Primary immunodeficiencies are an heterogeneous group of diseases characterized by an increased risk of infections and malignancies, but also by autoimmune and inflammatory complications, making them both a diagnostic and a therapeutic challenge. This seems particularly true for pulmonary disease in primary immunodeficiency, where the risk and high frequency of infections sometimes mask the more ominous threat of interstitial lung diseases (ILD). ILDs are defined by a histopathological pattern of interstitial and alveolar inflammation. Allergens and toxins may cause ILD, but in most cases there seems to be an intrinsic inflammatory etiology. ILD in primary immunodeficiencies is associated with signs of systemic immune activation with inflammatory T- and B-cell phenotypes and carry high risk of other immune-driven complications like lymphoid infiltrates and autoimmune cytopenias. An increased frequency of interstitial lung disease (ILD) is observed in a number of primary immunodeficiencies, most notably Common variable immunodeficiency (CVID) and syndromes associated with mutations in CTLA4, LRBA and PI3Kd.
CVID is the most common symptomatic primary immunodeficiency characterized by defects in B-cell differentiation and function, and subsequent hypogammaglobulinemia. In CVID, a form of ILD due to concomitant granulomatous disease has been observed in 10-30% of patients, and termed granulomatous-lymphocytic interstitial lung disease (GLILD). In recent years, different studies are contributing to identify new aspects of GLILD, such as increased B-cell activating factor (BAFF) release. A better understanding of the mechanisms of GLILD pathogenesis may contribute to identify new potential treatment targets, since, despite different etiology and immunological characteristics, ILD in other forms of primary immunodeficiencies may follow a similar clinical and histopathological pattern.
Patients with immune-driven complications of a primary immunodeficiency have traditionally been treated with corticosteroids, but the advent of monoclonal antibodies and other specific treatments has now allowed for a more targeted approach. In CVID, B-cell depleting therapy with rituximab has shown promising results, as well as abatacept in CTLA4-disease and rapamycin in patients with PI3Kd-mutation. The increasing number of distinct primary immunodeficiency syndromes, together with the evidence that the molecular mechanisms of ILD can be very heterogeneous among different forms of primary immunodeficiencies, demands for a better understanding of such mechanisms, in order to improve diagnostic and therapeutic strategies for ILD.
In this Research Topic we welcome Original Research, Review and Minireview articles aimed to bring together the most recent advances regarding the understanding of ILD pathogenesis in primary immunodeficiencies in terms of immunological mechanisms, clinical presentation and potential therapeutic targets.
Primary immunodeficiencies are an heterogeneous group of diseases characterized by an increased risk of infections and malignancies, but also by autoimmune and inflammatory complications, making them both a diagnostic and a therapeutic challenge. This seems particularly true for pulmonary disease in primary immunodeficiency, where the risk and high frequency of infections sometimes mask the more ominous threat of interstitial lung diseases (ILD). ILDs are defined by a histopathological pattern of interstitial and alveolar inflammation. Allergens and toxins may cause ILD, but in most cases there seems to be an intrinsic inflammatory etiology. ILD in primary immunodeficiencies is associated with signs of systemic immune activation with inflammatory T- and B-cell phenotypes and carry high risk of other immune-driven complications like lymphoid infiltrates and autoimmune cytopenias. An increased frequency of interstitial lung disease (ILD) is observed in a number of primary immunodeficiencies, most notably Common variable immunodeficiency (CVID) and syndromes associated with mutations in CTLA4, LRBA and PI3Kd.
CVID is the most common symptomatic primary immunodeficiency characterized by defects in B-cell differentiation and function, and subsequent hypogammaglobulinemia. In CVID, a form of ILD due to concomitant granulomatous disease has been observed in 10-30% of patients, and termed granulomatous-lymphocytic interstitial lung disease (GLILD). In recent years, different studies are contributing to identify new aspects of GLILD, such as increased B-cell activating factor (BAFF) release. A better understanding of the mechanisms of GLILD pathogenesis may contribute to identify new potential treatment targets, since, despite different etiology and immunological characteristics, ILD in other forms of primary immunodeficiencies may follow a similar clinical and histopathological pattern.
Patients with immune-driven complications of a primary immunodeficiency have traditionally been treated with corticosteroids, but the advent of monoclonal antibodies and other specific treatments has now allowed for a more targeted approach. In CVID, B-cell depleting therapy with rituximab has shown promising results, as well as abatacept in CTLA4-disease and rapamycin in patients with PI3Kd-mutation. The increasing number of distinct primary immunodeficiency syndromes, together with the evidence that the molecular mechanisms of ILD can be very heterogeneous among different forms of primary immunodeficiencies, demands for a better understanding of such mechanisms, in order to improve diagnostic and therapeutic strategies for ILD.
In this Research Topic we welcome Original Research, Review and Minireview articles aimed to bring together the most recent advances regarding the understanding of ILD pathogenesis in primary immunodeficiencies in terms of immunological mechanisms, clinical presentation and potential therapeutic targets.
