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1.
Nat Commun ; 13(1): 151, 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013207

RESUMO

Thousands of non-coding variants have been associated with increased risk of human diseases, yet the causal variants and their mechanisms-of-action remain obscure. In an integrative study combining massively parallel reporter assays (MPRA), expression analyses (eQTL, meQTL, PCHiC) and chromatin accessibility analyses in primary cells (caQTL), we investigate 1,039 variants associated with multiple myeloma (MM). We demonstrate that MM susceptibility is mediated by gene-regulatory changes in plasma cells and B-cells, and identify putative causal variants at six risk loci (SMARCD3, WAC, ELL2, CDCA7L, CEP120, and PREX1). Notably, three of these variants co-localize with significant plasma cell caQTLs, signaling the presence of causal activity at these precise genomic positions in an endogenous chromosomal context in vivo. Our results provide a systematic functional dissection of risk loci for a hematologic malignancy.


Assuntos
Linfócitos B/patologia , DNA Intergênico/genética , Predisposição Genética para Doença , Mieloma Múltiplo/genética , Proteínas de Neoplasias/genética , Plasmócitos/patologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica , Linfócitos B/imunologia , Sequência de Bases , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/imunologia , Cromatina/química , Cromatina/imunologia , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/imunologia , DNA Intergênico/imunologia , Regulação Neoplásica da Expressão Gênica , Fatores de Troca do Nucleotídeo Guanina/genética , Fatores de Troca do Nucleotídeo Guanina/imunologia , Humanos , Padrões de Herança , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/patologia , Proteínas de Neoplasias/imunologia , Plasmócitos/imunologia , Polimorfismo Genético , Cultura Primária de Células , Locos de Características Quantitativas , Proteínas Repressoras/genética , Proteínas Repressoras/imunologia , Medição de Risco , Fatores de Elongação da Transcrição/genética , Fatores de Elongação da Transcrição/imunologia
2.
Biomed Res Int ; 2021: 9409836, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33688504

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC), one of the most common primary malignancies, is theoretically an epitope candidate for immune checkpoint inhibitors, and therefore, the identification of HCC biomarkers is important. Structure-specific recognition protein 1 (SSRP1) is involved in almost all chromatin-related processes, including DNA replication, repair, and transcription. However, its role in HCC remains to be elucidated. METHODS: This study investigated the expression of SSRP1 in HCCDB, Oncomine, HPA, and other databases. The prognostic value of SSRP1 in HCC and its relationship with clinical characteristics were then explored using Kaplan-Meier plotter. At the same time, SSRP1 coexpression genes were explored and functionally annotated in the LinkedOmics database. Finally, the correlation between the SSRP1 expression and HCC immune cell infiltration was explored in TIMER and online single-cell sequencing database. RESULTS: Significantly elevated transcriptional and proteomic SSRP1 expressions were found in HCC. Increased SSRP1 mRNA expression was significantly correlated with relevant clinicopathological parameters such as immune cells. Notably, the SSRP1 expression was positively correlated with the infiltration levels of Treg and CD8+ T cells, especially exhausted CD8+ T cells. Interestingly, the SSRP1 expression was higher in both tumor Treg and exhausted CD8+ T cells than in adjacent tissues. CONCLUSION: SSRP1, as a new prognostic marker for HCC, promotes HCC development by influencing the infiltration of depleted CD8+ T cells and may influence the effect of immunotherapy.


Assuntos
Biomarcadores Tumorais/imunologia , Linfócitos T CD8-Positivos/imunologia , Carcinoma Hepatocelular , Proteínas de Ligação a DNA/imunologia , Proteínas de Grupo de Alta Mobilidade/imunologia , Neoplasias Hepáticas , Linfócitos do Interstício Tumoral/imunologia , Proteínas de Neoplasias/imunologia , Fatores de Elongação da Transcrição/imunologia , Linfócitos T CD8-Positivos/patologia , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Linfócitos do Interstício Tumoral/patologia , Masculino , Taxa de Sobrevida
3.
PLoS One ; 14(12): e0226162, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31805175

