ABSTRACT
AIMS: Common variable immunodeficiency (CVID) is a primary antibody immunodeficiency with approximately 20% of patients reporting additional autoimmune symptoms. The primary aim of this study was to compare the levels of activated and regulatory T cells (Treg cells) in CVID patients in an attempt to clarify their possible interactions leading to the generation of autoimmunity. METHODS: Immunophenotyping of T cells was performed by flow cytometry using a whole blood approach. Surface expression of human leukocyte antigen HLA class II DR and intracellular levels of granzyme B in T cell subsets were assessed; Treg levels were measured using CD4 CD25, FOXp3 and CTLA-4. RESULTS: CVID patients had higher levels of granzyme B and HLA-DR on CD8(+) T cells compared with control values (mean of 59% vs 30% and 45% vs 21%, respectively). Patients also had reduced levels of Treg cells compared with control values (con mean=3.24% vs pat=2.54%). Patients with autoimmunity (5/23) had a similar level of T cell activation markers to the rest of the patients but with lower Treg cells (mean of 1.1%) and reduced CD25 and CTLA-4 expression. Patients with autoimmunity had a higher ratio of activated to Treg cells compared with patients with no autoimmune symptoms. CONCLUSIONS: These results highlight that reduced levels of Treg cells were associated with elevated levels of activated T cells, suggesting that reduced Treg cells in these patients may have functional consequences in allowing exaggerated T cell responses.
Subject(s)
Autoimmunity , Common Variable Immunodeficiency/enzymology , Common Variable Immunodeficiency/immunology , Granzymes/analysis , HLA-DR Antigens/analysis , T-Lymphocyte Subsets/enzymology , T-Lymphocyte Subsets/immunology , T-Lymphocytes, Regulatory/immunology , Adult , Biomarkers/analysis , CD8-Positive T-Lymphocytes/enzymology , CD8-Positive T-Lymphocytes/immunology , CTLA-4 Antigen/analysis , Case-Control Studies , Female , Flow Cytometry , Forkhead Transcription Factors/analysis , Humans , Immunophenotyping/methods , Interleukin-2 Receptor alpha Subunit/analysis , Lymphocyte Activation , Lymphocyte Count , Male , Middle Aged , Up-RegulationSubject(s)
Autoimmunity/immunology , B-Lymphocytes/immunology , Common Variable Immunodeficiency/immunology , T-Lymphocytes, Regulatory/immunology , Antigens, CD19/immunology , Antigens, CD19/metabolism , B-Lymphocytes/metabolism , Common Variable Immunodeficiency/metabolism , Flow Cytometry , Forkhead Transcription Factors/immunology , Forkhead Transcription Factors/metabolism , Humans , Immunologic Memory/immunology , Immunophenotyping , T-Lymphocytes, Regulatory/metabolismABSTRACT
BACKGROUND: Use of intravenous (IV) immunoglobulin (Ig) to obtain panel reactive antibody (PRA) A reduction in sensitized patients has been widely reported. Because no IVIg preparation is formulated specifically for this purpose, the authors have sought to determine whether, through laboratory testing, they could guide the rational choice of product for clinical use. METHODS: Using a flow cytometric approach, the authors have quantitatively determined the capacity of 22 different IVIg preparations to cause PRA reduction. RESULTS: IVIg preparations showed considerable variability in their individual capacity to reduce serum PRA. Protein-A pretreatment of IVIg preparations was found to reduce their capacity to cause PRA reduction. CONCLUSION: Laboratory screening of IVIg preparations provides a rational basis for the selection of product for administration to patients in whom the aim is to produce a PRA reduction. Experiments involving protein-A treatment of IVIg preparations indicate that immunoglobulin G is the principal factor involved in the abrogation of serum reactivity.
