Obesity, Lipid Profile and Cytokines in Spondyloarthritis.

Context: Chronic rheumatic diseases seem to be associated with a higher risk of developing cardiovascular diseases. The link between cytokines and lipid profile in spondyloarthritis is not well elucidated. Aims: We aimed to assess the relationship between cytokines and obesity, lipid profile and atherogenic indexes in spondyloarthritis. Methods and Material: We conducted a cross-sectional study including 45 patients with axial radiographic spondyloarthritis. For each patient, we measured the following pro-inflammatory cytokines: interleukin (IL-) 1, IL-8, IL-6, IL-17, IL-23 and tumor necrosis factor a (TNFa), and anti-inflammatory cytokines: IL-10. We also measured total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLc) and low-density lipoprotein cholesterol (LDLc). We calculated the following ratios: TC/HDLc, TG/HDLc, LDLc/HDLc and Log[TG/HDLc]. Statistical Analysis Used: SPSS. Results: The mean age was 46 ± 11.9 years. IL-8 levels were increased in obese patients (P = 0.003). IL-8 and IL-22 levels were significantly higher in patients with abdominal obesity (P = 0.024 and P = 0.042, respectively). IL-6 levels were lower in patients with hypercholesterolemia (P = 0.009). IL-1 levels correlated to TG (r = 0.413; P = 0.005). IL-1 and IL-6 were correlated to TG/HDLc (IL-1: r = 0.484, P = 0.001; IL-6; r = 0.700, P = 0.012) and Log[TG/HDLc] (IL-1: r = 0.354; P = 0.012; IL-6: r = 0.309, P = 0.041). IL-10 level was correlated to TC/HDLc (r = 0.333, P = 0.027) and LDLc/HDLc (r = 0.342, P = 0.023). Conclusions: IL-8 and IL-22 were higher in patients with abdominal obesity, highlighting the contribution of the adipocytes to the secretion of pro-inflammatory cytokines. The correlation between cytokines and atherogenic indexes suggests the role of these cytokines in the occurrence of cardiovascular diseases in spondyloarthritis.

High levels of proinflammatory cytokines IL-6, IL-8, TNF-Α, IL-23, and IFN- in Tunisian patients with type 1 autoimmune hepatitis.

Autoimmune hepatitis (AIH) is a chronic hepatitis of unknown etiology and several cytokines have been implicated in its pathogenesis and onset. Our objective was to determine the profile of pro and anti-inflammatory cytokines, including IL-1ß, IL-6, IL-8, IL-23, IFN-, TNF-α, IL-10 in autoimmune hepatitis and their association with HLA gene polymorphisms. Serum cytokine levels were determined in 50 autoimmune hepatitis patients and one hundred fifty controls using chemiluminescence and ELISA techniques and HLA genotyping performed by PCR SSP. The levels of IL-6 (12 pg/mL vs. 5.5 pg/mL, p = 0.017), IL-8 (24.1 pg/mL vs. 7.8 pg/mL, p = 0.006), and TNF-α (61.1 pg/mL vs. <4.00 pg/mL, p = 0.002) were significantly higher in AIH patients in pretreatment phase compared to levels after remission and in controls. HLA*DRB15 was significantly associated with higher levels of IL-8. IL-6, IL-8, and TNF-α may be biomarkers of AIH activity. HLA gene expression may play a role in higher cytokine production and could allow an earlier diagnosis and better management of the disease.

Cytotoxic T lymphocyte antigen-4 gene polymorphisms and susceptibility to type 1 autoimmune hepatitis in the Tunisian population.

Genetic factors and gene polymorphisms leading to the onset of autoimmune response in autoimmune hepatitis (AIH) are still not full elucidated. Since the CTLA-4 molecule is a key modulator of the lymphocytes responses we hypothezied that deficiencies or mutations in the gene encoding CTLA4 protein may be involved in AIH susceptibility and trigger the autoimmune response. We investigated 3 distinct polymorphic sites (+49A > G, CT60 G > A and -318C > T) of the CTLA4 gene in 50 AIH patients and 100 healthy controls using the KASP genotyping technology. A significant positive association with AIH susceptibility was found for the GG genotype in +49 position of the CTLA4 gene which was significantly higher in AIH patients compared to controls (28% vs 9%, p = 0.003, OR = 3.93 [1.56-9.88]). The CTLA4 A/A genotype in position CT60 was more significantly frequent in controls comparing to AIH patients and could be considered as a protective genotype for the tunisian patients. CTLA4 genotyping in position -318 did not show any statistically significant difference in genotype or allele distribution. The CTLA4 gene polymorphism in position +49 is associated to AIH susceptibility in the Tunisian population. Mutation in the CTLA4 gene may lead to a modification of the CTLA4 protein structure that could have functional relevance in AIH pathogenesis and onset.

Association of TNF-α-308 Polymorphism with Susceptibility to Autoimmune Hepatitis in Tunisians.

Autoimmune hepatitis (AIH) is a chronic hepatitis of unknown etiology and several proinflammatory cytokines are implicated in its pathogenesis. The association of TNF-α gene polymorphism with AIH onset is not fully elucidated especially in the Tunisian population. The aim of this study was to determine the association of TNF-α (-308 G > A) polymorphism with AIH susceptibility and with TNF-α expression or clinical manifestations of AIH. A total of 50 AIH patients and 150 controls were included. Evaluation of TNF-α polymorphism was performed by ARMS PCR method. A significantly higher frequence of the AA genotype was found in AIH patients compared to controls (34 vs. 8%, p = 0.00002, OR 5.88). The frequency of the A-allele was significantly higher in patients with AIH compared to controls (55 vs. 37.3%, p = 0.002, OR 2.05). The G-allele was significantly more frequent in healthy controls compared to AIH patients [43 vs. 61.3%, p = 0.001, OR 0.47 (0.3-0.75)]. There was a positive correlation between the A/A genotype and a higher serum expression of TNF-α. The TNF*A allele confer susceptibility to AIH in the Tunisian patients and is associated with increased production of TNF-α. Anti-TNF antibodies could be an alternative to the use of corticotherapy and may avoid the exacerbated immune response in AIH.