Toxic eosinophil granule protein deposition in corneal ulcerations and scars associated with atopic keratoconjunctivitis (original) (raw)
Related papers
Journal of Allergy and Clinical Immunology, 1998
Background: The pathophysiology of chronic ocular allergic disease is not well understood. An eosinophil infiltrate is characteristic of such disease and eosinophil activity can be related to disease severity and to keratopathy, the most serious complication. Recently, eosinophils have been shown capable of cytokine production, particularly in allergic disease, although the disease-specific cytokine spectrum of tissue eosinophils is unknown. Objectives: We sought to determine eosinophil numbers (absolute numbers and percentage of total leukocytes), cell surface antigen expression, and cytokine production in conjunctiva in chronic allergic eye disease and their relationship to corneal involvement. Methods: Ultrathin sections of conjunctiva were examined by tissue staining and by 1-and 2-color immunohistochemistry. Results: Eosinophil numbers were greater in giant papillary conjunctivitis (GPC) and vernal keratoconjunctivitis (VKC) and not related to corneal involvement. The eosinophil expression of the cell surface antigens intercellular adhesion molecule-1, CD4, IL-2R, and HLA-DR was greater in atopic keratoconjunctivitis (AKC) and VKC, the disorders with corneal disease, than in GPC, in which the cornea is not involved. For most cytokines, localization to eosinophils was greater for VKC and AKC than for GPC. RANTES, TGF-β, and TNF-α localized to eosinophils in all disorders. Variations in the pattern of eosinophil-cytokine localization were found. In VKC IL-3, IL-5, IL-6, and GM-CSF were prominent; in GPC IL-5 was prominent; and in AKC IL-4, IL-8, and GM-CSF were prominent. Conclusions: Chronic ocular allergic disorders affecting the cornea are distinguished from disorders that do not do so by greater expression of eosinophil surface antigens (which may imply greater cell activation) and differences in cytokine localization to eosinophils. These differences may be secondary to the variations in T-cell subsets or a primary phenomenon. Changes in eosinophil function, rather than cell numbers, may be important in clinical variations, such as keratopathy, and may allow future therapeutic exploitation.
Cellular characteristics of non-allergic eosinophilic conjunctivitis
Acta Ophthalmologica, 2010
Purpose: This study examines the histology of conjunctival biopsy samples from patients with persistent allergic eosinophilic conjunctivitis (AEC) or nonallergic eosinophilic conjunctivitis (NAEC). Methods: Fourteen patients with conjunctivitis and eosinophilia in cytology samples were included in the study. Seven had positive skin-prick tests (the AEC group) and seven had negative skin-prick tests (the NAEC group). Eight asymptomatic subjects with negative skin-prick tests served as a control group. In conjunctival biopsies eosinophils were identified with monoclonal antibodies. Mast cells were identified by specific immunostaining and tryptase-positive granules were counted around them. The percentage of degranulated mast cells was used as a measure of cell activation. Eosinophil and goblet cell numbers were counted, epithelial thickness was measured, and the symptoms were characterized and graded. Results: The numbers of eosinophils in biopsies were higher in patients with AEC than in healthy controls (p = 0.010). The proportion of activated mast cells tended to be higher in AEC patients (65%) than in NAEC patients (48%) or control subjects (40%). Patients with AEC had more goblet cells than control subjects (p = 0.049) and their epithelial layer was thicker (p = 0.054). Patients with AEC had more severe symptoms than control subjects (p = 0.0005), whereas the symptoms of NAEC patients did not differ statistically from those of controls (p = 0.065). Conclusions: Patients with NAEC were characterized by mild eosinophilic inflammation and only minor structural conjunctival changes. The condition seems to run a relatively mild but persistent clinical course.
Increase in CD45RO+ Cells and Activated Eosinophils in Chronic Allergic Conjunctivitis
Immunobiology, 2000
We assessed the infiltration of CD45RO+ cells in conjunctival biopsies of fifteen subjects affected by seasonal allergic conjunctivitis by means of immunohistochemistry. Correlations between infiltration of CD45RO+ cells and serum and mucosal indices of eosinophilic activation were investigated. The study was performed in autumn and all selected patients showed «red eyes» also in absence of sensitising pollens. Fifteen healthy subjects were used as controls.
T-cell characterization in chronic allergic eye disease
Current allergy and asthma reports, 2003
Chronic allergic eye disease encompasses several disorders, but it is vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC) that have sight-threatening sequelae. T cells, eosinophils, and mast cells are all found in the conjunctiva, and are thought to play a role in disease pathogenesis. Recently, the conjunctival epithelium has also been considered to play a key role. New and effective therapeutic strategies for the future for these patients depend on achieving a greater understanding of the roles and interactions of the cell populations in these sight-threatening disorders.
