Transcriptomic signatures in whole blood of patients who acquire a chronic inflammatory response syndrome (CIRS) following an exposure to the marine toxin ciguatoxin

BMC Medical Genomics

Ritchie C Shoemaker²  Qingzhong Wu¹  James C Ryan¹ 

[1] NOAA Center of Excellence for Oceans and Human Health at Hollings Marine Laboratory, Charleston, SC, USA;Center for Research on Biotoxin-Associated Illnesses, Pocomoke, MD, USA

关键词: Transcriptomics;    Chronic illness;    Chronic inflammation;    Immune;    Ciguatoxin;    HLA;    Gene expression;    Ciguatera;   

Others  :  1161247
DOI  :  10.1186/s12920-015-0089-x

 received in 2014-07-30, accepted in 2015-03-18,  发布年份 2015

【 摘 要 】

Background

Ciguatoxins (CTXs) are polyether marine neurotoxins found in multiple reef-fish species and are potent activators of voltage-gated sodium channels. It is estimated that up to 500,000 people annually experience acute ciguatera poisoning from consuming toxic fish and a small percentage of these victims will develop a chronic, multisymptom, multisystem illness, which can last years, termed a Chronic Inflammatory Response Syndrome (CIRS). Symptoms of ciguatera CIRS include fatigue, cognitive deficits, neurologic deficits, pain and sensitivity to light. There are few treatment options for ciguatera CIRS since little is known about its pathophysiology.

Methods

This study characterizes the transcriptional profile in whole blood of 11 patients with ciguatera-induced CIRS and 11 normal controls run in duplicate using Agilent one color whole genome microarrays. Differential expression was determined by using a combination of moderated t-test p-value and fold change (FC). Significant genes were subjected to gene ontology, principal component analysis and SVM classification. Seven significant genes found by microarray were validated by PCR.

Results

Using a low stringency (p < 0.05 and FC > 1.4) and a high stringency (p < 0.01 and FC > 1.5) filter, the resulting gene sets of 185 and 55, respectively, showed clear separation of cases and controls by PCA as well as 100% classification accuracy by SVM, indicating that the gene profiles can separate patients from controls. PCR results of 7 genes showed a 95% correlation to microarray data. Several genes identified by microarray are important in wound healing (CD9, CD36, vWF and Factor XIII), adaptive immunity (HLA-DQB1, DQB2, IL18R1 and IL5RA) and innate immunity (GZMK, TOLLIP, SIGIRR and VIPR2), overlapping several areas shown to be disrupted in a mouse model of acute exposure to ciguatoxin. Another area of interest was differential expression of long, non-coding sequences, or lncRNA.

Conclusions

Disruptions of innate and adaptive immune mechanisms were recorded at both the genomic and proteomic level. A disruption in the HLA-T cell receptor axis could indicate HLA haplotype sensitivity for this chronic syndrome, as noted in many autoimmune conditions. Taken together, these indicators of illness provide additional insights into pathophysiology and potential therapies.

【 授权许可】

   
2015 Ryan et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

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