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.