RESUMO

Although the etiology of multiple sclerosis is not yet understood, it is accepted that its pathogenesis involves both autoimmune and neurodegenerative processes, in which the role of autoreactive T-cells has been elucidated. Instead, the contribution of humoral response is still unclear, even if the presence of intrathecal antibodies and B-cells follicle-like structures in meninges of patients has been demonstrated. Several myelin and non-myelin antigens have been identified, but none has been validated as humoral biomarker. In particular autoantibodies against myelin proteins have been found also in healthy individuals, whereas non-myelin antigens have been implicated in neurodegenerative phase of the disease. To provide further putative autoantigens of multiple sclerosis, we investigated the antigen specificity of immunoglobulins present both in sera and in cerebrospinal fluid of patients using phage display technology in a new improved format. A human brain cDNA phage display library was constructed and enriched for open-read-frame fragments. This library was selected against pooled and purified immunoglobulins from cerebrospinal fluid and sera of multiple sclerosis patients. The antigen library was also screened against an antibody scFv library obtained from RNA of B cells purified from the cerebrospinal fluid of two relapsing remitting patients. From all biopanning a complex of 14 antigens were identified; in particular, one of these antigens, corresponding to DDX24 protein, was present in all selections. The ability of more frequently isolated antigens to discriminate between sera from patients with multiple sclerosis or other neurological diseases was investigated. The more promising novel candidate autoantigens were DDX24 and TCERG1. Both are implicated in RNA modification and regulation which can be altered in neurodegenerative processes. Therefore, we propose that they could be a marker of a particular disease activity state.


Assuntos
RNA Helicases DEAD-box/genética , Imunoglobulina G/metabolismo , Esclerose Múltipla Recidivante-Remitente/genética , Fatores de Elongação da Transcrição/genética , Adulto , Idoso , Autoantígenos/genética , Autoantígenos/imunologia , Linhagem Celular , RNA Helicases DEAD-box/imunologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/sangue , Esclerose Múltipla Recidivante-Remitente/líquido cefalorraquidiano , Fases de Leitura Aberta , Biblioteca de Peptídeos , Fatores de Elongação da Transcrição/imunologia
4.
Cells ; 8(12)2019 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-31775315

RESUMO

The critical aspect in multiple sclerosis (MS) progression involves insufficient regeneration of CNS resulting from deficient myelin synthesis by newly generated oligodendrocytes (OLs). Although many studies have focused on the role of autoreactive lymphocytes in the inflammatory-induced axonal loss, the problem of insufficient remyelination and disease progression is still unsolved. To determine the effect of myelin-specific lymphocytes on OL function in MS patients and in a mouse model of MS, we cultured myelin induced MS CD49d+CD154+ circulating lymphocytes as well as Experimental Autoimmune Encephalomyelitis (EAE) mouse brain-derived T and memory B cells with maturing oligodendrocyte precursor cells (OPCs). We found that myelin-specific CD49d+CD154+ lymphocytes affected OPC maturation toward formation of immune reactive OLs. Newly generated OLs were characterized by imbalanced myelin basic protein (MBP) and proteolipid protein (PLP) production as well as proinflammatory chemokine/cytokine synthesis. The analysis of cellular pathways responsible for OL reprogramming revealed that CD49d+CD154+ lymphocytes affected miRNA synthesis by dysregulation of polymerase II activity. miR-665 and ELL3 turned out to be the main targets of MS myelin-specific lymphocytes. Neutralization of high intracellular miR-665 concentration restored miRNA and MBP/PLP synthesis. Together, these data point to new targets for therapeutic intervention promoting CNS remyelination.


Assuntos
Linfócitos , Esclerose Múltipla , Oligodendroglia , Remielinização , Adulto , Animais , Linhagem Celular , Feminino , Humanos , Linfócitos/imunologia , Linfócitos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/imunologia , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Proteína Básica da Mielina/imunologia , Proteína Proteolipídica de Mielina/imunologia , Oligodendroglia/imunologia , Oligodendroglia/patologia , Fatores de Elongação da Transcrição/imunologia
5.
J Immunol ; 201(10): 3073-3083, 2018 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-30297340

