TY  - JOUR
A1  - Bumiller-Bini Hoch, Valéria
A1  - Kohler, Ana Flávia
A1  - Augusto, Danillo G.
A1  - Lobo-Alves, Sara Cristina
A1  - Malheiros, Danielle
A1  - Cipolla, Gabriel Adelman
A1  - Winter Boldt, Angelica Beate
A1  - Braun-Prado, Karin
A1  - Wittig, Michael
A1  - Franke, Andre
A1  - Pföhler, Claudia
A1  - Worm, Margitta
A1  - van Beek, Nina
A1  - Goebeler, Matthias
A1  - Sárdy, Miklós
A1  - Ibrahim, Saleh
A1  - Busch, Hauke
A1  - Schmidt, Enno
A1  - Hundt, Jennifer Elisabeth
A1  - Araujo-Souza, Patrícia Savio de
A1  - Petzl-Erler, Maria Luiza
T1  - Genetic associations and differential mRNA expression levels of host genes suggest a viral trigger for endemic pemphigus foliaceus
JF  - Viruses
N2  - The long search for the environmental trigger of the endemic pemphigus foliaceus (EPF, fogo selvagem) has not yet resulted in any tangible findings. Here, we searched for genetic associations and the differential expression of host genes involved in early viral infections and innate antiviral defense. Genetic variants could alter the structure, expression sites, or levels of the gene products, impacting their functions. By analyzing 3063 variants of 166 candidate genes in 227 EPF patients and 194 controls, we found 12 variants within 11 genes associated with differential susceptibility (p < 0.005) to EPF. The products of genes TRIM5, TPCN2, EIF4E, EIF4E3, NUP37, NUP50, NUP88, TPR, USP15, IRF8, and JAK1 are involved in different mechanisms of viral control, for example, the regulation of viral entry into the host cell or recognition of viral nucleic acids and proteins. Only two of nine variants were also associated in an independent German cohort of sporadic PF (75 patients, 150 controls), aligning with our hypothesis that antiviral host genes play a major role in EPF due to a specific virus–human interaction in the endemic region. Moreover, CCL5, P4HB, and APOBEC3G mRNA levels were increased (p < 0.001) in CD4+ T lymphocytes of EPF patients. Because there is limited or no evidence that these genes are involved in autoimmunity, their crucial role in antiviral responses and the associations that we observed support the hypothesis of a viral trigger for EPF, presumably a still unnoticed flavivirus. This work opens new frontiers in searching for the trigger of EPF, with the potential to advance translational research that aims for disease prevention and treatment.
KW  - endemic pemphigus foliaceus
KW  - virus
KW  - genetic association
KW  - differential gene expression
KW  - autoimmune disease
KW  - environmental factors
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-270572
SN  - 1999-4915
VL  - 14
IS  - 5
ER  -