Throughout the past decade, galectin-3 has attracted the attention of researchers due to its regulatory role in immune response, inflammation and fibrosis [9, 16]. Thus, several studies already showed that galectin-3 plays an important role in the development of different pathological conditions. Some studies proved that increased galectin-3 concentration is associated with high heart failure risk [17]. There are evidences that galectin-3 concentration increases significantly, both in chronic and acute heart failure, according to the progression of disease [18, 19]. Also in pulmonary and liver fibrosis serum concentration of galectin-3 was found to be elevated [9, 11, 12, 20]. Accordingly, mentioned studies proposed that determination of serum galectin-3 concentration could be a useful marker of active fibrosis in the course of these diseases. Similar studies suggested association of high serum galectin-3 levels with inflammatory disorders and autoimmune diseases, including rheumatic diseases [8, 16]. The diagnosis of rheumatic conditions, especially in early stages of the disease is still very difficult. Therefore, in recent years, interest in finding useful circulating biomarkers for early diagnosis and which may reflect the progression of rheumatic diseases, does not diminish.
Due to these facts, we try to assess the serum galectin-3 levels, its diagnostic values and potential association with progression of disease in the most common rheumatic diseases. The results of these study has shown increased serum concentration of galectin-3 in all studied rheumatic diseases: rheumatoid arthritis, systemic sclerosis, and systemic lupus erythematosus in comparison to the healthy subjects. The results of our study were comparable with those reported in literature. Previous studies documented the changed levels of galectin-3 in patients with RA, juvenile idiopathic arthritis (JIA), SSc, ankylosing spondylitis (AS) or Behcet’s diseases (BD) [6, 21–24]. For example, Ohshima et al. has demonstrated increased levels of galectin-3 both in RA synovial fluid and serum in comparison to patients with osteoarthritis and healthy subjects [6]. Similar results obtained Ezzat et al. in JIA patients [21]. Also Koca et al. reported higher serum galectin-3 concentration in systemic sclerosis and Cao et al. in patients with ankylosing spondylitis [22, 23]. Lee et al. showed a higher serum galectin-3 concentration in patients with Behcet’s disease than the healthy ones, and that the active BD patients had higher galectin-3 levels than these with the inactive BD. While, the levels of galectin-3 binding protein were not different between BD patients and controls, but it was higher in active BD than in non-active BD [24]. The mechanism by which galectin-3 is released into the extracellular space is still not fully understood. There are findings which suggested that galectin-3 molecule on its own has the capacity to traverse the lipid bilayer [25]. Against, galectin-3 has a direct effect on immune system and inflammatory responses by modulating cell adhesion of various type of immune cell. The most probably mechanism is that upon tissue injury, galectin-3 which is normally stored in the cytoplasm, is actively secreted to the blood and other biological fluids by activated and damaged cells. Therefore, inflammation and dysfunction of immune response may increase serum galectin-3 concentration in patients with different rheumatic diseases. There is well known that galectin-3 plays an important role in the development of inflammation by interacting with various cytokines and chemokines. Moreover, galectin-3 has been suggested to play a key role in inducing fibrosis in different tissues [9, 11, 12]. The effects of galectin-3 clearly depend on cellular or tissue localization.
In the most of diseases mentioned above the concentrations of galectin-3 were significantly associated with the C-reactive protein (CRP) and disease activity scores. It’s suggested that determination of serum galectin-3 may be utilized marker for the diseases prognosis. Although the increased level of galectin-3 is not specific for example in RA patients, as showed Ohshima et al. [6]. Also in our study we did not reported significantly correlation between galectin-3 concentration and CRP values, and also there were no correlation with DAS28. On the other hand, we observed positively correlation of galectin-3 with ESR in RA and SSc patients. Moreover, we denoted positive correlation with age of RA patients.
While increased serum levels of galectin-3 have been previously reported in patients with rheumatic diseases, this is probably the first study investigating the diagnostic values of serum galectin-3 in the diagnosis of selected rheumatic diseases. Our study showed that galectin-3 has the high diagnostic sensitivity (92.1% and 95.6%; respectively), PPV (92.1% and 82.7%; respectively) and diagnostic accuracy (87.5% and 83.1%; respectively) in rheumatoid arthritis and systemic sclerosis patients. For the SLE patients the sensitivity was lower than in RA and SSc. Besides, SLE patients has 100% specificity and PPV values. It is a consequence of the lack of false positive results. Moreover, we showed that galectin-3 had a very high diagnostic power (area under the ROC curve) for all tested rheumatic diseases, making galectin-3 a good diagnostic marker. Diagnostic power was excellent for RA and SSc patients (ACC over 0.9) and very good for SLE patients (ACC over 0.8).