RESUMO

In the transition from B cells to Ab-secreting cells (ASCs) many genes are induced, such as ELL2, Irf4, Prdm1, Xbp1, whereas other mRNAs do not change in abundance. Nonetheless, using splicing array technology and mouse splenic B cells plus or minus LPS, we found that induced and "uninduced" genes can show large differences in splicing patterns between the cell stages, which could influence ASC development. We found that ∼55% of these splicing changes depend on ELL2, a transcription elongation factor that influences expression levels and splicing patterns of ASC signature genes, genes in the cell-cycle and N-glycan biosynthesis and processing pathways, and the secretory versus membrane forms of the IgH mRNA. Some of these changes occur when ELL2 binds directly to the genes encoding those mRNAs, whereas some of the changes are indirect. To attempt to account for the changes that occur in RNA splicing before or without ELL2 induction, we examined the amount of the small nuclear RNA molecules and found that they were significantly decreased within 18 h of LPS stimulation and stayed low until 72 h. Correlating with this, at 18 h after LPS, endoplasmic reticulum stress and Ire1 phosphorylation are induced. Inhibiting the regulated Ire1-dependent mRNA decay with 4u8C correlates with the reduction in small nuclear RNA and changes in the normal splicing patterns at 18 h. Thus, we conclude that the RNA splicing patterns in ASCs are shaped early by endoplasmic reticulum stress and Ire1 phosphorylation and later by ELL2 induction.


Assuntos
Diferenciação Celular/genética , Regulação da Expressão Gênica/imunologia , Ativação Linfocitária/genética , Plasmócitos/citologia , Splicing de RNA/genética , Animais , Linfócitos B/citologia , Linfócitos B/imunologia , Diferenciação Celular/imunologia , Estresse do Retículo Endoplasmático/genética , Estresse do Retículo Endoplasmático/imunologia , Regulação da Expressão Gênica/genética , Ativação Linfocitária/imunologia , Camundongos , Plasmócitos/imunologia , Splicing de RNA/imunologia , RNA Nuclear Pequeno/genética , RNA Nuclear Pequeno/imunologia , Fatores de Elongação da Transcrição/genética , Fatores de Elongação da Transcrição/imunologia
6.
Mol Immunol ; 91: 8-16, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28858629

RESUMO

B cell activation is dependent on a large increase in transcriptional output followed by focused expression on secreted immunoglobulin as the cell transitions to an antibody producing plasma cell. The rapid transcriptional induction is facilitated by the release of poised RNA pol II into productive elongation through assembly of the super elongation complex (SEC). We report that a SEC component, the Eleven -nineteen Lysine-rich leukemia (ELL) family member 3 (ELL3) is dynamically up-regulated in mature and activated human B cells followed by suppression as B cells transition to plasma cells in part mediated by the transcription repressor PRDM1. Burkitt's lymphoma and a sub-set of Diffuse Large B cell lymphoma cell lines abundantly express ELL3. Depletion of ELL3 in the germinal center derived lymphomas results in severe disruption of DNA replication and cell division along with increased DNA damage and cell death. This restricted utilization and survival dependence reveal a key step in B cell activation and indicate a potential therapeutic target against B cell lymphoma's with a germinal center origin.


Assuntos
Linfócitos B/imunologia , Divisão Celular/imunologia , Regulação da Expressão Gênica/imunologia , Fatores de Elongação da Transcrição/imunologia , Divisão Celular/genética , Sobrevivência Celular/genética , Sobrevivência Celular/imunologia , Replicação do DNA/genética , Replicação do DNA/imunologia , Humanos , Células Jurkat , RNA Polimerase II/genética , RNA Polimerase II/imunologia , Fatores de Elongação da Transcrição/genética
7.
Crit Rev Immunol ; 34(6): 481-99, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25597311

