Because of their high prevalence, (co)morbidity, still unsatisfactory treatment options,
and imposed economic impact, chronic inflammatory skin diseases pose a major medical
Lamberts et al., 2019
- Lamberts A.
- Yale M.
- Grando S.A.
- Horváth B.
- Zillikens D.
- Jonkman M.F.
Unmet needs in pemphigoid diseases: an international survey amongst patients, clinicians
). In the past, multidimensional datasets unraveled novel pathways of disease pathogenesis
and have led to the discovery of innovative therapeutic targets, exemplified by the
discovery of Jak/nonreceptor tyrosine protein kinase 2 inhibitors for the treatment
of psoriasis and alopecia areata (
Xing et al., 2014
- Xing L.
- Dai Z.
- Jabbari A.
- Cerise J.E.
- Higgins C.A.
- Gong W.
- et al.
Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition.
). In addition to genetics and transcriptomics, analysis of metabolites revealed the
differences between patients with chronic inflammatory diseases and healthy controls,
which may translate into therapeutic consequences (
Saibeni et al., 2003
- Saibeni S.
- Cattaneo M.
- Vecchi M.
- Zighetti M.L.
- Lecchi A.
- Lombardi R.
- et al.
Low vitamin B(6) plasma levels, a risk factor for thrombosis, in inflammatory bowel
disease: role of inflammation and correlation with acute phase reactants.
Selhub et al., 2013
- Selhub J.
- Byun A.
- Liu Z.
- Mason J.B.
- Bronson R.T.
- Crott J.W.
Dietary vitamin B6 intake modulates colonic inflammation in the IL10-/- model of inflammatory
). Pemphigus vulgaris (PV) is an orphan but severe autoimmune skin blistering disease
that is clinically characterized by mucocutaneous blistering and erosions. The standard
of care is immunosuppression; however, approximately 20% of patients do not achieve
remission despite vigorous immunosuppression, and relapses are frequent (
). In contrast to common chronic inflammatory skin diseases, a limited number of multidimensional
data are available for PV. Previous studies showed associations with the HLA locus
as well as a few associated genes outside the HLA (
Olbrich et al., 2019
- Olbrich M.
- Künstner A.
- Witte M.
- Busch H.
- Fähnrich A.
Genetics and omics analysis of autoimmune skin blistering diseases.
). Transcriptomics showed unique profiles of autoreactive B cells contrasted to those
of nonautoreactive B cells (
Hébert et al., 2019
- Hébert V.
- Petit M.
- Maho-Vaillant M.
- Golinski M.L.
- Riou G.
- Derambure C.
- et al.
Modifications of the transcriptomic profile of autoreactive B cells from pemphigus
patients after treatment with rituximab or a standard corticosteroid regimen.
). Global peripheral blood gene expression showed unique signatures in patients with
pemphigus than in healthy controls (
Dey-Rao et al., 2013
- Dey-Rao R.
- Seiffert-Sinha K.
- Sinha A.A.
Genome-wide expression analysis suggests unique disease-promoting and disease-preventing
signatures in pemphigus vulgaris.
). However, these insights have not been translated into diagnostic or therapeutic
use. To contribute to the molecular understanding of pemphigus, we performed a longitudinal
analysis of the metabolome and lipidome of patients with pemphigus and controls because
these techniques allow us to capture the metabolites from the persons’ own metabolism
and from the environment, such as diet and microbiota, which have a significant impact
on the pathogenesis of chronic inflammatory diseases (
Vorobyev et al., 2019
- Vorobyev A.
- Gupta Y.
- Sezin T.
- Koga H.
- Bartsch Y.C.
- Belheouane M.
- et al.
Gene-diet interactions associated with complex trait variation in an advanced intercross
outbred mouse line.