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1.
Clin Chim Acta ; 564: 119928, 2025 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-39163897

RESUMO

BACKGROUND AND AIMS: Rheumatoid arthritis (RA) manifests through various symptoms and systemic manifestations. Diagnosis involves serological markers like rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). Past studies have shown the added value of likelihood ratios (LRs) in result interpretation. LRs can be combined with pretest probability to estimate posttest probability for RA. There is a lack of information on pretest probability. This study aimed to estimate pretest probabilities for RA. MATERIALS AND METHODS: This retrospective study included 133 consecutive RA patients and 651 consecutive disease controls presenting at a rheumatology outpatient clinic. Disease characteristics, risk factors associated with RA and laboratory parameters were documented for calculating pretest probabilities and LRs. RESULTS: Joint involvement, erosions, morning stiffness, and positive CRP, ESR tests significantly correlated with RA. Based on these factors, probabilities for RA were estimated. Besides, LRs for RA were established for RF and ACPA and combinations thereof. LRs increased with antibody levels and were highest for double high positivity. Posttest probabilities were estimated based on pretest probability and LR. CONCLUSION: By utilizing pretest probabilities for RA and LRs for RF and ACPA, posttest probabilities were estimated. Such approach enhances diagnostic accuracy, offering laboratory professionals and clinicians insights in the value of serological testing during the diagnostic process.


Assuntos
Anticorpos Antiproteína Citrulinada , Artrite Reumatoide , Fator Reumatoide , Humanos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/sangue , Artrite Reumatoide/imunologia , Fator Reumatoide/sangue , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Anticorpos Antiproteína Citrulinada/sangue , Masculino , Funções Verossimilhança , Probabilidade , Adulto , Autoanticorpos/sangue , Idoso
2.
Nat Commun ; 15(1): 8044, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39271654

RESUMO

Cell-cell junctions, and specifically desmosomes, are crucial for robust intercellular adhesion. Desmosomal function is compromised in the autoimmune blistering skin disease pemphigus vulgaris. We combine whole-genome knockout screening and a promotor screen of the desmosomal gene desmoglein 3 in human keratinocytes to identify novel regulators of intercellular adhesion. Kruppel-like-factor 5 (KLF5) directly binds to the desmoglein 3 regulatory region and promotes adhesion. Reduced levels of KLF5 in patient tissue indicate a role in pemphigus vulgaris. Autoantibody fractions from patients impair intercellular adhesion and reduce KLF5 levels in in vitro and in vivo disease models. These effects were dependent on increased activity of histone deacetylase 3, leading to transcriptional repression of KLF5. Inhibiting histone deacetylase 3 increases KLF5 levels and protects against the deleterious effects of autoantibodies in murine and human pemphigus vulgaris models. Together, KLF5 and histone deacetylase 3 are regulators of desmoglein 3 gene expression and intercellular adhesion and represent potential therapeutic targets in pemphigus vulgaris.


Assuntos
Adesão Celular , Desmogleína 3 , Queratinócitos , Fatores de Transcrição Kruppel-Like , Pênfigo , Humanos , Pênfigo/metabolismo , Pênfigo/patologia , Pênfigo/imunologia , Desmogleína 3/metabolismo , Desmogleína 3/genética , Animais , Queratinócitos/metabolismo , Camundongos , Fatores de Transcrição Kruppel-Like/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Autoanticorpos/imunologia , Desmossomos/metabolismo , Modelos Animais de Doenças , Histona Desacetilases/metabolismo , Histona Desacetilases/genética , Regulação da Expressão Gênica , Regiões Promotoras Genéticas/genética , Masculino
3.
Nutrients ; 16(17)2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39275294

RESUMO

Intestinal anti-endomysium antibodies are a specific marker of celiac disease. The diagnostic accuracy of this marker seems high in pediatric patients and has not yet been investigated in adults, so the aim of this prospective multicentric study was to evaluate the specificity and sensitivity of this marker in childhood and adulthood. Pediatric and adult patients undergoing intestinal endoscopy for any intestinal condition were enrolled. Serological celiac disease markers and HLA type were evaluated in all patients. Intestinal biopsies were analyzed for standard histology and for intestinal anti-endomysium antibodies with biopsy culture assay. In this study, 291 patients (145 adults and 146 children) were included. In the adult population, 34 were diagnosed with celiac disease, 105 were controls, and, in 6, celiac disease was not confirmed. In the pediatric population, 77 were diagnosed with celiac disease, 57 were controls, and, in 12, celiac disease was not confirmed. High diagnostic sensitivity and specificity of intestinal anti-endomysium antibodies were confirmed in children and additionally proven in adults. To conclude, we can affirm that intestinal anti-endomysium antibodies can be detected with high diagnostic accuracy in both children and adults. The implementation of this marker in the diagnostic work-up would help clinicians to correctly identify celiac disease.