Further Studies on the Immunopathology of Atopic Keratoconjunctivitis using Flow Cytometry
Experimental Eye Research, 1997
Atopic keratoconjunctivitis (AKC) is an ocular manifestation of systemic hypersensitivity. Although the pathogenesis of AKC is not fully understood, some previous data suggest that a decrease in numbers of suppressor T lymphocyte (Ts) and increase of Th, especially Th2 (the second subgroup of helper T lymphocyte), at the ocular surface may play an important role in the occurrence of the disease. In this study, the percentages of naive-Th (CD4\45RAj) and memory-Th (CD4\29j) cells, and the Th\Ts and memory-Th cells\naive-Th cells ratios were measured in the blood and tear samples of patients with AKC, atopic patients without ocular involvement and normal volunteers, using flow cytometry. Groups were compared using the Mann-Whitney U test. We found that patients with AKC had significantly higher memory-Th cell concentration, and Th\Ts and memory-Th cells\naive-Th cell ratios both in the tear and blood samples compared to normal subjects. While no significant difference existed between the tear samples of the atopic patients without ocular involvement and normal volunteers with respect to the above values, atopic patients had higher percentages of memory-Th cells and higher Th\Ts and memory-Th cells\naive-Th ratios in their blood than normal subjects. The percentages of memory-Th cells, and the Th\Ts and memory-Th cells\naive-Th cell ratios in the tear samples of AKC patients were also found to be higher than that of the atopic patients without ocular involvement, but no significant difference was present between the blood samples of these groups. The percentages of naive-Th cells did not show any significant difference between groups either in tear or blood samples. Since the mean memory-Th cells\naive-Th1 cells ratio in the tear samples of the patients with AKC was higher than in their blood samples, we propose that the localized accumulation of memory-Th2 cells, in addition to the increase of Th\Ts ratios in the external eye may cause AKC in atopic individuals.
Eosinophil cationic protein in sera of patients with atopic dermatitis
Journal of The American Academy of Dermatology, 1991
Patients with atopic dermatitis frequently show elevated blood eosinophil counts, and eosinophil-derived major basic protein has been demonstrated in the eczematous skin from patients with atopic dermatitis. To evaluate further the role of eosinophils in the pathogenesis of atopic dermatitis, the concentration of eosinophil cationic protein was measured in serum samples of 42 patients with moderate to severe disease. The results were compared with those obtained in 32 patients with psoriasis with (n = 9) or without (n = 23) a history of inhalant allergy, 12 patients with a history of pseudoallergie reactions to acetylsalicylic acid, 14 patients with a history of inhalant allergy, and 31 nonatopic healthy control subjects. Eosinophil cationic protein levels were significantly increased in the serum of patients with atopic dermatitis (p ~ 0.005) and patients with a history of pseudoallergic reactions to acetylsalicylic acid (p _< 0.01). There was no significant difference between eosinophil cationic protein levels in patients with psoriasis or a history of inhalant allergy and in control subjects. Moreover, eosinophil cationic protein levels did not differ significantly in psoriasis patients with or without inhalant aUergy. These studies support the concept of an active participation of eosinophils in atopic dermatitis and point to a possible role for eosinophils in pseudoallergy. (J AM ACAD DERMATOL 1991;24:555-8.) Patients with atopic dermatitis (AD) frequently have blood eosinophilia) There is also evidence for eosinophil degranulation in AD because deposits of eosinophil-derived major basic protein have been demonstrated in eczematous skin.l, 2 In addition, an active participation of eosinophils in patch test reactions to inhalant allergens has been shown in patients with atopic dermatitis) Eosinophil cationic protein (ECP) is a singlechain, highly basic protein (pI >__ 11) found in eosinophil granules. 4-6 Caused by differences in degree of glycosylation, at least three forms are known with molecular weights that range from 18.5 to 22 kD. 5 ECP is a cytotoxic agent involved in killing of parasites 4 and is important in the eosinophil-mediated killing of schistosomula of Schistosoma mansoni. 7 ECP is secreted by activated eosinophils during allergic and inflammatory processes. 6, 8 Elevated levels of ECP have been detected in serum, sputum, or nasal secretion during allergic reactions. 81~
Journal of Allergy and Clinical Immunology, 1997
The present studies were undertaken to characterize the potential role of eosinophil programmed cell death (PCD) in atopic diseases. Peripheral blood eosinophil PCD was found to be delayed in inhalant allergy (p < 0.05) and delayed to an even greater extent in atopie dermatitis (AD) (p < 0.0001) when compared to nonatopic subjects. There was no difference in the occurrence of PCD between the extrinsic and the intrinsic type of AD, pointing to a secondary role of speeific sensitization. Blockade of eosinophil PCD was not responsible for peripheral blood eosinophilia, because we found no obvious relationship of eosinophil survival to blood eosinophil count. Eosinophil supernatants of more patients with AD than of patients with inhalant allergy dose-dependently inhibited PCD in nonatopic eosinophils, and it was shown that this effect was possibly due to autocrine production of granulocyte-maerophage-colony stimulating factor, probably IL-5. Eosinophil expression of CD95 (Fas antigen) did not change over time in culture and was not modulated by cytokines prolonging eosinophil survival. In contrast , IL-3, IL-5, and granulocyte-macrophage-colony stimulating factor caused an upregulated expression of CD69. However, in AD, CD69 on eosinophils was upregulated without the need of exogenous growth factor or factors over time in culture, thus confirming an autocrine production of proeosinophUic eytokines. In conclusion, our data clearly indicate that eosinophil PCD is markedly delayed in the so-called atopic diseases irrespective of allergen sensitization and suggest that this effect is mediated by the autocrine production of growth factors by eosinophils. (J Allergy Clin Immunol 1997;100:536-43.)