-CAART, DNA4 and DNA6 demonstrated superior selectively cytotoxic activity against anti-dsDNA+ B cells. Notably, DNA4-CAART exhibited improvements in organoid morphology, apoptosis, and the inflammatory process in the presence of IFNα-stimulated anti-dsDNA+ B cells. Based on these findings, DNA4-CAART emerge as promising candidates for modulating autoimmunity and represent a novel approach for the treatment of LN.


Assuntos
Autoantígenos , Linfócitos B , Nefrite Lúpica , Linfócitos T , Humanos , Nefrite Lúpica/imunologia , Nefrite Lúpica/terapia , Nefrite Lúpica/patologia , Linfócitos B/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Autoantígenos/imunologia , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/metabolismo , Receptores de Antígenos Quiméricos/genética , Feminino , Anticorpos Antinucleares/imunologia , Autoanticorpos/imunologia , Adulto , Masculino , Citocinas/metabolismo
14.
Biochim Biophys Acta Mol Basis Dis ; 1870(5): 167168, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38641012

RESUMO

OBJECTIVES: Testing for anti-SSA/Ro antibodies in serum is essential in the diagnostic work-up for primary Sjögren's syndrome (pSS). In this study, we aimed to validate our previous assay for detection of salivary anti-SSA/Ro52, and to develop assays for detection of salivary anti-SSA/Ro60 and for detection of anti-Ro52 and -Ro60 in plasma using the electric field-induced release and measurement (EFIRM) platform. METHODS: Whole saliva samples from two independent Danish cohorts (DN1 and DN2) including 49 patients with pSS, 73 patients with sicca symptoms, but not fulfilling the classification criteria for pSS (non-pSS sicca), and 51 healthy controls (HC), as well as plasma samples from the DN1 cohort were analyzed using EFIRM to detect anti-SSA/Ro52 and -Ro60. RESULTS: In the DN1 cohort, 100 % in the pSS group and 16 % in the non-pSS sicca group were serum anti-SSA/Ro positive by ELISA. EFIRM detected anti-SSA (Ro52 and/or -Ro60) in plasma and saliva in 100 % and 96 % patients with pSS, and 16 % and 29 % with non-pSS sicca. In the DN2 cohort, 80 % patients with pSS and 26 % with non-pSS sicca were serum anti-SSA/Ro positive. Salivary anti-SSA discriminated patients with pSS from HC and non-pSS sicca with an AUC range of 0.74-0.96 in the DN1 and DN2 cohorts. EFIRM discriminated pSS from non-pSS sicca with an AUC of 0.98 in plasma. CONCLUSION: Our findings suggest that salivary anti-SSA/Ro antibodies are potential discriminatory biomarkers for pSS, which may also identify seronegative patients, addressing the unmet clinical need of early detection and stratification of pSS.


Assuntos
Ribonucleoproteínas , Saliva , Síndrome de Sjogren , Humanos , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/sangue , Saliva/imunologia , Saliva/metabolismo , Feminino , Masculino , Pessoa de Meia-Idade , Ribonucleoproteínas/imunologia , Adulto , Idoso , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologia , Estudos de Casos e Controles , Autoanticorpos/sangue , Autoanticorpos/imunologia , Ensaio de Imunoadsorção Enzimática , Autoantígenos , RNA Citoplasmático Pequeno
15.
Clin Rheumatol ; 43(6): 1971-1978, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38642252