Assuntos
Biomarcadores , Doença Celíaca , Sensibilidade e Especificidade , Doença Celíaca/diagnóstico , Doença Celíaca/imunologia , Doença Celíaca/sangue , Humanos , Criança , Adulto , Masculino , Feminino , Estudos Prospectivos , Adolescente , Pessoa de Meia-Idade , Biomarcadores/sangue , Pré-Escolar , Autoanticorpos/sangue , Adulto Jovem , Idoso , Biópsia , Intestinos/imunologia , Intestinos/patologia
4.
CNS Neurosci Ther ; 30(9): e70042, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39279053

RESUMO

OBJECTIVE: The objective of this study is to investigate the presence of astrocyte antibodies in patients, excluding aquaporin-4 or glial fibrillary acidic protein (GFAP) antibodies, while evaluating associated biomarkers and pathologies. METHODS: Patient serum and cerebrospinal fluid (CSF) were tested for antibodies using tissue- and cell-based assays. Neurofilament light chain (NFL) and GFAP in the CSF were detected using single-molecule array (SIMOA). RESULTS: 116 patients accepted SIMOA. Fifteen functional neurological disorders patients without antibodies were designated as controls. Thirty-five patients were positive for astrocyte antibodies (Anti-GFAP: 7; Anti-AQP4: 7; unknown antibodies: 21, designed as the double-negative group, DNAP). The most frequent phenotype of DNAP was encephalitis (42.9%), followed by myelitis (23.8%), movement disorders (19.0%), and amyotrophic lateral sclerosis-like (ALS-like) disease (14.2%). The levels of CSF GFAP and NFL in DNAP were higher than in the control (GFAP: 1967.29 [776.60-13214.47] vs 475.38 [16.80-943.60] pg/mL, p < 0.001; NFL: 549.11 [162.08-2462.61] vs 214.18 [81.60-349.60] pg/mL, p = 0.002). GFAP levels decreased in DNAP (n = 5) after immunotherapy (2446.75 [1583.45-6277.33] vs 1380.46 [272.16-2005.80] pg/mL, p = 0.043), while there was no difference in NFL levels (2273.78 [162.08-2462.61] vs 890.42 [645.06-3168.06] pg/mL, p = 0.893). Two brain biopsy patterns were observed: one exhibited prominent tissue proliferation and hypertrophic astrocytes, with local loss of astrocytes, while the other showed severe astrocyte depletion with loss of neurofilaments around the vessels. Eighteen patients received immunotherapy, and improved except one with ALS-like symptoms. We identified anti-vimentin in this patient. DISCUSSION: There are unidentified astrocyte antibodies. The manifestations of double-negativity are heterogeneous; nevertheless, the pathology and biomarkers remain consistent with astrocytopathy. Immunotherapy is effective.


Assuntos
Aquaporina 4 , Astrócitos , Biomarcadores , Proteína Glial Fibrilar Ácida , Imunoglobulina G , Humanos , Proteína Glial Fibrilar Ácida/líquido cefalorraquidiano , Proteína Glial Fibrilar Ácida/imunologia , Feminino , Masculino , Aquaporina 4/imunologia , Pessoa de Meia-Idade , Astrócitos/imunologia , Astrócitos/metabolismo , Astrócitos/patologia , Estudos Retrospectivos , Adulto , Biomarcadores/líquido cefalorraquidiano , Biomarcadores/sangue , Idoso , Imunoglobulina G/líquido cefalorraquidiano , Imunoglobulina G/sangue , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Proteínas de Neurofilamentos/sangue , Autoanticorpos/líquido cefalorraquidiano , Autoanticorpos/sangue , Adulto Jovem , Adolescente
5.
Int J Mol Sci ; 25(17)2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39273179

RESUMO

Autoantibody production is a hallmark of systemic sclerosis (SSc) and the most extensively studied role of B cells in the pathogenesis of the disease. However, the potential involvement of innate immune molecules in B-cell dysfunction in SSc is less understood. B-cell activation is an early event in the pathogenesis of SSc and is influenced by complement receptors (CRs) and Toll-like receptors (TLRs), shaping antibody responses. CR2 and CR1 modulate B-cell activation, and the roles of CR3 and CR4 are associated with autoimmune conditions. We investigated the expression of CRs in B cells from patients with the more severe form of the disease, diffuse cutaneous SSc (dcSSc), and the effect of TLR CD180 ligation on their expression. We found no significant difference in the basal expression of CD21 and CD11c in B cells between dcSSc and healthy controls (HCs). However, reduced basal CD11b expression in B cells in dcSSc compared to HCs, accompanied by a decrease in CD35 and an increase in CD11c expression following CD180 ligation may promote plasma cell formation and autoantibody production. Additionally, we searched for correlations between dcSSc-associated anti-DNA topoisomerase I (Scl-70) autoantibody, anti-citrate synthase (CS) natural autoantibody and complement component 3 (C3) levels and found a negative correlation between C3 and anti-CS autoantibody in dcSSc but not in HCs, supporting the hypothesis that natural autoantibodies could activate the complement system contributing to tissue injury in SSc.


