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Titill: 
  • Titill er á ensku Selective Immunoglobulin A deficiency in Iceland. Epidemiology, clinical features and genetic analysis
  • Sértækur skortur á immúnóglóbúlíni A á Íslandi. Faraldsfræði, sjúkdómsbirting og tengsl við arfgerðarbreytingar
Námsstig: 
  • Doktors
Útdráttur: 
  • Útdráttur er á ensku

    Background: To date, more than 200 different types of primary immunodeficiencies (PID) have been identified. Selective IgA deficiency (SIgAD) is the most common PID within the human adaptive immune system, affecting approximately 1:600 in the Western world and in the Nordic countries alone more than 41,000 individuals can be expected to have SIgAD. While some SIgAD individuals appear healthy, others suffer from various diseases, and the clinical significance of SIgAD remains to be better defined. Moreover, the role of SIgAD in the pathogeneses of different diseases is often unclear and may be dependent on different environmental or genetic/epigenetic factors. Although recent multinational genetic studies have provided some insight in the pathogenesis of SIgAD they have also brought into light the true complexity of the matter.
    The aims of this study: (i) investigation of the prevalence of SIgAD in both healthy individuals and disease cohorts. (ii) investigation of the potential clinical consequences of SIgAD, including the effect on health-related quality of live, using a randomly selected cohort for comparison. (iii) evaluations of the association of HLA genotypes with specific clinical phenotypes.
    Material and methods: SIgAD individuals were recruited by screening for IgA deficiency among blood donors, re-evaluating SIgAD individuals from an earlier screening of blood donors (1974-1979) and by evaluating individuals that were found during the time period 1992-2006 to have low serum IgA levels when analysed at the departments of clinical chemistry and immunology, Landspitali – The National University Hospital of Iceland. A total of 43 SIgAD individuals (32 adults and 11 children) were identified. The adult cohort was compared with an age- and gender-matched control cohort, randomly selected from the Icelandic National Registry (63 adults). Serum IgA was also evaluated in cohorts of patients with diabetes type 1 in Iceland and patients with Graves´ disease and/or with positive thyrotropin receptor autoantibody (TRAb+) in serum, in both Iceland and Sweden.
    Initially the SIgAD individuals and the controls answered 3 self-administered questionnaires, collecting self-reported clinical data and health related quality of live (HRQL) measures. They were then subjected to an extensive interview, physical examination and laboratory assessments, including skin prick test, lung spirometry and urea breath test. A detailed oral examination was also performed by a dentist. A comprehensive family history was obtained from the SIgAD individuals and serum IgA was measured in all consenting first-degree relatives and their disease history confirmed.
    Results: From the screening of 4004 Icelandic blood donors, 7 SIgAD individuals were found, giving the prevalence 1:572. No SIgAD individuals were found among 204 type 1 diabetes patients and 299 Icelandic TRAb-seropositive individuals. In contrast, 14 SIgAD individuals were identified in a Swedish cohort of 841 TRAb-seropositive individuals (1:60).
    The SIgAD individuals reported significantly more frequent and severe upper and lower respiratory infections, compared with the controls, and they also had more often had tonsillectomy (44% versus 24%) and adenoidectomy (31% versus 8%) as well as reporting more often pharyngitis, stomatitis and labial herpes. Moreover, the SIgAD individuals had more often been diagnosed with allergic diseases, and they had more severe allergic- and asthma manifestations. They also had significantly higher prevalence of IgE sensitization (56.3% vs. 22.2%). High prevalence of autoimmunity was also found among the adult SIgAD individuals (25%) and their 1° relatives (10%). Moreover, TRAb-seropositivity was high within the SIgAD cohort or 5/43 (11.6%). Altogether, 27 of the 32 adult SIgAD individuals (84.4%) were affected by recurrent infections, allergic diseases and/or autoimmunity, compared with 30 (47.6%) of the controls. Detailed dental examination did not reveal a significant difference in periodontal or dental health, between the SIgAD individuals and the controls. The SIgAD individuals did not report significantly worse global HRQL, compared with the controls. However, the SIgAD individuals reported a worse infection-related HRQL, with increased fear of getting infections and perceived increased susceptibility to infections correlating with poorer physical health and HRQL. Similarly, the number of antibiotic treatments prescribed during the preceding year was found to be independent risk factors for worse global HRQL.
    The HLA genotyping revealed a high prevalence of the HLA-B8,DR3,DQ2 haplotype in the Icelandic SIgAD cohort (41.1%) and possibly a protective role of HLA-DQ6 in thyroid autoantibody formation.
    Conclusion: The findings indicate that clinical complications of SIgAD may be more common than previously stated. Thus, most of the SIgAD individuals were affected by recurrent infections, allergy or autoimmunity. The high prevalence o

Samþykkt: 
  • 10.7.2013
URI: 
  • http://hdl.handle.net/1946/15994


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