RESUMO
Although complexin 1 (CPLX1) is not known as an inflammation factor, recent identification of a complexin 1 (CPLX1) polymorphism in Behçet's disease (BD) has sparked an interest in the role of this molecule in autoinflammation. DNA samples were isolated from peripheral blood mononuclear cells (PBMC) of BD and neuro-Behçet's disease (NBD) patients and expression levels of CPLX1 and miR-185, a predicted target miRNA for CPLX1 and an inflammation-related miRNA, were investigated by real time PCR assays. PBMC expression levels of CPLX1 were significantly increased in BD and NBD patients. By contrast, levels of miR-185 were reduced in both patient groups. A moderate inverse correlation was found between levels of CPLX1 and miR-185. No correlation could be found between expression levels and clinical features of patients. Significant expression alterations of CPLX1 in BD and NBD patients suggest that this molecule has a proinflammatory action. The putative role of CPLX1 in BD pathogenesis remains to be further studied.
Assuntos
Proteínas Adaptadoras de Transporte Vesicular/sangue , Síndrome de Behçet/sangue , MicroRNAs/sangue , Proteínas do Tecido Nervoso/sangue , Doenças do Sistema Nervoso/sangue , Proteínas Adaptadoras de Transporte Vesicular/genética , Adolescente , Adulto , Síndrome de Behçet/genética , Feminino , Técnicas de Genotipagem , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Doenças do Sistema Nervoso/genética , Polimorfismo de Nucleotídeo Único , Reação em Cadeia da Polimerase em Tempo Real , Índice de Gravidade de Doença , Adulto JovemRESUMO
OBJECTIVE: To identify an antibody biomarker for prediction of conversion from radiologically isolated syndrome (RIS) to relapsing remitting multiple sclerosis (RRMS). METHODS: Sera of 13 RIS patients were screened by a protein macroarray derived from human fetal brain cDNA library. RESULTS: Sequencing of a clone with the highest signal intensity revealed sorcin as a potential target autoantigen in RIS patients. ELISA studies showed high-titer sorcin-antibodies in 3 of 4 RIS patients who converted to RRMS in a 5-year follow-up period and 13 of 23 control RRMS patients. CONCLUSION: The value of sorcin antibody as a predictor of conversion from RIS to RRMS requires to be tested in larger prospective studies.
Assuntos
Proteínas de Ligação ao Cálcio/imunologia , Imunoglobulina G/sangue , Esclerose Múltipla Recidivante-Remitente/sangue , Adulto , Biomarcadores/sangue , Feminino , Humanos , Masculino , Esclerose Múltipla Recidivante-Remitente/imunologia , SíndromeRESUMO
OBJECTIVE: This study was conducted to identify a biomarker for multiple sclerosis (MS) that can be used as a predictor of relapse and disability. MATERIALS AND METHODS: Sera of 26 consecutive relapsing-remitting MS (RRMS) patients were screened for switch-associated protein 70 (SWAP-70) antibody, which was previously identified by protein macroarray. The serum levels of several cytokines, chemokines and soluble adhesion molecules related to MS attacks were measured by enzyme-linked immunosorbent assay (ELISA). A possible correlation was sought among levels of SWAP-70 antibody, measured humoral factors and disability scores. RESULTS: ELISA studies showed high-titre SWAP-70 antibodies in 16 (61.5%) RRMS sera obtained during the attack period and 9 (34.6%) sera obtained during remission. There was a significant inverse correlation between SWAP-70 antibody levels and expanded disability status scale scores, CXCL10, soluble VCAM-1, CXCL13 and soluble VLA-4 levels. CONCLUSION: Our results showed that SWAP-70 antibodies could potentially be utilized as relapse and prognostic biomarkers in MS. Whether or not SWAP-70 antibodies have any effect on disease mechanisms requires further investigation.
