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CCR6+ Th cell distribution differentiates systemic lupus erythematosus patients based on anti-dsDNA antibody status.

ABSTRACT: Background:Systemic lupus erythematosus (SLE) disease has been shown to be associated with the generation of multiple auto-antibodies. Among these, anti-dsDNA antibodies (anti-DNAs) are specific and play a pathogenic role in SLE. Indeed, anti-DNA+ SLE patients display a worse disease course. The generation of these pathogenic anti-DNAs has been attributed to the interaction between aberrant T helper (Th) cells and autoimmune B cells. Thus, in this study we have investigated whether CCR6+Th cells have the ability to differentiate SLE patients based on anti-DNA status, and if their distribution has any correlation with disease activity. Methods:We recruited 25 anti-DNA+ and 25 anti-DNA- treatment-naive onset SLE patients, matched for various clinical characteristics in our nested matched case-control study. CCR6+ Th cells and their additional subsets were analyzed in each patient by flow cytometry. Results:Anti-DNA+ SLE patients specifically had a higher percentage of Th cells expressing CCR6 and CXCR3. Further analysis of CCR6+ Th cell subsets showed that anti-DNA+ SLE patients had elevated proportions of Th9, Th17, Th17.1 and CCR4/CXCR3 double-negative (DN) cells. However, the proportions of CCR6- Th subsets, including Th1 and Th2 cells, did not show any association with anti-DNA status. Finally, we identified a correlation between CCR6+ Th subsets and clinical indicators, specifically in anti-DNA+ SLE patients. Conclusions:Our data indicated that CCR6+ Th cells and their subsets were elevated and correlated with disease activity in anti-DNA+ SLE patients. We speculated that CCR6+ Th cells may contribute to distinct disease severity in anti-DNA+ SLE patients.

SUBMITTER: Zhong W

PROVIDER: S-EPMC5808313 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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CCR6<sup>+</sup> Th cell distribution differentiates systemic lupus erythematosus patients based on anti-dsDNA antibody status.

Zhong Wei W Jiang Zhenyu Z Wu Jiang J Jiang Yanfang Y Zhao Ling L

PeerJ 20180209

<h4>Background</h4>Systemic lupus erythematosus (SLE) disease has been shown to be associated with the generation of multiple auto-antibodies. Among these, anti-dsDNA antibodies (anti-DNAs) are specific and play a pathogenic role in SLE. Indeed, anti-DNA<sup>+</sup> SLE patients display a worse disease course. The generation of these pathogenic anti-DNAs has been attributed to the interaction between aberrant T helper (Th) cells and autoimmune B cells. Thus, in this study we have investigated wh ...[more]

PMID: 29441231

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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

CCR6+ Th cell distribution differentiates systemic lupus erythematosus patients based on anti-dsDNA antibody status.

Publications

CCR6<sup>+</sup> Th cell distribution differentiates systemic lupus erythematosus patients based on anti-dsDNA antibody status.

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