Multicenter experience in hematopoietic stem cell transplantation for serious complications of common variable immunodeficiency

Wehr, Claudia; Gennery, Andrew R.; Lindemans, Caroline A.; Schulz, Ansgar; Hoenig, Manfred; Marks, Reinhard; Recher, Mike; Gruhn, Bernd; Holbro, Andreas; Heijnen, Ingmar; Meyer, Deborah; Grigoleit, Goetz Ulrich; Einsele, Hermann; Baumann, Ulrich; Witte, T.J. de; Sykora, Karl Walter; Goldacker, Sigune; Regairaz, Lorena; Aksoylar, Serap; Ardeniz, Ömür; Zecca, Marco; Zdziarski, Przemysław; Meyts, Isabelle; Matthes‐Martin, Susanne; Imai, Kohsuke; Kamae, Chikako; Fielding, Adele K.; Seneviratne, Suranjith L.; Mahlaoui, Nizar; Slatter, Mary; Güngör, Tayfun; Arkwright, Peter D.; Montfrans, Joris van; Sullivan, Kathleen E.; Grimbacher, Bodo; Cant, Andrew J.; Peter, Hans; Finke, Juergen; Gaspar, H. Bobby; Warnatz, Klaus; Rizzi, Marta

doi:10.1016/j.jaci.2014.11.029

Cited by 126 publications

(95 citation statements)

References 43 publications

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“…4,5,29–31 These complications require treatment with immunosuppressants, immunomodulators, or, in the worst cases, stem cell transplantation. 32–34 Seeking to understand the underlying differences in CVID groups, investigators have examined immunologic profiles, clinical phenotypes, cell populations and functions, 4,6,35 molecular aspects, 36 and cytokines, as previously reviewed. 37 Our recent work used a modular whole blood RNA approach to probe the inflammatory signature in patients with CVID.…”

Section: Discussionmentioning

confidence: 99%

Expansion of inflammatory innate lymphoid cells in patients with common variable immune deficiency

Cols

Rahman

Maglione

et al. 2016

Journal of Allergy and Clinical Immunology

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Background Common variable immunodeficiency (CVID) is an antibody deficiency treated with immunoglobulin; however, patients can have noninfectious inflammatory conditions that lead to heightened morbidity and mortality. Objectives Modular analyses of RNA transcripts in whole blood previously identified an upregulation of many interferon-responsive genes. In this study we sought the cell populations leading to this signature. Methods Lymphoid cells were measured in peripheral blood of 55 patients with CVID (31 with and 24 without inflammatory/autoimmune complications) by using mass cytometry and flow cytometry. Surface markers, cytokines, and transcriptional characteristics of sorted innate lymphoid cells (ILCs) were defined by using quantitative PCR. Gastrointestinal and lung biopsy specimens of subjects with inflammatory disease were stained to seek ILCs in tissues. Results The linage-negative, CD127+, CD161+ lymphoid population containing T-box transcription factor, retinoic acid–related orphan receptor (ROR) γt, IFN-γ, IL-17A, and IL-22, all hallmarks of type 3 innate lymphoid cells, were expanded in the blood of patients with CVID with inflammatory conditions (mean, 3.7% of PBMCs). ILCs contained detectable amounts of the transcription factors inhibitor of DNA binding 2, T-box transcription factor, and RORγt and increased mRNA transcripts for IL-23 receptor (IL-23R) and IL-26, demonstrating inflammatory potential. In gastrointestinal and lung biopsy tissues of patients with CVID, numerous IFN-γ+RORγt+CD3− cells were identified, suggesting a role in these mucosal inflammatory states. Conclusions An expansion of this highly inflammatory ILC population is a characteristic of patients with CVID with inflammatory disease; ILCs and the interferon signature are markers for the uncontrolled inflammatory state in these patients.

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Section: Discussionmentioning

confidence: 99%

Expansion of inflammatory innate lymphoid cells in patients with common variable immune deficiency

Cols

Rahman

Maglione

et al. 2016

Journal of Allergy and Clinical Immunology

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“…239 More recently, a retrospective study of 25 patients with CVID receiving HSCT in 14 worldwide centers has been reported. 240 The indication for HSCT was hematologic malignancy in 7 patients; 6 (83%) of these survived. The other 18 patients had 1 or more of the following conditions refractory to conventional therapies: autoimmune cytopenias, respiratory or gastrointestinal infections, interstitial/granulomatous lung disease, and/or autoimmune enteropathy.…”

Section: Managementmentioning

confidence: 99%

International Consensus Document (ICON): Common Variable Immunodeficiency Disorders

Bonilla

Barlan

Chapel

et al. 2016

The Journal of Allergy and Clinical Immunology: In Practice

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681

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The International Collaboration in Asthma, Allergy and Immunology initiated an international coalition among the American Academy of Allergy, Asthma & Immunology; the European Academy of Allergy and Clinical Immunology; the World Allergy Organization; and the American College of Allergy, Asthma & Immunology on common variable immunodeficiency. An author group was formed and then divided into individual committees. Within the committee, teams of authors were subgrouped to generate content for specific sections of the document. Content was derived from literature searches, relevant published guidelines, and clinical experience. After a draft of the document was assembled, it was collectively reviewed and revised by the authors. Where evidence was lacking or conflicting, the information presented represents the consensus expert opinion of the group. The full document was then independently reviewed by 5 international experts in the field, none of whom was among the authors of the original. The comments of these reviewers were incorporated before submission for publication.

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“…These 2 studies suggest the possibility of defects in stem cells of IgA-deficient patients. However, to develop a full picture of bone marrow transplantations’ efficacy in IgA-deficient patients, additional studies will be needed as side effects may arise, as experienced in patients with CVID [49]. …”

Section: Pathogenesis Of Sigadmentioning

confidence: 99%

The Heterogeneous Pathogenesis of Selective Immunoglobulin A Deficiency

Bagheri¹,

Sanaei²,

Yazdani³

et al. 2019

Int Arch Allergy Immunol

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Selective immunoglobulin A deficiency (SIgAD) is the most prevalent type of primary immunodeficiency disorder. The phenotypic feature of SIgAD is related to a defect in B lymphocyte differentiation into plasma cell-producing immunoglobulin A (IgA). In this review, we summarize the recent advances in this regard. Genetic (including major histocompatibility complex [MHC] and non-MHC genes), immunologic (including B and T lymphocyte subsets abnormality), cytokines/chemokines and their related receptors, apoptosis and microbiota defects are reviewed. The mechanisms leading to SIgAD are most likely multifactorial and it can be speculated that several pathways controlling B cells functions or regulating epigenetic of the IGHA gene encoding constant region of IgA heavy chain and long-term survival of IgA switched memory B cells and plasma cells may be defective in different SIgAD patients.

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Multicenter experience in hematopoietic stem cell transplantation for serious complications of common variable immunodeficiency

Cited by 126 publications

References 43 publications

Expansion of inflammatory innate lymphoid cells in patients with common variable immune deficiency

Expansion of inflammatory innate lymphoid cells in patients with common variable immune deficiency

International Consensus Document (ICON): Common Variable Immunodeficiency Disorders

The Heterogeneous Pathogenesis of Selective Immunoglobulin A Deficiency

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