Assuntos
Proteínas de Ligação a DNA/imunologia , Fatores de Troca do Nucleotídeo Guanina/imunologia , Esclerose Múltipla Recidivante-Remitente/imunologia , Proteínas Nucleares/imunologia , Adulto , Biomarcadores , Citocinas/imunologia , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Antígenos de Histocompatibilidade MenorRESUMO
Efforts for the identification of diagnostic autoantibodies for neuro-Behcet's disease (NBD) have failed. Screening of NBD patients' sera with protein macroarray identified mitochondrial carrier homolog 1 (Mtch1), an apoptosis-related protein, as a potential autoantigen. ELISA studies showed serum Mtch1 antibodies in 68 of 144 BD patients with or without neurological involvement and in 4 of 168 controls corresponding to a sensitivity of 47.2% and specificity of 97.6%. Mtch1 antibody positive NBD patients had more attacks, increased disability and lower serum nucleosome levels. Mtch1 antibody might be involved in pathogenic mechanisms of NBD rather than being a coincidental byproduct of autoinflammation.
Assuntos
Autoanticorpos/biossíntese , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/imunologia , Proteínas de Membrana/imunologia , Proteínas Mitocondriais/imunologia , Adulto , Animais , Autoanticorpos/sangue , Síndrome de Behçet/etiologia , Biomarcadores/sangue , Feminino , Humanos , Masculino , Proteínas de Membrana/sangue , Proteínas Mitocondriais/sangue , Nucleossomos/imunologia , Nucleossomos/metabolismo , RatosRESUMO
BACKGROUND/AIMS: To better characterize progressive encephalomyelitis with rigidity and myoclonus (PERM) syndrome and identify novel PERM phenotypes. METHODS: The clinical features and antibody status of PERM patients were investigated using immunoblots, cell-based assays, RIA, protein macroarray and ELISA. RESULTS: Two patients with supratentorial involvement showed abnormal PET or EEG findings. One patient was discovered to have renal cell carcinoma, and protein macroarray revealed Ma3-antibodies. Another patient with leucine-rich, glioma-inactivated 1 (LGI1) and glutamic acid decarboxylase (GAD) antibodies showed a good response to immunotherapy. CONCLUSION: The heterogeneity of the immunological features suggests that PERM is caused by diverse pathogenic mechanisms. Seropositivity to well-characterized neuronal cell surface antigens might indicate a good treatment response.
Assuntos
Autoanticorpos/sangue , Encefalomielite/sangue , Encefalomielite/complicações , Rigidez Muscular/sangue , Rigidez Muscular/complicações , Mioclonia/sangue , Mioclonia/complicações , Idoso , Encefalomielite/tratamento farmacológico , Ensaio de Imunoadsorção Enzimática , Glutamato Descarboxilase/imunologia , Células HEK293 , Humanos , Imunossupressores/uso terapêutico , Peptídeos e Proteínas de Sinalização Intracelular , Canais Iônicos/imunologia , Masculino , Proteínas de Membrana/imunologia , Pessoa de Meia-Idade , Rigidez Muscular/tratamento farmacológico , Mioclonia/terapia , Proteínas do Tecido Nervoso/imunologia , Análise Serial de Proteínas , Proteínas/imunologia , TransfecçãoRESUMO
OBJECTIVE: To identify an antibody biomarker for multiple sclerosis (MS) that can be used as a predictor of MS relapses. METHODS: MS patients' sera were screened by a protein macroarray derived from human fetal brain cDNA library (hEX1). Sera of 90 consecutive relapsing remitting MS (RRMS) patients and age-matched 145 Behçet's disease (BD) patients, 40 infectious meningoencephalitis patients, and 70 healthy controls were screened by ELISA for serum antibodies against the selected clone. RESULTS: Sequencing of the clone with the highest signal intensity revealed switch-associated protein 70 (SWAP70) as a potential target autoantigen in RRMS. ELISA studies showed high-titer SWAP70-antibodies in 21 (23.3 %) RRMS and 7 (4.8 %) BD patients. SWAP70 antibodies were more likely to be found positive in sera obtained during or shortly after a relapse. CONCLUSION: Detection of SWAP70 antibodies during the attack period might suggest that SWAP70 is involved in MS relapse pathogenesis. Whether serum SWAP70 antibody detection may be utilized as an MS relapse predictor should be tested in prospective studies.