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

Abstract

BackgroundCiguatoxins (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.MethodsThis 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.ResultsUsing 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.ConclusionsDisruptions 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12920-015-0089-x) contains supplementary material, which is available to authorized users.

Dysregulated expression of death, stress and mitochondrion related genes in the sciatic nerve of presymptomatic SOD1G93A mouse model of Amyotrophic Lateral Sclerosis

“…After normalization, the probes were tested for differential expression. GeneSpring GX was also used in the statistical analyses of gene expressions between genotypes (SOD1 G93A × wild-type), according to previous publications (Smyth, 2004 ; Fu et al, 2014 ; Yang et al, 2014 ; Ryan et al, 2015 ; Wang et al, 2015 ). Genes with p < 0.05 were considered differentially expressed.…”

An Updated Review of Ciguatera Fish Poisoning: Clinical, Epidemiological, Environmental, and Public Health Management

“…In the effort to develop biomarkers, progress has been made particularly in animal studies [112,113,114,115,116]. In humans, attempts have been made to identify CTX in human blood [335] and other potential markers of effect of CTX exposure [336,337,338], but studies are needed with larger sample sizes, clearly delineated case definitions, confirmatory fish testing across laboratories with appropriate blinding, and replication of candidate biomarkers across multiple study populations.…”

Non-Thyroidal Illness Syndrome in Patients Exposed to Indoor Air Dampness Microbiota Treated Successfully with Triiodothyronine

“…Long-term exposure to molds in water-damaged buildings (WDB) has been associated with numerous health problems including allergic airway symptoms ( 1 – 3 ), fungal sinusitis ( 1 , 2 , 4 ), abnormalities in T and B cells ( 5 – 7 ), infection sensitivity ( 6 , 8 ), asthma ( 9 – 11 ), respiratory infections ( 3 , 11 , 12 ), central and peripheral neuropathy and polyendocrinopathy ( 8 ), neurologic symptoms ( 1 , 4 , 13 ), neuropsychological cognitive dysfunction (CD) ( 14 – 16 ), neuropsychiatric symptoms ( 3 , 14 , 17 ), and chronic fatigue (CF) ( 6 , 14 , 18 ). It is now well established that mold and mycotoxins are important constituents of the milieu in WDB and that they can provoke a huge spectrum of illnesses ( 3 , 8 , 12 , 15 , 18 – 37 ).…”