Serum Concentrations of Th17-Associated Interleukins and Autoimmune Phenomena are Associated with the Degree of Liver Damage in Alcoholic Liver Disease
Anna Parfieniuk-Kowerda1*, Magdalena Swiderska1*, Tomasz Szulzyk1, Jerzy Jaroszewicz1,2, Tadeusz W. Lapinski1, Robert Flisiak1
1) Department of Infectious Diseases and Hepatology, Medical University Bialystok;
2) Department of Infectious Diseases and Hepatology, Bytom Medical University of Silesia, Poland
Background & Aims: Recent reports suggest an involvement of Th17 responses in inflammatory and autoimmune reactions in alcoholic liver disease (ALD). Our study aimed to assess serum levels of Th17-interleukins in ALD with regard to the frequency of liver-specific autoantibodies and degree of liver damage.
Methods: Ninety-five patients with ALD were enrolled. Serum concentrations of IL-17F, IL-17A, IL-22 were assessed by ELISA. The presence of autoantibodies AMA-M2, SLA/LP, LKM-1, LC1, anti-F-actin, anti-desmin and anti-myosin in serum was assessed by immunoblotting, ANA antibodies were detected by ELISA. The results were analysed with regard to the degree of hepatic damage.
Results: Serum IL-17F was significantly elevated in ALD patients compared to controls (p=0.03). There was a correlation between serum IL-17F and degree of liver failure evaluated by the MELD score (rs=0.23, p=0.03). Serum IL-22 also correlated with MELD score (rs=0.32, p=0.007) and CTP score (rs=0.28, p=0.02). Anti-F-actin antibodies were present in 19% and ANA-antibodies in 11% of the patients in the study group, and in no subjects in the control group. The prevalence of anti-F-actin autoantibodies was higher in subjects with more advanced liver diseases but also independently associated with IL-17A in the regression analysis. Furthermore, serum IL-22 in anti-F-actin(+)-patients was significantly higher compared to anti-F-actin(-)-patients (p=0.03).
Conclusions: Elevation of serum IL-17A, IL-17F, IL-22 correlated with the progression of liver damage and also with presence of F-actin in ALD. Alcoholic liver disease may trigger autoimmunity and formation of autoantibodies, especially anti-F-actin, with possible engagement of Th17-related cytokines in this process.
Key words: alcoholic liver diseases – autoantibodies – Th17 cytokines – IL17A – IL17F – IL22.
Abbreviations: AA: acetaldehyde; Abs: antibodies; AFP: α-fetoprotein; ALD: alcoholic liver disease; ALT: alanine aminotransferase; AMA-M2: antimitochondrial antibodies; ANA: antinuclear antibodies; ASMA: anti-smooth muscle antibodies; α-SMA: alpha smooth muscle actin; CTP Score: Child-Turcotte-Pugh Score; GAHS: Glasgow Alcoholic Hepatitis Score; GGT: γ-glutamyl transpeptidase; HBV: hepatitis B virus; HCV: hepatitis C virus; HIV: human immunodeficiency virus; HSCs: hepatic stellate cells; IL-β1: interleukin β1; IL-6: interleukin 6; IL-17A: interleukin 17A; IL-17F: interleukin 17F; IL-22: interleukin 22; KCs: Kupffer cells; LC1: liver cytosol antigen type 1; LKM-1: liver kidney microsomal antigen; MA: malondialdehyde; MELD: Model of End-Stage Liver Disease; NASH: non-alcoholic steatoheptatitis; SLA/LP: soluble liver antigen/liver-pancreas; TGF-β: tumour growth factor β; TNF-α: tumour necrosis factor α.