Changes In HLA-DR Expression Research Articles

Myeloid and lymphoid activation markers in AIDS and non-AIDS presenters

HIV infection is characterized by a state of chronic activation of the immune system, which is not completely reversed by antiretroviral treatment (ART). The aim of this study was to assess myeloid and lymphoid activation markers during HIV infection, before and one year after ART initiation, in AIDS and non-AIDS presenters. Treatment naïve HIV positive patients were enrolled in this study. Myeloid dendritic cell (mDC), plasmacytoid dendritic cell (pDC), slanDC, monocyte and T-lymphocyte cell counts and activation status, were assessed by flow cytometry in peripheral blood samples. Soluble (s)CD14 and sCD163 were assessed in plasma samples using ELISA assays. Statistical analyses were performed using GraphPad Prism and Minitab Express.Thirty-four ART naïve HIV-1 infected subjects were enrolled in this study (22 non-AIDS and 12 AIDS presenters). Seventeen healthy donors (HD) were included as control group. Although circulating mDC levels resulted unchanged, HLA-DR expression was decreased on mDCs of HIV positive subjects compared to HD (p < 0,0001). AIDS presenters showed the lowest level of expression of HLA-DR on mDCs. Circulating levels of pDCs were decreased in HIV patients compared to HD (p < 0,001), without any changes in HLA-DR expression. SlanDC cell counts were extremely reduced in AIDS presenters, compared to non-AIDS presenters and HD (p < 0,01 and p < 0,0001, respectively) and showed higher HLA-DR expression in HIV patients compared to HD (p < 0,01). Intermediate monocyte (IM) cell counts were increased in AIDS and non-AIDS presenters compared to HD (p < 0,001 and p < 0,001 respectively). Furthermore, IM expansion was directly correlated to HIV viral load (p = 0,036) and independent from CD4 cell counts and activation levels. Plasma concentrations of sCD14 and sCD163 resulted increased in HIV infected subjects compared to HD (p < 0,0001 and p < 0,001), with the highest levels observed in AIDS presenters. After 1 year, ART was able to increase pDC and decrease IM absolute cell counts and modify HLA-DR expression on mDCs and slanDCs, approaching the levels observed in HD. ART reduced also CD4 and CD8 activation levels. In conclusion, in untreated HIV infected subjects circulating dendritic cells resulted altered either in numbers or in HLA-DR expression, especially in AIDS presenters. IM absolute counts were equally increased in AIDS and non-AIDS presenters. ART was able to reduce myeloid and lymphoid inflammation in both advanced and non-advanced HIV patients, confirming the role of ART in hampering disease progression and immune activation associated non-AIDS events.

Dynamic changes in HLA-DR expression during short-term and long-term ibrutinib treatment in patients with chronic lymphocytic leukemia

There is the first evidence of changes in the kinetics of B cell antigen receptor (BCR) internalisation of neoplastic cells in chronic lymphocytic leukemia (CLL) after the short-term and long-term administration of ibrutinib. We aimed to assess the influence of short-term and long-term ibrutinib treatment on the HLA-DR expression on CLL cells, T cells and monocytes. The immunophenotyping of CLL and immune cells in peripheral blood was performed on 16 high-risk CLL patients treated with ibrutinib. After early ibrutinib administration, the HLA-DR expression on CLL cells reduced (P = 0.032), accompanied by an increase in CLL cell counts in peripheral blood (P = 0.001). In vitro culturing of CLL cells with ibrutinib also revealed the reduction in the HLA-DR expression at protein and mRNA levels (P < 0.01). The decrease in HLA-DR on CLL cells after the first month was followed by the gradual increase of its expression by the 12th month (P = 0.001). A one-month follow-up resulted in elevated absolute counts of CD4+ (P = 0.002) and CD8+ (P < 0.001) T cells as well as CD4+ and CD8+ cells bearing HLA-DR (P < 0.01). The long-term administration of ibrutinib was associated with the increased numbers of CD4+ bearing HLA-DR (P = 0.006) and elevation of HLA-DR expression on all monocyte subsets (P ≤ 0.004). Our results provide the first evidence of the time-dependent immunomodulatory effect of ibrutinib on CLL and T cells and monocytes. The clinical consequences of time-dependent changes in HLA-DR expression in ibrutinib treated patients deserve further investigation.

Changes in HLA-DR Expression on Monocytes and Lymphocytes in Neonatal Sepsis

HLA-DR is a key marker of leukocyte activation, which suppression determines the effectiveness of immune response and prognosis in neonatal sepsis (NS). The aim of this study was to evaluate the HLA-DR expression on lymphocytes and monocytes in the peripheral blood of neonates with sepsis. The study involved 21 neonates with sepsis and 10 healthy neonates born during the study period. Bacteremia was detected in five cases (24%). The most frequent pathogens found were Klebsiella pneumoniae (n = 2) and Staphylococcus aureus (n = 2) followed by Streptococcus agalactae (n = 1). NS was associated with pneumonia (n = 17), meningitis (n = 3), and necrotizing enterocolitis (n = 1). The onset of NS was accompanied with high blood monocyte activity which ranged from 96 to 100%. Blood CD3+ lymphocyte population and CD4+ and CD8+ lymphocyte subset levels were decreased, with their median values being 1.7, 2.2, and 2.4 times lower than those in the control group, respectively (р = 0.005, р = 0.0002, р = 0.003). The HLA-DR expression on CD3+ lymphocytes, as well as on CD4+ and CD8+ lymphocyte subsets, was extremely low ranging from 0.1 to 7% both in the onset of the disease and in a week after admission to a hospital. Absolute counts of activated CD4+ and CD8+ lymphocyte subsets were significantly lower on the disease first days as compared to the control group (р = 0.02 and р = 0.003, respectively). These results demonstrate adaptive immunity to be non-effective in neonates with sepsis. Low expression of HLA-DR on CD3 lymphocytes as well as on CD4 and CD8 lymphocyte subsets is a reason for immunostimulating therapy.