RESUMO

B cells can be activated by cognate antigen, anti-B-cell receptor antibody, complement receptors, or polyclonal stimulators like lipopolysaccharide; the overall result is a large shift in RNA processing to the secretory-specific form of immunoglobulin (Ig) heavy chain mRNA and an upregulation of Igh mRNA amounts. Associated with this shift is the large-scale induction of Ig protein synthesis and the unfolded protein response to accommodate the massive quantity of secretory Ig that results. Stimulation to secretion also produces major structural accommodations and stress, with extensive generation of endoplasmic reticulum and Golgi as part of the cellular architecture. Reactive oxygen species can lead to either activation or apoptosis based on context and the high or low oxygen tension surrounding the cells. Transcription elongation factor ELL2 plays an important role in the induction of Ig secretory mRNA production, the unfolded protein response, and gene expression during hypoxia. After antigen stimulation, activated B cells from either the marginal zones or follicles can produce short-lived antibody secreting cells; it is not clear whether cells from both locations can become long-lived plasma cells. Autophagy is necessary for plasma cell long-term survival through the elimination of some of the accumulated damage to the ER from producing so much protein. Survival signals from the bone marrow stromal cells also contribute to plasma cell longevity, with BCMA serving a potentially unique survival role. Integrating the various information pathways converging on the plasma cell is crucial to the development of their long-lived, productive immune response.


Assuntos
Cadeias Pesadas de Imunoglobulinas/biossíntese , Plasmócitos/imunologia , RNA Mensageiro/biossíntese , Resposta a Proteínas não Dobradas/imunologia , Anticorpos/farmacologia , Autofagia/imunologia , Antígeno de Maturação de Linfócitos B/genética , Antígeno de Maturação de Linfócitos B/imunologia , Diferenciação Celular , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Lipopolissacarídeos/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Plasmócitos/citologia , Plasmócitos/efeitos dos fármacos , Plasmócitos/metabolismo , RNA Mensageiro/genética , Receptores de Antígenos de Linfócitos B/genética , Receptores de Antígenos de Linfócitos B/imunologia , Receptores de Complemento/imunologia , Transdução de Sinais , Fatores de Elongação da Transcrição/genética , Fatores de Elongação da Transcrição/imunologia , Resposta a Proteínas não Dobradas/genética
8.
PLoS Genet ; 8(4): e1002675, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22570620

RESUMO

Class-switch recombination (CSR), induced by activation-induced cytidine deaminase (AID), can be divided into two phases: DNA cleavage of the switch (S) regions and the joining of the cleaved ends of the different S regions. Here, we show that the DSIF complex (Spt4 and Spt5), a transcription elongation factor, is required for CSR in a switch-proficient B cell line CH12F3-2A cells, and Spt4 and Spt5 carry out independent functions in CSR. While neither Spt4 nor Spt5 is required for transcription of S regions and AID, expression array analysis suggests that Spt4 and Spt5 regulate a distinct subset of transcripts in CH12F3-2A cells. Curiously, Spt4 is critically important in suppressing cryptic transcription initiating from the intronic Sµ region. Depletion of Spt5 reduced the H3K4me3 level and DNA cleavage at the Sα region, whereas Spt4 knockdown did not perturb the H3K4me3 status and S region cleavage. H3K4me3 modification level thus correlated well with the DNA breakage efficiency. Therefore we conclude that Spt5 plays a role similar to the histone chaperone FACT complex that regulates H3K4me3 modification and DNA cleavage in CSR. Since Spt4 is not involved in the DNA cleavage step, we suspected that Spt4 might be required for DNA repair in CSR. We examined whether Spt4 or Spt5 is essential in non-homologous end joining (NHEJ) and homologous recombination (HR) as CSR utilizes general repair pathways. Both Spt4 and Spt5 are required for NHEJ and HR as determined by assay systems using synthetic repair substrates that are actively transcribed even in the absence of Spt4 and Spt5. Taken together, Spt4 and Spt5 can function independently in multiple transcription-coupled steps of CSR.


Assuntos
Cromatina , Proteínas Cromossômicas não Histona , Reparo do DNA , Recombinação Homóloga , Switching de Imunoglobulina , Imunoglobulinas , Fatores de Elongação da Transcrição , Animais , Antígenos Nucleares/genética , Antígenos Nucleares/metabolismo , Linfócitos B/imunologia , Linfócitos B/metabolismo , Técnicas de Cultura de Células , Cromatina/genética , Cromatina/metabolismo , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/imunologia , Citidina Desaminase/genética , Clivagem do DNA , Reparo do DNA por Junção de Extremidades/genética , Reparo do DNA/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Rearranjo Gênico/imunologia , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Histonas/genética , Histonas/metabolismo , Recombinação Homóloga/genética , Recombinação Homóloga/imunologia , Switching de Imunoglobulina/genética , Switching de Imunoglobulina/imunologia , Imunoglobulinas/genética , Imunoglobulinas/metabolismo , Autoantígeno Ku , Camundongos , Processamento de Proteína Pós-Traducional , Transdução de Sinais , Fatores de Elongação da Transcrição/genética , Fatores de Elongação da Transcrição/imunologia
9.
J Biol Chem ; 286(39): 33795-803, 2011 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-21832080

