Common Variable Immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency in adults. The diagnostic criteria have been revised and criticized in the past. The main features include decreased or absent class-switched immunoglobulins, decreased responses to vaccines, defects in B-cell differentiation, susceptibility to infections, and on the other hand autoimmunity, granulomatous disease, and lymphoproliferative.
There is a wide variety of clinical manifestations in CVID patients ranging from “infections only” to different autoimmune and inflammatory manifestations, probably representing different entities.
Modern genetic methods have unveiled monogenic primary immunodeficiencies in less than 25% of patients under the umbrella diagnosis of CVID. To make things more complicated, some monogenic PIDs that originally were described with a clinical picture distinct from CVID have also been found in CVID cohorts, e.g. ADA2, RAC2, and STAT3 GOF.
The lack of monogenic defects in the majority of CVID cases suggests polygenic inheritance, epigenetic and environmental risk factors contributing to the disease pathogenesis, which therefore requires a careful recognition of general principles of immune dysregulation underlying CVID.
Research will not only include B- or T-cell intrinsic defects but will have to address at the same time the environment in the immunological niches like the bone marrow, secondary lymphoid tissues, and the different sites of inflammation.
Currently, the role of epigenetic, environmental, or host-intrinsic factors like dysregulated microbiome or somatic mutations in the development of CVID is largely unknown.
In this Research Topic, we aim to bring together researchers to broaden the view to the different ways CVID, as well as its complications, originate and develop.
We welcome the submission of Review, Original Research (both clinical and experimental), and Perspective articles covering, but not limited to, the following sub-topics:
• Functional studies of the rare monogenic defects that can cause CVID. Also, case reports of unexpected genetic defects resulting in CVID-like phenotype are welcome.
• The functional role of polygenic/risk gene inheritance in CVID
• The role of altered B- and T cell differentiation and their interplay in CVID
• The role of other cells in antibody failure and immune dysregulation in CVID
• The functional role of epi- and metagenetic alterations in CVID-like diseases
• Potential role of somatic mutations of immunologic genes in CVID patients
• Potential role of environmental factors in the pathogenesis of CVID
• Potential roles of niche-specific (e.g. bone marrow, lymph node, gut, lung) environmental factors in the development of CVID or its complications
• The role of infectious diseases experienced by the individual in the pathogenesis of CVID
Topic Editor Dr. Klaus Warnatz received research grants from BMS and TAKEDA. Dr. Klaus Warnatz also received honoraria for participation in advisory boards for LFB and TAKEDA. All other Topic Editors declare no competing interests with regards to the Research Topic subject.
Common Variable Immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency in adults. The diagnostic criteria have been revised and criticized in the past. The main features include decreased or absent class-switched immunoglobulins, decreased responses to vaccines, defects in B-cell differentiation, susceptibility to infections, and on the other hand autoimmunity, granulomatous disease, and lymphoproliferative.
There is a wide variety of clinical manifestations in CVID patients ranging from “infections only” to different autoimmune and inflammatory manifestations, probably representing different entities.
Modern genetic methods have unveiled monogenic primary immunodeficiencies in less than 25% of patients under the umbrella diagnosis of CVID. To make things more complicated, some monogenic PIDs that originally were described with a clinical picture distinct from CVID have also been found in CVID cohorts, e.g. ADA2, RAC2, and STAT3 GOF.
The lack of monogenic defects in the majority of CVID cases suggests polygenic inheritance, epigenetic and environmental risk factors contributing to the disease pathogenesis, which therefore requires a careful recognition of general principles of immune dysregulation underlying CVID.
Research will not only include B- or T-cell intrinsic defects but will have to address at the same time the environment in the immunological niches like the bone marrow, secondary lymphoid tissues, and the different sites of inflammation.
Currently, the role of epigenetic, environmental, or host-intrinsic factors like dysregulated microbiome or somatic mutations in the development of CVID is largely unknown.
In this Research Topic, we aim to bring together researchers to broaden the view to the different ways CVID, as well as its complications, originate and develop.
We welcome the submission of Review, Original Research (both clinical and experimental), and Perspective articles covering, but not limited to, the following sub-topics:
• Functional studies of the rare monogenic defects that can cause CVID. Also, case reports of unexpected genetic defects resulting in CVID-like phenotype are welcome.
• The functional role of polygenic/risk gene inheritance in CVID
• The role of altered B- and T cell differentiation and their interplay in CVID
• The role of other cells in antibody failure and immune dysregulation in CVID
• The functional role of epi- and metagenetic alterations in CVID-like diseases
• Potential role of somatic mutations of immunologic genes in CVID patients
• Potential role of environmental factors in the pathogenesis of CVID
• Potential roles of niche-specific (e.g. bone marrow, lymph node, gut, lung) environmental factors in the development of CVID or its complications
• The role of infectious diseases experienced by the individual in the pathogenesis of CVID
Topic Editor Dr. Klaus Warnatz received research grants from BMS and TAKEDA. Dr. Klaus Warnatz also received honoraria for participation in advisory boards for LFB and TAKEDA. All other Topic Editors declare no competing interests with regards to the Research Topic subject.