Adriaan Holm

Dynamics of mast cells in the nasal mucosa of patients with allergic rhinitis and non‐allergic controls: a biopsy study

Mast cell degranulation is thought to be an important component of the pathogenesis of allergic rhinitis. Quantitative studies on mast cells in nasal mucosa after allergen exposure have given widely divergent results, ranging from an overall decrease via redistribution to an overall increase. We investigated this problem by employing a combination of anti‐IgE and toluidine blue staining of biopsy specimens. In allergic patients anti‐IgE was found to identify all mast cells and toluidine blue to detect mast cells that were not (totally) degranulated.

Antigen presenting cells in the nasal mucosa of patients with allergic rhinitis during allergen provocation

Background The role of antigen presenting cells (APC) in allergic rhinitis is underexposed. Allergen presentation to T lymphocytes is probably an important aspect of the pathophysiological mechanism of allergic rhinitis.

Dynamics of nasal eosinophils in response to a nonnatural allergen challenge in patients with allergic rhinitis and control subjects: a biopsy and brush study

BACKGROUND Eosinophils are thought to play an important role in the symptomatology and pathophysiology of allergic rhinitis. Most quantitative studies on eosinophils in nasal mucosa have focused on the dynamics of eosinophils in the acute and late phases of the allergic reaction by using different cell sampling techniques. Little is known about the dynamics of eosinophils during a more prolonged period of allergen exposure and the activation of eosinophils induced by allergen challenge. OBJECTIVE The aim of this study was to investigate the dynamics and activation of the eosinophils in the nasal mucosa of patients with an isolated grass pollen allergy during an out-of-season 2-week allergen exposure, mimicking the natural grass pollen season. METHODS Seventeen patients with isolated grass pollen allergy and four control subjects were challenged daily with the allergen during a 2-week period in the winter. Nasal brush specimens were obtained before provocation and each day during the provocation period. Biopsy specimens were obtained once before, six times during, and once after the provocation period. Preparations made of nasal brush and nasal biopsy specimens were stained with the monoclonal antibody BMK 13 and Giemsa stain as paneosinophil markers and with the monoclonal antibody EG2 to identify activated eosinophils. RESULTS We found significant increases in the total number of eosinophils and the number of activated eosinophils in the epithelium and lamina propria. These increases were most explicit in the second week. BMK 13 was found to be a paneosinophil marker superior to Giemsa staining. CONCLUSION Eosinophils are not only involved in the acute and late phases of the allergic reaction but are probably even more involved in the chronic phase.

Effect of 3 months' nasal steroid therapy on nasal T cells and Langerhans cells in patients suffering from allergic rhinitis

The effect of nasal corticosteroid therapy on allergic rhinitis is uncertain. In a double‐blind, placebo‐controlled study over 3 months, we investigated the influence of a new corticosteroid spray, fluticasone propionate aqueous nasal spray (FPANS), on Langerhans cells (CD1a+ cells), HLA‐DR+ cells, and T cells in nasal mucosa. Efficacy was evaluated by nasal symptom score. This treatment significantly decreased the number of CDla+ cells and HLA‐DR+ cells in the nasal mucosa. Furthermore, a clear trend of decreasing numbers of T cells in nasal epithelium was found. No change in nasal symptom score was found after the treatment period. These findings suggest that fluticasone propionate aqueous nasal spray decreases the antigen presentation in nasal allergy.

Characterization and quantification of cellular infiltrates in nasal mucosa of patients with grass pollen allergy, non-allergic patients with nasal polyps and controls.

Little is known about cellular infiltrates in nasal mucosa and the differences between these infiltrates in allergic and non-allergic patients. A reproducible and objective method making use of monoclonal antibodies for the quantification and characterization of cellular infiltrates in biopsy specimens of nasal mucosa is described. This method was used to study quantitative differences in cellular infiltrates in the epithelium and lamina propria of the nasal mucosa of patients with isolated grass pollen allergy, non-allergic patients with nasal polyps, and controls. A surprisingly wide variation was found in all groups. In all groups the T lymphocytes were much more numerous than the B lymphocytes. The number of CD8+ cells exceeded the number of CD4+ cells in the epithelium but in the lamina propria the numbers were approximately equal. Significant differences between the three groups were found with respect to the number of CD1+, IgE+, neutrophils and cytoplasmic IgG4+ cells. No significant differences were found in the numbers of CD4+, CD8+, CD14+, CD22+, HLA-DR+, IgG1-3+ cells or eosinophils. The use of biopsy in combination with monoclonal antibodies is an easy and well-tolerated method to study immunological reactions in the nasal mucosa. The results of this study indicate a possible role for a T-cell-mediated response in allergic rhinitis.