RESUMO

In plasma cells, immunoglobulin heavy chain (IgH) secretory-specific mRNA is made in high abundance as a result of both increased promoter proximal poly(A) site choice and weak splice-site skipping. Ell2, the eleven-nineteen lysine rich leukemia gene, is a transcription elongation factor that is induced ∼6-fold in plasma cells and has been shown to drive secretory-specific mRNA production. Reducing ELL2 by siRNA, which reduced processing to the secretion-specific poly(A) site, also influenced the methylations of histone H3K4 and H3K79 on the IgH gene and impacted positive transcription factor b (pTEFb), Ser-2 carboxyl-terminal phosphorylation, and polyadenylation factor additions to RNA polymerase II. The multiple lineage leukemia gene (MLL) and Dot1L associations with the IgH gene were also impaired in the absence of ELL2. To investigate the link between histone modifications, transcription elongation, and alternative RNA processing in IgH mRNA production, we performed chromatin immunoprecipitation on cultured mouse B and plasma cells bearing the identical IgH γ2a gene. In the plasma cells, as compared with the B cells, the H3K4 and H3K79 methylations extended farther downstream, past the IgH enhancer to the end of the transcribed region. Thus the downstream H3K4 and H3K79 methylation of the IgH associated chromatin in plasma cells is associated with increased polyadenylation and exon skipping, resulting from the actions of ELL2 transcription elongation factor.


Assuntos
Histonas/metabolismo , Cadeias gama de Imunoglobulina/biossíntese , Plasmócitos/metabolismo , Sinais de Poliadenilação na Ponta 3' do RNA/fisiologia , Transcrição Gênica/fisiologia , Fatores de Elongação da Transcrição/metabolismo , Animais , Linhagem Celular , Cromatina/genética , Cromatina/imunologia , Cromatina/metabolismo , Éxons/fisiologia , Histona-Lisina N-Metiltransferase , Histonas/genética , Histonas/imunologia , Cadeias gama de Imunoglobulina/genética , Cadeias gama de Imunoglobulina/imunologia , Metilação , Camundongos , Proteína de Leucina Linfoide-Mieloide/genética , Proteína de Leucina Linfoide-Mieloide/imunologia , Proteína de Leucina Linfoide-Mieloide/metabolismo , Plasmócitos/citologia , Plasmócitos/imunologia , Poliadenilação/fisiologia , RNA Polimerase II/genética , RNA Polimerase II/imunologia , RNA Polimerase II/metabolismo , RNA Interferente Pequeno/genética , Fatores de Elongação da Transcrição/genética , Fatores de Elongação da Transcrição/imunologia
10.
Nat Immunol ; 10(10): 1102-9, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19749764

RESUMO

Immunoglobulin secretion is modulated by competition between the use of a weak promoter-proximal poly(A) site and a nonconsensus splice site in the final secretory-specific exon of the heavy chain pre-mRNA. The RNA polymerase II transcription elongation factor ELL2, which is induced in plasma cells, enhanced both polyadenylation and exon skipping with the gene encoding the immunoglobulin heavy-chain complex (Igh) and reporter constructs. Lowering ELL2 expression by transfection of heterogenous ribonucleoprotein F (hnRNP F) or small interfering RNA resulted in lower abundance of secretory-specific forms of immunoglobulin heavy-chain mRNA. ELL2 and the polyadenylation factor CstF-64 tracked together with RNA polymerase II across the Igh mu- and gamma-gene segments; the association of both factors was blocked by ELL2-specific small interfering RNA. Thus, loading of ELL2 and CstF-64 on RNA polymerase II was linked, caused enhanced use of the proximal poly(A) site and was necessary for processing of immunoglobulin heavy-chain mRNA.


