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 , IdosoRESUMO
The presence of anti-thyroid antibodies (ATAs) is a biomarker for the development of thyroid dysfunction induced by anti-programmed cell death-1 antibodies (PD-1-Abs). While patients with thyroid dysfunction reportedly showed better overall survival (OS), it remains unknown if ATAs at baseline can predict OS. Therefore, in this study, we examined the association of ATAs at baseline with OS in non-small cell lung cancer (NSCLC) patients with different levels of programmed cell death-1 ligand 1 (PD-L1) positivity associated with PD-1-Ab treatment efficacy. A total of 81 NSCLC patients treated with PD-1-Abs were evaluated for ATAs at baseline and prospectively for OS. Among the 81 patients, 49 and 32 patients had ≥50% (group A) and <50% (group B) PD-L1 positivity, respectively. Median OS did not differ significantly between patients with (n = 13) and without (n = 36) ATAs at baseline in group A. In contrast, median OS was significantly longer in patients with (n = 10) versus without (n = 22) ATAs at baseline in group B (not reached vs 378 days, respectively; 95% CI, 182 to 574 days, p = 0.049). These findings suggest that the presence of ATAs at baseline is a biomarker to predict better treatment efficacy of PD-1-Abs in NSCLC patients with low PD-L1 positivity, while the difference in OS in those with high PD-L1 positivity may be masked by increased tumor expression of PD-L1.
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Autoanticorpos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Masculino , Feminino , Autoanticorpos/sangue , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/imunologia , Idoso , Pessoa de Meia-Idade , Estudos Prospectivos , Antígeno B7-H1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Glândula Tireoide/imunologia , Glândula Tireoide/patologia , Idoso de 80 Anos ou mais , Inibidores de Checkpoint Imunológico/uso terapêuticoRESUMO
Acute immune thrombotic thrombocytopenic purpura (iTTP) is a medical emergency. In the setting of any thrombotic microangiopathy (TMA), blood should be drawn to measure ADAMTS13 activity and inhibitor levels, and an assessment should be made of TTP risk before receiving ADAMTS13 results. This can include the use of PLASMIC and French scores. Plasma exchange (PE) is then initiated. Upon confirmation of iTTP, with ADAMTS13 less than 10% in the presence of an inhibitor, interventions targeting all facets of iTTP pathophysiology should be instituted: replenishing ADAMTS13 via continued PE; suppressing anti-ADAMTS13 autoantibodies with glucocorticoids and rituximab; and inhibiting the thrombotic process-uncontrolled formation of platelet/Von Willebrand factor (VWF) microthrombi-with caplacizumab. The latter, an addition to existing standards of care, is based on International Society on Thrombosis and Haemostasis guidelines and emphasizes tracking of ADAMTS13 activity. In HERCULES, a pivotal randomized controlled trial, caplacizumab use resulted in fewer recurrent iTTP episodes, decreased PE, and shortened hospital stay. In settings of high suspicion for iTTP, clinicians should consider the administration of caplacizumab before receiving ADAMTS13 results because the greatest benefits of caplacizumab accrued starting it within 3 days of TMA recognition. In HERCULES, serious bleeding events occurred among 11% of those in the caplacizumab group vs 1% in the placebo group, but all resolved, most without intervention. iTTP survivors receiving PE and immunosuppression alone are at a heightened risk for stroke, other cardiovascular disorders, neurocognitive impairment, and kidney disease. Whether rapid prevention of VWF multimer/platelet formation with caplacizumab can suppress such long-term sequelae, and whether caplacizumab can replace PE in initial therapy, are under investigation.
