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.