Memory B cells in common variable immunodeficiency: Clinical associations and sex differences

Sánchez-Ramón, Silvia; Radigan, Lin; Yu, Joyce E.; Bard, Susan; Cunningham‐Rundles, Charlotte

doi:10.1016/j.clim.2008.02.013

Cited by 131 publications

(115 citation statements)

References 49 publications

(62 reference statements)

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“…+ population from CVID-derived B cells (mean, 1.69%) compared with the normal range (6.5-29.1%), which is in agreement with previous reports (2,35). Because of the very limited number of CD19 + B cells (range, 0.8-1.5 3 10 6 ) that could be obtained from the 35 ml of whole blood taken from each patient, it was impossible to subdivide the CD19 + fraction of cells into numbers that allow functional studies on IgG secretion.…”

Section: Discussionsupporting

confidence: 92%

Retinoic Acid Improves Defective TLR9/RP105-Induced Immune Responses in Common Variable Immunodeficiency–Derived B Cells

Indrevær

Holm

Aukrust

et al. 2013

The Journal of Immunology

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Common variable immunodeficiency (CVID) is a disease that is characterized primarily by low levels of serum Igs, resulting in a high incidence of infections. It also has been associated with impaired B cell signaling via TLR9 and reduced serum levels of vitamin A. Given the established link between vitamin A deficiency and increased susceptibility to infections, we investigated the ability of the vitamin A metabolite all-trans retinoic acid (RA) to restore the defective immune responses in CVID-derived B cells activated through the TLRs TLR9 and RP105. We demonstrate that RA almost normalizes proliferation and IL-10 secretion in patient-derived B cells. IgG secretion is also partially restored, but to a more moderate extent. This can be explained by impaired RA-mediated isotype switching in TLR9/RP105-stimulated CVID-derived B cells owing to reduced induction of activation-induced deaminase. Accordingly, these B cells secreted higher levels of IgM than did normal B cells, and RA augmented IgM secretion. The ability of RA to improve critical immune parameters in CVID-derived B cells stimulated through TLR9 and RP105 support the possibility of combining RA with TLR stimulation for the treatment of CVID.

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Section: Discussionsupporting

confidence: 92%

Retinoic Acid Improves Defective TLR9/RP105-Induced Immune Responses in Common Variable Immunodeficiency–Derived B Cells

Indrevær

Holm

Aukrust

et al. 2013

The Journal of Immunology

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“…Other known factors exacerbating CVID, such as chronic infections by EBV or CMV or malignancies, were also excluded. However, gender-related clinical differences between female and male CVID patients have been documented by two previous reports showing that male patients are generally more severely affected (10,40). Nevertheless, the precise co-modulating factors besides gender accounting for the difference between P1 and P2 remain unknown.…”

Section: Discussionmentioning

confidence: 98%

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

Warnatz

Salzer²,

Rizzi³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

332

254

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“…In one such study, females were found to have significantly higher numbers of switched memory B cells in comparison with males (38). The significance of this finding is unknown.…”

Section: Immunologic Features Of Cvidmentioning

confidence: 99%

Common Variable Immunodeficiency

Bonilla

Geha

2009

Pediatr Res

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ABSTRACT:Common variable immunodeficiency is the most prevalent clinically significant antibody deficiency at all ages. The disorder is defined principally by characteristic infection susceptibility with hypogammaglobulinemia and impaired-specific antibody response. Several recent large registry-based studies have defined distinct phenotypic subtypes. Several studies have also correlated specific immunologic markers with these phenotypes. The biochemical or genetic abnormality in the majority of patients remains unknown. Recently, several molecular genetic lesions have been defined. Among these, mutations of inducible costimulator, and CD19, appear to be disease causing by themselves. These account for about 1% of cases. Other mutations or polymorphisms, such as in the human homolog of Escherichia coli MutS 5 (MSH5), and transmembrane activator and calcium mobilizing ligand interactor, seem to be disease associated in 5-10% of patients, but may require additional immunologic abnormalities for full expression of the phenotype, as unaffected heterozygotes have also been described. Clinical Features of CVIDCommon variable immunodeficiency (CVID) is a form of predominantly humoral primary immunodeficiency. Symptoms may begin at any time of life, including the extremes of both young and old age (1-3). Major characteristics include recurrent infections, principally bacterial and viral of the respiratory tract. In one recent French registry study (DEFI Study) of 252 patients, 95% had one or more of the following: bronchitis, sinusitis, and pneumonia. Not surprisingly, common bacterial pathogens such as Streptococcus pneumoniae and Hemophilus influenzae were most often isolated. Granulomatous or lymphocytic interstitial lung disease occurs in a subset of patients and may be associated with human herpesvirus 8 (4). Granulomas may also involve other organs and resemble sarcoid. Furthermore, in the DEFI study, 47% of patients had diarrhea (intermittent or chronic); Giardia, Salmonella, and Campylobacter were common isolates (2). Enteroviral intestinal infections may disseminate and cause meningoencephalitis.Autoimmune disease is common in CVID (5). One recent survey reviewed seven published studies comprising 831 patients altogether (6). The reported prevalences of autoimmune disease ranged from 17 to 50%, and it was present in 27% of the overall patient population. Immune thrombocytopenic purpura and autoimmune hemolytic anemia were by far the most common diagnoses, followed by aseptic nonerosive seronegative inflammatory arthritis. Additional disorders observed include inflammatory bowel disease, vasculitides (some resembling systemic lupus erythematosus), and others. 1 Approximately 10% of patients with CVID have a lymphoproliferative disorder (7). This manifests most frequently as splenomegaly, lymphadenopathy and interstitial lung disease, as described above. The relative risk of lymphoma in patients with CVID compared with the general population is in the range of 10-to 20-fold higher (7). Most of these are B-cell n...

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Memory B cells in common variable immunodeficiency: Clinical associations and sex differences

Cited by 131 publications

References 49 publications

Retinoic Acid Improves Defective TLR9/RP105-Induced Immune Responses in Common Variable Immunodeficiency–Derived B Cells

Retinoic Acid Improves Defective TLR9/RP105-Induced Immune Responses in Common Variable Immunodeficiency–Derived B Cells

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

Common Variable Immunodeficiency

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