Assuntos
Cadeias Pesadas de Imunoglobulinas/genética , Cadeias Pesadas de Imunoglobulinas/metabolismo , Plasmócitos/metabolismo , Precursores de RNA/genética , Processamento Pós-Transcricional do RNA/imunologia , Fatores de Elongação da Transcrição/imunologia , Animais , Fator Estimulador de Clivagem/genética , Fator Estimulador de Clivagem/imunologia , Fator Estimulador de Clivagem/metabolismo , Camundongos , Análise de Sequência com Séries de Oligonucleotídeos , Plasmócitos/imunologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Elongação da Transcrição/genética , Fatores de Elongação da Transcrição/metabolismo , Transfecção
11.
Proc Natl Acad Sci U S A ; 104(44): 17494-9, 2007 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-17954908

RESUMO

Ovarian cancer is a leading cause of deaths, yet many aspects of the biology of the disease and a routine means of its detection are lacking. We have used protein microarrays and autoantibodies from cancer patients to identify proteins that are aberrantly expressed in ovarian tissue. Sera from 30 cancer patients and 30 healthy individuals were used to probe microarrays containing 5,005 human proteins. Ninety-four antigens were identified that exhibited enhanced reactivity from sera in cancer patients relative to control sera. The differential reactivity of four antigens was tested by using immunoblot analysis and tissue microarrays. Lamin A/C, SSRP1, and RALBP1 were found to exhibit increased expression in the cancer tissue relative to controls. The combined signals from multiple antigens proved to be a robust test to identify cancerous ovarian tissue. These antigens were also reactive with tissue from other types of cancer and thus are not specific to ovarian cancer. Overall our studies identified candidate tissue marker proteins for ovarian cancer and demonstrate that protein microarrays provide a powerful approach to identify proteins aberrantly expressed in disease states.


Assuntos
Neoplasias Ovarianas/metabolismo , Proteínas/metabolismo , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/metabolismo , Autoanticorpos/sangue , Autoanticorpos/imunologia , Autoantígenos/imunologia , Autoantígenos/metabolismo , Biomarcadores Tumorais/metabolismo , Proteínas de Ligação a DNA/imunologia , Feminino , Proteínas de Grupo de Alta Mobilidade/imunologia , Humanos , Estadiamento de Neoplasias , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/patologia , Análise Serial de Proteínas , Sensibilidade e Especificidade , Células Estromais/metabolismo , Análise Serial de Tecidos , Fatores de Elongação da Transcrição/imunologia
12.
Lupus ; 13(6): 463-8, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15303574

RESUMO

Antibodies (Abs) against the structure specific recognition protein 1 (SSRP1) were reported in a small systemic lupus erythematosus (SLE) series but not in other systemic autoimmune diseases. The aim of the study was to confirm the selective presence of anti-SSRP1 Abs in a larger SLE series and to evaluate their relationship with disease activity and other immune markers. Anti-SSRP1 Abs were investigated by a 'home made' ELISA in: 120 SLE, 65 rheumatoid arthritis (RA), 51 systemic sclerosis (SSc), 23 Churg-Strauss syndrome (CSS) and 40 idiopathic autoimmune urticaria (IAU) patients and 190 healthy controls. Sera from MRL lpr/lpr and Balb-c mice were also tested. Anti-SSRP1 Abs were detected in 43 SLE (35.8%), nine SSc (17.6%), eight RA (12.3%), six IAU (15%), three CSS (13%) patients and five healthy controls (2.6%). Antibody prevalence and titers were significantly higher in SLE patients than in sera from both normal and disease controls. Anti-SSRP1 Ab activity was also detected in sera from MRL lpr/lpr but not Balb-c mice. The antibodies did not correlate with the disease activity evaluated as the ECLAM index score and were more prevalent in patients without renal involvement. No correlation was found with other serum autoantibodies. Our results confirm that anti-SSRP1 Abs are associated with but not specific for the lupus disease.


Assuntos
Autoanticorpos/sangue , Proteínas de Ligação a DNA/imunologia , Proteínas de Grupo de Alta Mobilidade/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Fatores de Elongação da Transcrição/imunologia , Adolescente , Adulto , Idoso , Animais , Modelos Animais de Doenças , Feminino , Humanos , Lúpus Eritematoso Sistêmico/sangue , Masculino , Camundongos , Pessoa de Meia-Idade , Prevalência
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