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1.
BMC Infect Dis ; 20(1): 828, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176707

RESUMO

BACKGROUND: Severe and disseminated non-tuberculous mycobacterial (NTM) infections are frequently linked to a genetic predisposition but acquired defects of the interferon gamma (IFNγ) / interleukin 12 (IL-12) pathway need to be considered in adult patients with persistent or recurrent infections. Neutralizing anti-IFNγ autoantibodies disrupting IFNγ signalling have been identified as the cause of a severe and unique acquired immunodeficiency syndrome with increased susceptibility to NTM and other intracellular pathogens. CASE PRESENTATION: An adult Asian female with a previous history of recurrent NTM infections presented with persistent diarrhea, abdominal pain, night sweats and weight loss. Severe colitis due to a simultaneous infection with cytomegalovirus (CMV) and Salmonella typhimurium was diagnosed, with both pathogens also detectable in blood samples. Imaging studies further revealed thoracic as well as abdominal lymphadenopathy and a disseminated Mycobacterium intracellulare infection was diagnosed after a lymph node biopsy. Further diagnostics revealed the presence of high-titer neutralizing anti-IFNγ autoantibodies, allowing for the diagnosis of adult-onset immunodeficiency with anti-IFNγ autoantibodies (AIIA). CONCLUSIONS: We here present a severe case of acquired immunodeficiency with anti-IFNγ autoantibodies with simultaneous, disseminated infections with both viral and microbial pathogens. The case illustrates how the diagnosis can cause considerable difficulties and is often delayed due to unusual presentations. Histological studies in our patient give further insight into the pathophysiological significance of impaired IFNγ signalling. B-cell-depleting therapy with rituximab offers a targeted treatment approach in AIIA.


Assuntos
Autoanticorpos/imunologia , Infecções por Citomegalovirus/diagnóstico , Citomegalovirus/isolamento & purificação , Síndromes de Imunodeficiência/diagnóstico , Interferon gama/imunologia , Linfadenopatia/diagnóstico , Complexo Mycobacterium avium/isolamento & purificação , Infecção por Mycobacterium avium-intracellulare/diagnóstico , Infecções por Salmonella/diagnóstico , Salmonella typhimurium/isolamento & purificação , Adulto , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Autoanticorpos/sangue , Biópsia , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/virologia , Diagnóstico Tardio , Feminino , Seguimentos , Humanos , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Interferon gama/metabolismo , Interleucina-12/metabolismo , Linfadenopatia/complicações , Linfadenopatia/tratamento farmacológico , Linfadenopatia/patologia , Infecção por Mycobacterium avium-intracellulare/complicações , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Infecção por Mycobacterium avium-intracellulare/microbiologia , Infecções por Salmonella/complicações , Infecções por Salmonella/tratamento farmacológico , Infecções por Salmonella/microbiologia , Resultado do Tratamento
2.
Artigo em Japonês | MEDLINE | ID: mdl-33148926

RESUMO

Immunity, which denotes the protection of multicellular organisms against various bacterial and viral infections, is an essential protective mechanism for living organisms. Allergy is a reaction to a foreign substance existing in the environment that is basically not a component of the self. Additionally, autoimmune diseases are associated with the dysfunction in the recognition of self and non-self, and are pathological conditions caused by immune cells attacking their own tissues and cells. In this paper, we outline the current status of immunity with respect to the environment from the epidemiological perspective with regard to the following: (1) evolution and immunity, (2) allergy, (3) autoantibodies, (4) autoimmune diseases, (5) relationships of immunity with the environment, allergy, autoantibodies, and autoimmune diseases, and (6) celiac disease.


Assuntos
Doenças Autoimunes/imunologia , Autoimunidade , Hipersensibilidade/imunologia , Adolescente , Adulto , Idoso , Autoanticorpos , Doenças Autoimunes/epidemiologia , Evolução Biológica , Doença Celíaca/imunologia , Criança , Pré-Escolar , Meio Ambiente , Feminino , Humanos , Hipersensibilidade/epidemiologia , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem
3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1740-1745, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067983

