The miRNA and mRNA Signatures of Peripheral Blood Cells in Humans Infected with Trypanosoma brucei gambiense

Abstract

Simple, reliable tools for diagnosis of human African Trypanosomiases could ease field surveillance and enhance patient care. In particular, current methods to distinguish patients with (stage II) and without (stage I) brain involvement require samples of cerebrospinal fluid. We describe here an exploratory study to find out whether miRNAs from peripheral blood leukocytes might be useful in diagnosis of human trypanosomiasis, or for determining the stage of the disease. Using microarrays, we measured miRNAs in samples from Trypanosoma brucei gambiense-infected patients (9 stage I, 10 stage II), 8 seronegative parasite-negative controls and 12 seropositive, but parasite-negative subjects. 8 miRNAs (out of 1205 tested) showed significantly lower expression in patients than in seronegative, parasite-negative controls, and 1 showed increased expression. There were no clear differences in miRNAs between patients in different disease stages. The miRNA profiles could not distinguish seropositive, but parasitologically negative samples from controls and results within this group did not correlate with those from the trypanolysis test. Some of the regulated miRNAs, or their predicted mRNA targets, were previously reported changed during other infectious diseases or cancer. We conclude that the changes in miRNA profiles of peripheral blood lymphocytes in human African trypanosomiasis are related to immune activation or inflammation, are probably disease-non-specific, and cannot be used to determine the disease stage. The approach has little promise for diagnostics but might yield information about disease pathology.

Circulating MicroRNAs: Potential and Emerging Biomarkers for Diagnosis of Human Infectious Diseases

“…Therefore, the molecular biomarker such as miRNAs can be used to identify the infection of the trypanosomes or sleeping sickness using peripheral blood leukocytes. However, trypanosomiasis patients have shown the higher expression level of miRNA-193b and miRNA-338 compared to control ( Lueong et al, 2013 ). At present time available molecular tools are very invasive, less sensitive for detection of trypanosomiasis infection.…”

Let-7, ascendant miR-181a

“…In the times of transition from centuries of organ-based to the decades of molecular medicine [2], microRNAs are the odds-on favorites of correlation for diagnosis, prognosis, patient stratification, choice of treatment and prediction of therapeutic efficiency [3e5]. These tiny, about 20 nucleotides long noncoding RNA molecules, that lead to translational repression through imperfect match to messenger RNAs in animal cells wrote one of the most spectacular success stories of modern biology [4,6] e from a neglected curiosity in worms in 1993 to one of the main classes of gene regulatory molecules known to date [6,7].…”

“…Currently, microRNAs maintain close relations with the buzzwords biomarkers and personalized medicine [2]. The reason is that microRNA expression tends to be easily deregulated in a vast array of pathologies and in response to environmental natural and chemical compounds [4,7].…”

“…Diagnosis is still based much on morphological and histopathological features of the tumor plus a handful of protein markers with limited sensitivity and specificity, especially in the case of poorly differentiated tumors, although the determination of tumor subtypes conditions the subsequent treatment decisions [2,3]. A plethora of laboratory studies has shown however that certain microRNA levels correlate not only with precise cancer types, but also with patient survival, risk of recurrence, metastasis, toxicity and the sensitivity to specific drugs [4,5].…”

“…Hence, the quasi-totality of the about 20 ongoing clinical trials focusing on microRNAs (and mainly cancer) are "observational studies", evaluating the concrete usefulness of various microRNas as biomarkers and the US Food and Drug Administration (FDA) consented to the development of kit-assays for microRNA analysis [2,5].…”