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Title: Immune correlates of SLE
Keywords: Systemic lupus erythematosus, Magnetic cell separation, microarray, gene expression, prognostic subgroups, IL-7R
Issue Date: 29-Dec-2008
Citation: NEDA SALEHI (2008-12-29). Immune correlates of SLE. ScholarBank@NUS Repository.
Abstract: AbstractSystemic lupus erythematosus (SLE) is a systemic autoimmune disease which is chronic, debilitating and may have life-threatening manifestations, such as renal failure or cerebral involvement. It is 4-8 times more common in Chinese compared to Caucasians and predominantly affects young women. A lack of clear evidence to direct patient-targeted therapy, prognostic indices and treatment duration potentially expose more patients to longer period of toxic treatments. Both disease and treatment-related morbidity remain high while heterogeneity of clinical features is reflected by variability in both the presence and levels of a wide range of tested biomarkers. Much of the substantial morbidity and mortality caused by the disease and by the toxic immunosuppressive therapy could be avoided if biomarkers were available to allow therapy to be tailored to the individual patient.Two distinct prognostic subgroups have been identified in CD4 T cells by our collaborators in Cambridge University (termed 4.1/4.2) in both SLE patients and controls. These subgroups predicted clinical outcome in SLE patients. Clinical follow up showed that in patients, these two subgroups correlate with the relapse rate of the disease. Patients belonging to subgroup 4.1 experience more severe disease than patients in subgroup 4.2.We have used a cell separation stage in microarray protocol in order to identify gene expression signatures in SLE patients and healthy controls of Chinese ethnicity from Singapore, to compare the gene expression profile with those found in the Cambridge cohort.Microarray analysis showed that the transcriptional signature defining the poor prognosis group (4.1), was enriched for genes associated with the IL-7R signalling pathway. A similar transcriptional signature defined 2 subgroups of the normal population. These findings may help personalise therapy in SLE and perhaps in other autoimmune diseases. Its existence in the normal population in addition to the patients raises the possibility that it might control immunity more broadly, for example in responses to infection.
Appears in Collections:Master's Theses (Open)

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