RESUMO

OBJECTIVE: To identify the difficult antibody specificity of 1 PNH patient with blood transfusion history by genotyping. METHODS: RH typing of this patient was performed using gel card method, the antibody specificity was identified by panel cells, the RH-unrelated phenotype were excluded by genotyping method in difficult condition of serologic identification, furthmore different RH phenotype cells were used for adsorption-elution so as to re-examine the reactivity of antibodies in this patient's serum, and finally different RH phenotype cells were combined to exclude other unrelated antibodies. RESULTS: The RH phenotype presented as double population for C antigen, and positive agglutination for the other antigens. The results of RHD zygote, together with RHD and RHCE sequencing showed that the RHD genotype was homozygous RHD/RHD, and the c.122A>G mutation did not found in RHCE gene, thus CW antigen was excluded; 48G lies in the 1st exon, the 5th exon showed nt676 G/C heterozygosity, the 2nd-4th, 6th-10th exons did not show mutations, however a new mutation was found in the 4th intron IVS4+29A>C. It can be judged that the RH genotype was Dce/DcE, and its phenotype should be ccDEe. The anti-C alloantibody and rare anti-f autoantibody mimicking alloantibody in serum was determined by different RH phenotypic cell absorption-elution. Finally, cross-matched AB ccDEE blood units were selected for the patient and there was no adverse reactions of blood transfusion occurred. CONCLUSION: Genotyping can be auxiliarily applied to the identification of difficult antibodies in serum of a patient, thereby reducing the risk of blood transfusion.


Assuntos
Antígenos de Grupos Sanguíneos , Sistema do Grupo Sanguíneo Rh-Hr , Autoanticorpos , Antígenos de Grupos Sanguíneos/genética , Genótipo , Humanos , Isoanticorpos , Sistema do Grupo Sanguíneo Rh-Hr/genética
4.
Clin Exp Rheumatol ; 38 Suppl 126(4): 271-282, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33025890

RESUMO

Primary Sjögren's syndrome (pSS) is often considered a B cell-mediated disease, yet the precise role of B cells in the pathogenesis is not fully understood. This is exemplified by the failure of multiple clinical trials directed at B cell depletion or inhibition. To date, most prognostic markers for severe disease outcomes are autoantibodies, but the underlying mechanisms by which B cells drive diverse disease presentations in pSS likely extend beyond autoantibody production. Here we outline an expanded role of B cells in disease pathogenesis drawing on examples from animal models of SS, and from other autoimmune diseases that share similar clinical or immunological abnormalities. We focus on recent findings from the detailed analysis of pathogenic B cells in patients with pSS to propose strategies for patient stratification to improve clinical trial outcomes. We conclude that an integrated cellular, molecular and genetic analysis of patients with pSS will reveal the underlying pathogenic mechanisms and guide precision medicine.


Assuntos
Doenças Autoimunes , Síndrome de Sjogren , Animais , Autoanticorpos , Linfócitos B , Humanos , Síndrome de Sjogren/diagnóstico
5.
Clin Exp Rheumatol ; 38 Suppl 126(4): 95-102, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33025893

RESUMO

OBJECTIVES: To characterise autoimmune congenital heart block (CHB) associated with a maternal diagnosis of primary Sjögren's syndrome (pSS) confirmed either before, concomitant or after the first pregnancy complicated with CHB. METHODS: The following inclusion criteria were applied: (i) Mothers with positive Ro/La autoantibodies detected previously or at the time of diagnosis of the first case of CHB; (ii) diagnosis of CHB confirmed by fetal echocardiography; (iii) AV block diagnosed in uterus, at birth or within the neonatal period (0-27 days after birth) (8); (iv) absence of anatomical cardiac abnormalities which might be causal of AV block; and (v) maternal fulfillment of the 2002 SS criteria before, during or after having a pregnancy complicated with CHB. RESULTS: We identified 49 cases of autoimmune CHB in children born from 44 mothers who had a mean age at the time of pregnancy of 30.3 years (range 18 to 41). At the time of diagnosis of autoimmune CHB, all mothers had positive anti-Ro antibodies and 28/44 (64%) were positive for anti-La antibodies. Only 10 (22%) mothers with affected pregnancies had a diagnosis of primary SS at the time of diagnosis of the first pregnancy complicated by CHB (a mean of 4 years before, ranging from 1 to 10 years). In 6 (14%) mothers, primary SS was diagnosed during pregnancy or less than 12 months after the delivery/termination. In the remaining 28 (64%) mothers, pSS was confirmed 1-5 years after CHB diagnosis (n=19, 68%), 6-10 years after (n=2, 7%), or more than 10 years after the first case of CHB was diagnosed (n=7, 25%). CHB was diagnosed in uterus in all cases but two. AV block was initially incomplete in 11 fetuses and complete in 36 (no available data in 2 cases). Among the 35 (71%) surviving children with CHB, 5 (14%) developed other features of neonatal lupus. After the index pregnancy, 12 women had 20 subsequent pregnancies: five were complicated by a CHB (recurrence rate of CHB of 25%). The 4 women who had recurrent CHB were double-positive for anti-Ro and anti-La antibodies, and all had a confirmed pSS before having the first index case of CHB. CONCLUSIONS: In pSS, autoimmune CHB could be one of the first "indirect" signs of the disease in women of childbearing-age, in whom the diagnosis is confirmed several years later. Some maternal characteristics could be related with recurrent CHB, such as having an already-confirmed diagnosis of pSS and carrying the two Ro/La autoantibodies.


