RA patients express increased serum levels of several cytokines, but the evidence for a clinical relevance of such measurements in the assessment of prognosis is limited. In this 1-year prospective study of 84 early RA patients, we found that a high serum level of eotaxin in the early disease course was associated with less subsequent radiographic progression. The association between eotaxin level at baseline and radiographic progression remained strong when adjusting for other known predictors of joint destruction. Serum levels of the other tested cytokines in this study were not associated with radiographic progression.
Chemokines are suggested to be important in RA pathology and elevated levels have been measured in the synovium and serum of RA patients [8
]. Hueber et al
. found elevated serum levels of chemokines to be the most evident difference between early RA patients and controls [10
]. Eotaxin (chemokine C-C motif ligand 11 (CCL11)), a member of the CC chemokine family, recruits eosinophils to sites of inflammation, particularly in allergic diseases and asthma [11
]. It is produced by lymphocytes, eosinophils and monocytes/macrophages, and interacts with C-C chemokine receptor 3 (CCR3) [11
]. This receptor is expressed by T-lymphocytes, eosinophils, basophils, dendritic cells, and a recent study has also suggested expression of CCR3 on osteoclasts [11
A Korean study has suggested a link between eotaxin gene polymorphisms and RA [14
]. Two recent studies have shown increased eotaxin in the plasma of juvenile idiopathic arthritis (JIA) and serum of RA patients compared to normal controls [10
], and it has been suggested that eotaxin may be one of several cytokines denoting low activity in JIA joint disease [15
]. The possible expression of the CCR3 receptor on osteoclasts and the suggested involvement in osteoporosis might indicate a role in bone resorption [12
The role of eotaxin in RA patients and thus the pathophysiological impact of the negative association to radiographic progression, however, are currently unclear. One may speculate whether high eotaxin levels denote a more T-helper (Th) 2-type response in individual RA patients, possibly protecting against joint damage.
Our study has some limitations. Patients were treated according to clinical judgment before inclusion and during the study. The 1-year follow-up could be insufficient to reveal an association between progression and serum levels of any of the other tested biomarkers. We cannot exclude that the association between eotaxin levels and radiographic progression is an arbitrary finding due to multiple testing or an unknown confounder. The p values, however, were far below 0.01, despite the relatively small number of patients included.
One can question whether measurements of cytokines in serum reflect the cytokine levels in the joint; however serum measurements of cytokines might regardless be clinically useful if associated to important patient outcome. To our knowledge this is the first prospective study to explore the associations between radiographic progression and a broad spectrum of cytokines.