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L-selectin in patients with common variable immunodeficiency (CVID): a comparative study with normal individuals
J G Zhang1, L Morgan, G P Spickett
1Department of Immunology, University of Newcastle upon Tyne, UK.
Insights
Common Variable Immunodeficiency (CVID) patients show reduced L-selectin on lymphocytes, with increased soluble L-selectin in plasma. This may impact immune cell function and trafficking in CVID.
Area of Science:
- Immunology
- Cell Adhesion Molecules
Background:
- L-selectin mediates leukocyte adhesion to high endothelial venules.
- Soluble L-selectin is detectable in biological fluids and elevated in various diseases.
Purpose of the Study:
- To investigate L-selectin expression on leukocytes in CVID patients.
- To measure soluble L-selectin levels in CVID patient plasma.
Main Methods:
- Flow cytometry to assess L-selectin expression on peripheral blood leukocytes.
- ELISA to quantify soluble L-selectin in plasma.
Main Results:
- Significant loss of L-selectin expression on CVID B cells and CD4+ T cells (CD45RO+).
- Normal L-selectin expression on non-lymphoid leukocytes.
- Significantly elevated soluble L-selectin levels in CVID plasma compared to healthy controls.
Conclusions:
- Reduced lymphocyte L-selectin in CVID may result from aberrant lymphocyte activation.
- Down-regulation of L-selectin contributes to increased soluble L-selectin levels.
- Altered lymphocyte trafficking is suggested in CVID patients.
Abstract:
L-selectin in one of the key members of the selectin family of adhesion molecules and initiates leucocyte attachment to specialized high endothelial venules. The shed form, which retains functional activity, can be detected in biological fluids and is increased in diseases of many kinds. In the present study, we investigated L-selectin expression on leucocytes and measured the soluble form in the plasma of healthy individuals and patients with CVID. A significant loss of L-selectin expression is found on CVID B cells, which is marked by the presence of a substantial population of L-selectin-negative B cells in the peripheral blood of some CVID patients. On CD4+ T cells, the loss in L-selectin expression affects mostly the CD45RO+ population. Peripheral blood leucocytes other than lymphocytes express L-selectin molecule normally. Moreover, soluble L-selectin was detected in significantly increased levels in CVID plasma compared with healthy controls. Our data suggest that the loss of L-selectin expressed by lymphocytes may be due to increased or aberrant lymphocyte activation in CVID patients who remain immunodeficient, and down-regulation of L-selectin from these lymphocytes may significantly contribute to the elevated levels of soluble L-selectin in the plasma, which may in turn affect further lymphocyte trafficking.
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