Assuntos
Síndrome de Sjogren , Adolescente , Adulto , Autoanticorpos , Criança , Feminino , Bloqueio Cardíaco/congênito , Bloqueio Cardíaco/etiologia , Humanos , Mães , Gravidez , Síndrome de Sjogren/diagnóstico , Adulto Jovem
6.
PLoS One ; 15(10): e0239756, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33017427

RESUMO

BACKGROUND: It is popularly believed that myasthenia gravis (MG) patients show acetylcholine receptor antibody (AChRAb) production associated with the thymus (germinal centers, approximately 80%). It has been suggested that thymectomy can remove the area of autoantibody production. This study aimed to determine whether the solid volume of the thymus calculated using three-dimensional (3D) imaging could be used to predict the efficacy of thymectomy. Additionally, the study assessed the relationships of the solid volume with germinal centers, change in the serum AChRAb level, postoperative MG improvement, and prednisolone (PSL) dose reduction extent. METHODS: This retrospective study included 12 consecutive non-thymomatous MG patients (9 female and 3 male patients), who underwent extended thymectomy at our institution over the last 10 years. The mean patient age was 43.3 ± 14.2 years (range, 12-59 years). The study assessed the number of germinal centers per unit area, change in the serum AChRAb level, postoperative MG improvement, PSL dose reduction extent, and solid volume of the thymus. RESULTS: The number of germinal centers per unit area was significantly correlated with the solid volume of the thymus. The PSL dose reduction extent tended to be correlated with the solid volume. CONCLUSIONS: Our findings suggest that the solid volume of the thymus can possibly predict steroid dose reduction. Additionally, the solid volume of the thymus in 3D images is the most important indicator for predicting the efficacy of extended thymectomy.


Assuntos
Miastenia Gravis/patologia , Miastenia Gravis/cirurgia , Timoma/patologia , Timoma/cirurgia , Adulto , Autoanticorpos/metabolismo , Feminino , Humanos , Masculino , Receptores Colinérgicos/metabolismo , Estudos Retrospectivos , Timectomia/métodos , Timoma/metabolismo , Neoplasias do Timo/metabolismo , Neoplasias do Timo/patologia , Neoplasias do Timo/cirurgia
7.
Neurol Sci ; 41(12): 3391-3394, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33006723

RESUMO

We report the clinical and immunological features in a case of SARS-CoV-2-induced Guillain-Barré syndrome (Si-GBS), suggesting that (1) Si-GBS can develop even after paucisymptomatic COVID-19 infection; (2) a distinctive cytokine repertoire is associated with this autoimmune complication, with increased CSF concentration of IL-8, and moderately increased serum levels of IL-6, IL-8, and TNF-α; (3) a particular genetic predisposition can be relevant, since the patient carried several HLA alleles known to be associated with GBS, including distinctive class I (HLA-A33) and class II alleles (DRB1*03:01 and DQB1*05:01). To the best of our knowledge, this is the first case of GBS in which SARS-CoV-2 antibodies were detected in the CSF, further strengthening the role of the virus as a trigger. In conclusion, our study suggests that SARS-CoV-2 antibodies need to be searched in the serum and CSF in patients with GBS living in endemic areas, even in the absence of a clinically severe COVID-19 infection, and that IL-8 pathway can be relevant in Si-GBS pathogenesis. Further studies are needed to conclude on the relevance of the genetic findings, but it is likely that HLA plays a role in this setting as in other autoimmune neurological syndromes, including those triggered by infections.


