We examined serum concentration of FABP5 in psoriatic patients with respect to clinical and laboratory data. We demonstrated a significantly higher levels of FABP5 in both groups of psoriatic patients (with and without obesity) compared to the healthy control subjects. We have obtained different results to Miyake et al. who found similar average serum FABP5 level in psoriatic patients and healthy individuals . However authors discovered higher FABP5 level in skin-stripping lesions and uninvolved skin of patients than the skin of healthy individuals. There were some differences between our study group and patients of Miyake. We studied 74 patients with less severe disease (PASI mean 11.3) versus 31 patients (PASI mean 17.3). Our patients did not use any topical or systemic treatment prior to the study. Patients of Miyake used topical steroids and/or vitamin D ointments. Topical treatment, specially steroids and vitamin D, may have some immunomodulatory effect and influence the results. There are several studies confirming high expression of FABP5 in psoriatic skin lesions and in uninvolved skin of psoriatic patients compared to the healthy skin [14, 17, 18]. Authors suggest that FABP5 plays an important role in keratinocyte differentiation . Higher serum concentration of FABP5 in our study may reflect its epidermal level. The underlying mechanism of the association of FABP5 and psoriasis is not clear yet, but one of the possible explanation is role of the adaptive immune system, particularly of Th1 and Th17 lymphocytes, which has been regarded as prominent in the immunopathogenesis of psoriasis . Interestingly, studies have shown that FABP5 can increase Th17-cell differentiation  and aberrant FABP5 activity may over activate immune cells leading to inflammatory autoimmune diseases .
The positive correlation of serum FABP5 with basic inflammation indices: C-reactive protein, white blood cell count and the platelet count in our study, seems to confirm the notion that FABP5 follows the inflammatory process in psoriasis and may play an important role in the pathogenesis of psoriasis and, what is more, may be used as a biomarker of severity of the disease.
High level of FABP5 can have also some metabolic implications. In the other studies serum FABP5 levels correlated positively with parameters of adiposity, adverse lipid profiles, serum insulin, adipocyte fatty acid binding proteins (A-FABP, FABP4), C-reactive protein levels and were higher in subjects with the metabolic syndrome (MS). The association of FABP5 with the MS and carotid atherosclerosis in humans was independent of FABP4. According to Yeung et al FABP5 is a new circulating biomarker associated with increased cardio-metabolic risk . Similar results have been obtained by Bagheri et al. whose findings suggested that FABP4 and FABP5 may represent mediators of and biomarkers for metabolic and cardiovascular disease in type 2 diabetes mellitus . Furthermore, Ibarretxe et al. revealed that FABP5 was associated with increased subclinical atherosclerosis and higher FABP5 plasma levels was associated with the presence of type 2 diabetes, obesity, metabolic syndrome, or atherogenic dyslipidemia . The meta-analysis of 35 studies and 1,450,188 participants revealed that psoriatic patients have higher prevalence to MS compared to general population. . In psoriasis MS is diagnosed in about 31.4% of patients . Subsequently, numerous studies have demonstrated that psoriasis, particularly severe disease, is associated with increased risk of cardiovascular diseases [8, 25]. Our results may indicate that elevated serum FABP5 represents another link between psoriasis MS and cardiovascular comorbidities.
On the other hand, in the last decade, modern epidemiological studies have provided strong evidence that obesity predisposes patients to the development of psoriasis and amplifies psoriatic inflammation [26, 27] The analysis of metabolic factors indicated that adiposity is a central factor in this association . Zhang Y et al. reported that FABP5 expression from the high-fat diet-induced obese mice was 2-fold higher in keratinocytes and 6-fold higher in macrophages as compared to the controls. This results indicate the high-fat diet upregulates FABP5 in the skin tissues and promotes inflammation of the skin . Sometimes it is difficult to point out what has came first in the metabolic dysregulation or inflammation. On both sides, elevated serum FABP5 observed in our study may contribute to the further immunologic and metabolic dysregulation.
Additionally, we have found a negative correlation of serum FABP5 with serum concentration of arachidonic (AA), eicosapentaenoic (EPA), docosahexaenoic (DHA) fatty acids and positive correlation with n-6/n-3 ratio of polyunsaturated fatty acids (PUFA). According to the literature, FABP5 has a broad range of ligands, including saturated and unsaturated fatty acids like: linoleic acid, EPA, DHA, AA and their derivatives . In general, EPA and DHA are able to inhibit different mechanism of inflammation while n-6 PUFA promote production of inflammatory cytokines and T cell reactivity through production of prostaglandins and leukotrienes from AA . Positive correlation of FABP5 with n-6/n-3 ratio highlights the pro-inflammatory state promoting metabolic disturbances in psoriatic patients.
Psoriasis is often accompanied by NAFLD. We have not observed correlation of FABP5 with liver function tests in the present study. However, such connection was reported by Ishimura in general population . Our study group was free of liver diseases and the levels of transaminases were within the normal range so, based on our results, we cannot conclude about connection of FABP5 and NAFLD in psoriasis.
To the best of our knowledge, this is the first study evaluating influence of NB-UVB on serum concentration of FABP5 in patients with chronic plaque psoriasis. We have observed significant decrease of serum FABP5 after the effective NB-UVB treatment. There was only one study comparing an effect of different methods of treatment on FABP5 levels in skin-stripping . The authors have reported decreased levels of skin FABP5 among 7 (out of 10) studied patients. Two of them were treated with adalimumab, 3 with infliximab and 2 with NB-UVB. It is difficult to compare this results with our study. Firstly, because FABP5 was evaluated in different tissue and secondly, it was very small group of patients. Nevertheless, we can again speculate that the serum concentration of FABP5 may reflect its level in the skin. What was interesting, according to Miyake et al., skin- stripping FABP5 decreased prior to the clinical improvement, so it could help to predict the result of the treatment. Further prospective studies are needed to investigate if the serum concentration decrease also precedes the improvement of skin lesions. Reduction of FABP5 after treatment may indicate improvement of metabolic condition of psoriatic patients. Similar results (reduction of plasma FABP5) were obtained in morbid obese patients after gastric binding-induced weight loss . Authors also suggested that FABP5 may be associated with metabolic improvement. In this context, it should further be noted that weight loss in obese psoriatic patients may improve skin lesions .
The main limitation of our study is lack of metabolic control after the NB-UVB. We have studied only the FABP5 and vitamin D concentration after the treatment, so we are not able to compare the FABP5 with inflammation and metabolic indices. However, significant reduction of PASI is relatively strong evidence clinical improvement. Subsequent limitation of the study is small group of patients. To have more comprehensive view, it would be the best to extend the number of patients and make a comparison in subgroups with different comorbidities.