Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Behçhet disease (BD) is a rare, systemic, inflammatory disorder with multiorgan damage and various clinical manifestations such as oral ulcers, genital ulcers and uveitis. Pathogenesis is still unknown but it is considered a MHC-I-opathy1. Despite HLA-B51 and some gene polymorphisms have been associated with BD2, the diagnosis is based on clinical parameters and currently laboratory tests are only of a little help in the diagnosis of BD. The aims of this study were: 1) to increase the knowledge about BD pathogenesis; 2) to identify laboratory tests which can support BD diagnosis.
Methods: Peripheral blood mononuclear cells (PBMCs) were collected from 40 BD patients (according to 1990 ISGB criteria) and 15 healthy subjects, aged and sex matched, used as controls. The frequency of Natural Killer (NK), Natural Killer T cells (NKT) and T cells expressing the Natural Killer Group 2D activating receptor (NKG2D) was assessed by flow cytometry using anti-CD56, anti-CD3 and anti-NKG2D antibodies. NK, NKT and T cells were defined as CD56+CD3neg, CD56+CD3+and CD56negCD3+ cells respectively. Cytotoxic potential of NK cells was evaluated by flow cytometry as the percentage of cells expressing on their surface the degranulation marker CD107a, after incubation with K562 cells, optimal target for NK cell activation3. Statistical analyses were performed by Mann-Whitney and Spearman test. P-values less than 0.05 were considered statistically significant.
Results: A significant increase in the percentages of NKG2D+ lymphocytes in the NK, NKT and T lymphocyte gates was detected in BD patients respect to healthy subjects (P < 0.01). ROC curve analysis showed that the evaluation of NKG2D+ NKT cell percentage better allowed to discriminate between BD patients and healthy subjects (AUC = 0.7385; P = 0.0071). In particular, a frequency higher than 75% could identify BD patients with a 93.3% specificity and 38.5% sensitivity. After incubation of PBMCs with K562 cells, a significant higher frequency of NK cells expressing CD107a was detected in BD patients respect to healthy subjects (13.4% versus 9.5%, P = 0.0124). In BD patients we also observed a correlation between frequencies of NK cells positive for NKG2D and CD107a (r = 0.3573; P = 0.0255). Instead the median percentages of NKT and T cells expressing CD107a was low: 0.88% and 0.51% and similar between groups.
Conclusion: We found that expression of NKG2D by NK, NKT and T lymphocytes might be involved in the pathogenesis of BD in a subset of patients. BD patients were also characterized by a higher cytotoxic potential of NK cells than healthy subjects. We can speculate that NK and NKT cells of BD patients are more prone to respond to stress signals when exposed on target cells leading to cyclic auto-inflammation. Monitoring both the frequencies of NKT cells positive for NKG2D and of NK cells positive for CD107a after activation with K562 cells could help to identify BD patients.
1. McGonagle D. et al. Nat. Rev. Rheumatol. 2015, 11:731–740
2. Ombrello MJ. Et al. Proc Natl Acad Sci U S A. 2014, 111:8867-72
3. Alter G. et al. J Immunol Methods. 2004, 294:15-22
To cite this abstract in AMA style:Bonacini M, Croci S, Soriano A, Calò E, Zerbini A, Cimino L, Muratore F, Fontana L, Parmeggiani M, Salvarani C. Higher Frequencies of Lymphocytes Expressing the Natural Killer Group 2D Receptor and Cytotoxic Potential of NK Cells in Patients with Behcet Disease [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/higher-frequencies-of-lymphocytes-expressing-the-natural-killer-group-2d-receptor-and-cytotoxic-potential-of-nk-cells-in-patients-with-behcet-disease/. Accessed January 19, 2021.
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