Assuntos
Infecções por Coronavirus/complicações , Síndrome de Guillain-Barré/genética , Síndrome de Guillain-Barré/imunologia , Síndrome de Guillain-Barré/virologia , Pneumonia Viral/complicações , Anticorpos Antivirais/imunologia , Autoanticorpos/imunologia , Autoantígenos/imunologia , Betacoronavirus , Citocinas/imunologia , Genótipo , Antígenos HLA/genética , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias
8.
Front Immunol ; 11: 587517, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33123171

RESUMO

Background and Objectives: Understanding the pathophysiology of respiratory failure in coronavirus disease 2019 (COVID-19) is indispensable for development of therapeutic strategies. Since we observed similarities between COVID-19 and interstitial lung disease in connective tissue disease (CTD-ILD), we investigated features of autoimmunity in SARS-CoV-2-associated respiratory failure. Methods: We prospectively enrolled 22 patients with RT-PCR-confirmed SARS-CoV-2 infection and 10 patients with non-COVID-19-associated pneumonia. Full laboratory testing was performed including autoantibody (AAB; ANA/ENA) screening using indirect immunofluorescence and immunoblot. Fifteen COVID-19 patients underwent high-resolution computed tomography. Transbronchial biopsies/autopsy tissue samples for histopathology and ultrastructural analyses were obtained from 4/3 cases, respectively. Results: Thirteen (59.1%) patients developed acute respiratory distress syndrome (ARDS), and five patients (22.7%) died from the disease. ANA titers ≥1:320 and/or positive ENA immunoblots were detected in 11/13 (84.6%) COVID-19 patients with ARDS, in 1/9 (11.1%) COVID-19 patients without ARDS (p = 0.002) and in 4/10 (40%) patients with non-COVID-19-associated pneumonias (p = 0.039). Detection of AABs was significantly associated with a need for intensive care treatment (83.3 vs. 10%; p = 0.002) and occurrence of severe complications (75 vs. 20%, p = 0.03). Radiological and histopathological findings were highly heterogeneous including patterns reminiscent of exacerbating CTD-ILD, while ultrastructural analyses revealed interstitial thickening, fibroblast activation, and deposition of collagen fibrils. Conclusions: We are the first to report overlapping clinical, serological, and imaging features between severe COVID-19 and acute exacerbation of CTD-ILD. Our findings indicate that autoimmune mechanisms determine both clinical course and long-term sequelae after SARS-CoV-2 infection, and the presence of autoantibodies might predict adverse clinical course in COVID-19 patients.


Assuntos
Doenças do Tecido Conjuntivo/patologia , Infecções por Coronavirus/patologia , Doenças Pulmonares Intersticiais/patologia , Pneumonia Viral/patologia , Síndrome Respiratória Aguda Grave/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Betacoronavirus/imunologia , Doenças do Tecido Conjuntivo/imunologia , Infecções por Coronavirus/imunologia , Feminino , Humanos , Pulmão/patologia , Doenças Pulmonares Intersticiais/imunologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/imunologia , Estudos Prospectivos , Síndrome Respiratória Aguda Grave/imunologia
9.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(6): 693-700, 2020 Jun 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-32879127

RESUMO

OBJECTIVES: To evaluate the value of thrombospond in Type I domain-containing 7A (THSD7A) and M-type phospholipase A2 receptor (PLA2R) in primary membranous nephropathy (PMN) and to explore the relationship between their antibody levels and prognosis. METHODS: Renal tissues in 128 patients with membranous nephropathy in the Second Xiangya Hospital of Central South University were collected from February 2015 to August 2017, including 108 patients with primary membranous nephropathy (PMN group) and 20 patients with secondary membranous nephropathy (SMN) (SMN group). Indirect immunofluorescence method was used to detect the expression of PLA2R antigen in kidney tissues,and the glomerular expression of THSD7A antigen was examined by immunohistochemistry and indirect immunofluorescence. The serum levels of anti-PLA2R antibodies and THSD7A antibodies were also detected by ELISA. According to the results of PMN examination,the patients were also divided into a PLA2R-related membranous nephropathy group and a THSD7A-related membranous nephropathy group. RESULTS: The positive rate of PLA2R in the renal tissues in the PMN group was higher than that in the SMN group (78% in the PMN group, 35% in the SMN group, P<0.01),while the positive rate of anti-PLA2R antibody in the PMN group was also higher than that in the SMN group (50% in the PMN group, 25% in the SMN group, P<0.05).The serum level of anti-PLA2R antibody was positively correlated with 24 h urine protein (r=0.254, P<0.05) and negatively correlated with serum albumin (r=-0.236, P<0.05). The expression of THSD7A was positive in glomeruli in 7 cases of the PMN group (6%) by immuno-histochemistry, and which was positive in 1case of the SMN group (5%).The serum levels of anti-THSD7A antibody in the PMN group were higher than those in the SMN group [(0.49±0.26) pg/mL in the PMN group,(0.34±0.27) pg/mL in the SMN group, P<0.05]. There was no difference in the clinical characteristics between the PLA2R-related membranous nephropathy group and the THSD7A-related membranous nephropathy group. CONCLUSIONS: PLA2R and THSD7A are the target antigen of PMN, and the associated autoantibodies are helpful for the differential diagnosis of PMN. The anti-PLA2R antibody levels can reflect the severity of the disease and evaluate the effect of treatment. The incidence of THSD7A membranous nephropathy is low, and monitoring the serum anti-THSD7A antibody levels can assess patients' condition and predict disease outcome.