Assuntos
Autoanticorpos , Linfócitos B , Receptores de Complemento , Humanos , Linfócitos B/imunologia , Linfócitos B/metabolismo , Feminino , Pessoa de Meia-Idade , Masculino , Autoanticorpos/imunologia , Adulto , Receptores de Complemento/metabolismo , Esclerodermia Difusa/imunologia , Esclerodermia Difusa/metabolismo , Idoso , Antígenos CD/metabolismo , DNA Topoisomerases Tipo I/metabolismo , DNA Topoisomerases Tipo I/imunologia , Receptores Toll-Like/metabolismo
6.
Clin Immunol ; 267: 110350, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39218194

RESUMO

Platelets are crucial for thrombosis and hemostasis. Importantly, they contain mitochondria that are responsible for energy generation and therefore vital for platelet survival and activation. Activated platelets can release mitochondria that may be free or encapsulated in platelet extracellular vesicles (EVs). Extruded mitochondria are a well-known source of mitochondrial DNA, and mitochondrial antigens that can be targeted by autoantibodies forming immune complexes (IC). Interaction of IC with the platelet cell surface FcγRIIA receptor results in platelet activation and release of platelet granule components. In this review, we summarize how platelets and mitochondria may contribute to the pathogenesis of different autoimmune and musculoskeletal diseases. Targeting key drivers of mitochondrial extrusion may ultimately lead to urgently needed targeted pharmacological interventions for treating inflammation and thrombotic diathesis, and halting organ damage in some of these rheumatological conditions.


Assuntos
Doenças Autoimunes , Plaquetas , Mitocôndrias , Doenças Musculoesqueléticas , Humanos , Plaquetas/imunologia , Plaquetas/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/imunologia , Doenças Autoimunes/imunologia , Doenças Musculoesqueléticas/imunologia , Animais , Ativação Plaquetária/imunologia , Autoanticorpos/imunologia
7.
Neurol Neuroimmunol Neuroinflamm ; 11(6): e200311, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39270144

RESUMO

BACKGROUND AND OBJECTIVES: Idiopathic/isolated REM sleep behavior disorder (iRBD) has been strongly linked to neurodegenerative synucleinopathies such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. However, there have been increasing reports of RBD as a presenting feature of serious and treatable autoimmune syndromes, particularly IGLON5. This study's objective was to investigate the frequency of autoantibodies in a large cohort of participants with iRBD. METHODS: Participants were enrolled in the North American Prodromal Synucleinopathy cohort with polysomnography-confirmed iRBD, free of parkinsonism and dementia. Plasma samples were systematically screened for the autoantibodies IGLON5, DPPX, LGI1, and CASPR2 using plasma IgG cell-based assay. Positive or equivocal results were confirmed by repeat testing, plus tissue-based indirect immunofluorescence assay for IGLON5. RESULTS: Of 339 samples analyzed, 3 participants (0.9%) had confirmed positive IGLON5 autoantibodies in the cell-based assay, which were confirmed by the tissue-based assay. An additional participant was positive for CASPR2 with low titer by cell-based assay only (of lower clinical certainty). These cases exhibited a variety of symptoms including dream enactment, cognitive decline, autonomic dysfunction, and motor symptoms. In 1 IGLON5 case and the CASPR2 case, evolution was suggestive of typical synucleinopathy, suggesting the possibility that findings were incidental. However, 2 participants with IGLON5 died before diagnosis was clinically suspected, with a final clinical picture highly suggestive of autoimmune disease. DISCUSSION: Our finding that nearly 1% of a large iRBD cohort may have a serious but potentially treatable autoantibody syndrome has important clinical implications. In particular, it raises the question of whether autoantibody testing for IGLON-5-IgG should be widely implemented for participants with iRBD, considering the difficulty in diagnosis of autoimmune diseases, their response to treatment, and the potential for rapid disease progression. However, any routine testing protocol will also have to consider costs and potential adverse effects of false-positive findings. TRIAL REGISTRATION INFORMATION: NCT03623672.


Assuntos
Autoanticorpos , Moléculas de Adesão Celular Neuronais , Transtorno do Comportamento do Sono REM , Humanos , Transtorno do Comportamento do Sono REM/imunologia , Transtorno do Comportamento do Sono REM/diagnóstico , Masculino , Feminino , Autoanticorpos/sangue , Idoso , Moléculas de Adesão Celular Neuronais/imunologia , Pessoa de Meia-Idade , Estudos de Coortes
8.
Adv Rheumatol ; 64(1): 69, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39272166

