Immunogenetic investigation in vernal keratoconjunctivitis

Zicari, Anna Maria; Mora, Barbara; Lollobrigida, Valeria; Occasi, Francesca; Marcelli, Azzurra Cesoni; Megiorni, Francesca; Pizzuti, Antonio; Nebbioso, Marcella; Duse, Marzia

doi:10.1111/pai.12231

Cited by 15 publications

(14 citation statements)

References 9 publications

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“…Patients with VKC have been shown to have increased levels of activated CD4+, Th2-lymphocites, and of inflammatory cytokines IL-3, IL-4, IL-5, and IL-6, indicating that there is a hypersensitivity reaction to an unknown pathogen [ 3 , 21 – 23 ]. Inflammatory cytokines may regulate the secretion, proliferation, and apoptosis of goblet cells [ 24 – 26 ], while allergic mediators such as histamine, leukotrienes, and prostaglandins directly stimulate the secretory activity of these cells [ 24 – 27 ].…”

Section: Discussionmentioning

confidence: 99%

Tear Ferning Test and Pathological Effects on Ocular Surface before and after Topical Cyclosporine in Vernal Keratoconjunctivitis Patients

Nebbioso

Sacchetti

Bianchi

et al. 2018

Journal of Ophthalmology

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Background Vernal keratoconjunctivitis (VKC) is a rare ocular surface inflammatory disease that affects mainly boys in the first decade of life. Clinical observations show that it generally regresses spontaneously with the onset of puberty, but therapeutic measures must be taken before then to control the course of the disease. PurposeTo evaluate the role of the lacrimal mucous component in VKC patients and compare tear ferning test (TFT) modifications, MUC5AC levels in tears, and density of conjunctival goblet cells to clinical characteristics before and after treatment with cyclosporine A (CY) in eye drops. Methods Forty-seven patients affected by VKC and 30 healthy subjects aged between 3 and 16 years of life were enrolled. All individuals were submitted to complete eye examination and skin prick test (SPT) for the most common allergens. Then, they were subjected to collection of the tears and to impression cytology to evaluate TFT, MUC5AC levels, and conjunctival goblet cell density, before and after treatment with CY in eye drops. Results Comparing the VKC group vs. the control group at baseline, a significant alteration in the degree of the ferns was found, indicating a pathological condition of the lacrimal mucous layer. In addition, an increased number of goblet cells were observed in the patients. The concentration of lacrimal secretory mucins (MUC5AC) did not show significant differences between the 2 groups. Patients treated with CY have reported improvements of some signs and symptoms of disease activity, including TFT, and a tendency of conjunctival goblet cell density to normalise. Conclusions The results obtained demonstrated for the first time a significant alteration of the lacrimal mucin component evaluated in the VKC group, and an improvement of the latter after CY therapy.

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Section: Discussionmentioning

confidence: 99%

Tear Ferning Test and Pathological Effects on Ocular Surface before and after Topical Cyclosporine in Vernal Keratoconjunctivitis Patients

Nebbioso

Sacchetti

Bianchi

et al. 2018

Journal of Ophthalmology

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“…The role of Th2 responses in VKC has been studied for a long time, and VKC is actually not regarded just as an ocular disease but as a systemic disease with a T-cell-activated response. Many studies underlined the role of single cytokines and mediators in the development of the disease, such as the IL-17 and the HMGB-1 [ 11 – 13 , 15 ]. In the present study, we focused on the assessment and quantification of the VEGF, comparing the concentration of such a molecule in tear and blood samples from VKC and control subjects.…”

Section: Discussionmentioning

confidence: 99%

“…Genetic predisposition also contributes to the development of this disease, and although no relationship has been found yet between VKC and a particular genotype, the constant and increased presence of eosinophils in blood, tears, and conjunctival scrapings, the expression of a multitude of mediators and cytokines, and the predominance of CD4 cells locally suggest that VKC may be a phenotypic model of upregulation of the cytokine gene cluster on chromosome 5q [ 7 – 12 ]. In addition, multiple studies have investigated the family history of allergic diseases (asthma, rhinitis, eczema, urticaria, and dermatitis) and immunological diseases (Hashimoto's thyroiditis, type I diabetes, psoriasis, rheumatoid arthritis, and systemic lupus erythematosus), reporting such an association in roughly half of the patients diagnosed with VKC [ 3 , 5 , 6 , 13 , 14 ]. At this point, the accumulation of a large amount of immunological data has established that the pathogenesis of VKC is much more complex than a mere type 1 hypersensitivity reaction, also involving IgE-independent (type IV) mechanisms and cytokines, such as the interleukin 17 (IL-17) [ 7 , 10 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Vascular Endothelial Growth Factor (VEGF) Serological and Lacrimal Signaling in Patients Affected by Vernal Keratoconjunctivitis (VKC)