Assuntos
Glomerulonefrite Membranosa , Receptores da Fosfolipase A2 , Autoanticorpos , Humanos , Imuno-Histoquímica , Trombospondinas
10.
PLoS Med ; 17(9): e1003296, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32960885

RESUMO

BACKGROUND: Based on different genetic and environmental risk factors and histology, it has been proposed that rheumatoid arthritis (RA) consists of 2 types: autoantibody-positive and autoantibody-negative RA. However, until now, this remained hypothetical. To assess this hypothesis, we studied whether the long-term outcomes differed for these 2 groups of RA patients. METHODS AND FINDINGS: In the Leiden Early Arthritis Clinic cohort, 1,285 consecutive RA patients were included between 1993 and 2016 and followed yearly. Treatment protocols in routine care improved over time, irrespective of autoantibody status, and 5 inclusion periods were used as instrumental variables: 1993-1996, delayed mild disease-modifying antirheumatic drug (DMARD) initiation (reference period); 1997-2000, early mild DMARDs; 2001-2005, early methotrexate; 2006-2010, early methotrexate followed by treat-to-target adjustments; 2011-2016, similar to 2006-2010 plus additional efforts for very early referral. Three long-term outcomes were studied: sustained DMARD-free remission (SDFR) (persistent absence of clinical synovitis after DMARD cessation), mortality, and functional disability measured by yearly Health Assessment Questionnaire (HAQ). Treatment response in the short term (disease activity) was measured by Disease Activity Score-28 with erythrocyte sedimentation rate (DAS28-ESR). Linear mixed models and Cox regression were used, stratified for autoantibody positivity, defined as IgG anti-CCP2 and/or IgM rheumatoid factor positivity. In total, 823 patients had autoantibody-positive RA (mean age 55 years, 67% female); 462 patients had autoantibody-negative RA (age 60 years, 64% female). Age, gender, and percentage of autoantibody-positive patients were stable throughout the inclusion periods. Disease activity significantly decreased over time within both groups. SDFR rates increased after introduction of treat-to-target (hazard ratio [HR] 2006-2010 relative to 1993-1996: 3.35 [95% CI 1.46 to 7.72; p = 0.004]; HR 2011-2016: 4.57 [95% CI 1.80 to 11.6; p = 0.001]) in autoantibody-positive RA, but not in autoantibody-negative RA. In autoantibody-positive RA, mortality decreased significantly after the introduction of treat-to-target treatment adjustments (HR 2006-2010: 0.56 [95% CI 0.34 to 0.92; p = 0.023]; HR 2011-2016: 0.33 [95% CI 0.14 to 0.77; p = 0.010]), but not in autoantibody-negative RA (HR 2006-2010: 0.79 [95% CI 0.40 to 1.56; p = 0.50]; HR 2011-2016: 0.36 [95% CI 0.10 to 1.34; p = 0.13]). Similarly, functional disability improved in autoantibody-positive RA for the periods after 2000 relative to 1993-1996 (range -0.16 [95% CI -0.29 to -0.03; p = 0.043] to -0.32 [95% CI -0.44 to -0.20; p < 0.001] units of improvement), but not in autoantibody-negative RA (range 0.10 [95% CI -0.12 to 0.31; p = 0.38] to -0.13 [95% CI -0.34 to 0.07; p = 0.20] units of improvement). Limitations to note were that treatment was not randomized-but it was protocolized and instrumental variable analysis was used to obtain comparable groups-and that a limited spread of ethnicities was included. CONCLUSIONS: Although disease activity has improved in both autoantibody-positive and autoantibody-negative RA in recent decades, the response in long-term outcomes differed. We propose that it is time to subdivide RA into autoantibody-positive RA (type 1) and autoantibody-negative RA (type 2), in the hope that this leads to stratified treatment in RA.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/genética , Adulto , Idoso , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Autoanticorpos/genética , Autoanticorpos/imunologia , Biomarcadores Farmacológicos/sangue , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Índice de Gravidade de Doença
11.
Medicine (Baltimore) ; 99(39): e22341, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991448