RESUMO

OBJECTIVE: To evaluate whether anti-PL7 and anti-PL12 autoantibodies are associated with a greater extent of the fibrotic component of ILD in ASSD patients. METHODS: Patients with ILD-ASSD who were positive for one of the following autoantibodies: anti-Jo1, anti-PL7, anti-PL12, and anti-EJ were included. Clinical manifestations, CPK levels, pulmonary function tests, and HCRT assessments were prospectively collected according to the Goh index. The fibrotic, inflammatory, and overall extension of the Goh index and DLCO were assessed by multiple linear analyses and compared between ASSD antibody subgroups. RESULTS: Sixty-six patients were included; 17 were positive for anti-Jo1 (26%), 17 for anti-PL7 (26%), 20 for anti-PL12 (30%), and 9 (14%) for anti-EJ. Patients with anti-PL7 and anti-PL12 had a more extensive fibrotic component than anti-Jo1. Anti-PL7 patients had a 7.9% increase in the fibrotic extension (cß = 7.9; 95% CI 1.863, 13.918), and the strength of the association was not modified after controlling for sex, age, and time of disease evolution (aß = 7.9; 95% CI 0.677, 15.076) and also was associated with an increase in ILD severity after adjusting for the same variables, denoted by a lower DLCO (aß = - 4.47; 95% CI - 8.919 to - 0.015). CONCLUSIONS: Anti-PL7-positive ASSD patients had more extensive fibrosis and severe ILD than the anti-Jo1 subgroup. This information is clinically useful and has significant implications for managing these patients, suggesting the need for early consideration of concurrent immunosuppressive and antifibrotic therapy.


Assuntos
Autoanticorpos , Doenças Pulmonares Intersticiais , Miosite , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Doenças Pulmonares Intersticiais/imunologia , Doenças Pulmonares Intersticiais/complicações , Estudos Transversais , Miosite/imunologia , Miosite/complicações , Autoanticorpos/sangue , Autoanticorpos/imunologia , Adulto , Idoso , Testes de Função Respiratória , Fibrose , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologia
16.
Viruses ; 16(4)2024 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-38675842

RESUMO

TREX1 acts in the initial prevention of an autoimmune response, but it may contribute to the permissiveness of retrovirus infections. This study investigated the association between the levels of TREX1 gene expression with the polymorphisms TREX1 rs3135941 (T/C) and TREX1 rs3135945 (G/A), and the presence of antinuclear antibodies (ANA) in antiretroviral therapy (ART)-naïve individuals and after 1 year of treatment. Blood samples from 119 individuals with HIV-1 were subjected to genotyping of polymorphisms and quantification of TREX1 gene expression and HIV-1 viral load by qPCR. The concentration of IFN-α and the number of CD4+/CD8+ T lymphocytes were determined by ELISA and flow cytometry, respectively; ANA was investigated by immunofluorescence. A control group of 167 seronegative individuals was used for the comparison of genotypic frequencies. The frequency of the polymorphisms were not associated with HIV infection or with variations in the expression of TREX1 and IFN-α (p > 0.05). ART-naïve individuals exhibited higher TREX1 expression and lower IFN-α expression. After 1 year of ART, TREX1 levels were reduced, while IFN-α and CD4+ T lymphocytes were elevated (p < 0.05). Some individuals on ART presented ANA. These results suggest that ART-mediated restoration of immune competence is associated with a reduction in TREX1 expression, which may induce the development of ANA, regardless of the polymorphism investigated.


Assuntos
Exodesoxirribonucleases , Infecções por HIV , HIV-1 , Reconstituição Imune , Fosfoproteínas , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Antinucleares/sangue , Linfócitos T CD4-Positivos/imunologia , Exodesoxirribonucleases/genética , Exodesoxirribonucleases/metabolismo , Genótipo , Infecções por HIV/imunologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Infecções por HIV/virologia , HIV-1/imunologia , Reconstituição Imune/genética , Reconstituição Imune/imunologia , Interferon-alfa/sangue , Interferon-alfa/metabolismo , Fosfoproteínas/genética , Polimorfismo de Nucleotídeo Único , Carga Viral , Antirretrovirais/efeitos adversos , Antirretrovirais/uso terapêutico
17.
Clin Exp Med ; 24(1): 72, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38598028

