Introduction
Vernal keratoconjunctivitis (VKC) is a chronic, allergic disease of the
cornea and conjunctiva, mostly affecting boys in pre-pubertal
age.1, 2 Patients with VKC experience recurrent
flare-ups of ocular surface inflammation, characterized by intense
symptoms of photophobia, redness and secretion, often associated with
corneal involvement and impairment of visual function and decrease of
quality of life. 1, 3-5
Several studies demonstrated that ocular surface inflammation in VKC is
characterized by a T-helper cells type 2 (Th2)-driven allergic reaction,
associated with conjunctival infiltration of mast cells, eosinophils and
CD4 lymphocytes.6, 7 However, the immunopathogenesis
of VKC has not been completely understood.2 Recent
evidence demonstrated a role of the innate immunity in the pathogenesis
of VKC, including changes of conjunctival expression of toll-like
receptors (TLRs) 2, 4 and 9.8-10 TLRs are a family of
pattern-recognition receptors expressed by resident and immune cells,
which recognize microbial compounds such as lipopolysaccharide (LPS),
endotoxins, CpG-DNA and Poly(I:C)/double-stranded
RNA.11 Different findings demonstrated that TLRs
requires additional proteins to be stimulated by their
ligands.12 Among them, the role of CD14 as ligand of
TLR-4 and TLR-9 has been demonstrated.13 CD14 is a
multifunctional receptor expressed by resident and immune cells in a
membrane-bound form and it also exists as a soluble form
(sCD14).14 It has been shown that CD14 and TLRs
binding with microbial compounds activates adaptive immune T-helper type
1 (Th1) response, by inducing production and release of cytokines such
as IL-1, IL-12, TNF-α, IL-6 and IL-8.11, 12, 15-17Alterations of sCD14 and CD14 in allergic conditions such as asthma, has
been previously described.17 The role of TLRs in the
pathogenesis of ocular surface diseases has been extensively
studied.8 An experimental study in a model of allergic
conjunctivitis demonstrated that TLR-4 stimulation by LPS suppressed
Th2-associated allergic response, suggesting a role of TLR-4 and CD14 in
the development of allergic conjunctivitis.18 In
humans, the presence of CD14 has been described in cornea and
conjunctival epithelial cells and sCD14 in tears of healthy subjects,
but not in allergic diseases.19
Therefore, the aim of this study is to investigate the involvement of
tear sCD14 and conjunctival CD14 in patients with VKC. Specifically,
expression of sCD14 in tears and of CD14, TLR4 and TLR9 in conjunctival
epithelium was assessed in patients with VKC in the quiescent phase and
during flare-ups of ocular inflammation before and after topical
corticosteroid treatment.