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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.
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
3.
Front Immunol ; 15: 1455602, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39234247

RESUMO

Although blood autoantibodies were initially associated with autoimmune diseases, multiple evidence have been accumulated showing their presence in many types of cancer. This has opened their use in clinics, since cancer autoantibodies might be useful for early detection, prognosis, and monitoring of cancer patients. In this review, we discuss the different techniques available for their discovery and validation. Additionally, we discuss here in detail those autoantibody panels verified in at least two different reports that should be more likely to be specific of each of the four most incident cancers. We also report the recent developed kits for breast and lung cancer detection mostly based on autoantibodies and the identification of novel therapeutic targets because of the screening of the cancer humoral immune response. Finally, we discuss unsolved issues that still need to be addressed for the implementation of cancer autoantibodies in clinical routine for cancer diagnosis, prognosis, and/or monitoring.


Assuntos
Autoanticorpos , Biomarcadores Tumorais , Neoplasias , Humanos , Autoanticorpos/imunologia , Autoanticorpos/sangue , Neoplasias/imunologia , Neoplasias/diagnóstico , Biomarcadores Tumorais/imunologia , Prognóstico , Detecção Precoce de Câncer , Animais
4.
Exp Dermatol ; 33(9): e15173, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39246287

RESUMO

In this study, we aimed to examine the relationship between the serum cytokine levels of patients with pemphigus vulgaris (PV) and the Pemphigus Disease Area Index (PDAI), along with the presence of anti-desmoglein (Dsg) 1 antibody, anti-Dsg3 antibody and co-infection among patients with pemphigus vulgaris. This retrospective study included 62 PV patients and 59 healthy individuals who attended the Second Affiliated Hospital of Kunming Medical University from November 2014 to November 2022. The serum concentrations of cytokines and chemokines were assessed using the Luminex 200 System (a high-throughput cytokine detection method). Additionally, anti-Dsg1 and anti-Dsg3 antibodies were determined through enzyme-linked immunosorbent assay, while disease severity was evaluated using the PDAI scoring system. The PV group exhibited elevated levels of Th1 cytokines (such as interleukin (IL)-1RA, IL-1ß, IL-2, IL-12p70, GM-CSF, TNF-α, IL-18, IFN-γ), Th2 cytokines (IL-5, IL-10, IL-13) and Th17/Th22-related cytokines (IL-17A, IL-22) compared to the healthy control group (p < 0.05). Conversely, the levels of chemokines (macrophage inflammatory protein-1 alpha (MIP-1α), stromal cell-derived factor-1 alpha (SDF-1α), interferon-inducible protein-10 (IP-10), Regulated on Activation in Normal T-Cell Expressed And Secreted (RANTES), growth-regulated on-gene-alpha (GRO-α), MIP-1ß) and Th2 (IL-31) were lower in the PV group compared to the healthy control group (p < 0.05). No significant differences were observed in other cytokines and chemokines (p > 0.05). Additionally, IL-7, IFN-γ, IL-18 and GRO-α showed positive correlations with PDAI, IL-6 correlated positively with anti-Dsg3 antibody levels, and IL-12p70, IL-18, and IFN-γ correlated positively with anti-Dsg1 antibody levels. Furthermore, IL-15 exhibited a positive association with skin infections. PV patients have elevated levels of various cytokines and chemokines, and there are different degrees of elevation in cytokines and chemokines associated with the activation of various T cell subsets. PDAI and the Dsg1 antibody levels are mainly related to the Th1-related cytokines.


Assuntos
Quimiocinas , Citocinas , Desmogleína 1 , Pênfigo , Humanos , Pênfigo/sangue , Pênfigo/imunologia , Estudos Retrospectivos , Masculino , Feminino , Citocinas/sangue , Pessoa de Meia-Idade , Adulto , Desmogleína 1/imunologia , Quimiocinas/sangue , Desmogleína 3/imunologia , Índice de Gravidade de Doença , Idoso , Autoanticorpos/sangue , Estudos de Casos e Controles , Relevância Clínica
5.
BMC Immunol ; 25(1): 58, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39242985

