L-selectin in patients with common variable immunodeficiency (CVID): a comparative study with normal individuals

Abstract

SUMMARYL-selectin is 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 Lselectin 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.

Adhesion molecules in common variable immunodeficiency (CVID)—a decrease inl-selectin-positive T lymphocytes

“…In B lymphocytes we confirmed previous reports of a lower percentage of L-selectinpositive B lymphocytes in CVID [25,26], but only in a subset of patients. B lymphocytes have been suggested to be a source of the elevated sL-selectin levels observed in CVID [25], but our results also indicate a contribution from T lymphocytes. Furthermore, we found an increase in the percentage of ICAM-1 þ B lymphocytes in CVID patients that has not previously been reported.…”

“…Recently, Zhang et al demonstrated elevated serum levels of Lselectin in CVID patients [25]. To our knowledge, sICAM-1 and sVCAM-1 have not previously been examined in this patient category.…”

The Genetics of Hypogammaglobulinemia

“…T-cell defects described in CVID include decreased activation and proliferation [51], impaired cytokine production [52][53][54], and altered expression of some activation-induced surface molecules, such as CD40L [55,56], L-selectin [57], and attractin [58], suggesting some abnormalities in the Tcell receptor signaling [59][60][61]. Other reports describe a reduced generation of antigen-specific memory T cells [62] and an increased T-cell suppression [63].…”

The effects of vitamin A derivatives on in vitro antibody production by peripheral blood mononuclear cells (PBMC) from normal blood donors and patients with common variable immunodeficiency (CVID)

“…This is particularly important for evaluating the potentiation of immunoglobulin production of functional B cells from CVID patients by the drugs, since CVID patients have low serum immunoglobulin levels, with possible defects in B cells or B cell subpopulation (as patients can be subdivided according to L-selectin expression [20]). The index should reflect the elevation or reduction of immunoglobulin synthesis by B cells under the influence of retinoids.…”