Background: Dysfunctional antigen presentation may underlie the impaired antibody response to hepatitis B vaccination in hemodialysis patients. Dendritic cells are considered to be the most important antigen presenting cells, but their presence and function in hemodialysis patients is unclear. Granulocyte-monocyte-colony stimulating factor (GM-CSF) has been given successfully to hemodialysis patients to increase the proportion of responders to hepatitis B vaccination. Although GM-CSF acts on both monocytes and dendritic cells, the mechanisms underlying its adjuvant quality are largely unknown.
Methods: In this study we analyzed monocytes and dendritic cells in the peripheral blood of hemodialysis patient that had responded to a standard hepatitis B vaccination procedure (responders), patients who had not responded (nonresponders), and healthy controls. The nonresponders were given two additional booster vaccines, both preceded by administration of GM-CSF the day before.
Results: After two booster vaccinations with GM-CSF, six out of seven patients developed a protective antibody response to hepatitis B. The memory T-cell response to tetanus toxoid was significantly lower in nonresponders compared to controls. The monocytes of dialysis patients and healthy controls showed a similar expression of relevant cell surface molecules. However, the numbers of circulating dendritic cells were on average 50% reduced compared to healthy controls, with a further reduction after GM-CSF administration. This was accompanied by a decrease of T-cell proliferation in antigen presentation assays. Monocytes showed increased major histocompatibility complex (MHC) class II, CD54, and CD40 expression, while their antigen-presenting capacity remained unchanged.
Conclusion: GM-CSF is an effective adjuvant for hepatitis B vaccination in primary nonresponding hemodialysis patients, but paradoxically decreases the antigen presenting capacity of peripheral blood mononuclear cells and the number of circulating dendritic cells.