RESUMO

BACKGROUND: Ankylosing spondylitis (AS) has been known to have auto-inflammatory nature; hence, the efficacy of autoantibodies is low. However, studies on autoantibodies are ongoing, with some studies showing associations. Previous studies showed that anti-protein phosphatase magnesium-dependent 1A (PPM1A) IgG was increased in patients with AS and associated with radiographic progression. However, the diagnostic usefulness was limited due to relatively low sensitivity and specificity. This pilot study evaluated the diagnostic utility of anti-PPM1A-IgM and anti-PPM1A-IgG in patients with active AS. METHODS: Serum samples were obtained from the registry cohort of a single tertiary center in Korea. Serum levels of anti-PPM1A-IgG/IgM were measured by direct ELISA. Receiver operating characteristic (ROC) analysis was used to predict the diagnostic sensitivity and specificity of serum anti-PPM1A-IgG/IgM. RESULTS: Samples were collected from 28 patients with active AS, 16 healthy controls (HCs), and 28 patients with rheumatoid arthritis (RA). Although total serum IgM was lower in the RA and AS groups than in the HC group, anti-PPM1A-IgM was significantly lower in the AS group than in the other groups. In evaluating the diagnostic utility of anti-PPM1A-IgG/IgM for AS patients compared with HCs, the area under the curve (AUC) of anti-PPM1A-IgM was 0.998 (sensitivity 96.4%, specificity 100.0%). When ROC analysis of anti-PPM1A-IgM for AS patients compared with RA patients was conducted, sensitivity was 78.6% and specificity was 71.4%, with an AUC of 0.839. CONCLUSION: Decreased anti-PPM1A-IgM levels in AS patients suggests a potential role for anti-PPM1A-IgM in the diagnosis of active AS.


Assuntos
Autoanticorpos , Biomarcadores , Imunoglobulina M , Proteína Fosfatase 2C , Curva ROC , Sensibilidade e Especificidade , Espondilite Anquilosante , Humanos , Espondilite Anquilosante/sangue , Espondilite Anquilosante/diagnóstico , Masculino , Biomarcadores/sangue , Feminino , Adulto , Imunoglobulina M/sangue , Autoanticorpos/sangue , Proteína Fosfatase 2C/sangue , Pessoa de Meia-Idade , Imunoglobulina G/sangue , Estudos de Casos e Controles , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Projetos Piloto , Ensaio de Imunoadsorção Enzimática
9.
Rev Assoc Med Bras (1992) ; 70(8): e20240447, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39230146

RESUMO

OBJECTIVE: Stroke is a chronic health problem that affects all areas of life. The presence of thyroid autoantibodies can augment the severity of stroke. The aim of this work is to investigate whether there is a relationship between the site of stroke involvement and the anti-thyroid peroxidase antibody (anti-TPO) or not. This is the first study in the English-language literature. METHODS: A total of 39 patients with a diagnosis of acute ischemic stroke were included, and the cases under 18 years of age with an infection and the ones with autoimmune diseases other than Hashimoto's thyroiditis were excluded from the study design. The patients' age, gender, smoking status, comorbid conditions, and stroke localization in brain imaging were recorded. The region involving the anterior circulation area originating from the internal carotid artery was evaluated as anterior, and the region possessing the vertebrobasilar circulation area from the vertebral arteries was considered posterior involvement. Thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), C-reactive protein (CRP), sedimentation, and anti-TPO were retrospectively analyzed. RESULTS: As a consequence, gender distribution, smoking, comorbid conditions, TSH, T3, T4, triglyceride, HDL, LDL, CRP, and sedimentation did not differ significantly, while the age of the posterior-located stroke was lower than that of the cases with the anterior. The anti-TPO value was significantly lower in posterior-located strokes than in the anterior system. CONCLUSION: In summary, the anti-TPO value was recognized as higher in the anterior stroke localization. Thyroiditis and accompanying anti-TPO autoantibody positivity are conditions that should not be ignored by thyroidologists and thyroid-health providers.


Assuntos
Autoanticorpos , Iodeto Peroxidase , Humanos , Feminino , Masculino , Autoanticorpos/sangue , Pessoa de Meia-Idade , Iodeto Peroxidase/imunologia , Idoso , Estudos Retrospectivos , Acidente Vascular Cerebral/imunologia , Acidente Vascular Cerebral/diagnóstico por imagem , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/imunologia , AVC Isquêmico/sangue , Adulto , Idoso de 80 Anos ou mais , Fatores de Risco
10.
Neurol Neuroimmunol Neuroinflamm ; 11(6): e200313, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39250722

RESUMO

BACKGROUND AND OBJECTIVES: In this retrospective longitudinal study, we aimed at exploring the role of (a) MuSK-immunoglobulin G (IgG) levels, (b) predominant MuSK-IgG subclasses, and (c) antibody affinity as candidate biomarkers of severity and outcomes in MuSK-MG, using and comparing different antibody testing techniques. METHODS: Total MuSK-IgGs were quantified with radioimmunoassay (RIA), ELISA, flow cytometry, and cell-based assay (CBA) serial dilutions using HEK293 cells transfected with MuSK-eGFP. MuSK-IgG subclasses were measured by flow cytometry. SAffCon assay was used for determining MuSK-IgG affinity. RESULTS: Forty-three serum samples were obtained at different time points from 20 patients with MuSK-MG (median age at onset: 48 years, interquartile range = 27.5-72.5; women, 16/20), with 9 of 20 (45%) treated with rituximab. A strong correlation between MuSK-IgG levels measured by flow cytometry and RIA titers was found (rs = 0.74, 95% CI 0.41-0.89, p = 0.0003), as well as a moderate correlation between CBA end-point titers and RIA titers (rs = 0.47, 95% CI 0.01-0.77, p = 0.0414). A significant correlation was found between MuSK-IgG flow cytometry levels and disease severity (rs = 0.39, 95% CI 0.06-0.64, p = 0.0175; mixed-effects model estimate: 2.296e-06, std. error: 1.024e-06, t = 2.243, p = 0.032). In individual patients, clinical improvement was associated with decrease in MuSK-IgG levels, as measured by either flow cytometry or CBA end-point titration. In all samples, MuSK-IgG4 was the most frequent isotype (mean ± SD: 90.95% ± 13.89). A significant reduction of MuSK-IgG4 and, to a lesser extent, of MuSK-IgG2, was seen in patients with favorable clinical outcomes. A similar trend was confirmed in the subgroup of rituximab-treated patients. In a single patient, MuSK-IgG affinity increased during symptom exacerbation (KD values: 62 nM vs 0.6 nM) while total MuSK-IgG and IgG4 levels remained stable, suggesting that affinity maturation may be a driver of clinical worsening. DISCUSSION: Our data support the quantification of MuSK antibodies by flow cytometry. Through a multimodal investigational approach, we showed that total MuSK-IgG levels, MuSK-IgG4 and MuSK-IgG2 levels, and MuSK-IgG affinity may represent promising biomarkers of disease outcomes in MuSK-MG.


