α-Chemokine CXCL10 and β-chemokine CCL2 serum levels in patients with hepatitis C–associated cryoglobulinemia in the presence or absence of autoimmune thyroiditis

Abstract

Chemokines have been identified to play an important role in endocrine autoimmune disease and hepatitis C chronic infection. To our knowledge, no study has evaluated serum levels of CXCL10 and CCL2 in patients with “mixed cryoglobulinemia and hepatitis C virus chronic infection” (MC) in the presence or absence of autoimmune thyroiditis (AT). Serum CXCL10 and CCL2 were assayed in 60 patients with MC, in 45 patients with “MC with AT” (MC + AT), and in controls (60 without [control 1] and 45 with AT [control 2]). CXCL10 was significantly higher (1) in control 2 than in control 1 (P < .001), (2) in MC than in control 1, and (3) in MC + AT than in controls 1 and 2 and in MC (P = .002). A high CXCL10 level (>mean + SD control 1; >167 pg/mL) was present in 7% control 1, 21% control 2, 49% MC, and 78% MC + AT (P < .0001). CCL2 was significantly higher in MC and in MC + AT than in control 1 or in control 2 (P < .01). A high CCL2 level (>mean + SD control 1; >730 pg/mL) was present in 2% control 1, 1% control 2, 18% MC, and 21% MC + AT (P < .0001). The study demonstrates high CXCL10 and CCL2 serum levels in patients with MC; CXCL10 in MC + AT is significantly higher than that in MC. Future studies in larger series will be needed to evaluate the potential usefulness of serum CXCL10 and CCL2 determination as a prognostic marker in the follow-up of MC patients, also in relation to the presence of AT.

Introduction

Chemokines are a group of peptides (more than 50) of low molecular weight that induce the recruitment of leukocytes to inflammation sites, which have been classified into 4 major families [1].

Two of these families have been extensively studied, namely, the CC and CXC chemokines. Chemokines from the CC family are chemoattractant to T lymphocytes, monocytes, and natural killer cells. The prototype CC chemokine is monocyte chemoattractant protein 1, which is a crucial factor for the development of adaptive Th2 responses by directing the differentiation of Th0 cells to Th2 in vitro [2], [3].

CXC chemokines attract neutrophils [1]. Among CXC chemokines, CXCL10 displays a strong chemoattractant activity for Th1 lymphocytes secreting interferon (IFN)γ; and it is a reliable marker of aggressive Th1-mediated autoimmune disease [4].

More recently, chemokines have been identified to play an important role in endocrine autoimmune disease; and particular attention has been raised by studies demonstrating both CC and CXC chemokines overexpression in Hashimoto thyroiditis and in early phases of Graves disease (GD) and Hashimoto thyroiditis [5], [6], [7], [8], [9], [10], [11].

The role of circulating α- and β-chemokines in hepatitis C–associated cryoglobulinemia has been less extensively studied. Regarding CXCL10, there is no study to our knowledge; with regard to CCL2, only 1 study suggests that CCL2 may play a major role in modulating the inflammatory process observed in cryoglobulinemic glomerulonephritis [12].

However, other studies in hepatitis C chronic infection (HCV+) reported that CXCL10 is expressed in hepatocytes in chronic hepatitis C patients, is high in serum of HCV patients, and correlates with histologic severity and lobular inflammation [13], [14], [15]. Regarding serum CCL2, discordant results have been found in HCV+: high serum levels of CCL2 have been found in HCV patients by Narumi et al [16], but not by Panasiuk et al [17].

We have previously demonstrated a high frequency of autoimmune thyroid disorders in cryoglobulinemic patients [18]; the immunologic base of this association remains to be investigated.

To our knowledge, no study evaluated serum levels of CXCL10 and CCL2 in patients with “mixed cryoglobulinemia and hepatitis C virus chronic infection” (MC) in the presence or absence of autoimmune thyroiditis (AT). The aim of the study is to evaluate serum levels of CXCL10 and CCL2 in a series of MC patients in the presence or absence of AT, and to relate CXCL10 levels to the clinical phenotype of these patients.