HLA-DR expression on monocytes is decreased in polytraumatized patients

BackgroundSepsis, systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) remain the most frequent causes of complications and death in severely injured patients. A main reason for the development of these syndromes is a post-traumatic dysregulation of the immune system. Several studies in intensive care unit (ICU) patients could detect a pivotal role of HLA-DR expression on monocytes. So far, its importance for development of SIRS, sepsis or MODS in the severely injured patient is not clear.MethodsTherefore, we have analysed HLA-DR expression on monocytes from severely injured patients (ISS > 16) during the post-traumatic course, which was on the day of trauma, as well as on days 3, 7 and 14 post trauma. Clinical data were analysed and the HLA-DR expression levels of patients who developed post-traumatic sepsis, SIRS or MODS were compared to those with a more favourable outcome. Young and healthy volunteers as well as patients undergoing prosthetic hip replacement after trauma were enrolled as control groups. HLA-DR molecules on monocytes were marked with PE-conjugated antibodies and the mean fluorescence intensity (MFI) was analysed via flow cytometry.Results24 severely injured patients (mean age 34 ± 2.7 years) mainly after high energy motor vehicle accidents as well as 8 controls (total hip replacement) and 9 healthy volunteers (mean age 26.2 ± 1.2 years) were enrolled. A total of eight patients suffered from sepsis (33.3 %) (six males, two females) and 17 patients suffered from SIRS (70.9 %) (10 males, 7 females). MODS was present in five patients (20.8 %), three male and two female patients. In four of these five patients the MODS developed subsequent to sepsis. HLA-DR expression significantly decreased after trauma and slowly returned to normal after 14 days, irrespective of the complications developed.ConclusionIn conclusion, post-traumatic HLA-DR expression on monocytes is significantly reduced after multiple trauma and it is back to normal on day 14. No significant changes in HLA-DR expression on monocytes from severely injured patients suffering from SIRS, MODS or sepsis compared to those who did not have complications could be detected. Nevertheless, HLA-DR expression on monocytes may be used to identify the immunological pro- or anti-inflammatory phase the patient is going through.

Changes in HLA-DR expression, cytokine production and coagulation following endotoxin infusion in healthy human volunteers

The infusion of a low dose of endotoxin into healthy subjects triggers a complex inflammatory response but the intricacies of which, despite extensive research, are still being unraveled. Nine healthy male volunteers received a dose of 30 Units endotoxin/kg bodyweight as an intravenous bolus. Following endotoxin infusion the concentration of TNF-alpha in their serum rapidly increased within 30 min, peaked after 1–2 h and returned to baseline by 4 h. This corresponded to a similarly rapid increase in anti-inflammatory soluble TNF receptor (sTNFR) levels, which remained elevated for up to 48 h. Increased levels of other cytokines were measured, including IL-6, IL-8, G-CSF, IL-1ra and IL-10. However, these cytokines lagged behind that of TNF-alpha and remained elevated for up to 8 h. Endotoxin injection resulted in complex changes in HLA-DR expression, a marker of monocyte activation state. Initially, following a lag of 2–4 h, HLA-DR expression decreased with a nadir at 8 h, followed by an increase in expression above baseline at 22 h. HLA-DR levels returned to baseline 48 h post-endotoxin challenge. This was in contrast to endotoxin-induced changes in white blood cell (WBC) numbers, which dropped rapidly (at 2–3 h) while HLA-DR levels were stable and then peaked during the nadir in HLA-DR expression (8 h). Furthermore, endotoxin injection caused activation of both fibrinolytic and coagulation pathways. Thus, endotoxin infusion results in complex changes in HLA-DR expression, production of pro- and anti-inflammatory cytokines and activation of coagulation.

Cow's milk protein induced changes in the expression of HLA-DR antigens on colonic epithelial cells

Normal colonic epithelial cells do not express HLA-DR antigens unless they become inflamed. It is possible that colonic epithelial cells may function as antigen-presenting cells once HLA-DR is induced by infection or inflammation. The aim of this study was to investigate whether cow's milk protein (CMP) is capable of inducing changes in HLA-DR expression on colonic epithelial cells, providing indirect evidence that CMP may activate cell-mediated immune mechanisms within intestinal mucosa. HLA-DR expression was evaluated by flow cytometry on cultured human colonic epithelial cell line (HT-29) before and after treatment with bacterial lipopolysaccharide (LPS) or recombinant gamma interferon (IFN-gamma). Untreated and LPS- or IFN-gamma-treated HT-29 cells were then cultured in the presence of CMP. The changes in epithelial HLA-DR expression induced by CMP on untreated and LPS- or IFN-gamma-treated HT-29 cells were examined. Untreated HT-29 cells expressed very little HLA-DR molecule. Bacterial LPS or IFN-gamma induced a significant HLA-DR expression on HT-29 cells. When untreated HT-29 cells were cultured in the presence of CMP, there was little induction of HLA-DR expression. Culture of LPS- or IFN-gamma-treated HT-29 cells in the presence of CMP induced a significant increase in HLA-DR expression, which was much greater than on HT-29 cells treated with bacterial LPS or IFN-gamma only. Our results suggest that CMP initiates an immune response in the intestinal mucosa and may be responsible for the activation of cell-mediated immunity after enteric infection or inflammation.