Assuntos
Proteína ADAMTS13 , Troca Plasmática , Púrpura Trombocitopênica Trombótica , Rituximab , Anticorpos de Domínio Único , Padrão de Cuidado , Humanos , Proteína ADAMTS13/metabolismo , Anticorpos de Domínio Único/uso terapêutico , Púrpura Trombocitopênica Trombótica/terapia , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Rituximab/uso terapêutico , Fator de von Willebrand/metabolismo , Fator de von Willebrand/antagonistas & inibidores , Fator de von Willebrand/uso terapêutico , Púrpura Trombocitopênica Idiopática/terapia , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Autoanticorpos/imunologia , Autoanticorpos/sangue , Glucocorticoides/uso terapêuticoRESUMO
Heparin-induced thrombocytopenia (HIT) was widely known as a disease characterized by development of thrombosis with thrombocytopenia after heparin exposure. In addition, vaccine-induced immune thrombotic thrombocytopenia (VITT) has been described as a fatal disease involving simultaneous bleeding and thrombosis after COVID-19 adenovirus vector vaccination. These were caused by HIT antibodies and anti-PF4 antibodies, respectively, but both were autoantibodies that recognized PF4, and were found to have the same pathology with different severities. In recent years, many pathologies in which anti-PF4 antibodies are produced have been reported, and a new concept of anti-PF4 disorder has been proposed. Anti-PF4 disorders are often difficult to identify due to their diverse range of causes, and the prognosis varies greatly depending on whether anti-PF4 antibodies can be measured and early treatment performed after observation of thrombocytopenia of unknown cause or thrombosis at an unusual site. To avoid overlooking anti-PF4 disorders, clinicians should become familiar with the classification of these disorders and accurately select the necessary tests.
Assuntos
Heparina , Fator Plaquetário 4 , Trombocitopenia , Humanos , Trombocitopenia/terapia , Trombocitopenia/imunologia , Fator Plaquetário 4/imunologia , Heparina/efeitos adversos , Autoanticorpos/imunologia , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , COVID-19/imunologia , COVID-19/complicações , Trombose/etiologia , Trombose/imunologiaRESUMO
Autoimmune hemolytic anemia (AIHA) is caused by autoantibodies that can be divided into two types-warm and cold-depending on their thermal amplitudes. The pathology differs depending on the type of autoantibody involved; however, the underlying etiology can differ even when the pathology is the same. Therefore, understanding the underlying mechanisms and making an accurate diagnosis is critical, as inappropriate treatment not only results in treatment failure, but can also cause life-threatening complications and reduce patient quality of life. Corticosteroids are the first-line treatment for warm AIHA, but have limited efficacy against cold agglutinin disease (CAD). Moreover, long-term and high-dose administration of corticosteroids increases risk of infection, fracture, and thromboembolism. A novel therapeutic agent for CAD targeting the complement system is effective only against hemolysis, but does not improve symptoms induced by red blood cell aggregation. In addition, elderly patients who present with either warm AIHA or CAD should also be assessed for possible malignancy. This review discusses the etiologies and pathological conditions associated with AIHA and describes the recommendations for diagnosis and treatment according to the Japanese guideline for AIHA revised in 2022.
Assuntos
Anemia Hemolítica Autoimune , Anemia Hemolítica Autoimune/diagnóstico , Anemia Hemolítica Autoimune/terapia , Anemia Hemolítica Autoimune/etiologia , Humanos , Guias de Prática Clínica como Assunto , AutoanticorposRESUMO
OBJECTIVE: To investigate changes in proportions of peripheral blood lymphocyte subsets, the correlation between the lymphocyte subsets and cytokine levels in patients with GluR3B antibody-positive epilepsy, analyze the role of GluR3B antibodies and cytokines in the progression of epilepsy. In addition, the immunotherapeutic effect in patients with GluR3B antibody-positive epilepsy will be evaluated. METHODS: Patients with epilepsy hospitalized in the Department of Neurology of the affiliated Hospital of Xuzhou Medical University from December 2016 to May 2023 were recruited. GluR3B antibody levels were measured by enzyme-linked immunosorbent assay (ELISA). Lymphocyte subset proportions were determined using flow cytometry, and serum concentrations of 12 cytokines were measured using cytometric beads array. Differences in T lymphocyte subsets and inflammatory factors were analysed between GluR3B antibody positive