RESUMO

BACKGROUND: Systemic Lupus Erythematosus (SLE) has a strong genetic susceptibility, but little is known about the impact of diet on disease severity. The Western diet is typically deficient in magnesium (Mg), and given the immunomodulatory effects of Mg, we hypothesized that the low Mg intake increases disease risk and that increasing Mg intake would reduce severity of murine lupus. Here, we placed 12-week old MRL/lpr female lupus mice on a normal (Mg500) or a high (Mg2800) Mg diet for 9 weeks. Urine and blood were collected during the study for quantification of urinary albumin, BUN, anti-dsDNA antibodies, and immune phenotyping. RESULTS: MRL/lpr lupus mice on high Mg2800 diet had significantly fewer skin lesions and less severe skin histology score, and reduced levels of pathogenic anti-dsDNA antibodies, compared with the Mg500 group (143.8±75.0 vs. 47.4±36.2 × 106U/ml; P < 0.05). The high Mg2800 group had a nearly two-fold increase in the percentage of CD4+FOXP3+ Treg cells compared to controls (19.9±5.4 vs. 11.4±5.5%; P < 0.05). Treg percentages inversely correlated with the concentration of anti-dsDNA. None of the mice developed arthritis during the observation period and there were no significant differences in weight, proteinuria, BUN or kidney histology. CONCLUSION: In conclusion, oral supplementation of Mg has a protective effect in a murine lupus model and may represent an inexpensive and safe adjuvant in the treatment of SLsE.


Assuntos
Anticorpos Antinucleares , Lúpus Eritematoso Sistêmico , Magnésio , Linfócitos T Reguladores , Animais , Lúpus Eritematoso Sistêmico/imunologia , Feminino , Camundongos , Anticorpos Antinucleares/imunologia , Anticorpos Antinucleares/sangue , Magnésio/administração & dosagem , Linfócitos T Reguladores/imunologia , Modelos Animais de Doenças , Administração Oral , Camundongos Endogâmicos MRL lpr , Autoanticorpos/imunologia , Autoanticorpos/sangue , Pele/patologia , Pele/imunologia , Pele/efeitos dos fármacos , Dermatopatias/imunologia , Dermatopatias/tratamento farmacológico , Dermatopatias/patologia
6.
Neurol Neuroimmunol Neuroinflamm ; 11(6): e200291, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39231384

RESUMO

BACKGROUND AND OBJECTIVES: The 2022 International Consortium for Optic Neuritis diagnostic criteria for optic neuritis (ON) include optical coherence tomography (OCT). The diagnostic value of intereye difference (IED) metrics is high for ON in patients with multiple sclerosis and aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorders, but unknown in myelin oligodendrocyte glycoprotein antibody-associated ON (MOG-ON). METHODS: A multicenter validation study was conducted on the published IED cutoff values (>4% or >4 µm in the macular ganglion cell and inner plexiform layer [mGCIP] or >5% or >5 µm in the peripapillary retinal nerve fiber layer [pRNFL]) in individuals with MOG-ON and age-matched and sex-matched healthy controls (HCs). Structural data were acquired with Spectralis spectral-domain OCT >6 months after ON. We calculated sensitivity, specificity, and receiver operating characteristics for both intereye percentage (IEPD) and absolute difference (IEAD). RESULTS: A total of 66 individuals were included (MOG-ON N = 33; HCs N = 33). ON was unilateral in 20 and bilateral in 13 subjects. In the pooled analysis, the mGCIP IEPD was most sensitive (92%), followed by the mGCIP IEAD (88%) and pRNFL (84%). The same pattern was found for the specificity (mGCIP IEPD 82%, IEAD 82%; pRNFL IEPD 82%, IEAD 79%).In subgroup analyses, the diagnostic sensitivity was higher in subjects with unilateral ON (>99% for all metrics) compared with bilateral ON (61%-78%). DISCUSSION: In individuals with MOG-ON, the diagnostic accuracy of OCT-based IED metrics for ON was high, especially of mGCIP IEPD. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that the intereye difference on OCT can distinguish between those with MOG and normal controls.


Assuntos
Autoanticorpos , Glicoproteína Mielina-Oligodendrócito , Neurite Óptica , Tomografia de Coerência Óptica , Humanos , Glicoproteína Mielina-Oligodendrócito/imunologia , Neurite Óptica/imunologia , Neurite Óptica/diagnóstico , Neurite Óptica/diagnóstico por imagem , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Autoanticorpos/sangue , Sensibilidade e Especificidade , Adulto Jovem
7.
BMC Neurol ; 24(1): 320, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39237863

RESUMO

Neurolymphomatosis (NL) is a rare neurologic manifestation of non-Hodgkin lymphoma (NHL) with poor prognosis. Investigations including MRI, PET/CT, nerve biopsy and cerebrospinal fluid (CSF) analysis can aid the diagnosis of NL. In this study, we presented a case of NL with co-existing myelin-associated glycoprotein (MAG) antibody. The patient first presented with symptoms of peripheral neuropathy involving multiple cranial nerves and cauda equina, and later developed obstructive hydrocephalus and deep matter lesions. He also had persistently positive MAG antibody, but did not develop electrophysiologically proven neuropathy and monoclonal immunoglobulin. The final brain biopsy confirmed diffuse large B cell lymphoma.


