DOI: 10.5061/dryad.kh18932hj
title: Data from: Immune profiling links autoimmune hepatitis to human herpes virus 6 and relaxin receptor antigens

description: 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. 
description: DNA libraries were barcoded and amplified, gel purified, and
 subjected to Next-Generation Sequencing on an Illumina NextSeq or NovaSeq
 Instruments (Illumina, San Diego, CA). Sequencing reads from raw fastq
 files were aligned to the reference library using RAPSearch2, and RPK was
 calculated. This data is uploaded here.
description: # PhIP-Seq in Autoimmune Hepatitis
 [https://doi.org/10.5061/dryad.kh18932hj](https://doi.org/10.5061/dryad.kh18932hj) ## Description of the data and file structure Two files have been uploaded:  1\) "AIH PhIP-Seq Phaser Epitope Scanning.csv" - this file contains the peptide level PhIP-seq data generated in deep mutational scanning experiments using a selected PhIP-seq library for epitope mapping. Raw sequencing were aligned to the input PhIP-seq library using RAPSearch2, and then RPK were calculated, and uploaded in this csv file.  2\) "AIH PhIP Seq Experimental Data.csv" - this file contains the peptide level PhIP-seq data generated in the AIH and control patient PhIP-seq experiments using a phage display library spanning the entire human proteome. Raw sequencing were aligned to the input PhIP-seq library using RAPSearch2, and then RPK were calculated, and uploaded in this csv file.  ### Files and variables #### File: AIH_PhIP-Seq_Phaser_Epitope_Scanning.csv **Description:** Phaser data generated from PhIP-seq experiment ##### Variables * peptide: List of peptides screened in the PhIP-seq experiment, which are the row names * Patient Samples and control samples, which are the column names Units: RPK #### File: AIH_PhIP_Seq_Experimental_Data.csv **Description:**  AIH PhIP-seq experiment results ##### Variables * peptide: List of peptides screened in the PhIP-seq experiment, which are the row names * Patient Samples and control samples, which are the column names Units: RPK ## Human subjects data We confirm that all participants provided explicit consent for their de-identified data to be shared in the public domain. All personal identifiers, including names, contact information, and any other data that could reasonably be used to identify individual participants, have been removed or anonymized. Any remaining data have been generalized or aggregated as needed to prevent re-identification. This ensures that the dataset is fully de-identified and safe for public use.