B-cell activating factor receptor deficiency is associated with an adult-onset antibody deficiency syndrome in humans

Warnatz, Klaus; Salzer, Ulrich; Rizzi, Marta; Fischer, Bernh.; Gutenberger, Sylvia; Böhm, Joachim; Kienzler, Anne‐Kathrin; Pan‐Hammarström, Qiang; Hammarström, Lennart; Rakhmanov, Mirzokhid; Schlesier, Michael; Grimbacher, Bodo; Peter, Hans‐Hartmut; Eibel, Hermann

doi:10.1073/pnas.0903543106

Cited by 321 publications

(268 citation statements)

References 46 publications

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“…Defects have been found in the genes that encode for B cell antigen receptor associated complex (CD19, CD81, and CD21) (25 27), CD20 (28), inducible co-stimulator (ICOS) (29), and B cell activating factor receptor (BAFF-R) (30). Nevertheless, taken together, these defects account for less than 3% of patients (31).…”

Section: Genetics Of Cvidmentioning

confidence: 99%

Common variable immunodeficiency: Crossroads between infections, inflammation and autoimmunity

Baldovino

Montin

Martino

et al. 2013

Autoimmunity Reviews

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Section: Genetics Of Cvidmentioning

confidence: 99%

Common variable immunodeficiency: Crossroads between infections, inflammation and autoimmunity

Baldovino

Montin

Martino

et al. 2013

Autoimmunity Reviews

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“…2,3 In about 90% of patients diagnosed with agammaglobulinemia and about 75% of cases with a Hyper-IgM syndrome, the underlying genetic defect has been identified. 2 Whereas mutations have been described in patients diagnosed with CVID, [4][5][6][7][8][9][10][11][12] in over 90% of these patients no associated genetic defect has been found. In fact, in most CVID patients a complex genetic trade rather than a single affected gene is likely to contribute to development of the disease.…”

Section: Introductionmentioning

confidence: 99%

B-cell maturation and antibody responses in individuals carrying a mutated CD19 allele

et al. 2010

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Homozygous CD19 mutations lead to an antibody deficiency due to disruption of the CD19 complex and consequent impaired signaling by the B-cell antigen receptor. We studied the effects of heterozygous CD19 mutations on peripheral B-cell development and antibody responses in a large family with multiple consanguineous marriages. Sequence analysis of 96 family members revealed 30 carriers of the CD19 mutation. Lymphocyte subset counts were not significantly different between carriers and noncarriers in three different age groups (0-10 years; 11-18 years; adults). B cells of carriers had reduced CD19 and CD21 median expression levels, and had reduced proportions of transitional (0-10 years) and CD5 þ B cells (adults). CD19 carriers did not show clinical signs of immunodeficiency; they were well capable to produce normal serum Ig levels and had normal responses to primary and booster vaccinations. The frequency of mutated Vk alleles was not affected. Heterozygous loss of CD19 causes some changes in the naive B-cell compartment, but overall in vivo B-cell maturation or humoral immunity is not affected. Many antibody deficiencies are not monogenetic, but likely caused by a combination of multiple genetic variations. Therefore, functional analyses of immune cell function should be carried out to show whether heterozygous mutations contribute to disease.

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“…B cells are arrested at the transitional B-cell stage and this condition presents with adult-onset antibody-deficiency syndrome [68]. Humans with this condition have diminished numbers of mature B cells, e.g., follicular, marginal zone and memory B cells and their T-independent immune responses are severely impaired.…”

Section: Human Autoimmune Diseasesmentioning

confidence: 99%

The Roles of the TNF-Family Member B-Cell Activation Factor Belonging to the TNF-Family (BAFF) in Autoimmunity

Hirayama¹,

Nagai²

2017

Immunopathogenesis and Immune-Based Therapy for Selected Autoimmune Disorders

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The tumor necrosis factor superfamily (TNFSF) member and cytokine known as B-cell activation factor belonging to the TNF-family (BAFF) has been identified as one of the key factors in the selection and survival of B cells. Overexpression of BAFF in mice leads to autoimmunity, whereas BAFF-deficient mice lack mature B cells. Although under normal concentrations of BAFF, non-self-reactive B cells survived and autoreactive B cells were deleted, a higher concentration of BAFF contributed to the survival of autoreactive B cells and elevated autoantibody production. Lupus-prone mice have increased serum levels of BAFF during the onset and progression of disease. The serum BAFF levels are elevated in patients with autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome and ANCA-associated vasculitis, and showed positive correlations with autoantibodies.

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B-cell activating factor receptor deficiency is associated with an adult-onset antibody deficiency syndrome in humans

Cited by 321 publications

References 46 publications

Common variable immunodeficiency: Crossroads between infections, inflammation and autoimmunity

Common variable immunodeficiency: Crossroads between infections, inflammation and autoimmunity

B-cell maturation and antibody responses in individuals carrying a mutated CD19 allele

The Roles of the TNF-Family Member B-Cell Activation Factor Belonging to the TNF-Family (BAFF) in Autoimmunity

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