From Dysgammaglobulinemia to Autosomal-Dominant Activation-Induced Cytidine Deaminase Deficiency: Unraveling an Inherited Immunodeficiency after 50 Years

Fadlallah, Jehane; Chentout, Loïc; Boisson, Bertrand; Pouliet, Aurore; Masson, Cécile; Morin, Florence; Durandy, Anne; Casanova, Jean‐Laurent; Oksenhendler, Éric; Kracker, Sven

doi:10.1016/j.jpeds.2020.03.024

Cited by 6 publications

(12 citation statements)

References 22 publications

(15 reference statements)

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“…These probably represent the first reports of XL and AR hyper-IgM syndrome ( Fig. 3 ; Fadlallah et al, 2020 ; Rosen and Bougas, 1963 ). Cooper et al (1965) and Siegal et al (1971) extended Rosen’s observation by reporting additional cases of “XL immunodeficiency with hyper-IgM syndrome” (HIGM) and likely cases of AR HIGM, as well as examples of “agammaglobulinemia with B cells” ( Cooper and Lawton, 1972 ; Siegal et al, 1971 ).…”

Section: Introductionmentioning

confidence: 54%

“…These patients presented with recurrent infection, increased levels of serum IgM, reduced serum IgG and IgA, and impaired Ab responses to vaccines and infection. However, whilst CSR was abolished in vivo and in vitro, SHM was unaffected in these patients ( Durandy et al, 2007 ; Fadlallah et al, 2020 ; Imai et al, 2005 ; Kasahara et al, 2003 ; Kermode et al, 2022 ; Fig. 2 ).…”

Section: Introductionmentioning

confidence: 92%

“…Interestingly, monoallelic AICDA variants that truncate the last 10–12 amino acids of AID protein have been identified in 18 patients from seven kindreds with a hyper-IgM-type phenotype ( Durandy et al, 2007 ; Fadlallah et al, 2020 ; Imai et al, 2005 ; Kasahara et al, 2003 ; Kermode et al, 2022 ; Fig. 3 ).…”

Section: Introductionmentioning

confidence: 99%

“…Thus, AD AICDA variants affecting the C-terminal domain of AID can disrupt Ig CSR resulting in humoral immunodeficiency. This likely results from a DN effect of the truncated AID protein, rather than haploinsufficiency, because carriers of heterozygous AICDA variants—including null mutation—that are pathogenic in the homozygous state are healthy ( Durandy et al, 2007 ; Fadlallah et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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Inborn errors of human B cell development, differentiation, and function

Tangye

Nguyen

Deenick

et al. 2023

Journal of Experimental Medicine

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B cells develop from hematopoietic stem cells in the bone marrow. Once generated, they serve multiple roles in immune regulation and host defense. However, their most important function is producing antibodies (Ab) that efficiently clear invading pathogens. This is achieved by generating memory B cells that rapidly respond to subsequent Ag exposure, and plasma cells (PCs) that continually secrete Ab. These B cell subsets maintain humoral immunity and host protection against recurrent infections for extended periods of time. Thus, the generation of antigen (Ag)-specific memory cells and PCs underlies long-lived serological immunity, contributing to the success of most vaccines. Our understanding of immunity is often derived from animal models. However, analysis of individuals with monogenic defects that disrupt immune cell function are unprecedented models to link genotypes to clinical phenotypes, establish mechanisms of disease pathogenesis, and elucidate critical pathways for immune cell development and differentiation. Here, we review fundamental breakthroughs in unraveling the complexities of humoral immunity in humans that have come from the discovery of inborn errors disrupting B cell function.

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Section: Introductionmentioning

confidence: 54%

Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inborn errors of human B cell development, differentiation, and function

Tangye

Nguyen

Deenick

et al. 2023

Journal of Experimental Medicine

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“…In addition to autosomal dominant mutations in TCF3, which was included in the agammaglobulinemia phenotype, autosomal recessive mutations in TCF3 have also been shown to result in E47 transcription factor deficiency [13]. Although autosomal recessive mutations in AID are well known to be associated with primary antibody deficiency with normal or elevated IgM, recently, autosomal dominant mutations in AID have also been shown to result in a similar phenotypic disorder [14]. Five new genes associated with a CVID-like phenotype have been reported since 2017, including ARHGEF1 , SH3KBP1 (CIN85), SEC61A1 , RAC2 , PIK3CG.…”

Section: New Inborn Errors Of Immunity For 2019 and 2020mentioning

confidence: 99%

New primary immunodeficiencies 2021 context and future

Demirdağ

Fuleihan

Orange

et al. 2021

Current Opinion in Pediatrics

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Purpose of review Primary immunodeficiency diseases (PIDs), also called inborn errors of immunity (IEI), are genetic disorders classically characterized by an increased susceptibility to infection and/or disruption in the regulation of an immunologic pathway. This review summarizes and highlights the new IEI disorders in the IUIS 2019 report and 2020 interim report and discusses the directions for the future management of PIDs. Recent findings Since 2017, the International Union of Immunologic Societies (IUIS) IEI committee has updated the IUIS classification of IEIs with 88 new gene defects and 75 new immune disorders. The increased utilization of genetic testing and advances in the strategic evaluation of genetic variants have identified, not only novel IEI disorders, but additional genetic causes for known IEI disorders. Investigation of potential immune susceptibilities during the ongoing COVID-19 pandemic suggests that defects in Type I interferon signalling may underlie more severe disease. Summary The rapid discovery of new IEIs reflects the growing trend of applying genetic testing modalities as part of medical diagnosis and management. In turn, elucidating the pathophysiology of these novel IEIs have enhanced our understanding of how genetic mutations can modulate the immune system and their consequential effect on human health and disease.

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