Article

Frequent respiratory tract infections in the canine model of X-linked ectodermal dysplasia are not caused by an immune deficiency

University of California, Davis, Davis, California, United States
Veterinary Immunology and Immunopathology (Impact Factor: 1.75). 09/2005; 107(1-2):95-104. DOI: 10.1016/j.vetimm.2005.04.005
Source: PubMed

ABSTRACT As in many human patients with X-linked hypohidrotic ectodermal dysplasia (XHED), XHED dogs are at an increased risk for pulmonary disorders. Localized immune system defects had been suspected previously in affected dogs because of frequent infections and unexpected deaths due to opportunistic respiratory tract infections. Experiments were designed to examine systemic and localized humoral and cellular responses, development and function of T cells, and thymic morphology. All dogs used in these experiments were clinically healthy at the time of examination and their immune responses were compared to normal littermates. Serum immunoglobulin concentrations differed somewhat between normal dogs and dogs affected with XHED but they were all within normal ranges. The XHED dogs responded appropriately to vaccination with tetanus toxoid suggesting normal systemic B and plasma cell function. Thymic morphology was compared between normal and affected dogs and T cells were assessed for functionality. Numbers and phenotypes of T and B cells in blood and thymus of affected dogs were within normal limits suggesting normal development of T cells. Cytotoxic and phagocytic ability of macrophages and neutrophils was also normal in affected dogs. In contrast, the secretory IgA concentrations found in affected dogs were significantly higher than in normal dogs, while lacrimal secretions were significantly decreased. These results suggest a compensatory mechanism for secretory IgA, so that the total amount equals that in normal dogs. The results presented in this study indicate that the XHED dogs have a relatively intact immune system and suggest that the same is true for humans with the homologous form of XHED.

Download full-text

Full-text

Available from: Margret L Casal, Jan 13, 2015
0 Followers
 · 
86 Views
  • Source
    • "Our XLHED dogs, however, have consistently shown signs of respiratory tract disease, which were fatal in two cases. Earlier studies demonstrated the lack of tracheal and bronchial glands, decreased mucociliary clearance, and frequent pneumonia [Casal et al., 2005]. In this same study we were able to show that the respiratory immunity did not appear to be impaired. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Patients with defective ectodysplasin A (EDA) have X-linked hypohidrotic ectodermal dysplasia (XLHED; OMIM#305100), a condition comprising hypotrichosis, inability to sweat, abnormal teeth, and frequent pulmonary infections. The XLHED dogs show the same clinical signs as humans with the disorder, including frequent respiratory infections that can be fatal. The respiratory disease in humans and dogs is thought to be due to the absence of tracheal and bronchial glands which are a vital part of the mucociliary clearance mechanism. In our XLHED model, the genetically missing EDA was replaced by postnatal intravenous administration of recombinant EDA resulting in long-term, durable corrective effect on adult, permanent dentition. After treatment with EDA, significant correction of the missing tracheal and bronchial glands was achieved in those dogs that received higher doses of EDA. Moreover, successful treatment resulted in the presence of esophageal glands, improved mucociliary clearance, and the absence of respiratory infection. These results demonstrate that a short-term treatment at a neonatal age with a recombinant protein can reverse a developmental disease and result in vastly improved quality of life.
    American Journal of Medical Genetics Part A 09/2009; 149A(9):2045-9. DOI:10.1002/ajmg.a.32916 · 2.05 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Alopecia, that is, lack of hair in any quantity, is a frequent complaint of pet owners. Although mostly acquired, rare congenital forms of alopecia exist that are associated with abnormalities in hair follicle morphogenesis. Congenital alopecias can result in changes in quality or quantity of hair follicles and the hair fibres produced by them. They vary in terms of clinical presentation and mode of inheritance. Histopathology is usually needed in order to differentiate between a reduced number of otherwise normal hair follicles and qualitative hair follicle abnormalities. Although our understanding of the molecular mechanisms that drive hair follicle morphogenesis in mice and humans has significantly increased during the last decade, still very little is known about congenital alopecias in domestic animals. Because of their rarity and the general lack of knowledge about their pathophysiology, classification of congenital alopecias in domestic animals is still unsatisfactory. This article reviews hair follicle morphogenesis and its most important molecular mechanisms, and it discusses the various forms of congenital alopecia occurring in domestic animals that have been described in the literature, differentiating between hair follicle aplasia, hair follicle dysplasia (i.e. defects associated with hair follicle development and defects associated with hair shaft formation), and neuroectodermal dysplasias, the latter involving the hair follicle pigmentary system.
    Veterinary Dermatology 01/2007; 17(6):393-410. DOI:10.1111/j.1365-3164.2006.00544.x · 1.99 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Every breath holds the potential to introduce infectious organisms and irritating particulates into the respiratory tract. Despite this continuous exposure, the lungs usually remain sterile. Further, potential pathogens are distinguished from innocuous particulates, thus sparing the respiratory tract from damaging inflammation. The article reviews the complex defenses used to protect the respiratory tract and also discusses the implications of failed defense systems.
    Veterinary Clinics of North America Small Animal Practice 10/2007; 37(5):845-60, v. DOI:10.1016/j.cvsm.2007.05.003 · 1.04 Impact Factor
Show more