DNAH11 Localization in the Proximal Region of Respiratory Cilia Defines Distinct Outer Dynein Arm Complexes.

Primary ciliary dyskinesia (PCD) is a recessively inherited disease that leads to chronic respiratory disorders owing to impaired mucociliary clearance. Conventional transmission electron microscopy (TEM) is a diagnostic standard to identify ultrastructural defects in respiratory cilia but is not useful in approximately 30% of PCD cases, which have normal ciliary ultrastructure. DNAH11 mutations are a common cause of PCD with normal ciliary ultrastructure and hyperkinetic ciliary beating, but its pathophysiology remains poorly understood. We therefore characterized DNAH11 in human respiratory cilia by immunofluorescence microscopy (IFM) in the context of PCD. We used whole-exome and targeted next-generation sequence analysis as well as Sanger sequencing to identify and confirm eight novel loss-of-function DNAH11 mutations. We designed and validated a monoclonal antibody specific to DNAH11 and performed high-resolution IFM of both control and PCD-affected human respiratory cells, as well as samples from green fluorescent protein (GFP)-left-right dynein mice, to determine the ciliary localization of DNAH11. IFM analysis demonstrated native DNAH11 localization in only the proximal region of wild-type human respiratory cilia and loss of DNAH11 in individuals with PCD with certain loss-of-function DNAH11 mutations. GFP-left-right dynein mice confirmed proximal DNAH11 localization in tracheal cilia. DNAH11 retained proximal localization in respiratory cilia of individuals with PCD with distinct ultrastructural defects, such as the absence of outer dynein arms (ODAs). TEM tomography detected a partial reduction of ODAs in DNAH11-deficient cilia. DNAH11 mutations result in a subtle ODA defect in only the proximal region of respiratory cilia, which is detectable by IFM and TEM tomography.

Agreement rate of skin prick test with tissue eosinophil count in patients with nasal polyps.

The pathogenetic mechanism of nasal polyps remains unknown, although allergy has been cited as an important factor in the etiology of nasal polyposis. Currently there is no definite histological criterion for differentiation of allergic from inflammatory nasal polyp. However, in a few studies, tissue eosinophil count has been used for this. This study aimed to find out the agreement rate of skin prick test and tissue eosinophil count in patients with nasal polyposis. Twenty five patients (18 males, 7 females) with nasal polyp were enrolled in this study. For each patient tissue sample from polyp material was taken for histopathological investigation. Moreover, skin prick test was performed for each patient using eleven common aeroallergens. Skin prick test was positive in 48% of the patients. Tissue eosinophil count of more than 50% was found in 75% of skin prick positive and in 69.2% of skin prick negative patients. Also tissue eosinophil count of more than 50% was found in 69.2% of patients with typical allergic symptoms as well as 75% of patients without allergic symptoms. No agreement was found between skin prick tests and tissue eosinophil counts in patients with nasal polyp. Also no difference was found between the tissue eosinophil counts in allergic and non allergic patients. Considering these results, it can be concluded that having a high tissue eosinophil count in patients with nasal polyp does not indicate that the polyp is allergic.

Prevalence of aeroallergens in allergic rhinitis in shiraz.

Allergic rhinitis is an extremely common disease worldwide. Aeroallergens are very often involved in allergic rhinitis and their prevalence may vary in different regions. The causative allergens of allergic rhinitis in our area are unknown.The purpose of this study was to determine the prevalence of skin reactivity to different aeroallergens in patients with allergic rhinitis in the city of Shiraz, Iran.A total of 212 patients who were referred to Motahari Allergy Clinic with chronic rhinitis were subjected to skin prick test (SPT) with a series of common allergenic extracts including grasses, weeds, trees, house dust mites and moulds. One hundred and thirty two subjects (62.2%) had positive SPT to at least one aeroallergen. Male to female ratio was 1.2 and mean age was 18.2 years. The prevalence rates for allergen groups were: pollens (92.4%), mites (22.7%) and moulds (8.3%). Among 122 patients reactive to pollens, 92 (75.4%) showed skin reactivity to weeds, 78 (63.9%) to grasses and 68 (55.7%) to trees. Polysensitization was common, with 75.7% of all sensitized patients being positive to more than one aeroallergen.Pollens are the main sensitizing allergens among patients with allergic rhinitis in Shiraz. This pattern of prevalence was expected based on herbal geography, climate and also found to be compatible with the results from studies carried out in places with the same habitat.