Dataset Information

IgD⁺IgM^- B Cells in Common Variable Immunodeficiency.

ABSTRACT: Common variable immunodeficiency (CVID) is the most frequent form of primary hypogammaglobulinemia in adults. In addition to recurrent infections and respiratory manifestations, CVID patients may present several non-infection complications such as autoimmune diseases. The mechanisms that lead to immune dysregulation in CVID are not completely understood. Given the role of IgD on naïve B cells in the maintenance of tolerance and secreted IgD in the respiratory mucosa, we evaluated the frequency of IgD⁺ naïve and IgD⁺ memory B cells in CVID patients. Here, no differences were observed in the percentages and proliferative responses of anergic IgD⁺IgM^-CD27^- B cells between CVID patients, with or without autoimmune disease, and the control group. Interestingly, in the compartment of memory B cells, the percentage of IgD⁺IgM^- cells was higher only in CVID patients with allergic rhinitis/allergic asthma. Our results may indicate that anergic IgD⁺IgM^-CD27^- B cells may not be compromised in our CVID cohort. However, IgD⁺IgM^- memory B cells may play a role in the immunopathogenesis of allergic rhinitis/allergic asthma in CVID patients. Further studies are needed to better understand the participation of IgD⁺IgM^- memory B cells in the immunopathogenesis of allergic rhinitis/allergic asthma in CVID patients.

SUBMITTER: Kasahara TM

PROVIDER: S-EPMC10891963 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

IgD<sup>+</sup>IgM<sup>-</sup> B Cells in Common Variable Immunodeficiency.

Kasahara Taissa de M TM Gupta Sudhir S

Pathogens (Basel, Switzerland) 20240201 2

Common variable immunodeficiency (CVID) is the most frequent form of primary hypogammaglobulinemia in adults. In addition to recurrent infections and respiratory manifestations, CVID patients may present several non-infection complications such as autoimmune diseases. The mechanisms that lead to immune dysregulation in CVID are not completely understood. Given the role of IgD on naïve B cells in the maintenance of tolerance and secreted IgD in the respiratory mucosa, we evaluated the frequency o ...[more]

PMID: 38392874

Similar Datasets

Project description:The origin and function of blood IgM+IgD+CD27+ B cells is controversial, and they are considered a heterogeneous population. Previous staining of circulating B cells of healthy donors with rotavirus fluorescent virus-like particles allowed us to differentiate two subsets of IgM+IgD+CD27+: IgMhi and IgMlo B cells. Here, we confirmed this finding and compared the phenotype, transcriptome, in vitro function, and Ig gene repertoire of these two subsets. Eleven markers phenotypically discriminated both subsets (CD1c, CD69, IL21R, CD27, MTG, CD45RB, CD5, CD184, CD23, BAFFR, and CD38) with the IgMhi phenotypically resembling previously reported marginal zone B cells and the IgMlo resembling both naïve and memory B cells. Transcriptomic analysis showed that both subpopulations clustered close to germinal center-experienced IgM only B cells with a Principal Component Analysis, but differed in expression of 78 genes. Moreover, IgMhi B cells expressed genes characteristic of previously reported marginal zone B cells. After stimulation with CpG and cytokines, significantly (p < 0.05) higher frequencies (62.5%) of IgMhi B cells proliferated, compared with IgMlo B cells (35.37%), and differentiated to antibody secreting cells (14.22% for IgMhi and 7.19% for IgMlo). IgMhi B cells had significantly (p < 0.0007) higher frequencies of mutations in IGHV and IGKV regions, IgMlo B cells had higher usage of IGHJ6 genes (p < 0.0001), and both subsets differed in their HCDR3 properties. IgMhi B cells shared most of their shared IGH clonotypes with IgM only memory B cells, and IgMlo B cells with IgMhi B cells. These results support the notion that differential expression of IgM and IgD discriminates two subpopulations of human circulating IgM+IgD+CD27+ B cells, with the IgMhi B cells having similarities with previously described marginal zone B cells that passed through germinal centers, and the IgMlo B cells being the least differentiated amongst the IgM+CD27+ subsets.

Project description:BackgroundCommon variable immunodeficiency (CVID) is one of the most common primary immunodeficiency syndromes, affecting one in 25,000-50,000 people. Renal insufficiency occurs in approximately 2% of patients with CVID. To date, there are no case series of renal biopsies from patients with CVID, making it difficult to determine whether individual cases of renal disease in CVID represent sporadic events or are related to the underlying pathophysiology. We performed a retrospective analysis of renal biopsy specimens in our database from patients with a clinical history of CVID (n=22 patients, 27 biopsies).MethodsLight, immunofluorescence, and electron microscopy were reviewed. IgG subclasses, PLA2R immunohistochemistry, and THSD7A, EXT1, and NELL1 immunofluorescence were performed on all membranous glomerulopathy cases. CD3, CD4, CD8, and CD20 immunohistochemistry was performed on cases of tubulointerstitial nephritis.ResultsAKI and proteinuria were the leading indications for renal biopsy in patients with CVID. Immune-complex glomerulopathy was present in 12 of 22 (54.5%) cases, including nine cases with membranous glomerulopathy, one case with a C3 glomerulopathy, and one case with membranoproliferative GN with IgG3κ deposits. All membranous glomerulopathy cases were PLA2R, THSD7A, EXT1, and NELL1 negative. The second most common renal biopsy diagnosis was chronic tubulointerstitial nephritis, affecting 33% of patients. All tubulointerstitial nephritis cases showed tubulitis and a lymphocytic infiltrate with >90% CD3+ T cells. Other renal biopsy diagnoses within our cohort included acute tubular injury (n=1), amyloid light-chain amyloidosis (n=1), diabetic glomerulosclerosis (n=1), thin basement membranes (n=1), pauci-immune GN (n=1), and arterionephrosclerosis (n=1).ConclusionsMembranous glomerulopathy and tubulointerstitial nephritis were the predominant pathologic findings in patients with CVID. Membranous glomerulopathy cases in patients with CVID were IgG1 subclass dominant and showed mesangial immune deposits. Four of the membranous glomerulopathy cases had associated proliferation, with mesangial and/or endocapillary hypercellularity, with or without crescent formation. CVID should be considered as a potential cause when membranous glomerulopathy or chronic tubulointerstitial nephritis is seen in a young patient with a history of recurrent infections.

Dataset Information

IgD⁺IgM^- B Cells in Common Variable Immunodeficiency.

Publications

IgD<sup>+</sup>IgM<sup>-</sup> B Cells in Common Variable Immunodeficiency.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

IgD+IgM- B Cells in Common Variable Immunodeficiency.

Publications

IgD&lt;sup&gt;+&lt;/sup&gt;IgM&lt;sup&gt;-&lt;/sup&gt; B Cells in Common Variable Immunodeficiency.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

IgD⁺IgM^- B Cells in Common Variable Immunodeficiency.

IgD<sup>+</sup>IgM<sup>-</sup> B Cells in Common Variable Immunodeficiency.