MicroRNA155 Expression in Different Phenotypes and Genotypes of Behçet’s Disease in a Sample of Egyptian Patients

Aim: To display microRNA155 (miRNA155) expression in different entities of Behçet’s disease (BD), and to find out if expression is affected in more than one of disease status than another, either phenotypically, according to HLA B51 expression, presence of family history, or patients’ age. Methods: Thirty BD patients (13 of which were HLAB51 positive) and 15 healthy subjects’ samples were obtained. White blood cell miRNA155 expression in both types of samples was estimated. Results: Results showed that there is a degree of relation between decrease of miRNA155 expression and different disease aspects, and also, that miRNA155 has an inverse relation with the patients’ ages. Conclusion: MiRNA155 might be used as a measure of disease of different phenotypes, and that any manifestation of the disease can happen when the expression level decreases.


RESULTS AND DISCUSSION
MiRNA155 expression levels were decreased non-significantly not only in the whole patients group compared to the control group, but also decreased non-significantly in all disease clinical presentations except for those not having eye problems who significantly had a decreased expression from the control group p= 0.013, and from patients with ocular involvement (p=0.041) (Figures 1 and 2). HLA B51 positivity in involved patients was 43.3%, and there was no significant difference between miRNA155 expression in either HLA positive or HLA B51 negative patients and the control group (p = 0.201). Also, there was no significant difference between miR-NA155 expression in patients having positive family his-tory of BD (7 patients) and those who did not (p=0.081).
MiRNA155 expression appeared to be directly proportional to age (rs=0.374, P=0.042) (Figure 3): this may be explained by decreased disease activity with increasing age. These findings prove what was mentioned in several studies, that miRNA155 decreases with increase of BD activity, such as Hassouna et al. 5 The results shown are coherent with researches telling that increase in miRNA155 is related to decreased expression in some cytokine, eg, interleukin (IL)1, IL 6 and IL 17, as is shown in Zhou et al. 6 These ILs play important roles in BD pathogenesis, as noted in many studies, eg, Yamakawa et al. 7 and Emmi et al., 8 and this increased miRNA155 expression leads to increased expression of inhibitory IL 10, 6 and results in a healthy immune system and may lead to balance of macrophages (M1/M2) through IL13 receptor alpha targeting (Martinez-Nunez et al.). 9 A study showed that high level of MiRNA155 was found in Tregs in a FOXP3-dependent way, and Treg homeostasis is disabled in miRNA155 insufficiency. When miRNA155 is missing in Treg, miRNA155 target of cytokine signalling 1 expression suppression increase with diminished responses to IL2, which is an imperative Treg homeostasis controller this was found by Lu et al. 10 Moreover, it was discovered by Ceppi et al. that miR-NA155 down-regulates lipopolysaccharide induced inflammatory pathways through inhibition of monocyte-derived DCs. 11 A few other researches revealed an inverse result to ours, that miRNA155 expression is expanded in activity of BD, and that MiR-155 focusing on Ets-1 controls Th17

MICRORNA155 EXPRESSION IN DIFFERENT PHENOTYPES AND GENOTYPES OF BEHÇET'S DISEASE IN A SAMPLE OF EGYPTIAN PATIENTS
response and that concealment of miR-155 diminishes pathogenic IL-17-expressing T cells, as was seen in the study of Na et al. 12 Another research found that T cells miR-155 lack in mice did not lead to advancement of extreme autoimmune encephalomyelitis (EAE) and has a diminished IL-17 generation which is a critical cytokine for EAE pathogenesis. 13 Moreover, Blüml et al. 14 found that mice lacking in miRNA155 have impedance in Th17 differentiation and in turn are protected from joint inflammation initiated by collagen.
The opposite findings to our research results shown in some other studies may be due to ethnic differences, and different activity levels of the disease in the involved patients from one study to another. Also, several studies (either those having same results to ours, or the contrary) were built on animal research, which cannot be relied on. Thus, there is a controversy about miRNA155 role in the pathogenesis of BD disease.

CONCLUSION
MiRNA155 might be used as a measure of disease state. Any manifestation of the disease can happen when the expression level decreases.

ACKNOWLEDGEMENT
It is a duty to thank, all the patients and healthy volunteers who have taken part in this work, and for lab technicians for being fastidious at their work.

ETHICS APPROVAL
Approval of Ethics Committee was obtained from the Local Ethics Committee of Alexandria University, with