Levels of Soluble CD40 Ligand (CD154) in Serum Are Increased in Human Immunodeficiency Virus Type 1-Infected Patients and Correlate with CD4⁺T-Cell Counts

Abstract

CD40 ligand (CD40L or CD154) is a costimulatory molecule expressed mainly on activated CD4؉ T cells. Concentrations of the soluble form of CD40L (sCD40L) in serum were determined for a cohort of 77 human immunodeficiency virus type 1 (HIV-1)-infected patients before and after initiation of highly active antiretroviral treatment (HAART) by a quantitative enzyme-linked immunosorbent assay. Circulating sCD40L levels were higher by twofold in untreated patients than in healthy controls (means ؎ standard deviations [SD]: 1.41 ؎ 1.48 versus 0.69 ؎ 0.59 ng/ml; P < 0.001). HIV-1-infected patients classified as CD4 T-cell category 1 had significantly higher sCD40L levels than patients classified as CD4 categories 2 and 3 (mean ؎ SD: 2.08 ؎ 1.46 ng/ml versus 1.57 ؎ 1.58 [category 2] and 0.94 ؎ 1.25 ng/ml [category 3]; P ‫؍‬ 0.046), while no correlation with clinical categories A, B, and C was found. Individual serum sCD40L levels correlated with CD4 ؉ T-cell counts (P ‫؍‬ 0.039) but not with viral load, gamma globulin levels, or acute-inflammatory-response markers. After 8 to 12 months of HAART, a further threefold increase of serum sCD40L levels, which paralleled the increase of CD4 ؉ T-cell counts, was observed. These novel findings suggest that sCD40L measurement in HIV-1-infected patients could serve as a new surrogate marker useful in the assessment of treatment efficacy, especially in settings where well-equipped laboratories and funding required for CD4 ؉ T-cell count and viral load measurements are not available.

Soluble CD40 Iigand and Oxidative Response Are Reciprocally Stimulated during Shiga Toxin-Associated Hemolytic Uremic Syndrome

“…The sCD40L plasmatic values showed by HUS patients were similar to those reported in other pathological conditions such as cardiovascular diseases, diabetes, HIV infection or smokers [41,[45][46][47][48][49] and it can be considered as a marker of thrombotic risk [26]. Therefore, and based on the present results, we propose that quantification of sCD40L in plasma could be used as a surrogate and early marker of microvascular dysfunction and/or platelet activation in Stx-associated diarrheas.…”

Functional Synergy between CD40 Ligand and HIV-1 Tat Contributes to Inflammation: Implications in HIV Type 1 Dementia

“…Untreated HIV-1 infection is associated with increases in markers of vascular activation, including the release of soluble markers of both endothelial and platelet activation (12)(13)(14)(15). These include the candidate HIV-1 neurotoxin, platelet-activating factor (PAF) (16), as well as soluble VCAM and von Willebrand factor (12,13).…”

“…These include the candidate HIV-1 neurotoxin, platelet-activating factor (PAF) (16), as well as soluble VCAM and von Willebrand factor (12,13). HAART has been shown to reduce markers of endothelial activation (soluble VCAM, von Willebrand factor) in HIV-1-infected individuals (17,18), but to have no effect on soluble platelet activation markers such as PAF acetylhydrolase (19) and soluble CD40L (sCD40L, also known as CD154) (15); indeed, in at least one study, HAART has been associated with an increase in serum sCD40L levels (14).…”

The Role of Cd40 Ligand in Early Detection of Chromium-Induced Immunotoxic Effects Among Exposed Workers

“…In this work, estimating the levels of CD40L revealed lower levels among the exposed (mean 2.04 ± 2.18 ng/ml) than the control groups (mean 2.69 ± 1.12 ng/ml); the difference obtained was statistically non-significant. The CD40 molecule is barely detectable on resting cells, but is found in plasma of normal individuals as a soluble protein [6] .…”

“…These proinflammatory mediators up-regulate the expression of some adhesion molecules. CD40 Ligand (CD40L), also known as CD154 or gp39, is a trans-membrane protein expressed on T-cells, B-cells, mast cells, basophils, eosinophils, natural killer cells, macrophages, endothelial cells, vascular smooth muscle cells, activated platelets and is also found in plasma as a soluble protein, sCD40L [6] .…”