Assuntos
Biomarcadores , Imunoglobulina G , Miastenia Gravis , Receptores Colinérgicos , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/sangue , Miastenia Gravis/imunologia , Miastenia Gravis/tratamento farmacológico , Miastenia Gravis/diagnóstico , Adulto , Estudos Retrospectivos , Idoso , Imunoglobulina G/sangue , Biomarcadores/sangue , Receptores Colinérgicos/imunologia , Estudos Longitudinais , Autoanticorpos/sangue , Receptores Proteína Tirosina Quinases/imunologia , Receptores Proteína Tirosina Quinases/sangue , Células HEK293 , Rituximab/farmacologia , Fatores Imunológicos/farmacologia
11.
Neurol Neuroimmunol Neuroinflamm ; 11(6): e200309, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39250723

RESUMO

BACKGROUND AND OBJECTIVES: To identify predictors for relapse in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and to develop and validate a simple risk score for predicting relapse. METHODS: In China National Registry of Neuro-Inflammatory Diseases (CNRID), we identified patients with MOGAD from March 2023 and followed up prospectively to September 2023. The primary endpoint was MOGAD relapse, confirmed by an independent panel. Patients were randomly divided into model development (75%) and internal validation (25%) cohorts. Prediction models were constructed and internally validated using Andersen-Gill models. Nomogram and relapse risk score were generated based on the final prediction models. RESULTS: A total of 188 patients (comprising 612 treatment episodes) were included in cohorts. Female (HR: 0.687, 95% CI 0.524-0.899, p = 0.006), onset age 45 years or older (HR: 1.621, 95% CI 1.242-2.116, p < 0.001), immunosuppressive therapy (HR: 0.338, 95% CI 0.239-0.479, p < 0.001), oral corticosteroids >3 months (HR 0.449, 95% CI 0.326-0.620, p < 0.001), and onset phenotype (p < 0.001) were identified as factors associated with MOGAD relapse. A predictive score, termed MOG-AR (Immunosuppressive therapy, oral Corticosteroids, Onset Age, Sex, Attack phenotype), derived in prediction model, demonstrated strong predictive ability for MOGAD relapse. MOG-AR score of 13-16 indicates a higher risk of relapse (HR: 3.285, 95% CI 1.473-7.327, p = 0.004). DISCUSSION: The risk of MOGAD relapse seems to be predictable. Further validation of MOG-AR score developed from this cohort to determine appropriate treatment and monitoring frequency is warranted. TRIAL REGISTRATION INFORMATION: CNRID, NCT05154370, registered December 13, 2021, first enrolled December 15, 2021.


Assuntos
Glicoproteína Mielina-Oligodendrócito , Recidiva , Sistema de Registros , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Glicoproteína Mielina-Oligodendrócito/imunologia , Adulto Jovem , China , Medição de Risco , Autoanticorpos/sangue , Adolescente , Fatores de Risco , Seguimentos , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/imunologia , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/diagnóstico
12.
Mult Scler Relat Disord ; 90: 105848, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39236487