and negative patients. Structural equation modeling (SEM) was used to analyse the role of GluR3B antibodies and inflammatory factors in drug-resistant epilepsy (DRE). Finally, the therapeutic effect of immunotherapy on epilepsy patients with GluR3B antibodies was assessed. RESULTS: In this study, sixty-four cases of DRE, sixty-six cases of drug-naïve epilepsy (DNE), and forty-one cases of drug-responsive epilepsy were recruited. (1) DRE patients with positive GluR3B antibody were characterized by a significant increase in the proportion of cluster of differentiation (CD)4+ T lymphocytes, a decrease in CD8+ T lymphocytes, and an increase of CD4+/CD8+ ratio. Similar alterations in T lymphocyte subsets were observed in GluR3B antibody-positive patients with DNE. GluR3B antibody levels correlated positively with CD4+ T lymphocytes (r = 0.23) and negatively with CD8+ T lymphocytes (r=-0.18). (2) In patients with DRE, the serum concentrations of interleukin-1ß (IL-1ß), IL-8, and interferon-gamma (IFN-γ) were significantly higher in those with positive GluR3B antibody compared to those with negative GluR3B antibody. Serum IL-1ß levels were also higher in GluR3B antibody-positive DNE patients compared to antibody-negative DNE patients. In drug-responsive epilepsy patients with GluR3B antibody-positive, both serum IL-1ß and IFN-γ levels were higher than those with GluR3B antibody-negative. Moreover, the concentrations of serum GluR3B antibody were positively correlated with the levels of IL-1ß, IL-8, and IFN-γ. (3) SEM analysis indicated that GluR3B antibody may be a direct risk factor for DRE (direct effect = 4.479, 95%CI 0.409-8.503), or may be involved in DRE progression through affecting IFN-γ and IL-8 levels (total indirect effect = 5.101, 95%CI 1.756-8.818). (4) Immunotherapy significantly decreased seizure frequency and serum GluR3B antibody levels, and the seizure frequency was positively correlated with the levels of GluR3B antibody levels in patients receiving immunotherapy. CONCLUSIONS: This study demonstrates that GluR3B antibody may influence the progression of epilepsy through altering the proportion of CD4+ and CD8+ lymphocyte subsets and increasing proinflammatory cytokines. The seizure suppression of immunotherapy is associated with the decrease of GluR3B antibody levels. Thus, the present study contributes to a better understanding of the immunoregulatory mechanisms of autoimmune-associated epilepsy and provides a potential target for DRE.
Assuntos
Citocinas , Progressão da Doença , Epilepsia , Subpopulações de Linfócitos T , Humanos , Masculino , Feminino , Epilepsia/imunologia , Epilepsia/sangue , Adulto , Citocinas/sangue , Subpopulações de Linfócitos T/imunologia , Receptores de AMPA/imunologia , Adulto Jovem , Mediadores da Inflamação/sangue , Mediadores da Inflamação/metabolismo , Pessoa de Meia-Idade , Adolescente , Autoanticorpos/sangue , Autoanticorpos/imunologia , Inflamação/sangue , Inflamação/imunologiaRESUMO
BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complicated, heterogeneous condition distinguished by post-exertional neuroimmune exhaustion and multisystem symptoms. Its complexity poses challenges for physicians, researchers and those inflicted by its presence. Due to conflicting evidence and limiting consensus, the association and contribution autoimmunity serves in the pathophysiology or aetiology of ME/CFS is yet to be confirmed. This systematic review synthesises the currently available data to clarify the role autoimmunity has in the pathogenesis of ME/CFS and explore the therapeutic limitations. METHODS: This systematic review was conducted in accordance with the PRISMA and Cochrane guidelines. Full-text articles containing the primary key terms "Autoimmunity/Autoimmune" and "ME/CFS" were included provided their suitability to the inclusion and exclusion criteria. RESULTS: Ten publications investigating the role of autoimmunity in ME/CFS were examined. One investigated the role of cytokine signalling; Three investigated the genetic nature of autoimmunity in ME/CFS patients; One examined the immune lineage of ME/CFS patients; Six investigated the presence and role of autoantibodies in ME/CFS patients. CONCLUSION: The findings generated from this systematic review highlight inconsistent and insufficient evidence to classify ME/CFS as an autoimmune disease. Additionally, it further emphasises the complexity of ME/CFS and highlights the challenges in distinguishing autoreactivity from deregulatory processes. Future research is urgently needed to advance the development of diagnostic and treatment strategies. PROSPERO REGISTRATION CODE: CRD42024533447.
