Abstract
Behçet disease (BD) is an inflammatory systemic disease with a fluctuating course, which can affect the skin, eyes, central nervous system, musculoskeletal, gastrointestinal, and vascular systems. No laboratory tests are currently available for the diagnosis of BD and monitoring disease activity. Moreover there is a lack of knowledge on BD pathogenesis. This study focused on circulating Natural Killer (NK), NKT and T cells evaluated as CD3neg CD56pos, CD3pos CD56pos, and CD3pos CD56neg. Peripheral blood mononuclear cells (PBMCs) were collected from 38 BD patients and 20 healthy controls (HC). The frequencies of NK, NKT, and T cells expressing CD16, CD69, NKG2D, Nkp30, Nkp46, and NKG2A were assessed by flow cytometry. Cytotoxic potential of NK cells was evaluated by flow cytometry as the percentage of cells expressing the degranulation marker CD107a after incubation with K562 cells. The levels of 27 cytokines were determined in plasma with a multiplex bead-based assay. Higher percentages of NK, NKT, and T cells expressing NKG2D were detected in PBMCs of BD patients than HC. ROC curve analysis showed that the evaluation of NKG2Dpos NK, NKT, and T cell percentages discriminated between BD patients and HC. Moreover, there was a positive correlation between the BD Current Activity Form (BDCAF) scores and the frequencies of NKG2Dpos NK and NKT cells. A higher frequency of NK cells expressing CD107a was induced in PBMCs from BD patients than HC after incubation with K562 cells. Concentrations of IL-5, IL-6, IL-10, IL-13, IP-10, and MIP-1β were higher in plasma of BD patients than HC. Monitoring the frequencies of NKG2Dpos lymphocytes could help the clinicians in BD patients management. In addition, the increased expression of NKG2D in BD patients is likely involved in disease pathogenesis.
Highlights
Behçet disease (BD) is a rare, systemic, inflammatory chronic disease with multiorgan damage and various clinical manifestations and characterized by alternation of active and remitting phases
We did not find any differences in the percentages of Natural Killer (NK), NKT, and T cells if BD patients were classified according to the presence (n = 28) or absence (n = 10) of therapy (Figure 1C)
We reported an increased frequencies of circulating NK, NKT, and T cells positive for the activatory surface marker NKG2D in BD patients compared to healthy controls (HC)
Summary
Behçet disease (BD) is a rare, systemic, inflammatory chronic disease with multiorgan damage and various clinical manifestations and characterized by alternation of active and remitting phases. BD can affect mucocutaneous, ocular, musculoskeletal, nervous, vascular, gastrointestinal, and cardiac compartments [1]. Both genders are affected and the onset is more common in the third decade of life, but in young males the course of disease is more severe [1]. No laboratory assays or imaging approaches are available to support the clinical diagnosis. The BD Current Activity Form (BDCAF) is the most widely used index to assess disease activity in BD [5]. BDCAF was developed in 1999 [6] and it scores the presence or absence of clinical features (oral ulcers, genital ulcers, skin lesions, etc.) which were present during the 4 weeks prior to the day of assessment
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