RESUMO

RATIONALE: The Goodpasture syndrome is an extremely rare disease, with renal and pulmonary manifestations, and is mediated by anti-glomerular basement membrane (anti-GBM) antibodies. Renal pathological changes are mainly characterized by glomerular crescent formation and linear immunofluorescent staining for immunoglobulin G on the GBM. There are few reports on the atypical course of the syndrome involving serum-negative anti-GBM antibodies. Therefore, we present a case of Goodpasture syndrome that presented with nephrotic-range proteinuria and was seronegative for anti-GBM antibodies. PATIENT CONCERNS: A 38-year-old Chinese man presented with a lung lesion that was discovered by physical examination a month prior to presentation. The chief concern was occasional hemoptysis without fever, cough, chest pain, and edema. DIAGNOSES: Laboratory testing revealed that the urinary protein level and urine erythrocyte count were 7.4 g/24 hours and 144/high-power field (HPF), respectively. Serological testing for anti-GBM antibodies was negative. Chest computed tomography revealed multiple exudative lesions in both lungs, indicating alveolar infiltration and hemorrhage. Electronic bronchoscopy and pathological examination of the alveolar lavage fluid indicated no abnormalities. However, kidney biopsy suggested cellular crescent formation and segmental necrosis of the globuli, with linear IgG and complement C3 deposition on the GBM. These findings were consistent with the diagnosis of anti-GBM antibody nephritis. INTERVENTIONS: The patient underwent 7 sessions of double filtration plasmapheresis. He was also administered with intravenous methylprednisolone and cyclophosphamide. After renal function stabilization, he was discharged under an immunosuppressive regimen comprising of glucocorticoids and cyclophosphamides. OUTCOMES: Three months later, follow-up examination revealed that the 24-hour urine protein had increased to 13 g. Furthermore, the urine erythrocyte count was 243/HPF. After a 6-month follow-up, the patient achieved partial remission, with a proteinuria level of 3.9 g/24 hours and a urine erythrocyte count of 187/HPF. LESSONS: This extremely rare case of Goodpasture syndrome manifested with seronegativity for anti-GBM antibodies and nephrotic-range proteinuria. Our findings emphasize the importance of renal biopsy for the clinical diagnosis of atypical cases. Furthermore, because renal involvement achieved only partial remission despite therapy, early detection and active treatment of the Goodpasture syndrome is necessary to improve the prognosis of patients.


Assuntos
Doença Antimembrana Basal Glomerular/complicações , Doença Antimembrana Basal Glomerular/imunologia , Autoanticorpos/sangue , Proteinúria/etiologia , Administração Intravenosa , Adulto , Assistência ao Convalescente , Doença Antimembrana Basal Glomerular/diagnóstico , Doença Antimembrana Basal Glomerular/terapia , Grupo com Ancestrais do Continente Asiático/etnologia , Complemento C3/metabolismo , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Quimioterapia Combinada , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Hemoptise/diagnóstico , Hemorragia/etiologia , Hemorragia/patologia , Humanos , Imunoglobulina G/metabolismo , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Rim/patologia , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Nefrite/diagnóstico , Nefrite/imunologia , Plasmaferese/métodos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
12.
Rev Prat ; 70(1): 79-87, 2020 Jan.
Artigo em Francês | MEDLINE | ID: mdl-32877037

RESUMO

Autoimmune hemolytic anemias. Autoimmune hemolytic anemias (AIHA) are a rare cause of acquired hemolytic anemia, linked to the presence of an autoantibody directed against one or more antigens expressed on the surface of the red blood cell and certified by a positive direct antiglobulin test (DAT). AIHA can be non regenerative (10-20% of cases) and DAT may be negative (5% of cases). There are two main forms: warm antibodies AIHA (IgG positive TDA +/- C3d) and cold antibodies AIHA (C3d positive TDA), which differ in their underlying causes and treatment. Warm antibodies AIHA are in 50% of cases associated to B-cell chronic lymphoid leukemia, variable common immune deficiency, systemic lupus or drug; the treatment is based on short corticosteroid therapy (3 to 6 months) and rituximab is the 2nd line treatment. Cold antibodies AIHA are of two types: either post-infectious (mycoplasma, EBV), or linked to cold agglutinin disease that is indolent B clonal hemopathy; the treatment is primarily symptomatic and relies on cold protection measures. Corticosteroid therapy and splenectomy are ineffective. In cases of severe anemia, treatment with rituximab alone or in combination with chemotherapy is indicated.


