Data from: Immune profiling links autoimmune hepatitis to human herpes virus 6 and relaxin receptor antigens

Autoimmune hepatitis (AIH) is a severe, chronic disease where IgG
elevation and autoantibody profile are defining features. However, linking
autoantibodies to AIH pathogenesis remains elusive. We employed Phage
Immunoprecipitation-Sequencing (PhIP-seq) and uncovered a novel humoral
signature specific to AIH. Embedded within this
signature were antibodies against the known AIH autoantigen SLA/LP and
novel reactivities to disco interacting protein 2 homolog A (DIP2A), and
the relaxin family peptide receptor 1 (RXFP1). Fine mapping of the DIP2A
epitope revealed preferential enrichment for a nearly-identical 9-amino
acid sequence derived from the U27 protein of human herpes virus 6
(HHV-6). Pre-incubation with the HHV-6 epitope blocked DIP2A binding,
consistent with cross-reactivity. AIH patients positive for
anti-DIP2A had higher titers of HHV6 IgG, suggestive of
reactivation. AIH patients had antibodies against the
anti-fibrotic receptor, RXFP1, which inhibited relaxin-2 signaling in an
IgG-dependent manner. These data provide evidence for a novel
serological profile in AIH, linking HHV-6 reactivation anti-RXFP1
antibodies to disease pathogenesis.