Patients with Common Variable Immunodeficiency Complicated by Autoimmune Phenomena Have Lymphopenia and Reduced Treg, Th17, and NK Cells

Most patients with primary immune deficiency suffer from recurrent infections; however, paradoxical autoimmune phenomena can also manifest. The aim of this study was to identify immunological markers of autoimmune phenomena associated with common variable immunodeficiency (CVID). The study included 33 adults with CVID divided into two groups: (1) those with noninfectious autoimmune complications (CVID-C (n = 24)) and (2) those with only infectious symptoms (CVID-OI (n = 9)). Flow cytometry of peripheral blood was performed and compared with systemic lupus erythematosus (SLE) patients (n = 17) and healthy controls (n = 20). We found that all lymphocytes were lower in CVID-C and SLE. NK cells were lowest in CVID-C. Th17 cells were significantly reduced in CVID-C and SLE. Tregs were significantly lower in CVID-C and SLE. Bregs did not significantly differ between any groups. Class-switched memory B cells were significantly lower in CVID-C and CVID-OI. Lastly, plasmablasts were significantly higher in SLE. Among the T cell subsets, CVID-C patients had lower naive and recent thymic emigrant CD4+ T cells. In conclusion, reduced Treg, Th17, and NK cells are features of CVID with autoimmune complications, and class-switched memory B cells can help distinguish patients with different causes of autoimmunity. Future studies are needed to confirm whether reductions of Treg, Th17, and NK cells might be a biomarker of more complicated CVID cases.

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Pediatric common variable immunodeficiency: Immunologic and phenotypic associations with switched memory B cells

Pediatric Allergy and Immunology ◽

10.1111/j.1399-3038.2010.01004.x ◽

2010 ◽

Vol 21 (5) ◽

pp. 852-858 ◽

Cited By ~ 30

Author(s):

Pierre L. Yong ◽

Jordan S. Orange ◽

Kathleen E. Sullivan

Keyword(s):

B Cells ◽

Common Variable Immunodeficiency ◽

Memory B Cells ◽

Common Variable

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CD21low B cells in common variable immunodeficiency do not show defects in receptor editing, but resemble tissue-like memory B cells

Blood ◽

10.1182/blood-2010-05-285585 ◽

2010 ◽

Vol 116 (18) ◽

pp. 3682-3683 ◽

Cited By ~ 16

Author(s):

Mirzokhid Rakhmanov ◽

Sylvia Gutenberger ◽

Baerbel Keller ◽

Michael Schlesier ◽

Hans-Hartmut Peter ◽

...

Keyword(s):

B Cells ◽

Common Variable Immunodeficiency ◽

Memory B Cells ◽

Receptor Editing ◽

Common Variable

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Absence of Memory B Cells in Patients with Common Variable Immunodeficiency

Clinical Immunology ◽

10.1006/clim.2001.5197 ◽

2002 ◽

Vol 103 (1) ◽

pp. 34-42 ◽

Cited By ~ 94

Author(s):

Kazunaga Agematsu ◽

Takeshi Futatani ◽

Sho Hokibara ◽

Norimoto Kobayashi ◽

Masaya Takamoto ◽

...

Keyword(s):

B Cells ◽

Common Variable Immunodeficiency ◽

Memory B Cells ◽

Common Variable

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G1/260 – Correlation between switched memory B cells and development of bronchietasis in patients with Common variable immunodeficiency

Paediatric Respiratory Reviews ◽

10.1016/j.prrv.2006.04.091 ◽

2006 ◽

Vol 7 ◽

pp. S306-S307

Author(s):

Asghhar Aghamohammadi ◽

Mostafa Moin ◽

Mohammad Vodjgani ◽

Morteza Samadi ◽

Abdolfattah Sarraf Nejad ◽

...

Keyword(s):

B Cells ◽

Common Variable Immunodeficiency ◽

Memory B Cells ◽

Common Variable

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The loss of IgM memory B cells correlates with clinical disease in common variable immunodeficiency

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2004.10.048 ◽

2005 ◽

Vol 115 (2) ◽

pp. 412-417 ◽

Cited By ~ 163

Author(s):

Rita Carsetti ◽

Maria Manuela Rosado ◽

Simona Donnanno ◽

Vanessa Guazzi ◽

Annarosa Soresina ◽

...

Keyword(s):

B Cells ◽

Common Variable Immunodeficiency ◽

Memory B Cells ◽

Clinical Disease ◽

Common Variable

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Functional abnormalities of CD8+ T cells define a unique subset of patients with common variable immunodeficiency

Blood ◽

10.1182/blood.v82.1.192.bloodjournal821192 ◽

1993 ◽

Vol 82 (1) ◽

pp. 192-201 ◽

Cited By ~ 43

Author(s):

JS Jaffe ◽

W Strober ◽

MC Sneller

Keyword(s):