RESUMO

BACKGROUND: The coexistence of neuromyelitis optica spectrum disorders (NMOSD) with other autoimmune diseases (AID) has been increasingly reported. The prevalence and significance of this association are not fully understood. OBJECTIVES: This study aimed to compare the clinical and laboratory characteristics in NMOSD patients with and without AID. METHODS: Retrospective cross-sectional observational study was conducted involving adults meeting NMOSD criteria followed in a neuroimmunology clinic at a tertiary center. Descriptive analysis of clinical/paraclinical/treatment/outcome data collected from the medical records was compared between NMOSD patients with AID (polyautoimmunity) and those without AID. RESULTS: From a cohort of 46 NMOSD patients, 16 (34.8 %) patients, mostly women around 40 years of age, presented with polyautoimmunity: 10 anti-AQP4 positive, 4 anti-MOG positive, and 2 seronegative. Five different organ -specific AID, and six systemic AID were identified in the polyautoimmunity patients group, in addition to 6 cases of multiple autoimmune syndrome. The AID manifestation preceded NMOSD in 10 (62.5 %) patients, with a median interval of 7 years. The NMOSD with polyautoimmunity and NMOSD without AID groups had similar initial clinical manifestations with optic neuritis and/or myelitis being most frequent. Inflammatory CSF, namely elevated proteins, was more common in the polyautoimmunity group (13.0 % in NMOSD vs. 31.3 % in NMOSD+AID, p = 0.003). After a 10±6 years follow-up period, more patients with polyautoimmunity had a relapsing disease (75.0 % in NMOSD vs. 46.7 % in NMOSD+AID, p = 0.012) but no difference in the functional outcome evaluated by the EDSS score was identified. CONCLUSIONS: Polyautoimmunity was common in AQP4 positive NMOSD patients leading to a significantly higher risk of disease recorrence. The presence of polyautoimmunity and multiple autoimmune syndrome in NMOSD patients suggests the existence of common susceptibility factors or pathophysiological mechanisms, emphasizing the importance of a multidisciplinary approach to those patients.


Assuntos
Neuromielite Óptica , Humanos , Neuromielite Óptica/imunologia , Neuromielite Óptica/epidemiologia , Feminino , Adulto , Masculino , Estudos Transversais , Estudos Retrospectivos , Pessoa de Meia-Idade , Aquaporina 4/imunologia , Adulto Jovem , Autoanticorpos/sangue
14.
BMC Neurol ; 24(1): 334, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39256712

RESUMO

BACKGROUND: Anti-IgLON5 disease is an autoimmune encephalitis overlapping with neurodegenerative disorders due to pathological accumulation of hyperphosphorylated tau. It is characterized by several clinical manifestations determined by involvement of different brain areas, and mild response to first-line immunotherapies. We report a case of anti-IgLON5 disease with a multifaceted semiology and an unusually good response to glucocorticoid monotherapy. CASE PRESENTATION: A 68-year-old man with type 2 diabetes was evaluated for an 8-month history of progressive gait disorder causing frequent falls. He also suffered from obstructive sleep apneas and complained of dysphonia, dysarthria, occasional dysphagia, urinary incontinence, and upper limb action tremor. Neurological examination demonstrated bilateral eyelid ptosis, limitation of ocular horizontal smooth pursuit movements, slow horizontal saccades, and lack of inhibition of the vestibulo-ocular reflex during rapid horizontal head torsions. The patient also displayed involuntary, slow, rhythmic movements of the left periorbital and perioral muscles, spreading to the ipsilateral hemipalate and hemitongue, along with bilateral negative upper limb myoclonus. There were proximal muscle wasting in the upper limbs, proximal weakness of the four limbs, and diffuse fasciculations. Ataxia of stance and gait and of the four limbs was noted. MRI of the brain and spine was unremarkable; nerve conduction studies revealed a chronic, predominantly demyelinating, sensory-motor polyneuropathy, probably due to diabetes. Routine CSF examination was unrevealing and serum GFAP level was 89.6 pg/mL; however, the autoimmunity tests revealed a high-titer positivity for anti-IgLON5 autoantibodies in both CSF and serum, leading to the diagnosis of anti-IgLON5 disease. Symptoms improved significantly after intravenous methylprednisolone. CONCLUSIONS: Hemifacial and hemiorolingual myorhythmia along with peculiar oculomotor abnormalities characterizes the multifaceted clinical picture of our case. The complex semiology of our patient may reflect multifocal targeting of the autoimmune process or sequential spreading of tau inclusions in different brain areas. Our patient's optimal response to glucocorticoid monotherapy could be underpinned by a slightly different phenotype in which autoimmunity plays a greater pathogenic role than tauopathy, with a lower burden of tau deposition. In such patients, neurodegeneration and tau accumulation could be merely secondary to immune-mediated neuronal dysfunction, supporting the existence of a group of glucocorticoid-responsive patients.


Assuntos
Moléculas de Adesão Celular Neuronais , Humanos , Masculino , Idoso , Moléculas de Adesão Celular Neuronais/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia
15.
Arthritis Res Ther ; 26(1): 158, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39261921

