The aim of this study was to investigate the subclasses and the immunophenotypic profile of peripheral mononuclear cells in patients with Behçet's disease (BD) and to assess associations between the expression of HLA-B51 antigen and that of other cell markers. Thirty healthy volunteer blood donors and forty patients with BD were enrolled into this study. Phenotyping was performed using two color flow cytometry. HLA-B51 typing was performed using the complement dependent microlymphocytotoxicity assay. Unlike controls, patients with BD presented a modified immunophenotypic profile of lymphocytes. Compared to those in the remission phase, patients with active BD showed an increased mean of MFI ratio of CD56 on CD16+CD56+ cells (32.47 ± 14.26 versus 23.87 ± 10.3; p = 0.032), increased absolute numbers of CD4(-)CD8(bright) and CD4(+)CD8(+) cells (657.1 ± 463.6 cells/µL versus 319.24 ± 116.4 cells/µL; p = 0.017 and 40.77 ± 36.41 cells/µL versus 10.77 ± 9.78 cells/µL; p < 0.0001, respectively) and an elevated mean of MFI ratio of CD19 on B cells (252.3 ± 56.7 versus 205.67 ± 32.3; p = 0.021). However, expression of HLA-B51 was not associated with any specific immunophenotypic profile. In conclusion, abnormal immunophenotypic profile of peripheral lymphocytes was found in patients with BD, especially in active phase, reflecting an immune dysregulation. Moreover, HLA-B51 expression was not found to be related to the expression of other cell markers.
Background Behcet’s disease (BD) is a chronic relapsing multisystemic inflammatory disease. Although the actual etiology is still unclear, BD symptoms are considered to be the resultant of genetic intrinsic factors and triggering extrinsic factors [1]. HLA-G is a non-classical HLA-class I molecule and has multiple immunoregulatory properties. A 14 bp insertion/deletion polymorphism in the HLA-G gene has been suggested to influence the level of soluble HLA-G and then to associate with certain pathological conditions, including inflammatory diseases [2]. Objectives The aim of this study was to investigate the HLA-G 3′UTR 14bp polymorphism and sHLA-G levels in Tunisian patients with BD. Methods 120 patients with BD, 77 males and 43 females (mean age: 38.13±11.7 years), were recruited from the internal medicine department at Fattouma Bourguiba Hospital of Monastir in Central region of Tunisia. 168 volunteer donors were recruited as healthy controls (HC) (mean age: 30.41± 9.05 years). HLA-G 14bp deletion/insertion polymorphism was detected by PCR amplification of the target sequence followed by agarose gel electrophoresis. Serum levels of soluble HLA-G (sHLA-G) were measured for 49 patients with BD (34 inactive cases, 15 active cases) and 49 healthy controls using a commercial ELISA kit. Results A significant decreased frequency of the +14bp HLA-G allele was detected in patients with BD compared to HC (0.36 vs 0.77, P = 0.036). A significant increased frequency of HLA-G -14/-14bp was observed in patients with BD compared to HC [0.36 vs 0.22, P = 0.022, OR 0.52 (95% CI 0.29–0.93)]. The median plasmatic concentration of sHLA-G was higher in patients with BD compared to HC without significant difference (96.4 (56.4-150.65) vs 65.1 (47-136.9) U/ml, P=0.1]. However, sHLA-G levels were significantly increased in patients with active disease [150.3 (91.4-265) U/ml] compared to patients with inactive disease [85.7 (55-1127.9) U/ml, P=0.038] and HC (P=0.044). Furthermore, our results showed that the 14bp polymorphism was significantly associated with the level of sHLA-G expression. In fact, +14/+14bp subjects had significantly lower plasmatic levels of sHLA-G compared to the group with the +14/-14bp genotype (P = 0.011) or the group of individuals +14/-14bp or -14/-14bp (P = 0.004). Conclusions The homozygous 14pb insertion is associated with decreased plasmatic levels of sHLA-G in Tunisians. Moreover, homozygous deletions are more frequent in patients with BD compared to controls and sHLA-G levels are higher in patients with active disease, suggesting a possible involvement in the disease physiopathology. References Kaneko, F., et al., Behcet’s disease (Adamantiades-Behcet’s disease). Clin Dev Immunol, 2011. 2011: p. 681956. Hviid, T.V., et al., HLA-G and IL-10 in serum in relation to HLA-G genotype and polymorphisms. Immunogenetics, 2004. 56(3): p. 135-41. Disclosure of Interest None Declared
Background Behçet’s disease (BD) is a multisystemic inflammatory disorder characterized by spontaneous remissions and relapses [1]. An association between Behçet’s disease and HLA-B51 has been regarded as the strongest evidence for involvement of genetic factors in its pathogenesis. The exact mechanisms illustrating the involvement of HLA-B51 in BD development are still unknown [2]. Objectives The aim of this study was to assess possible associations between the expression of HLA-B51 antigen and particular profiles of peripheral T cell subsets in patients with BD. Methods 30 patients with BD, 19 males and 11 females (mean age: 39.65±10.7 years) were enrolled in this study. Ten of them had active disease. The following monoclonal antibody combination was used to characterize the phenotypes of T cells: anti-CD4-Chrome orange/anti-CD3-PacificBlue/anti-CD62L-PE/anti-CD127-APC-Cy7/anti-CD25-PerCP-Cy5/anti-CD45RA-PCy7 and anti-CD8-APC. Analysis was performed on a FACSDiva™ flow cytometer using FACSDiva™ software. The HLA-B51 typing was performed using the complement dependent microlymphocytotoxicity technique. Results Our study showed that 38.46 % of patients with BD were HLA-B51 positive (positive group). This group, as compared with HLA-B51 negative patients (negative group), tend to have fewer CD45RA+CD62L+CD4+ naïve T cells (6.77 ± 4.7% versus 8.18 ± 6.5%, p=0.9 ) and higher CD45RA-CD62L+CD4+ central memory T cells (22.7 ± 13.6% versus 13.18 ± 12.2%, p=0.2). The HLA-B51 positive group showed also lesser terminally differentiated CD45RA+CD62L–CD4+ effector memory T cells than the negative group (8.18±3.1% versus 16.86 ± 5%; P = 0.018). However, regarding CD45RA–CD62L–CD4+ effector memory T cells and CD4+CD25brightCD127- T reg cells, no differences were found between the two groups. Moreover, the HLA-B51 positive group seems to be characterized by decreased percentage of CD45RA+CD62L+CD8+ naïve T cells compared to negative group (8.11±3.7% versus 14.02±6.7%; P=0.08). Finally, no differences were found between the two groups regarding CD45RA-CD62L+CD8+ central memory T cells, CD45RA–CD62L–CD8+ effector memory T cells and terminally differentiated CD45RA+CD62L– CD8+ effector memory T cells. Conclusions Our study showed that HLA-B51 positive patients with BD are characterized by particular profiles of T cells. The understanding of these findings could contribute in elucidating the role of HLA-B51 antigen expression in the pathogenesis of BD. References Kaneko, F., et al., Behcet’s disease (Adamantiades-Behcet’s disease). Clin Dev Immunol, 2011. 2011: p. 681956. Disclosure of Interest None Declared
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