T Cells ◽

T Cell ◽

B Cells ◽

Cd8 T Cells ◽

Common Variable Immunodeficiency ◽

Cytokine Production ◽

Interleukin 2 ◽

T Cell Subsets ◽

Cell Phenotype ◽

Common Variable

A substantial subgroup of patients with common variable immunodeficiency (CVI) exhibit an abnormal T-cell phenotype characterized by a low CD4/CD8 ratio associated with a significant increase in the absolute number of CD8+ T cells (CVI4/8low patients). In the present study, we examined the phenotypic and functional properties of purified T-cell subsets in this group of CVI patients. CD8+ T cells from CVI4/8low patients manifested increased expression of HLA-DR and CD57 and decreased expression of CD45RA as compared with CD8+ T cells from normal controls. When stimulated with anti-CD3 and phorbol 12-myristate 13-acetate, purified patient CD8+ T cells exhibited significantly decreased proliferation, c-myc expression, and interleukin-2 (IL-2) production compared with that of normal CD8+ T cells. Nevertheless, mitogen-activated patient CD8+ T cells secreted elevated amounts of gamma-interferon and IL-5 and normal amounts of IL- 4. This abnormal pattern of proliferation and cytokine production was limited to the CD8+ T-cell subset as CD4+ T cells from these patients exhibited normal proliferation and cytokine production. In further functional studies, purified CD8+ T cells from CVI4/8low patients manifested increased cytotoxic T-lymphocyte activity and suppressor activity, as compared with normal CD8+ T cells, when they were tested in (1) an anti-CD3 “redirected” cytotoxicity assay and (2) a suppressor assay consisting of CD8+ T cells and Staphylococcus aureus Cowan I (SAC) plus IL-2-stimulated normal (allogeneic) B cells. In the latter case, patient CD8+ T cells suppressed IgG production, but not IgM production. Finally, in studies to evaluate the role of patient CD8+ T cells in the pathogenesis of hypogammaglobulinemia, we determined the capacity of SAC and IL-2 to induce Ig production in highly purified patient B cells, ie, in the absence of patient CD8+ T cells. We found that, whereas B cells from one patient produced normal amounts of IgG, B cells from three patients were unable to produce normal amounts of IgG under these conditions. These data establish the phenotypic and functional characteristics of CD8+ T cells in CVI4/8low and clearly distinguish CVI4/8low patients from other patients with this syndrome. The data do not support the contention that hypogammaglobulinemia in CVI4/8low patients is due to a direct effect of CD8+ T cells on terminal B-cell differentiation, except in the occasional patient. The abnormal CD8+ T cells may, nevertheless, have more subtle effects of lymphoid function that play a role in disease pathogenesis.

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Chronic meningococcaemia and immunoglobulin A deficiency

Journal of Medical Microbiology ◽

10.1099/jmm.0.021980-0 ◽

2010 ◽

Vol 59 (11) ◽

pp. 1375-1378 ◽

Cited By ~ 2

Author(s):

Arnaud Theulin ◽

Murielle Rondeau-Lutz ◽

Cornelia Kuhnert ◽

Julien Boileau ◽

Jean-Christophe Weber

Keyword(s):

B Cells ◽

Neisseria Meningitidis ◽

Common Variable Immunodeficiency ◽

Clinical Presentation ◽

Immunoglobulin A ◽

Iga Deficiency ◽

Memory B Cells ◽

Igm Deficiency ◽

Common Variable

Chronic meningococcaemia is an unusual clinical presentation of Neisseria meningitidis infection. We describe the case of a patient, who presented with total IgA deficiency and partial IgM deficiency with a low switched memory B cells count, suggestive of a borderline form of common variable immunodeficiency (CVID). The role of IgA in the protection against Neisseria meningitidis, and the link between IgA deficiency and CVID are discussed.

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Potential Immune Biomarkers in Diagnosis and Clinical Management for Systemic Lupus Erythematosus

Journal of Medical Biochemistry ◽

10.1515/jomb-2017-0048 ◽

2018 ◽

Vol 37 (2) ◽

pp. 163-171 ◽

Cited By ~ 2

Author(s):

Lamija Zecevic ◽

Jasenko Karamehic ◽

Jozo Coric ◽

David Stubljar ◽

Nesina Avdagic ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

B Cells ◽

Nk Cells ◽

Lupus Erythematosus ◽

Peripheral Blood ◽

Clinical Management ◽

Memory B Cells ◽

Serum Cytokine ◽

Systemic Lupus ◽

Significant Difference

SummaryBackground:There is still no reliable, specific biomarker for precision diagnosis and clinical monitoring of systemic lupus erythematosus. The aim of this study was to investigate the importance of the determination of immunofenotypic profiles (T, B lymphocytes and NK cells) and serum cytokine concentrations (IL-17 and IFN-alpha) as potential biomarkers for this disease.Methods:The study included 55 patients with SLE and 25 healthy controls. The proportion of T, B, NK cells were assessed in peripheral blood using flow cytometric assays while the serum cytokine concentration (IL-17 and IFNalpha) was determined by ELISA test.Results:ROC curve analysis showed good accuracy to distinguish between patients and healthy individuals for activated T cells (AUC=0.798; p<0.001), Treg (AUC= 0.651; p=0.036), and memory B cells (AUC=0.285; p=0.002). We found statistically significant difference (p=0.036) in the levels of serum IL-17 between patients with SLE (IL-17=49.27 pg/mL) and controls (IL-17= 28.64 pg/mL).Conclusions:Significant increase in the relative number of Treg lymphocytes, and decrease in memory B cells, as well as decrease level of IL-17, in SLE patients may be implicated in the pathogenesis of the disease. These parameters, as biomarkers, could distinguish SLE patients and no-SLE patients. Monitoring subpopulations of immune cells in peripheral blood using flow cytometry provides insight into abnormal T and B cell function in SLE. Progress in understanding the immunity at SLE, results in concrete benefits for the SLE patients, which include new clinical management and therapeutic strategies.

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