Assuntos
Anemia Hemolítica Autoimune , Anemia Hemolítica , Autoanticorpos , Humanos , Rituximab , Esplenectomia
13.
PLoS One ; 15(9): e0237492, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32877432

RESUMO

Oncimmune's EarlyCDT®-Lung is a simple ELISA blood test that measures seven lung cancer specific autoantibodies and is used in the assessment of malignancy risk in patients with indeterminate pulmonary nodules (IPNs). The objective of this study was to examine the cost-effectiveness of EarlyCDT-Lung in the diagnosis of lung cancer amongst patients with IPNs in addition to CT surveillance, compared to CT surveillance alone which is the current recommendation by the British Thoracic Society guidelines. A model consisting of a combination of a decision tree and Markov model was developed using the outcome measure of the quality adjusted life year (QALY). A life-time time horizon was adopted. The model was parameterized using a range of secondary sources. At £70 per test, EarlyCDT-Lung and CT surveillance was found to be cost-effective compared to CT surveillance alone with an incremental cost-effectiveness ratio (ICER) of less than £2,500 depending on the test accuracy parameters used. It was also found that EarlyCDT-Lung can be priced up to £1,177 and still be cost-effective based on cost-effectiveness acceptance threshold of £20,000 / QALY. Further research to resolve parameter uncertainty, was not found to be of value. The results here demonstrate that at £70 per test the EarlyCDT-Lung will have a positive impact on patient outcomes and coupled with CT surveillance is a cost-effective approach to the management of patients with IPNs. The conclusions drawn from this analysis are robust to realistic variation in the parameters used in the model.


Assuntos
Autoanticorpos/imunologia , Análise Custo-Benefício , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/economia , Nódulos Pulmonares Múltiplos/complicações , Tomografia Computadorizada por Raios X , Progressão da Doença , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/imunologia , Cadeias de Markov , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Probabilidade , Análise de Sobrevida
16.
Eur J Gastroenterol Hepatol ; 32(12): 1523-1526, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32956181

RESUMO

OBJECTIVES: Recent guidelines for celiac disease have allowed a biopsy-free approach in endomysial antibodies (EMAs) positive children with high antitransglutaminase (TGA-IgA) titer [>10 time upper limit of normal (ULN)]. Esophagogastroduodenoscopy is still necessary for diagnosis in children with lower title. Because elective pediatric endoscopy has been substantially shouted down during coronavirus disease (COVID-19) pandemic, many children remained undiagnosed - and therefore untreated - for a long time. We aimed to analyze the feasibility and accuracy of a biopsy-free approach in suspected celiac disease children with TGA-IgA values <10 ULN to facilitate the diagnostic process by avoiding endoscopy. METHODS: In this study cohort, we retrospectively analyzed all biopsy-confirmed diagnosis of celiac disease in our center (between 2014 and 2019). The positive predictive value (PPV) of TGA-IgA titers between 5 and 10 ULN and positive EMA in diagnosing celiac disease were determined. Mucosal atrophy and resolution of symptoms after gluten-free diet (GFD) were considered to confirm initial diagnosis. RESULTS: Of 430 celiac disease patients (F: 274; mean age 7.54 years) diagnosed by endoscopy, 84 (F: 46; mean age 8 years) with TGA-IgA between 5 and 10 ULN and positive EMA were identified. The PPV of TGA-IgA between 5 and 10 ULN and positive EMA was 0.93 (95% confidence interval 0.90-0.96). All these children had a symptom resolution and antibodies normalization after GFD. CONCLUSION: During the COVID-19 outbreak, a temporarily reduction of the TGA-IgA threshold for biopsy-sparing approach seems feasible in EMA positive children with TGA-IgA between 5 and 10 ULN.


Assuntos
Autoanticorpos/sangue , Betacoronavirus , Doença Celíaca/diagnóstico , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Guias de Prática Clínica como Assunto , Transglutaminases/imunologia , Autoanticorpos/imunologia , Biópsia , Doença Celíaca/epidemiologia , Doença Celíaca/imunologia , Criança , Comorbidade , Infecções por Coronavirus/enzimologia , Infecções por Coronavirus/imunologia , Endoscopia do Sistema Digestório , Feminino , Humanos , Masculino , Pandemias , Pneumonia Viral/enzimologia , Pneumonia Viral/imunologia , Estudos Retrospectivos , Transglutaminases/sangue
18.
Science ; 370(6515)2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-32972996

RESUMO

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-ω (IFN-ω) (13 patients), against the 13 types of IFN-α (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.


