RESUMO
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is characterized by defective immune tolerance combined with immune cell hyperactivity resulting in the production of pathogenic autoantibodies. Previous gene expression studies employing whole blood or peripheral blood mononuclear cells (PBMC) have demonstrated that a majority of patients with active disease have increased expression of type I interferon (IFN) inducible transcripts known as the IFN signature. The goal of the current study was to assess the gene expression profiles of isolated leukocyte subsets obtained from SLE patients. Subsets including CD19(+) B lymphocytes, CD3(+)CD4(+) T lymphocytes and CD33(+) myeloid cells were simultaneously sorted from PBMC. The SLE transcriptomes were assessed for differentially expressed genes as compared to healthy controls. SLE CD33(+) myeloid cells exhibited the greatest number of differentially expressed genes at 208 transcripts, SLE B cells expressed 174 transcripts and SLE CD3(+)CD4(+) T cells expressed 92 transcripts. Only 4.4% (21) of the 474 total transcripts, many associated with the IFN signature, were shared by all three subsets. Transcriptional profiles translated into increased protein expression for CD38, CD63, CD107a and CD169. Moreover, these studies demonstrated that both SLE lymphoid and myeloid subsets expressed elevated transcripts for cytosolic RNA and DNA sensors and downstream effectors mediating IFN and cytokine production. Prolonged upregulation of nucleic acid sensing pathways could modulate immune effector functions and initiate or contribute to the systemic inflammation observed in SLE.
Assuntos
Linfócitos B/metabolismo , Interferons/genética , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/genética , Células Mieloides/metabolismo , Subpopulações de Linfócitos T/metabolismo , Transcriptoma/genética , Adulto , Linfócitos B/patologia , DNA/metabolismo , Feminino , Perfilação da Expressão Gênica , Humanos , Interferons/metabolismo , Lúpus Eritematoso Sistêmico/imunologia , Pessoa de Meia-Idade , Células Mieloides/patologia , Análise de Sequência com Séries de Oligonucleotídeos , RNA/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reprodutibilidade dos Testes , Subpopulações de Linfócitos T/patologia , Regulação para Cima/genética , Adulto JovemRESUMO
We describe a case of simultaneous severe lupus enteritis and lupus cystitis in a 38-year-old female with a 21-year history of systemic lupus erythematosus (SLE). The patient presented with acute abdominal pain, decreased urinary output, associated low-grade fever, nausea, and diarrhea. She had serologic evidence of an SLE flare with acute renal insufficiency. Computed tomography examination revealed dramatic edema of the large- and small-bowel walls with no evidence of bowel loop dilatation or pneumatosis intestinalis, marked diffuse thickening of the urinary bladder wall, and bilateral hydronephrosis and hydroureter. Lupus enteritis and lupus cystitis were diagnosed and treatment with intravenous corticosteroids led to prompt resolution of the abdominal pain and normalization of renal function. Because infarction of tissue and bowel rupture are potentially fatal complications, it is essential to consider lupus enteritis in SLE patients who present with abdominal pain. This case demonstrates that once lupus enteritis is suspected, coexistent lupus cystitis must also be considered.