Agammaglobulinemia with normal B-cell numbers in a patient lacking Bob1

Küry, Patrick; Staniek, Julian; Wegehaupt, Oliver; Janowska, Iga; Korinthenberg, Rudolf; Japaridze, Natia; Pendziwiat, Manuela; Helbig, Ingo; Verhoeyen, Els; Jung, Johannes; Oteyza, Andrés Caballero García de; Proietti, Michele; Phirtskhalaishvili, Tamar; Rtskhiladze, Irakli; Nielsen, Peter; Ehl, Stephan; Speckmann, Carsten; Rizzi, Marta

doi:10.1016/j.jaci.2021.01.027

Cited by 13 publications

(14 citation statements)

References 9 publications

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“…Novel gene defects have been found for most categories of IEI, including novel causes of: Combined immunodeficiencies ( LCP2 (SLP76) [ 12 ], PAX1 [ 13 , 14 ], ITPKB [ 15 ]; SASH3 [ 16 , 17 ], MAN2B2 [ 18 ], COPG1 [ 19 ], IKZF2 [ 20 – 23 ], CHUK [ 24 ], IKZF3 [ 25 , 26 ], CRACR2A [ 27 ], CD28 [ 28 ]) (Table 1 ; Supplementary Table 1 ); Combined immunodeficiencies with syndromic features ( MCM10 [ 29 , 30 ], IL6ST [ 31 – 33 ], DIAPH1 [ 34 ]) (Table 2 ; Supplementary Table 1 ); B cell deficiencies, agammaglobulinemia, or hypogammaglobulinemia ( FNIP1 [ 35 , 36 ], SP1I [ 37 ] , PIK3CG [ 38 , 39 ], POU2AF1 [ 40 ], CTNNBL1 [ 41 ], TNSRSF13 [ 42 ]) (Table 3 ; Supplementary Table 1 ); Immune dysregulation ( RHOG [ 43 ], SOCS1 [ 44 – 46 ], PDCD1 [ 47 ], ELF4 [ 48 , 49 ], TET2 [ 50 ], CEBPE [ 51 ], IKZF1 GOF [ 52 ]) (Table 4 ; Supplementary Table 1 ) neutropenia CXCR2 [ 53 ...…”

Section: Novel Inborn Errors Of Immunitymentioning

confidence: 99%

“…In addition to monogenic causes on this table, a small minority of patients with XLP (Table 4 ), WHIM syndrome (Table 6 ), ICF (Table 2 ), VODI (Table 2 ), thymoma with immunodeficiency (Good syndrome) or myelodysplasia are first seen by an immunologist because of recurrent infections, hypogammaglobulinemia and normal or reduced numbers of B cells Total number of mutant genes in Table 3 : 45. New inborn errors of immunity: 6 ( FNIP1 [ 35 , 36 ], SP1I [ 37 ] , PIK3CG [ 38 , 39 ], POU2AF1 [ 40 ], CTNNBL1 [ 41 ], TNSRSF13 [ 42 ]) EBV Epstein-Barr virus, COPD chronic obstructive pulmonary disease # Heterozygous variants in TNFRSF13B have been detected in healthy individuals, thus such variants are likely to be disease-modifying rather than disease-causing…”

Section: Novel Inborn Errors Of Immunitymentioning

confidence: 99%

“…B cell deficiencies, agammaglobulinemia, or hypogammaglobulinemia ( FNIP1 [ 35 , 36 ], SP1I [ 37 ] , PIK3CG [ 38 , 39 ], POU2AF1 [ 40 ], CTNNBL1 [ 41 ], TNSRSF13 [ 42 ]) (Table 3 ; Supplementary Table 1 );…”

Section: Novel Inborn Errors Of Immunitymentioning

confidence: 99%

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Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee

et al. 2022

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We report the updated classification of inborn errors of immunity, compiled by the International Union of Immunological Societies Expert Committee. This report documents the key clinical and laboratory features of 55 novel monogenic gene defects, and 1 phenocopy due to autoantibodies, that have either been discovered since the previous update (published January 2020) or were characterized earlier but have since been confirmed or expanded in subsequent studies. While variants in additional genes associated with immune diseases have been reported in the literature, this update includes only those that the committee assessed that reached the necessary threshold to represent novel inborn errors of immunity. There are now a total of 485 inborn errors of immunity. These advances in discovering the genetic causes of human immune diseases continue to significantly further our understanding of molecular, cellular, and immunological mechanisms of disease pathogenesis, thereby simultaneously enhancing immunological knowledge and improving patient diagnosis and management. This report is designed to serve as a resource for immunologists and geneticists pursuing the molecular diagnosis of individuals with heritable immunological disorders and for the scientific dissection of cellular and molecular mechanisms underlying monogenic and related human immune diseases.

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Section: Novel Inborn Errors Of Immunitymentioning

confidence: 99%

Section: Novel Inborn Errors Of Immunitymentioning

confidence: 99%

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Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee

et al. 2022

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“…However, it was already demonstrated that BOB.1/OBF.1 is highly expressed in TFH cells in mice and humans ( 22 , 31 , 45 , 46 ). Reduced TFH cell numbers were found in a patient with a mutation in the Pou2af1 gene leading to the absence of BOB.1/OBF.1 protein ( 27 ). Several studies also suggested an involvement of BOB.1/OBF.1 in TFH cell development.…”

Section: Discussionmentioning

confidence: 99%

“…Over the last years, a role for BOB.1/OBF.1 also in the human immune system has become more and more evident. A patient with a mutation in the Pou2af1 gene leading to the absence of BOB.1/OBF.1 protein was described with B cell developmental defects, agammaglobulinemia and a reduction in circulating TFH cells ( 27 ). Beyond that, dysregulated expression of BOB.1/OBF.1 in both B and T cells was described to contribute to the pathogenesis of several autoimmune diseases including Rheumatoid arthritis, Type 1 diabetes, multiple sclerosis and systemic lupus erythematosus ( 28 – 30 ).…”

Section: Introductionmentioning

confidence: 99%

T Cell Specific BOB.1/OBF.1 Expression Promotes Germinal Center Response and T Helper Cell Differentiation

et al. 2022

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The transcriptional co-activator BOB.1/OBF.1 is expressed in both B and T cells. The main characteristic of conventional BOB.1/OBF.1 deficient mice is the complete absence of germinal centers (GCs). This defect was mainly attributed to the defective B cell compartment. However, it is unknown whether and how BOB.1/OBF.1 expression in T cells contributes to the GC reaction. To finally clarify this question, we studied the in vivo function of BOB.1/OBF.1 in CD4+ T and follicular T helper (TFH) cell subpopulations by conditional mutagenesis, in the presence of immunocompetent B lymphocytes. BOB.1/OBF.1 deletion in CD4+ T as well as TFH cells resulted in impaired GC formation demonstrating that the impaired GC reaction described for conventional BOB.1/OBF.1-deficient mice cannot exclusively be traced back to the B cell compartment. Furthermore, we show a requirement of BOB.1/OBF.1 for T helper (TH) cell subsets, particularly for TFH cell differentiation.

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The Role of the Transcriptional Coactivator BOB.1/OBF.1 in Adaptive Immunity

Betzler,

Brunner

2024

Transcription Factors in Blood Cell Development

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Agammaglobulinemia with normal B-cell numbers in a patient lacking Bob1

Cited by 13 publications

References 9 publications

Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee

Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee

T Cell Specific BOB.1/OBF.1 Expression Promotes Germinal Center Response and T Helper Cell Differentiation

The Role of the Transcriptional Coactivator BOB.1/OBF.1 in Adaptive Immunity

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