Assuntos
Glicoproteína Associada a Mielina , Neurolinfomatose , Humanos , Masculino , Neurolinfomatose/diagnóstico por imagem , Neurolinfomatose/diagnóstico , Glicoproteína Associada a Mielina/imunologia , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/complicações , Idoso , Autoanticorpos/sangue , Autoanticorpos/imunologia , Autoanticorpos/líquido cefalorraquidiano
8.
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
9.
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
10.
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
11.
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
12.
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
13.
Sci Prog ; 107(3): 368504241278476, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39285783

RESUMO

This review article discusses neonatal lupus syndrome (NLS), an immune-mediated disease caused by maternal antibodies. Maternal antibodies in the fetal circulation are mostly but not always protective. NLS is a disease caused by pathogenic maternal autoantibodies in the fetal circulation. The passive immunization of the fetus by NLS-causing maternal antibodies may occur in the absence of a previously known maternal systemic autoimmune rheumatic disease (SARD). Screening for NLS-related antibodies in patients with related SARD or those in whom there is a risk of NLS including first-degree relatives should occur before pregnancy. This screening is best performed as part of a collaborative relationship between obstetrics and rheumatology. Pregnancy preparations in those with SARD include transitioning to pregnancy-safe medications. The symptoms of NLS range from minor skin rashes to fetal demise from heart block. Fetal screening allows for maternal therapeutic interventions that may be beneficial, as well as the use of fetal pacemakers in the more severe cases that include cardiac NLS.


Assuntos
Lúpus Eritematoso Sistêmico , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/congênito , Lúpus Eritematoso Sistêmico/diagnóstico , Gravidez , Recém-Nascido , Feminino , Autoanticorpos/imunologia , Autoanticorpos/sangue , Complicações na Gravidez/imunologia
14.
Front Immunol ; 15: 1439807, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39281689

RESUMO

Idiopathic inflammatory myopathies (IIMs) encompass a spectrum of autoimmune diseases characterized by muscle inflammation and systemic involvement. This review aimed to synthesize current evidence on the clinical significance and pathogenic mechanisms underlying autoantibodies associated with IIMs. Autoantibodies targeting aminoacyl-tRNA synthetases (ARS) play a pivotal role in antisynthetase syndrome (ASS), highlighting associations with interstitial lung disease (ILD) and distinctive clinical features. Anti-Mi-2 antibodies in dermatomyositis (DM) are hallmarked by characteristic cutaneous manifestations and favorable prognostic outcomes. Conversely, anti-TIF1 antibodies are correlated with DM and a higher risk of malignancies, implicating CD8+ T cells in its pathogenesis. Anti-MDA5 antibodies signify clinically amyopathic DM (CADM) with severe ILD, linked to dysregulated neutrophil extracellular trap (NET) formation. In immune-mediated necrotizing myopathies (IMNMs), anti-SRP and anti-HMGCR antibodies induce complement-mediated myopathy, typically following statin exposure. Additionally, anti-TRIM72 antibodies emerge as potential diagnostic markers in IIMs. Anti-cN1A autoantibodies are linked to inclusion body myositis (IBM) and play a decisive role in muscle protein degradation. Meanwhile, anti-FHL1 autoantibodies are associated with severe disease manifestations and muscle damage, as established in experimental models. Anti-eIF3 autoantibodies, recently identified in polymyositis (PM) patients, are rarely detected (<1%) and associated with a favorable prognosis. Elucidating these autoantibodies is anticipated to not only assist in early diagnosis and disease stratification but also inform targeted therapeutic interventions, emphasizing the intricate interplay between autoimmunity, cellular dysfunction, and clinical outcomes in IIMs.


Assuntos
Autoanticorpos , Miosite , Humanos , Autoanticorpos/imunologia , Miosite/imunologia , Animais , Biomarcadores
15.
Sci Rep ; 14(1): 20529, 2024 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-39227704

RESUMO

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by vascular thrombosis and obstetric morbidity, with accurate laboratory examination of antiphospholipid antibodies (aPLs) being crucial for diagnosis. This study focused on anti-ß2 glycoprotein I (aß2GPI) antibodies and aimed to establish the first population-based cutoff values for aß2GPI IgA/IgM/IgG antibodies in non-pregnant women of reproductive age in Southwest China. The study cohort comprised 181 healthy women of reproductive age for study. Blood samples were collected on an early morning fast. Anti-ß2GPI antibodies including IgA, IgM and IgG were measured in serum using the HOB® BioCLIA kit. According to the Clinical and Laboratory Standards Institute (CLSI) guidelines, the study used non-parametric percentile methods to calculate the 95th, 97.5th, and 99th percentiles cutoff values for aß2GPI IgA/IgM/IgG antibodies, along with corresponding 90% confidence intervals (CI), while excluding outliers. A total of 168 independent samples were collected for verification, including 85 samples from healthy subjects and 83 samples from APS patients, in order to evaluate the analytical performance of the obtained cutoff values. The 99th percentile cutoff values were 3.36 RU/mL for aß2GPI IgA, 27.54 RU/mL for aß2GPI IgM and 1.81 RU/mL for aß2GPI IgG, which indicated that the levels of aß2GPI IgM antibodies were generally higher compared to those of IgA and IgG antibodies. Our established reference range was confirmed to be successful in validating the detected values of aß2GPI antibodies in all healthy controls. With the 99th percentile cutoff value, the sensitivity was 14.46% for aß2GPI IgA, 22.89% for aß2GPI IgG, and 9.64% for aß2GPI IgM in APS patients. This study established population-based cutoff values that are applicable to the local population for the accurate laboratory examination of aß2GPI antibodies in non-pregnant women of reproductive age. The study also recommends paying more attention to IgM positivity in women of reproductive age.


