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AB0160 Interferon-Γ-inducible kynurenines inflammation pathway: the missing link between disease activity and symptoms in sjÖgren's syndrome
  1. V Valim1,
  2. WM Sardemberg1,
  3. JG Brun2,
  4. E Zandonade3,
  5. GM Balarini1,
  6. LV Tanure4,
  7. GV Ferreira4,
  8. ΈV Serrano1,
  9. JFV Tonini1,
  10. KA Brokstad5,
  11. PM Ueland6,
  12. R Jonsson5,
  13. PM Mydel5
  1. 1Medicine, Federal University of Espírito Santo, Vitόria, Brazil
  2. 2Clinical Science Department, University of Bergen, Bergen, Norway
  3. 3Statistic Department, Federal University of Espírito Santo
  4. 4Locomotor System Department, Federal University of Minas Gerais, Vitόria, Brazil
  5. 5Broegelmann Research Laboratory, University of Bergen, Bergen, Norway
  6. 6Bevital Laboratory A/S, University of Bergen, Vitόria, Brazil

Abstract

Background Tryptophan (TRYP) can be converted to kynurenine (KYN) by indoleamine 2,3-dioxygenase (IDO) drived by interferon-γ. Recent studies have suggested that the KYN pathway reflects an important interface between the immune and nervous system modulation.

Objectives The aim was to study KYN pathway and their correlation to clinical and immunological parameters in primary Sjögren's syndrome (pSS).

Methods We included 97 pSS (AECG) and 63 healthy controls matched to age, sex, ethnicity, and body mass index (BMI). KYN metabolites and TRYP were analysed by liquid chromatography mass spectrometry.

Results Patients aged 50±11 years showed anti-SSA-Ro of 63%, anti-SSB-La 31%, anti-nuclear antibody 81%, rheumatoid factor 24%, and systemic manifestations 67%. Most (68%) showed low disease activity measured by Eular Sjögren's Syndrome Disease Activity Index (ESSDAI), 22% moderate and 10% high ESSDAI. The kynurenine:tryptophan ratio (KTR) was (0.031±0.014 vs. 0.024±0.007, p=0.001), KYN (1.890±0.580 vs. 1.652±0.426, p=0.005), quinolinic acid (QA) (477.82±251.55 vs. 382.05±128.06, p=0.018), hydroxikynurenine (3HK) (53.45±52.05 vs. 39.15±9.67, p=0.056), anthranilic acid (AA) (19.86±6.26 vs. 16.78±4.71, p=0.001) were higher while xanthurenic acid (XA) (11.52±7.88 vs.13.00±5.68, p=0.019), and TRYP (64.90±13.43 vs. 71.02±8.88, p=0.012) were lower in pSS compared to controls. Higher KTR was associated with disease duration (r=0.211,p=0.042), CRP (r=0.254,p=0.029), lower hemoglobin (r=-0.219, p=0.34), creatinine (r=0.588, p=0.000), hypergammaglobulinemia (r=0.254, p=0.014), hyper IgG (r=0.354, p=0.004), lower C3 (r=0.262, p=0.011) and C4 (r=-0.294, p=0.004). Higher KTR was observed in those with Biological ESSDAI domain involvement (0.033±0.016 vs. 0.029±0.013, p=0.003), glandular manifestation (0.037±0.014 vs.0.029±0.013, p=0.007), in the other hand lower KTR in those with presence of musculoskeletal pain (0.029±0.011 vs. 0.032±0.015, p=0.003). ESSDAI showed a tendency to correlate with KTR (r=0.177, p=0.091) and ESSPRI inversely correlated with AA (r=-0.233, p=0.071). Either patient with pain showed lower AA (20.66±6.66 vs. 17.22±5.07, p=0.021).

Conclusions TRYP is decreased and KYN metabolites pathway is increased in pSS. IDO activity expressed like KTR was positively correlated with disease activity and glandular manifestations but negatively with pain. A better understanding of the KYN pathway can clear the dissociation of symptoms and disease activity in pSS.

References

  1. Maria NI, van Helden-Meeuwsen CG, Brkic Z, et al. Association of Increased Treg Cell LevelsWith Elevated Indoleamine 2,3-Dioxygenase Activity and an Imbalanced KynureninePathway in Interferon-Positive Primary Sjögren's Syndrome. Arthritis Rheumatol.2016 Jul;68(7):1688–99.

  2. Midttun Ø, Hustad S, Ueland PM. Quantitative profiling of biomarkers relatedto B-vitamin status, tryptophan metabolism and inflammation in human plasma byliquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom. 2009 May;23(9):1371–9.

References

Disclosure of Interest None declared

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