Assuntos
Autoanticorpos , Autoimunidade , Síndrome de Fadiga Crônica , Humanos , Síndrome de Fadiga Crônica/imunologia , Autoanticorpos/imunologia , Citocinas/metabolismo , Animais , Doenças Autoimunes/imunologiaRESUMO
Pemphigus is an IgG-mediated autoimmune condition characterized by autoantibodies targeting desmogleins, leading to acantholysis. Current treatments, including systemic corticosteroids and immunosuppressive drugs, are associated with significant adverse effects. Mesenchymal stem cells (MSCs) offer a promising alternative due to their immunomodulatory properties and low immunogenicity. This study evaluates the immunomodulatory effects of dental follicle mesenchymal stem cells (DF-MSCs) obtained from healthy donors on Pemphigus vulgaris (PV) patients and healthy controls by examining T-cell proliferation, apoptosis, cytokine levels, and anti-desmoglein 1/3 IgG profiles. Peripheral blood mononuclear cells (PBMCs) were isolated from twenty-one symptomatic PV patients and eleven healthy volunteers. DF-MSCs were characterized and differentiated into osteocytes, adipocytes, and chondrocytes. Peripheral blood mononuclear cells (PBMCs) were co-cultured with DF-MSCs, and various assays were conducted to evaluate T-cell proliferation, apoptosis, regulatory T cells, cytokine expression, and autoantibody levels. Results showed that DF-MSC co-cultures significantly reduced lymphocyte proliferation (43.58-16.27%), IL-4 (38.06 ng/L to 32.26 ng/L), TNF-α (32.45 ng/L to 29.41 ng/L), and DSG1 (3.29 ng/ml to 3.00 ng/ml) and DSG3 (262.40 ng/ml to 245.08 ng/ml) levels in PV patients. An increase in regulatory T cells (1.22-3.75%), IL-10 (47.46 pg/ml to 54.94 pg/ml), and IFN-γ (12.39 ng/ml to 19.70 ng/ml) was also observed. No significant changes were noted in healthy controls. These findings suggest that DF-MSCs could potentially offer a curative approach for treating pemphigus by restoring immune balance. However, further clinical trials are necessary to confirm their efficacy.
Assuntos
Autoanticorpos , Proliferação de Células , Células-Tronco Mesenquimais , Pênfigo , Humanos , Pênfigo/imunologia , Pênfigo/terapia , Pênfigo/sangue , Células-Tronco Mesenquimais/imunologia , Feminino , Masculino , Autoanticorpos/sangue , Autoanticorpos/imunologia , Adulto , Técnicas de Cocultura , Desmogleína 3/imunologia , Apoptose/imunologia , Saco Dentário/imunologia , Células Cultivadas , Citocinas/metabolismo , Pessoa de Meia-Idade , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Diferenciação Celular/imunologia , Desmogleína 1/imunologia , Leucócitos Mononucleares/imunologia , Linfócitos T Reguladores/imunologia , Estudos de Casos e ControlesRESUMO
Human inborn errors of thymic T cell tolerance underlie the production of autoantibodies (auto-Abs) neutralizing type I IFNs, which predispose to severe viral diseases. We analyze 131 female patients with X-linked dominant incontinentia pigmenti (IP), heterozygous for loss-of-function (LOF) NEMO variants, from 99 kindreds in 10 countries. Forty-seven of these patients (36%) have auto-Abs neutralizing IFN-α and/or IFN-ω, a proportion 23 times higher than that for age-matched female controls. This proportion remains stable from the age of 6 years onward. On imaging, female patients with IP have a small, abnormally structured thymus. Auto-Abs against type I IFNs confer a predisposition to life-threatening viral diseases. By contrast, patients with IP lacking auto-Abs against type I IFNs are at no particular risk of viral disease. These results suggest that IP accelerates thymic involution, thereby underlying the production of auto-Abs neutralizing type I IFNs in at least a third of female patients with IP, predisposing them to life-threatening viral diseases.
Assuntos
Autoanticorpos , Quinase I-kappa B , Incontinência Pigmentar , Interferon Tipo I , Timo , Humanos , Interferon Tipo I/imunologia , Interferon Tipo I/metabolismo , Feminino , Autoanticorpos/imunologia , Timo/imunologia , Timo/patologia , Criança , Incontinência Pigmentar/imunologia , Incontinência Pigmentar/genética , Incontinência Pigmentar/patologia , Pré-Escolar , Quinase I-kappa B/genética , Quinase I-kappa B/imunologia , Viroses/imunologia , Lactente , Adulto , Adolescente , Adulto JovemRESUMO
