Protein succination as a potential surrogate biomarker of airway obstruction. The ilervas project

Respir Med. 2020 Oct;172:106124. doi: 10.1016/j.rmed.2020.106124. Epub 2020 Sep 1.


Background: Airway obstruction (AO) is associated with hypoxemia, systemic inflammation and oxidative stress. These conditions can favor the formation of Advanced Glycation End-products (AGEs) and induce mitochondrial stress. The latter can alter metabolite intermediates in the Krebs cycle leading to the formation of the cysteine-fumarate adduct S-(2-succino) cysteine (2SC) in proteins (protein succination). Protein succination has not been described in airways diseases.

Research question: To assess differences in levels of AGEs and 2SC between patients with AO and normal spirometry.

Study design: and Methods: In this case-control study, we investigated 35 moderate to severe AO patients and 31 subjects with normal spirometry, matched for age, gender, body mass index (BMI), tobacco history, prediabetes and adherence to Mediterranean diet. Plasma 2SC and AGEs concentrations were measured by GS/MS, and AGEs in skin were determined measuring autofluorescence (SAF). Multivariate logistic regression models explored the association between AGEs in the skin, 2SC and the presence of AO.

Results: The population was predominantly middle-age (mean of 58.7 years-old), overweight (median of BMI 26.7 kg/m2) and male subjects (69.7%). Patients with AO showed higher values of SAF (p = 0.04) and 2SC (p = 0.047). No differences were observed for plasma AGEs. SAF and 2SC were significantly associated with the presence of AO after adjusting for age, gender, smoking history, BMI and Mediterranean diet score (p = 0.041 and p = 0.038, respectively).

Interpretation: Skin AGEs and 2SC are increased in patients with moderate to severe AO and independently associated with its presence. Further studies should confirm these findings and explore their potential role as a biomarker for the disease.

Keywords: Advanced glycation end-products; Mitochondrial metabolic stress; Oxidative stress; S-(2-succino) cysteine; Skin autofluorescence; Systemic inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Airway Obstruction / diagnosis*
  • Airway Obstruction / etiology*
  • Biomarkers / blood
  • Case-Control Studies
  • Citric Acid Cycle
  • Cysteine / analogs & derivatives*
  • Cysteine / blood
  • Female
  • Glycation End Products, Advanced / blood
  • Humans
  • Hypoxia
  • Inflammation
  • Male
  • Middle Aged
  • Mitochondria / metabolism
  • Oxidative Stress
  • Severity of Illness Index


  • Biomarkers
  • Glycation End Products, Advanced
  • S-(2-succinyl)cysteine
  • Cysteine