Nebbioso

Iannaccone

Duse

et al. 2018

Journal of Ophthalmology

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Background Vernal keratoconjunctivitis (VKC) is a rare inflammatory disease involving the ocular surface, with seasonally exacerbated symptoms. Both type-1 and type-4 hypersensitivity reactions play a role in the development of VKC. Purpose The aim of the present study was to assess the presence and evaluate the concentration of the vascular endothelial growth factor (VEGF) in tear and blood samples from patients with VKC, during the acute phase, based on the histopathological vasculostromal structure of the tarsal papillae. Methods Two groups of children aged between 6 and 16 years of life were enrolled: 21 patients (16 males, 76%) affected by VKC, tarsal or mixed form, and 13 healthy children (5 males, 38%) used as controls. Blood and tear samples were obtained from all patients, in order to specifically assess the presence of VEGF. Statistical analyses were performed with one-way ANOVA, followed by post hoc comparisons with the Bonferroni tests. Pearson's correlation was chosen as statistical analysis to assess the relationship between the expression levels of VEGF in tears and blood and the clinical parameters measured. Results Comparing the 2 groups for VEGF concentration, a statistically significant difference was found in tear samples: the mean value was 12.13 pg/mL (±5.54 SD) in the patient group and 7 pg/ml (±4.76 SD) in controls (p < 0.05). However, no statistically significant difference was found when comparing VEGF concentration in blood samples (p > 0.05), with a mean value of 45.17 pg/mL (±18.67 SD) in VKC patients and 38.08 pg/mL (±19.43 SD) in controls. Conclusions This pilot study highlights the importance of lacrimal and vascular inflammatory biomarkers that can be detected in VKC patients during the acute phase, but not in healthy children. The small group of patients warrants additional studies on a larger sample, not only to further investigate the role of VEGF but also to evaluate the angiogenic biomarkers before and after topical treatment.

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“…The association of specific human leukocyte antigen (HLA) classes I and II has been investigated and has led to the finding of a characteristic overexpression of HLA-DRB1 and HLA-DQB1 16…”

Section: Introductionmentioning

confidence: 99%

<p>Eye drop emulsion containing 0.1% cyclosporin (1 mg/mL) for the treatment of severe vernal keratoconjunctivitis: an evidence-based review and place in therapy</p>

Nebbioso¹,

Alisi²,

Giovannetti³

et al. 2019

OPTH

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Vernal keratoconjunctivitis (VKC) is a rare, recurrent and multifactorial ocular disease, which typically flares up during spring and affects especially male children and adolescents. This condition does not usually respond to common treatments with antihistamines or mast cells stabilizers, whereas corticosteroids have effective results. Corticosteroids need to be carefully administered, to avoid adverse effects, mainly the secondary development of glaucoma, cataracts, or infections. Immunosuppressive agents, such as cyclosporin (CyA) or tacrolimus are, therefore, frequently employed in VKC patients. Only the 0.1% CyA (1 mg/mL) concentration has an approved and specific clinical indication for the treatment of VKC and this drug was given the denomination of orphan drug by the European Commission (EU/3/06/360) in 2006. So far, few studies have been conducted to evaluate the efficacy and the side effects of topical 0.1% CyA. Different topical CyA concentrations, ranging from 0.05% to 2%, and various types of formulation are available at the moment. In the future, 0.1% CyA will presumably take an important part in the management of VKC. The present review focuses on eye drops containing 0.1% CyA; however, more studies will be needed to define its long-term efficacy in the natural course of this severe ocular disease.

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Immunogenetic investigation in vernal keratoconjunctivitis

Cited by 15 publications

References 9 publications

Tear Ferning Test and Pathological Effects on Ocular Surface before and after Topical Cyclosporine in Vernal Keratoconjunctivitis Patients

Tear Ferning Test and Pathological Effects on Ocular Surface before and after Topical Cyclosporine in Vernal Keratoconjunctivitis Patients

Vascular Endothelial Growth Factor (VEGF) Serological and Lacrimal Signaling in Patients Affected by Vernal Keratoconjunctivitis (VKC)

<p>Eye drop emulsion containing 0.1% cyclosporin (1 mg/mL) for the treatment of severe vernal keratoconjunctivitis: an evidence-based review and place in therapy</p>

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