Low Levels of IgG Recognizing the α-1-Antitrypsin Peptide and Its Association with Taiwanese Women with Primary Sjögren's Syndrome.

Yu-Sheng Chang,Yi-Ying Lu,Chih-Chun Tai,Yi-Fang Lin,Kai-Leun Tsai,Han-Wen Chou,Jin-Hua Chen,Sheng-Hong Lin,Chih-Hong Pan,Che-Chang Chang,Ching-Yu Lin

doi:10.3390/ijms18122750

Abstract

The aim of this study was to examine oxidative stress and low level of α-1-antitrypsin (A1AT) in primary Sjögren’s syndrome (pSS), and evaluate the associated autoreactivity against unmodified and their 4-hydroxy-2-nonenal (HNE)-modified peptides with pSS. Two differentially expressed proteins, α-1-acid glycoprotein 1 (A1AG1) and A1AT, exhibited 2-fold differences, and their HNE modifications were identified by depleted-albumin and immunoglobulin G (IgG) serum protein, in-solution digestion, in-gel digestion, and nano-liquid chromatography–tandem mass spectrometry (nano-LC-MS/MS) from pSS patients and age-matched healthy controls (HCs). Furthermore, levels of proteins, confirmation of HNE modifications, HNE-protein adducts and autoreactivity against unmodified and their HNE-modified peptides were further validated. Levels of the HNE-protein adduct and A1AG1 were significantly higher in pSS patients than HCs, but levels of A1AT were significantly lower in pSS patients compared to HCs. Only the HNE modification of A1AT was confirmed. Our study suggests that elevated HNE-protein adduct, oxidative stress, level (odds ratio (OR) 4.877, p = 0.003), lowered A1AT level (OR 3.910, p = 0.010) and a decreased level of anti-A1AT50–63 IgG (OR 3.360, p = 0.010) showed an increased risk in pSS patients compared to HCs, respectively.

Highlights

Primary Sjögren’s syndrome is a chronic inflammatory autoimmune disease characterized by dysfunction of the exocrine glands leading to dryness of the mouth and eyes [1]
Enrichment of depleted-albumin and immunoglobulin G (IgG) serum protein samples from a single pair of each of nine pooled serum samples was analyzed in triplicate by in-solution digestion coupled to nano-LC-MS/MS (Table 1)
There were seven upregulated proteins and 21 downregulated proteins; relative to the healthy controls (HCs) serum pools, two of the identified proteins, α-1-acid glycoprotein 1 (A1AG1) and A1AT, differed by a 2-fold increase or decrease in patients with Primary Sjögren’s syndrome (pSS) serum pools, and 26 proteins differed by a 1.7–1.9-fold increase or decrease (Table 1)

Summary

Introduction

Primary Sjögren’s syndrome (pSS) is a chronic inflammatory autoimmune disease characterized by dysfunction of the exocrine glands leading to dryness of the mouth and eyes [1]. Norheim et al reported that patients with pSS have high levels of oxidative stress compared to healthy controls (HCs) [5]. Wakamatsu et al found an increase in 4-hydroxy-2-nonenal (HNE)-protein adducts, marker of oxidative stress, in the conjunctiva of SS patients that may play a role in the pathogenesis of dry-eye disease [6,7]. Amino acid residues that can react with HNE include cysteine (C), histidine (H), lysine (K), arginine (R), glutamine (Q), alanine (A), and leucine (L) [8,9,10]. The HNE-protein adduct is an autoantigen and can elicit specific autoantibody formation [11,12]

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