RESUMO

OBJECTIVE: Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) autoantibodies are one of the myositis-specific antibodies which is associated with immune-mediated necrotizing myopathy (IMNM). However, the relationship between anti-HMGCR isotypes and prognosis has not yet been fully investigated. This study was conducted to gain insight into the association between anti-HMGCR isotypes and clinical, and prognosis in IMNM patients who were positive for anti-HMGCR antibodies. METHODS: Levels of anti-HMGCR isotypes (IgG, IgA and IgM) were assessed by enzyme-linked immunosorbent assay (ELISA) in 123 consecutive serum samples obtained from 71 patients who were positive for anti-HMGCR IgG at baseline. Disease activity was assessed by manual muscle testing (MMT) 8, Physician's Global Assessment (PGA) visual analog scale (VAS), and muscle VAS. RESULTS: Baseline anti-HMGCR IgG levels were correlated with PGA VAS (r = 0.24; p = 0.04), muscle VAS (r = 0.32; p < 0.01), and MMT8(r=-0.24; p = 0.04), and baseline anti-HMGCR IgM levels were positively correlated with PGA VAS (r = 0.27, p = 0.02), muscle VAS (r = 0.24, p = 0.04). Anti-HMGCR IgM positive patients had a lower age of onset [29(25,46) vs. 51(33,65), p = 0.006], and a higher proportion of neck weakness (63.5% vs. 34.6%, p = 0.031) compared with anti-HMGCR IgM negative patients. Longitudinal analysis showed that the changes in anti-HMGCR IgG levels were correlated with the changes in the PGA VAS (ß = 3.830; p < 0.0001), muscle VAS (ß = 2.893; p < 0.0001), MMT8 (ß=-19.368; p < 0.0001), and creatine kinase (CK) levels (ß = 3900.05, p < 0.0001). Anti-HMGCR IgM levels were weakly correlated with anti-HMGCR IgA levels at baseline (r = 0.33, p < 0.01), and the variations in anti-HMGCR IgA levels were correlated with the changes in anti-HMGCR IgM levels during follow-up (ß = 0.885; p < 0.0001). There were more patients with anti-HMGCR IgM who showed a refractory course than those who were with anti-HMGCR IgM negative (polycyclic course: 40% vs. 25%; chronic continuous course: 46.7% vs. 20.5%, p = 0.018). CONCLUSION: In anti-HMGCR IgG-positive IMNM patients, the levels of anti-HMGCR IgG are associated with disease activity, and anti-HMGCR IgM is associated with refractory outcome and poor prognosis.


Assuntos
Autoanticorpos , Hidroximetilglutaril-CoA Redutases , Imunoglobulina M , Humanos , Masculino , Feminino , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Pessoa de Meia-Idade , Autoanticorpos/imunologia , Autoanticorpos/sangue , Hidroximetilglutaril-CoA Redutases/imunologia , Adulto , Idoso , Miosite/imunologia , Miosite/sangue , Necrose/imunologia , Ensaio de Imunoadsorção Enzimática , Doenças Musculares/imunologia , Doenças Musculares/sangue , Imunoglobulina G/sangue , Imunoglobulina G/imunologia
17.
Nat Commun ; 15(1): 8004, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39266554

RESUMO

Maintaining normal thyroid function is crucial in pregnancy, yet thyroid dysfunction and the presence of thyroid peroxidase antibodies (TPOAb) affect 0.5% to 18% of pregnant women. Here, we conducted a genome-wide association study (GWAS) of eight thyroid traits, including two thyroid-related hormones, four thyroid dysfunctions, and two thyroid autoimmunity measurements among 85,421 Chinese pregnant women to investigate the genetic basis of thyroid function during pregnancy. Our study identified 176 genetic loci, including 125 previously unknown genome-wide associations. Joint epidemiological and Mendelian randomization analyses revealed significant associations between the gestational thyroid phenotypes and gestational complications, birth outcomes, and later-age health outcomes. Specifically, genetically elevated thyroid-stimulating hormone (TSH) levels during pregnancy correlated with lower glycemic levels, reduced blood pressure, and longer gestational duration. Additionally, TPOAb and thyroid functions during pregnancy share genetic correlations with later-age thyroid and cardiac disorders. These findings provide insights into the genetic determinants of thyroid traits during pregnancy, which may lead to new therapeutics, early pre-diagnosis and preventive strategies starting from early adulthood.


Assuntos
Autoimunidade , Estudo de Associação Genômica Ampla , Complicações na Gravidez , Hormônios Tireóideos , Tireotropina , Humanos , Feminino , Gravidez , Autoimunidade/genética , Adulto , Hormônios Tireóideos/sangue , China/epidemiologia , Complicações na Gravidez/genética , Complicações na Gravidez/imunologia , Complicações na Gravidez/epidemiologia , Tireotropina/sangue , Glândula Tireoide/imunologia , Doenças da Glândula Tireoide/genética , Doenças da Glândula Tireoide/epidemiologia , Doenças da Glândula Tireoide/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Povo Asiático/genética , Iodeto Peroxidase/genética , Iodeto Peroxidase/imunologia , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Predisposição Genética para Doença , População do Leste Asiático
18.
Front Endocrinol (Lausanne) ; 15: 1349117, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39247917