RESUMO

We aim at investigating the association between subclinical autoimmunity and immune-related adverse events (irAEs) in a cohort of patients treated by immune checkpoint inhibitors for solid metastatic cancer. In the context of an oncology/rheumatology outpatient clinic, we evaluated patients treated with anti-PD-1 or anti-PD-L1. Before treatment, each patient underwent a physical evaluation and a blood sample to identify the presence of a set of autoantibodies. Indeed, all the patients were followed during treatment to identify irAEs and to assess the association with autoantibodies. Fifty-one patients (M/F 16/35; median age 70 years, IQR 16.5) were evaluated; 34.8% of patients showed ANA positivity, 6.5% ENA positivity (anti-SSA), 4.3% Ratest positivity, and 2.1% (one patient) ACPA positivity. During a median period of 21 months (IQR 38.75), 39.2% of patients developed irAEs. Musculo-skeletal manifestations, in particular arthritis, were the most frequent. We found a significant association between the positivity for ANA and the development of irAES (p = 0.03, RR 2.01, 95% CI 1.03-3.92). Furthermore, the progression-free survival was significantly longer in patients developing irAEs compared to those who are not experiencing these events (p = 0.007). This study underlines the potential role of ANA positivity as a predictive biomarker for the development of irAEs.


Assuntos
Anticorpos Antinucleares , Artrite , Humanos , Idoso , Inibidores de Checkpoint Imunológico/efeitos adversos , Autoanticorpos , Autoimunidade
18.
Malays J Pathol ; 46(1): 63-69, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38682845

RESUMO

INTRODUCTION: Anti-nuclear antibody (ANA) testing is among the most common immunological test requested in the diagnostic immunology laboratory. The main purpose of this test is to screen for the underlying systemic autoimmune rheumatic diseases (SARDs). The gold standard laboratory method for ANA detection is by the indirect immunofluorescence (IIF) assay. In most laboratories, positive ANA-IIF is reported in terms of titration and pattern. OBJECTIVE: This study was conducted with the aim of determining the correlation between ANA-IIF titration and pattern for the diagnosis of SARDs. MATERIALS AND METHODS: A retrospective study was conducted whereby the positive ANA-IIF samples from 1st July 2018 until 31st December 2019 and 1st January 2021 until 31st March 2021 were included in this study. The duplicate samples were excluded. ANA-IIF titration and pattern were recorded for all patients. The demographic, clinical, and final diagnosis data were retrieved from each patient's clinical note. RESULTS: A total of 179 patients were included for analysis. The majority of the patients were female (79.9%) and from Malay ethnicity (66.5%). Sixty-five patients (36.3%) had ANA-IIF positive at 1:80 titration followed by 45 patients (25.1%) positive at titration of equal or more than 1:160. Speckled was the predominant pattern visualised in 90 patients (50.3%) followed by homogeneous in 76 patients (42.5%). Forty-five patients (25.1%) were finally diagnosed with SARDs with 41 of them diagnosed as SLE. ANA titration was significantly associated with the final diagnosis of SARDs at all titres (p<0.001) but the best cut-off was noted at a titre of equal or more than 1:320 with the sensitivity and specificity of 86.7% and 77.6% respectively. The homogeneous pattern was also significantly associated with SARDs (p=0.04). The final diagnosis of SARDs were significantly higher in female (p=0.03) and their age was significantly younger (p<0.001). CONCLUSION: ANA-IIF titration of equal or more than 1:320 can be used as the best titration for differentiating between SARDs and non-SARDs in a positive ANA sample. Patients with homogeneous pattern were more likely to be diagnosed with SARDs than other ANA-IIF patterns.