Mast cells, eosinophils and IgE-positive cells in the nasal mucosa of patients with vasomotor rhinitis: an immunohistochemical study

Vasomotor rhinitis (VMR) is a disorder of unknown pathogenesis. Forty patients with VMR were carefully selected on the basis of inclusion and exclusion criteria proposed by Mygind and Weeke. Nasal biopsy specimens were taken in the patient group as well as in a group of ten controls. Brush cytology was also taken in the VMR group. Inflammatory cells were identified and counted in the nasal mucosa, with the use of immunohistochemical techniques and a panel of monoclonal antibodies. Eosinophils were studied with the use of BMK13, EG2, and Giemsa. Mast cells were studied with anti-chymase (B7), anti-tryptase (G3) and toluidine blue. Sections were stained with IgE as well. There was no significant difference in the number of eosinophils, mast cells and IgE-positive cells between the two groups. Additionally, in contrast with other reports, in sections that were double-stained with anti-chymase and anti-tryptase, single chymase-positive cells were found.

Long-term effects of corticosteroid nasal spray on nasal inflammatory cells in patients with perennial allergic rhinitis

The effect of long‐term topical nasal corticosteroid therapy on nasal inflammatory cells is unclear.

Local corticosteroid treatment: the effect on cells and cytokines in nasal allergic inflammation

Regular and prophylactic use of topical corticosteroids is a well tolerated and effective treatment for allergic rhinitis. The symptomatology of allergic rhinitis is considered to be the result of the accumulation and activation of infiltrating inflammatory cells, releasing mediators, and cytokines. Corticosteroids can suppress many stages of the allergic inflammatory process. This may explain their potent effect on allergic symptomatology. The reduction in cell numbers and probably also cytokines by local corticosteroid therapy differs from cell to cell. Some cells, such as antigen presenting (Langerhans) cells and eosinophils, are highly sensitive to corticosteroid treatment. Others, like T cells, are only significantly reduced in exaggerated situations, for instance after provocation with a high allergen dose or after treatment with a high dose of corticosteroids. Some cells, like macrophages, are not influenced at all.

Preventive treatment of intranasal fluticasone propionate reduces cytokine mRNA expressing cells before and during a single nasal allergen provocation

The local production and release of a number of cytokines regulate allergic upper airway inflammation. Medication is usually used at the presentation of the first symptoms. There are, however, clues that it is advisable to start taking the corticosteroid before the grass pollen season begins.

The effect of fluticasone propionate aqueous nasal spray on nasal mucosal inflammation in perennial allergic rhinitis

Mast cell degranulation, and the subsequent recruitment of infiltrating inflammatory cells, such as eosinophils, into the nasal mucosa has long been considered the most important model to explain allergic rhinitis. Several studies show a decrease in the number of eosinophils and possibly also mast cells during local corticosteroid treatment. Over the last decade, a new model to explain allergic inflammation has evolved. In this model, Langerhans’cells and T‐cells play an important role. Langerhans’cells possess a high affinity receptor for IgE. In patients with allergic rhinitis, allergen provocation results in stimulation of T‐cells by the IgE‐positive Langerhans’cells. The T‐cells produce a number of cytokines which stimulate IgE production as well as the inflammatory reaction. The number of T‐cells is not usually influenced by corticosteroid treatment; however, the function of the T‐cells, shown by the spectrum of cytokines produced, is clearly influenced. The cells that are most dramatically affected by local corticosteroid treatment are the Langerhans’cells, which completely disappear during treatment. This decrease suggests that there is a reduction in antigen presentation. The subsequent decrease in T‐cell stimulation may result in a reduction of the reactions that are dependent on T‐cell‐derived mediators.