INTRODUCTION: Connective tissue diseases (CTDs) are autoimmune diseases with multiorgan involvement. CTDs present with a heterogeneous clinical manifestation, especially in the cutaneous system. This study aimed to describe the common cutaneous manifestations of CTDs, to determine the association with antinuclear antibody (ANA) and other associated antibodies, and to assess the impact of CTDs on patient's quality of life (QOL). MATERIAL AND METHODS: This was a cross-sectional study conducted among patients 18 years and above, with a confirmed diagnosis of systemic lupus erythematosus (SLE), systemic sclerosis, dermatomyositis, mixed connective tissue disease (MCTD) or overlap syndrome, who attended the rheumatology clinic at Hospital Sultan Ismail Johor Bahru between March 2023 to June 2023. The assessment instrument used was the Dermatology Quality Life Index (DLQI). RESULTS: Among 79 patients recruited, the majority were females with a mean age of 39 ± 14.5 years. Malay was the predominant ethnic group. SLE was the most common CTD (64 patients, 81%), followed by systemic sclerosis (six patients, 7.6%), overlap syndrome (four patients, 5.1%), dermatomyositis (four patients, 5.1%) and MCTD (one patient, 1.3%). All patients had cutaneous involvement with photodermatitis being the commonest cutaneous manifestation (65 patients, 82.3%). ANA and anti-double stranded DNA (dsDNA) positivity were significantly associated with SLE while anti-scl70 and anti-centromere antibodies (ACA) were strongly associated with systemic sclerosis (p < 0.05). The presence of anti-dsDNA and antiscl70 were significantly associated with renal involvement and interstitial lung disease (ILD) respectively (p < 0.05). CTD had a moderate effect on patient's QOL. CONCLUSION: Photosensitivity was the commonest cutaneous manifestation among CTD patients. ANA was positive in the majority of SLE patients. The presence of anti-dsDNA was significantly associated with lupus nephritis, while anti-scl70 and ACA were strongly associated with systemic sclerosis and ILD. CTD had a moderate effect on patient's QOL.
Assuntos
Autoanticorpos , Doenças do Tecido Conjuntivo , Qualidade de Vida , Humanos , Feminino , Estudos Transversais , Masculino , Adulto , Pessoa de Meia-Idade , Autoanticorpos/sangue , Doenças do Tecido Conjuntivo/imunologia , Dermatopatias/imunologia , Dermatopatias/etiologia , Malásia , Adulto Jovem , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologiaRESUMO
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/imunologiaRESUMO
BACKGROUND: There have been only few reports on Rhupus syndrome with severe visceral involvement. Moreover, there was little consensus regarding its treatment. Belimumab is one of the options for treating this disease. For patients with clinical symptoms and elevated levels of anti CCP antibodies and anti-double stranded DNA antibodies, and it suggests Rhupus syndrome. After effective treatment, the decrease in levels of anti CCP antibodies and anti-double stranded DNA (ds-DNA) antibodies can effectively delay the progression of the disease and protect target organs. METHODS: We used a chemiluminescence instrument, (Yahuilong; Shenzhen, China), to measure the changes in CCP and dsDNA before and after treatment. RESULTS: Prior to treatment, the patient presented with symptoms of rheumatoid arthritis and systemic lupus erythematosus. Her laboratory tests showed dsDNA (214 IU/mL) and CCP level of Ë 3,000 U/mL. After treatment with belimumab, the clinical symptoms were significantly relieved, and the patient's CCP IgG level decreased to 263.5 U/mL. A blood test found that her anti-dsDNA was negative. CONCLUSIONS: CCP and dsDNA can serve as indicators for the diagnosis and treatment of Rhupus syndrome.
Assuntos
Anticorpos Antinucleares , Anticorpos Monoclonais Humanizados , DNA , Humanos , Feminino , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologia , DNA/imunologia , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/sangue , Pessoa de Meia-Idade , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Artrite Reumatoide/sangue , Imunossupressores/uso terapêutico , Resultado do Tratamento , Autoanticorpos/sangue , Autoanticorpos/imunologia , Adulto , Biomarcadores/sangueRESUMO
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/sangueRESUMO
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 JovemRESUMO
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 cefalorraquidianoRESUMO
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/patologiaAssuntos
Autoanticorpos , Encefalomielite , Rigidez Muscular , Mioclonia , Receptores de Glicina , Humanos , Rigidez Muscular/etiologia , Rigidez Muscular/diagnóstico , Rigidez Muscular/imunologia , Encefalomielite/imunologia , Encefalomielite/diagnóstico , Encefalomielite/complicações , Mioclonia/etiologia , Mioclonia/diagnóstico , Mioclonia/imunologia , Autoanticorpos/imunologia , Autoanticorpos/sangue , Receptores de Glicina/imunologia , Poliendocrinopatias Autoimunes/complicações , Poliendocrinopatias Autoimunes/diagnóstico , Poliendocrinopatias Autoimunes/imunologia , Masculino , Feminino , AdultoRESUMO
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 AsiáticoRESUMO
IL-10 autoantibodies are detected in two patients with severe inflammatory bowel disease.