Assuntos
Síndrome Antifosfolipídica , Imunoglobulina G , Imunoglobulina M , beta 2-Glicoproteína I , Humanos , Feminino , beta 2-Glicoproteína I/imunologia , Adulto , China , Síndrome Antifosfolipídica/imunologia , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/diagnóstico , Imunoglobulina M/sangue , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina A/sangue , Pessoa de Meia-Idade , Anticorpos Antifosfolipídeos/sangue , Anticorpos Antifosfolipídeos/imunologia , Adulto Jovem , Valores de Referência , Autoanticorpos/sangue , Autoanticorpos/imunologia , Adolescente
16.
Ital J Pediatr ; 50(1): 163, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39227847

RESUMO

BACKGROUND: Systemic Lupus Erythematosus (SLE) patients are more likely than the general population to suffer from thyroid illness. The major goal was to assess the thyroid dysfunctions due to immunological factors in Egyptian SLE children and how they are related to the course and severity of the illness. METHODS: Fifty children and adolescents with SLE are included in this cross-sectional observational study. Every patient underwent a thorough physical examination and a comprehensive history taking. An enzyme-linked immunosorbent assay (ELISA) approach was used to evaluate the thyroid profile, anti-thyroglobulin (Anti-TG), and anti-thyroid peroxidase (anti-TPO) antibodies. RESULTS: Of the 50 patients, the female: male ratio (F: M = 7:1) was 44 females and 6 males (12%). They were between the ages of 5 and 17. Out of the patients, thirty-two (64%) had thyroid dysfunctions, 19 (38%) had euthyroid sick syndrome, ten (20%) had overt hypothyroidism, three (6%) had subclinical hypothyroidism, and none had hyperthyroidism. Of the 50 patients, one (2%) had increased anti-TPO, whereas all other patients had normal anti-TG levels. A statistically significant negative correlation (p-value 0.007) was seen between the disease duration and free thyroxine (FT4). Furthermore, a significant negative correlation (p-values 0.015 and 0.028) was found when comparing the disease duration with thyroid antibodies (anti-TG and anti-TPO). CONCLUSION: In Juvenile Systemic Lupus Erythematosus (JSLE), thyroid dysfunctions can be identified. The disease duration but not its activity was significantly correlated with thyroid antibodies. For children with JSLE, thyroid function testing should be done on a regular basis. It is preferable to carry out additional thyroid antibody tests when necessary.


Assuntos
Lúpus Eritematoso Sistêmico , Humanos , Feminino , Masculino , Criança , Estudos Transversais , Adolescente , Lúpus Eritematoso Sistêmico/complicações , Pré-Escolar , Egito/epidemiologia , Testes de Função Tireóidea , Tireoidite Autoimune/complicações , Tireoidite Autoimune/diagnóstico , Tireoidite Autoimune/epidemiologia , Doenças da Glândula Tireoide/complicações , Doenças da Glândula Tireoide/imunologia , Autoanticorpos/sangue , Ensaio de Imunoadsorção Enzimática , Índice de Gravidade de Doença
17.
J Nippon Med Sch ; 91(4): 422-424, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39231647

RESUMO

Anti-galactocerebroside (Gal-C) antibodies are present in patients with conditions such as Guillain-Barré syndrome and mycoplasma pneumonia. We report a rare case of left vocal cord paralysis in a patient with anti-Gal-C IgG antibodies that improved after administeration of antivirals and steroids.


Assuntos
Galactosilceramidas , Paralisia das Pregas Vocais , Humanos , Galactosilceramidas/imunologia , Paralisia das Pregas Vocais/etiologia , Antivirais/uso terapêutico , Imunoglobulina G/sangue , Masculino , Autoanticorpos/sangue , Resultado do Tratamento , Feminino , Pessoa de Meia-Idade
19.
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
20.
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
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