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Leukocyte Beta-Catenin Expression Is Disturbed in Systemic Lupus Erythematosus.

ABSTRACT: Wnt/?-catenin signaling is relatively understudied in immunity and autoimmunity. ?-catenin blocks inflammatory mediators and favors tolerogenic dendritic cell (DC) phenotypes. We show here that leukocytes from lupus-prone mice and SLE patients express diminished ?-catenin transcriptional activity, particularly in myeloid cells, although other leukocytes revealed similar trends. Serum levels of DKK-1, an inhibitor under transcriptional control of Wnt/?-catenin, were also decreased in lupus-prone mice. Surprisingly, however, preemptive deletion of ?-catenin from macrophages appears to have no effect on lupus development, even in mice with varying genetic loads for lupus. Although myeloid-specific loss of ?-catenin does not seem to be important for lupus development, the potential role of this transcription factor in other leukocytes and renal cells remain to be elucidated.

SUBMITTER: Orme JJ

PROVIDER: S-EPMC4993388 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Leukocyte Beta-Catenin Expression Is Disturbed in Systemic Lupus Erythematosus.

Orme Jacob J JJ Du Yong Y Vanarsa Kamala K Wu Tianfu T Satterthwaite Anne B AB Mohan Chandra C

PloS one 20160822 8

Wnt/β-catenin signaling is relatively understudied in immunity and autoimmunity. β-catenin blocks inflammatory mediators and favors tolerogenic dendritic cell (DC) phenotypes. We show here that leukocytes from lupus-prone mice and SLE patients express diminished β-catenin transcriptional activity, particularly in myeloid cells, although other leukocytes revealed similar trends. Serum levels of DKK-1, an inhibitor under transcriptional control of Wnt/β-catenin, were also decreased in lupus-prone ...[more]

PMID: 27548498

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Project description:The diagnosis of Systemic Lupus Erythematosus (SLE) is challenging due to its heterogeneous clinical presentation and lack of robust biomarkers for laboratory testing to distinguish it from other autoimmune or infectious diseases. Current diagnostic criterion relies on a combination of clinical examination and laboratory tests, and it does not readily distinguish between those with active clinical disease from those that are clinically quiescent. Several groups have attempted to apply emerging high throughput profiling technologies to diagnose SLE. Despite showing promising diagnostic potential, many of them are expensive and technically challenging for routine clinical uses. Here we report a pilot study of applying a technically simple and highly customisable leukocyte capture antibody microarray to profile healthy (n=24) and SLE patients (n=60) of various disease activities. Our analysis reveals a set of surface antigen biomarkers that have significant association with SLE. In addition, we present a computational method to calculate a score from the entire microarray profile to obtain a score that correlate most reliably with SLE disease activity. Although the current version of our microarray alone does not match the discriminatory power of the standard laboratory tests (serum dsDNA, complements C3 and C4), the combination of the two yields a test with significantly increased discriminatory ability than what can be achieved individually. This work paves the way for a customised SLE-specific antibody microarray for accurate diagnosis and monitoring of SLE that can be readily translated to routine clinical use. Blood samples were collected from 60 patients of Systemic Lupus Erythematosus (SLE) of different disease activity (11 active, 16 semi-active, and 33 inactive), and compared it with blood samples from 24 healthy blood donors. For each subject, we extracted PBMCs and apply them to a leukocyte capture antibody microarray. The microarray was then scaned by a DotScan™ slide reader (Medsaic; Eveleigh, NSW, Australia). The number of immobilized cells was proportional to the light scattered at each antibody spot. Binding of PBMCs to each antibody dot was monitored by light scatter and averaged between the duplicate spots on each slide. We then performed statistical analysis to identify CD antigen markers that are associated with SLE, as well as determining the potential diagnostic ability of this microarray for SLE.

Dataset Information

Leukocyte Beta-Catenin Expression Is Disturbed in Systemic Lupus Erythematosus.

Publications

Leukocyte Beta-Catenin Expression Is Disturbed in Systemic Lupus Erythematosus.

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