Assuntos
Autoanticorpos/sangue , Infecções por Coronavirus/imunologia , Interferon Tipo I/imunologia , Interferon alfa-2/imunologia , Pneumonia Viral/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/sangue , Infecções Assintomáticas , Betacoronavirus , Estudos de Casos e Controles , Estado Terminal , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Pandemias
19.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(7): 1029-1035, 2020 Jul 30.
Artigo em Chinês | MEDLINE | ID: mdl-32895158

RESUMO

OBJECTIVE: To investigate the classification of idiopathic inflammatory myopathies (IIM) based on clinical manifestations and myositis- specific antibodies using cluster analysis. METHODS: We retrospectively analyzed the data of patients with IIM admitted in Nanfang Hospital in 2015-2019. The clinical data of the patients including serum creatine kinase (CK), interstitial lung disease (ILD), cancer, and myositis-specific antibodies were collected for two-step cluster analysis to identify the distinct clusters of patients, whose clinical characteristics were subsequently analysed. RESULTS: A total of 71 patients with IIM were included in this study, including 30 (42.3%) with polymyositis (PM), 20 (28.2%) with classic dermatomyositis (DM), 16 (22.5%) with amyopathic dermatomyositis (CADM), and 5 (7.0%) with immune-mediated necrotizing myopathy (IMNM). Two-step cluster analysis identified 3 distinctive subgroups: Cluster 1 of 15 (51.7%) patients characterized by rash, positive anti-MDA5 antibody and hypoproteinemia (P < 0.05) with normal or slightly elevated CK level, mainly corresponding to CADM; Cluster 2 of 4 (57.1%) patients with significantly elevated CK and positive anti-SRP antibody (P < 0.001) corresponding to IMNM; and Cluster 3 of 17 (48.6%) patients consisting primarily of patients with PM, characterized by positivity for anti- aminoacyl transfer RNA synthetases antibodies (P=0.022) corresponding to antisynthetase syndrome (ASS). CONCLUSIONS: Patients with IIM can be divided into 3 subgroups based on their clinical and serological characteristics (especially myositis-specific antibodies), and among them ASS may represent an independent IIM subgroup with unique clinical characteristics.


Assuntos
Miosite , Anticorpos , Autoanticorpos , Dermatomiosite , Humanos , Doenças Pulmonares Intersticiais , Estudos Retrospectivos
20.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(8): 1081-1089, 2020 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-32895186

RESUMO

OBJECTIVE: To investigate the expression of citrullinated epitopes in articular cartilage protein and whether its expression is sufficient to induce anti-citrullinated protein antibody (ACPA) response in mice. METHODS: The experimental group was treated with different concentrations of lipopolysaccharide (LPS), heat-inactivated bacteria (Escherichia coli and Staphylococcus aureus) or specific monoclonal antibody against type Ⅱ collagen to induce citrullination of articular cartilage protein, with PBS as the control. Immunohistochemistry with the monoclonal antibody ACC4 (IgG1) that specifically binds to the citrullinated epitope of cartilage protein was performed for detecting the expression of citrullinated protein, with ACC1 (IgG2a) as a positive control antibody and L243 (IgG2a) and Hy2.15 (IgG1) as the negative isotype control. In the in vivo experiment, SD rats were subjected to injection of different doses of LPS in the right knee (with PBS as the controls in the left knee), and 3 days later frozen sections were prepared for immunohistochemical detection of the expression of citrullinated protein. Models of collagen-induced arthritis (CIA) established in different mouse strains were observed for incidence and severity of CIA. Serum samples collected from these models and the sera from rheumatoid arthritis patients were examined for anti-citrullinated protein antibody, and immunohistochemistry was performed to detect the expression of citrullinated protein in the cartilage of the mouse. RESULTS: The citrullinated CII epitope-specific antibody ACC4 did not bind to articular cartilage tissues with different treatments as compared with the positive control antibody ACC1. The ACC4 antibody and the antibodies from patients with rheumatoid arthritis with high titers of anti-citrullinated protein antibody were capable of binding to the synovial tissue around the articular cartilage of the CIA. Luminex analysis showed that the anti-citrullinated protein antibody was lowly expressed in mouse serum, but the anti-type Ⅱ collagen triple helix structure peptide antibody exhibited strong reactivity. CONCLUSIONS: Mild acute inflammatory response is not enough to cause citrullination of articular cartilage protein, and the expression of specific epitope requires a high-intensity inflammatory response. Inflammatory articular cartilage protein can express citrullinated epitopes in type Ⅱ collagen-induced arthritis in mice, but the expression of citrullinated epitopes is not sufficient to induce an immune response to anti-citrullinated antibodies. Stronger stimulation signals are required to induce an immune response for producing anti-citrullinated protein antibodies.


Assuntos
Cartilagem Articular , Inflamação , Animais , Artrite Experimental , Autoanticorpos , Citrulina , Humanos , Camundongos , Ratos , Ratos Sprague-Dawley
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