Serum Biomarkers for Discrimination between Hepatitis C-Related Arthropathy and Early Rheumatoid Arthritis

Abstract

In the present study, we aimed to estimate the concentrations of cytokines (interleukin 6, IL-6, tumor necrosis factor-α, TNF-α) and auto-antibodies (rheumatoid factor IgM isotype, IgM-RF, antinuclear auto-antibodies, ANA, anti–cyclic citrullinated peptide antibodies IgG isotype, IgG anti-CCP3.1, anti-cardiolipin IgG isotype, IgG anti-aCL) in serum of patients with eRA (early rheumatoid arthritis) and HCVrA (hepatitis C virus-related arthropathy) and to assess the utility of IL-6, TNF-α together with IgG anti-CCP and IgM-RF in distinguishing between patients with true eRA and HCVrA, in the idea of using them as differential immunomarkers. Serum samples were collected from 54 patients (30 diagnosed with eRA-subgroup 1 and 24 with HCVrA-subgroup 2) and from 28 healthy control persons. For the evaluation of serum concentrations of studied cytokines and auto-antibodies, we used immunoenzimatique techniques. The serum concentrations of both proinflammatory cytokines were statistically significantly higher in patients of subgroup 1 and subgroup 2, compared to the control group (p < 0.0001). Our study showed statistically significant differences of the mean concentrations only for ANA and IgG anti-CCP between subgroup 1 and subgroup 2. We also observed that IL-6 and TNF-α better correlated with auto-antibodies in subgroup 1 than in subgroup 2. In both subgroups of patients, ROC curves indicated that IL-6 and TNF-α have a higher diagnostic utility as markers of disease. In conclusion, we can say that, due to high sensitivity for diagnostic accuracy, determination of serum concentrations of IL-6 and TNF-α, possibly in combination with auto-antibodies, could be useful in the diagnosis and distinguishing between patients with true eRA and HCV patients with articular manifestation and may prove useful in the monitoring of the disease course.

Inflammatory and cardiovascular diseases biomarkers in chronic hepatitis C virus infection: A review

“…In addition, lipid levels, which are a component of many CVD risk stratification tools are known to be decreased in CHC patients, 173 45 Antonelli et al 51 Caliskan et al 55 Cielecka-Kuszyk et al 56 Falasca et al 164 Siloşi et al 166 Ramos-Casals et al 167 Riccio et al 169 Nascimento et al 162 45 Caliskan et al 55 Cielecka-Kuszyk et al 56 Mezher et al 68 Elsammak et al 74 Pawlak et al 160 Siloşi et al 166 Ramos-Casals et al 167 Antonelli et al 168 sTNFRI/II el-Din et al 165 Realdon et al 170 CRP/hsCRP Caliskan et al 55 Yelken et al 158 Chennu et al 159 Pawlak et al 160 Caliskan et al 161 Nascimento et al 162 HCV-infected and HCV uninfected patients, 100,174 and there is a growing concern that CVD risk assessment using current risk scoring tools may be suboptimal for patients with heightened inflammatory states leading to an underestimation of risk in these patients. 175 CRP is an established cardiac biomarker for increased CVD risk and has been included in traditional risk assessment algorithms.…”

“…The immune activation associated with CHC infection can lead to the development of immune related complications, which may further influence the levels of inflammatory markers associated with CVD. Increased levels of IL‐6, IL‐10, TNF‐α, and sTNFR in HCV‐infected patients with complications such as cryoglobulinemia, Sjogren syndrome, lymphoproliferative diseases, hemophilia, and HCV related arthritis have been reported compared to CHC‐infected patients without such complications or to healthy controls …”

“…Increased levels of IL-6, IL-10, TNF-α, and sTNFR in HCV-infected patients with complications such as cryoglobulinemia, Sjogren syndrome, lymphoproliferative diseases, hemophilia, and HCV related arthritis have been reported compared to CHC-infected patients without such complications or to healthy controls. 45,51,56,[164][165][166][167][168][169][170] Therefore, special consideration may be needed when interpreting serum inflammatory markers in HCV populations who have DM, ESRD, and/or concomitant immune complications. In these populations with HCV infection and inflammatory conditions, there we no studies evaluating the change of these markers with HCV treatment, and none evaluated the association of these markers to subclinical and/or clinical CVD.…”

JAK/STAT pathway in pathology of rheumatoid arthritis (Review)

“…The Th17-cells play a crucial role as mediators of autoimmunity, with IL-2 being a decisive inhibitory factor for their differentiation. Through the STAT5 mechanism, IL-2 suppresses the expansion of Th17 clones, which are antigen-specific (25)(26)(27). In RA, patients present with an altered profile when compared with healthy donor cells, a fact observed with a higher expression level of the IL-1 receptor type 1 (IL-1R1), IL-23 receptor (IL-23R), JAK2, C-C motif chemokine ligand 20 (CCL20) and the colony-stimulating factor 2 (CSF2) [granulocyte-macrophage colony-stimulating factor 2 (GM-CSF2)].…”

Hepatitis C, an unusual cause of inflammatory arthritis: a case report

“…Extra-hepatic complications of HCV are common and estimated to affect 74% of patients, with approximately 4% suffering from HCVrA. 1,2 A larger proportion will experience arthralgia rather than true arthritis. Development of arthritis does not appear to correlate with the type or severity of HCV, so should be considered in all…”