Introduction
Hemophagocytic lymphohistiocytosis (HLH) comprises a heterogeneous spectrum of systemic disorder that are congenital (primary) or acquired (secondary), with the most devastating characteristics and mortality rate more than 50% even with specific treatment1. Regardless of specific type, knowledge of the pathogenesis remains deficient. There is a well-established association between immune dysregulation and the development of HLH. Hyperplasia of mononuclear/macrophagocytic system, persistent activation of CD8+ T cells and dis-regulated function of natural killer (NK) cells caused by various triggers, leading to uncontrolled over-secretion of cytokines including interferon gamma (IFN-γ), tumor necrosis factor α(TNF-α), interleukin 6 (IL-6), IL-10, and macrophage-colony-stimulating factor (M-CSF), is widely believed to play a predominant part2-6. Therefore, it’s of part interest of realizing early diagnosis and judging prognosis, to initiate the most appropriate treatment. Emerging researches showed that low platelet, elevated serum lactic dehydrogenase, higher lymphocyte/monocyte ratio could predict poor survival of HLH patients7,8. However, a common limitation of these indicators in improving the overall picture is the inability to be intervened directly. Then, we attempted to explore an index of prognostic importance and therapeutic possiblity.
Vitamin D (VD) is one of the indispensable steroid hormones, with well-documented function of maintaining the metabolism balance of human calcium and the formation of bone9. In addition, awareness is growing of the role of VD in immune system optimization on the basis of extrarenal activation by monocytes/macrophages10. Combined with receptor expressed on immune cells (B cells, T cells and antigen presenting cells), VD is associated with increased autoimmunity as well as susceptibility to infection. With a long serum half-life, indistinctive regulation of liver production and dependent on substrate concentration, serum 25-hydroxyvitamin D (25(OH)D) provides the single best assessment of VD status11. Much recent works had demonstrated that VD deficiency was closely related to various autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus12,13. Also, suboptimal VD levels have been demonstrated to be a significant independent risk factor in chronic graft versus host disease and a promising prognostic predictor in various lymphoma14,15. So far, little research has described the characteristic findings of serum VD in patients with HLH. Therefore, the regulating activity of VD in immune processes-key components of HLH pathogenesis- prompted us to explore this role, on this account to extended treatment strategy and even improve overall survival of HLH patients. With our known etiology, we hypothesized that, for secondary HLH (sHLH) patients, vitamin D might possess a prognostic importance and might have the ability in distinguishing the primary triggers.