# Human Leukocyte Antigen-G is enriched in presence of trypanosome in the dermis of individuals exposed to gambiense Human African Trypanosomiasis in Guinea and Côte d’Ivoire

## TL;DR

This study shows that HLA-G, an immune molecule, is linked to trypanosome presence in the skin and could help detect sleeping sickness.

## Contribution

First evidence of HLA-G's role in the skin's immune response to trypanosome infection and its potential as a tissue biomarker.

## Key findings

- HLA-G levels in blood confirm its role as a biomarker for T. b. gambiense infection.
- Granular HLA-G patterns in skin correlate with trypanosome presence.
- Diffuse HLA-G halos in skin correlate with higher plasma HLA-G levels.

## Abstract

Human leukocyte antigen-G (HLA-G) is an immunomodulatory molecule known to play a crucial role in immune tolerance and regulation. In the context of human African trypanosomiasis (HAT), higher soluble HLA-G levels were detected in the plasma of confirmed cases, representing a serological marker of T. b. gambiense infection. As trypanosomes also invade extravascular tissues, especially the skin, this study explored the potential role of HLA-G in the dermal immune response during T. b. gambiense infection. Blood and skin samples from 50 seronegative individuals, 45 seropositive suspects and 36 confirmed HAT cases, collected between 2018 and 2022 in endemic foci of Guinea and Côte d’Ivoire, were analyzed. Plasmatic and dermal levels of HLA-G proteins were quantified by ELISA and immuno-histochemistry, respectively, and compared to the trypanosome detection results in the same samples. The implication of soluble HLA-G plasma level as a biomarker of T. b. gambiense infection was confirmed. In the dermis, HLA-G isoforms were expressed either with a granular distribution or with in diffuse halos. Granular patterns of dermal HLA-G were directly associated with the presence of trypanosomes in the dermis. The presence of diffuse halos was correlated to higher sHLA-G levels in the plasma. In total, this study provides the first evidence of the involvement of HLA-G in the extravascular immune response against parasites, especially in the skin. It shows that HLA-G distribution in the extravascular compartment also represents a biomarker of trypanosome infection.

Human leukocyte antigen-G (HLA-G) is a molecule known to play a crucial role in immune regulation. In the context of sleeping sickness, higher soluble HLA-G levels were previously detected in the blood of confirmed cases. As trypanosomes also invade tissues, this study explored the potential role of HLA-G in the immune response against trypanosomes in the skin. Blood and skin samples from 50 negative controls, 45 suspects and 36 confirmed cases of sleeping sickness, collected between 2018 and 2022 in Guinea and Côte d’Ivoire, were analyzed. Blood and skin levels of HLA-G were quantified and compared to the trypanosome detection results in the same samples. The implication of soluble HLA-G level in blood as a biomarker of T. b. gambiense infection was confirmed. HLA-G isoforms were expressed either with a granular distribution or in diffuse halos in the dermis. Granules were directly associated with presence of trypanosomes in the dermis whereas diffuse halos were correlated to higher HLA-G levels in the plasma. In total, this study provides the first evidence of the involvement of HLA-G in the immune response against parasites in tissues, especially in the skin. It shows that HLA-G distribution in tissues also represents a biomarker of the infection.