RESUMO

Objective: Currently, distinct use of clinical data, routine laboratory indicators or the detection of diabetic autoantibodies in the diagnosis and management of diabetes mellitus is limited. Hence, this study was aimed to screen the indicators, and to establish and validate a multifactorial logistic regression model nomogram for the non-invasive differential prediction of type 1 diabetes mellitus. Methods: Clinical data, routine laboratory indicators, and diabetes autoantibody profiles of diabetic patients admitted between September 2018 and December 2022 were retrospectively analyzed. Logistic regression was used to select the independent influencing factors, and a prediction nomogram based on the multiple logistic regression model was constructed using these independent factors. Moreover, the predictive accuracy and clinical application value of the nomogram were evaluated using Receiver Operating Characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and clinical impact curves (CIC). Results: A total of 522 diabetic patients were included in this study. These patients were randomized into training and validation sets in a 7:3 ratio. The predictors screened included age, prealbumin (PA), high-density lipoprotein cholesterol (HDL-C), islet cells autoantibodies (ICA), islets antigen 2 autoantibodies (IA-2A), glutamic acid decarboxylase antibody (GADA), and C-peptide levels. Based on these factors, a multivariate model nomogram was constructed, which had an Area Under Curve (AUC) of 0.966 and 0.961 for the training set and validation set, respectively. Subsequently, the calibration curves demonstrated a strong accuracy of the graph; the DCA and CIC results indicated that the graph could be used as a non-invasive valid predictive tool for the differential diagnosis of type 1 diabetes mellitus, clinically. Conclusion: The established prediction model combining patient's age, PA, HDL-C, ICA, IA-2A, GADA, and C-peptide can assist in differential diagnosis of type 1 diabetes mellitus and type 2 diabetes mellitus and provides a basis for the clinical as well as therapeutic management of the disease.


Assuntos
Autoanticorpos , Diabetes Mellitus Tipo 1 , Valor Preditivo dos Testes , Humanos , Autoanticorpos/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Nomogramas , Glutamato Descarboxilase/imunologia , Adulto Jovem , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/imunologia , Curva ROC , Biomarcadores/sangue , Adolescente , Idoso
19.
Front Immunol ; 15: 1426236, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39267735

RESUMO

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has highly heterogeneous clinical presentations, in which encephalitis is an important phenotype. Moreover, MOGAD has been reported to exhibit diverse imaging findings. However, there have been no previous reports of cases with perivascular radial gadolinium enhancement in periventricular regions, commonly reported in autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. In this paper, we present two cases of MOGAD with this MRI feature, both of which underwent brain biopsy for the lesions. Brain biopsies revealed perivenous demyelination and inflammation consistent with acute disseminated encephalomyelitis (ADEM), with pronounced axonal damage in Case 1 and minimal axonal involvement in Case 2. Case 1 exhibited more severe cerebral atrophy than Case 2, correlating with the extent of axonal damage. Through these cases, we highlight the heterogeneity of radiological manifestations of MOGAD, expanding the spectrum beyond previously defined MRI patterns. Furthermore, histopathological analysis revealed distinct axonal involvement as a potential prognostic marker of brain atrophy. These observations emphasize the importance of considering MOGAD in the differential diagnosis, even in cases with atypical imaging findings, and highlight the significance of brain biopsy in guiding both diagnosis and prognosis.


Assuntos
Autoanticorpos , Gadolínio , Imageamento por Ressonância Magnética , Glicoproteína Mielina-Oligodendrócito , Humanos , Glicoproteína Mielina-Oligodendrócito/imunologia , Masculino , Feminino , Autoanticorpos/imunologia , Encéfalo/patologia , Encéfalo/diagnóstico por imagem , Adulto , Pessoa de Meia-Idade , Biópsia , Encefalomielite Aguda Disseminada/diagnóstico por imagem , Encefalomielite Aguda Disseminada/imunologia , Encefalomielite Aguda Disseminada/patologia
20.
Front Immunol ; 15: 1416473, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39267741

RESUMO

Bullous pemphigoid (BP) is the most common autoimmune bullous disease: it most commonly affects individuals over 70 years old and impacts severely on their quality of life. BP represents a paradigm for an organ-specific autoimmune disease and is characterized by circulating IgG autoantibodies to hemidesmosomal components: BP180 and BP230. While the crucial role of these autoantibodies in triggering BP inflammatory cascade is fully acknowledged, many ancillary etiological mechanisms need to be elucidated yet. Cutaneous melanoma is due to a malignant transformation of skin melanocytes, that produce and distribute pigments to surrounding keratinocytes. Melanoma is the most fatal skin cancer because of its increasing incidence and its propensity to metastasize. Several data such as: i) reported cases of concomitant melanoma and BP; ii) results from association studies; iii) BP onset following immune check-point inhibitors therapy; iv) expression of BP antigens in transformed melanocytes; and vi) circulating autoantibodies to BP antigens in melanoma patients suggest an intriguing, although unproven, possible association between melanoma and BP. However, a possible causative link is still debated and the putative pathogenetic mechanism underlying this association is unclear. This review aims to describe and discuss the possible relationship between BP and melanoma and give an overview of the speculations for or against this association. Of note, if demonstrated, this association could unwrap considerations of clinical relevance that represent new research frontiers.


Assuntos
Autoanticorpos , Autoantígenos , Melanoma , Penfigoide Bolhoso , Humanos , Penfigoide Bolhoso/imunologia , Penfigoide Bolhoso/etiologia , Melanoma/imunologia , Melanoma/etiologia , Autoanticorpos/imunologia , Autoanticorpos/sangue , Autoantígenos/imunologia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/etiologia , Colágeno Tipo XVII , Colágenos não Fibrilares/imunologia , Melanócitos/imunologia , Melanócitos/patologia , Animais , Relevância Clínica
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