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Primary humoral immunodeficiency (PHID), such as common variable immunodefiency, are the most common symptomatic primary immunodeficiency in adults, in France. Patients are more prone to infections (particularly bacterial upper and lower respiratory tract infections), auto-immunity and atopic manifestations. Morbidity and mortality in PHID are mainly linked to the presence of bronchiectasis, which can lead to infections and to chronic respiratory failure. However, bronchiectasis in these patients can be asymptomatic for a long time. There is no known predictive factors to identify patients more susceptible to develop bronchiectasis and notably, there was no link between the number of previous infectious episodes and bronchiectasis. A marked IgM deficiency and switched memory B cell deficiency might be associated with bronchiectasis.
Thoracic CT-scan is recommended at PHID diagnosis but there is no guideline for follow-up, thus leading to bronchiectasis being under-diagnosis or leading to delayed diagnosis
Full description
Common variable immunodeficiency (CVID) and other antibody deficiencies like immunoglobin G subclass deficiency and selective IgM deficiency are the most frequent clinically significant primary immunodeficiencies (PID) in adults. Prevalence in France in 2009 was 2.11/100.000 people.
These immunodeficiencies are characterized by a significant decrease in serum immunoglobulin concentrations and antibodies production. In some patients, qualitative and/or quantitative alterations in B cells repertoire and sometimes in T cells repertoire are observed. Consequently, patients are more prone to bacterial infections, respiratory manifestations, auto-immune diseases, atopic manifestations, neoplastic complications. Respiratory manifestations are the main complication responsible for the morbidity and mortality in PHID. Bronchiectasis are one of the observed pulmonary complications. It is characterized by pathological and permanent dilatation of the airways, as demonstrated by a thoracic CT-scan. Its frequency varies from a study to another, ranging from 20% to 60% in different PHID populations. Some patients with bronchiectasis can be asymptomatic, while others can present daily symptoms of cough and sputum production with periodic worsening of their symptoms (exacerbations). It can lead to chronic respiratory failure, more infectious complications and altered quality of life. Moreover, mortality in patients with bronchiectasis (whatever the cause) is twice as high than in general population.
A thoracic CT-scan is therefore recommended at PHID diagnosis. However, there is no recommendation concerning screening of this complication during follow-up.
Pathophysiology of bronchiectasis in general is described as a cycle of events promoting impaired mucociliary clearance and retention of airways secretions, leading to chronic infection and thus to inflammatory response, leading to abnormal remodeling oh the airways.
To date, it is not known if some PHID patients are more prone to developing bronchiectasis. There is no statistical link with the number of past infectious events. Some studies suggested that patients with lower IgM concentration or lower switched memory B cell might be more at risk.
Concerning T-cell subset, polarization of CD4 T helper cells response as well as T follicular helper implication might be of interest. Indeed, in auto-immune manifestations in patients with primary immunodeficiency, T follicular helper cells (T cells implied in regulation of B -cells response in germinal centers) are sometimes impaired.
Another interesting phenomenon has been described in chronic obstructive pulmonary disease (another pulmonary disease, presenting similar clinical and pathophysiological mechanisms with bronchiectasis), where lung-infiltrating inflammatory cells secrete proteases participating in elastin breakdown a specific marker of elastin degradation genesis of elastin-derived peptides. These peptides modulate CD4+ T cell (T helper) response and pro-inflammatory cytokine production. As inflammatory response in patients with PHID can differ from immunocompetent patients, modulation of pro-inflammatory T helper cell response by elastin-derived peptides might also be different, participating in the abnormal remodeling of the airways.
In the Champagne-Ardenne region, PHID prevalence is high (5.37/100.000 habitants), however, we do not have data concerning bronchiectasis prevalence in this population and its repercussion on respiratory function and quality of life for our patients. Moreover, a better understanding of pathophysiology and factors associated with the presence of bronchiectasis may lead to better and more personalized care (diagnostic and therapeutic).
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inclusion criteria :
Patients with primary humoral immunodeficiency defined as following :
Adult patients
Patients with or without previously identified pulmonary complications
Patients agreeing to participate to the study
Patients insured under the French social security system
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46 participants in 1 patient group
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Ailsa ROBBINS; Amélie SERVETTAZ
Data sourced from clinicaltrials.gov
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