Cutaneous diagnosis of late Lyme borreliosis – DIABOLYC
Lyme borreliosis is the first vector-borne disease in the Northern Hemisphere. It is a bacterial infection transmitted by a hard tick, Ixodes. In the physiopathology of the disease, the skin is an essential interface since there, the tick inoculates the bacterium, Borrelia, which multiplies locally and then spreads to the target organs: the joint, heart, nervous system and the distant skin. Despite this dissemination, a number of bacteria persist in the skin for several months in the absence of antibiotic treatment, at least in the mouse model. This skin persistence is not established yet in humans. Antibiotic treatment for 2 to 3 weeks is usually sufficient to eradicate the bacteria from the body. The current diagnosis is based mainly on a patient's clinical examination coupled to a two-step serology (ELISA and Western Blot). Direct diagnosis relies on bacterial culture, often long and tedious, and PCR. Generally, early diagnosis will pose any problem because of the pathognomonic sign of the disease: the erythema migrans. However, this event is not present in all patients: only 80% of the population has this clinical manifestation. Late diagnosis is more complex given the multitude of organs targeted by the bacteria. In some patients, are described chronic Lyme disease or disease refractory to antibiotics, but these two concepts are controversial and seems to be very subjective since no live organisms are detected.
To elucidate possible persistence of the bacteria in the host, we have first developed a targeted proteomic approach using Selected Reaction Monitoring (SRM) mass spectrometry that detected bacterial proteins in the skin during early infection on mouse model. This method has been further validated in few patients at the early stage of the disease (erythema migrans). Now we plan to detect markers of active infection in disseminated infections. The persistence of the bacteria in the animal in the skin should allow us to detect markers of late infection in mice. We will then validate this hypothesis in patients with disseminated infections. In case the protein detection fails in the skin, we will look for late infection markers in cerebrospinal fluid (neuroborreliosis) or in the synovial liquid /membrane in articular manifestations.
Madame Nathalie BOULANGER (Virulence Bactérienne Précoce - Université de Strasbourg)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
IPHC - LSMBO Institut Pluridisciplinaire Hubert Curien - Laboratoire de Spectrométrie de Masse BioOrganique
Groupe Borréliose de Lyme - UNISTRA Virulence Bactérienne Précoce - Université de Strasbourg
Help of the ANR 352,080 euros
Beginning and duration of the scientific project: September 2016 - 36 Months