Assuntos
Anticorpos Antinucleares , Doenças Autoimunes , Doenças Reumáticas , Humanos , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/análise , Feminino , Masculino , Estudos Retrospectivos , Doenças Reumáticas/diagnóstico , Doenças Reumáticas/imunologia , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia , Doenças Autoimunes/sangue , Pessoa de Meia-Idade , Adulto , Técnica Indireta de Fluorescência para Anticorpo/métodos , Idoso , Adulto Jovem , Adolescente
19.
Eur Rev Med Pharmacol Sci ; 28(5): 1760-1767, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38497858

RESUMO

OBJECTIVE: This study aimed to describe the clinical spectrum of primary Sjögren's syndrome (pSS) patients with anti-Ro/SS-A and anti-La/SS-B negativity. PATIENTS AND METHODS: From a single-center study population of consecutive SS patients fulfilling the 2016 ACR-EULAR classification criteria, those with triple seronegativity anti-Ro/SS-A (anti-Sjögren's-syndrome-related antigen A autoantibody), anti-La/SS-B (anti-Sjögren's-syndrome-related antigen B autoantibody), rheumatoid factor (RF) (-) and antinuclear antibody (ANA)(+)] or [anti-Ro/SS-A(-), anti-La/ SS-B(-), RF(+) and ANA(-)] and quad¬ruple seronegativity [anti-Ro/SS-A(-), anti-La/SS-B(-), RF(-) and ANA(-)] were identified retrospectively. Clinical, serological, and laboratory features were compared. A comparison between triple and quadruple seronegative pSS patients was also performed. RESULTS: We included 184 patients (168 women, 16 men) with a mean age at diagnosis of 50.1±13.1 years. The most common subjective presenting features at the time of the diagnosis were dry mouth (94.5%) and dry eye (91.3 %). ANA positivity was 57.0%, and RF positivity was 30.4%. Salivary gland enlargement, arthritis, Raynaud's phenomenon, vasculitis, interstitial lung disease (ILD), neurological involvement, primary biliary cholangitis (PBC), lymphopenia, and thrombocytopenia were observed in ANA+ and RF+ patients but not in seronegative patients (p<0.0001). Arthritis was observed most frequently in RF-positive patients and secondly in ANA-positive patients, whereas arthritis was not observed in seronegative patients (p<0.0001). Autoimmune thyroiditis was present in 65 patients (35.0%), 84.6% of these patients were ANA positive while 12.3% were ANA negative (p=0.0014), RF positivity was 30.7% while RF negativity was 6.15% (p=0.001), 23.0% were both ANA and RF positive while 12.3% were seronegative (p<0.002). Cryoglobulinemia, renal disease, and lymphoma were not observed in any of the patients. CONCLUSIONS: We confirm the strong influence of immunological markers on the phenotype of primary SS at diagnosis.


Assuntos
Artrite , Síndrome de Sjogren , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Síndrome de Sjogren/diagnóstico , Estudos Retrospectivos , Fator Reumatoide , Anticorpos Antinucleares , Autoanticorpos
20.
Int J Mol Sci ; 25(5)2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38473808

RESUMO

Antibodies to DNA are a diverse set of antibodies that bind sites on DNA, a polymeric macromolecule that displays various conformations. In a previous study, we showed that sera of normal healthy subjects (NHS) contain IgG antibodies to Z-DNA, a left-handed helix with a zig-zig backbone. Recent studies have demonstrated the presence of Z-DNA in bacterial biofilms, suggesting a source of this conformation to induce responses. To characterize further antibodies to Z-DNA, we used an ELISA assay with brominated poly(dGdC) as a source of Z-DNA and determined the isotype of these antibodies and their binding properties. Results of these studies indicate that NHS sera contain IgM and IgA as well as IgG anti-Z-DNA antibodies. As shown by the effects of ionic strength in association and dissociation assays, the anti-Z-DNA antibodies bind primarily by electrostatic interactions; this type of binding differs from that of induced anti-Z-DNA antibodies from immunized animals which bind by non-ionic interactions. Furthermore, urea caused dissociation of NHS anti-Z-DNA at molar concentrations much lower than those for the induced antibodies. These studies also showed IgA anti-Z-DNA antibodies in fecal water. Together, these studies demonstrate that antibodies to Z-DNA occur commonly in normal immunity and may arise as a response to Z-DNA of bacterial origin.


Assuntos
DNA Forma Z , Animais , Humanos , Voluntários Saudáveis , Anticorpos Antinucleares , Imunoglobulina G , Imunoglobulina A
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