Reduced HLA-DR Expression Research Articles

Classical monocytes-low expressing HLA-DR is associated with higher mortality rate in SARS-CoV-2+ young patients with severe pneumonia

AimsThis study aimed to investigate whether monocyte dysregulation and hyperinflammation serve as predictive markers for mortality in young patients with SARS-CoV-2 severe pneumonia. MethodsA prospective cohort study was conducted in a tertiary-level public University Hospital in Colombia. Forty young adults (18–50 years of age) with severe pneumonia and SARS-CoV-2 infection confirmed by qPCR, were enrroled. Serum cytokines and the monocyte phenotype profile, including PDL1/HLA-DR expression, were determined during the first 24 h of hospitalization. Routine laboratory parameters were measured throughout patient follow-up until either death or hospital discharge. We also included a cohort of twenty-five healthy control subjects. Key findingsElevated levels of IL-10, IL-8, and IL-6 cytokines emerged as robust predictors of mortality in young adults with severe pneumonia due to SARS-CoV-2 infected. A descriptive analysis revealed a cumulative mortality rate of 30 % in unvaccinated and ICU-admitted patients. Patients who died had significantly lower expression of HLA-DR on their classical monocytes subsets (CD14+CD16−) than survivors and healthy controls. Lower expression of HLA-DR was associated with greater clinical severity (APACHE≥12) and bacterial coinfection (relative risk 2.5 95%CI [1.18–5.74]). Notably, the expression of HLA-DR in 27.5 % of CD14+/CD16- monocytes was associated with a significantly lower probability of survival. SignificanceThe early reduction in HLA-DR expression within classical monocytes emerged as an independent predictor of mortality, irrespective of comorbidities. Together with PD-L1 expression and cytokine alterations, these findings support the notion that monocyte immunosuppression plays a fundamental role in the pathogenesis and mortality of young patients infected with SARS-CoV-2. These findings hold significant implications for risk assessment and therapeutic strategies in managing critically ill young adults with SARS-CoV-2 infection.

Hemodialysis-Associated Immune Dysregulation in SARS-CoV-2-Infected End-Stage Renal Disease Patients.

Patients on hemodialysis show dysregulated immunity, basal hyperinflammation and a marked vulnerability to COVID-19. We evaluated the immune profile in COVID-19 hemodialysis patients and the changes associated with clinical deterioration after the hemodialysis session. Recruited patients included eight hemodialysis subjects with active, PCR-confirmed SARS-CoV-2 infection, five uninfected hemodialysis patients and five healthy controls. In SARS-CoV-2-infected hemodialysis patients TNF-α, IL-6 and IL-8 were particularly increased. Lymphopenia was mostly due to reduction in CD4+ T, B and central memory CD8+ T cells. There was a predominance of classical and intermediate monocytes with reduced HLA-DR expression and enhanced production of pro-inflammatory molecules. Immune parameters were analysed pre- and post-hemodialysis in three patients with COVID-19 symptoms worsening after the hemodialysis session. There was a higher than 2.5-fold increase in GM-CSF, IFN-γ, IL-1β, IL-2, IL-6, IL-17A and IL-21 in serum, and augmentation of monocytes-derived TNF-α, IL-1β and IL-8 and CXCL10 (p < 0.05). In conclusion, COVID-19 in hemodialysis patients associates with alteration of lymphocyte subsets, increasing of pro-inflammatory cytokines and monocyte activation. The observed worsening during the hemodialysis session in some patients was accompanied by augmentation of particular inflammatory cytokines, which might suggest biomarkers and therapeutic targets to prevent or mitigate the hemodialysis-related deterioration during SARS-CoV-2 infection.

MHCII Expression on Peripheral Blood Monocytes in Canine Lymphoma: An Impact of Glucocorticoids.

Simple SummaryLoss or decreased expression of human leukocyte antigen—D-related (HLA-DR) on the surface of monocytes is related to the dysfunction of the immune system and was reported in human neoplasia, including lymphoma. Canine lymphoma is frequently presented as a valuable comparative model for studies on human non-Hodgkin’s lymphoma. However, there are no studies on the expression of analogue proteins—MHCII antigens—on monocytes in canine lymphoma. In this study, we have evaluated the changes in the expression of MHCII on monocytes in the blood of dogs with lymphoma before any treatment and in dogs that had previously received glucocorticoids. Glucocorticoids are often used by clinicians as first drugs after diagnosis for immediate health improvement and are known to impact monocyte number. We have shown an increase in the percentage of MHCII− monocytes, regardless of treatment. However, only in dogs that had received glucocorticoids were changes in the proportion of MHCII+ and MHCII− monocytes reflected also by the changes in the number of MHCII− monocytes in the blood, which was significantly higher. Evaluating the changes in canine monocytes might be helpful in the diagnosis of various tumor types, monitoring of the treatment or assessing the immune status of dogs.An increase in the percentage of monocytes with reduced HLA-DR expression and immunosuppressive properties has been reported in numerous human neoplastic diseases, including lymphoma. However, there are no analogous studies on phenotypical variations in the peripheral blood monocytes in dogs with lymphoma. The aim of this study was to determine the difference in the expression of the MHCII molecule on peripheral blood monocytes in dogs with lymphoma before any treatment (NRG) and in dogs that had previously received glucocorticoids (RG) in comparison to healthy dogs. Flow cytometry immunophenotyping of peripheral blood leukocytes was performed using canine-specific or cross-reactive antibodies against CD11b, CD14 and MHCII. In the blood of dogs with lymphoma (NRG and RG), compared to that of healthy ones, the MHCII+ and MHCII− monocytes ratio was changed due to an increase in the percentage of MHCII− monocytes. The number of MHCII− monocytes was significantly higher only in RG dogs compared to healthy ones, which might result from the release of these cells from the blood marginal pool due to the action of glucocorticoids. Our results encourage further studies to assess if changes in MHCII expression affect immune status in dogs with lymphoma.

Patterns of dendritic cell and monocyte subsets are associated with disease severity and mortality in liver cirrhosis patients

Liver cirrhosis is often complicated by an immunological imbalance known as cirrhosis-associated immune dysfunction. This study aimed to investigate disturbances in circulating monocytes and dendritic cells in patients with acute decompensation (AD) of cirrhosis. The sample included 39 adult cirrhotic patients hospitalized for AD, 29 patients with stable cirrhosis (SC), and 30 healthy controls (CTR). Flow cytometry was used to analyze monocyte and dendritic cell subsets in whole blood and quantify cytokines in plasma samples. Cirrhotic groups showed higher frequencies of intermediate monocytes (iMo) than CTR. AD patients had lower percentages of nonclassical monocytes than CTR and SC. Cirrhotic patients had a profound reduction in absolute and relative dendritic cell numbers compared with CTR and showed higher plasmacytoid/classical dendritic cell ratios. Increased plasma levels of IL-6, IL-10, and IL-17A, elevated percentages of CD62L+ monocytes, and reduced HLA-DR expression on classical monocytes (cMo) were also observed in cirrhotic patients. Patients with more advanced liver disease showed increased cMo and reduced tissue macrophages (TiMas) frequencies. It was found that cMo percentages greater than 90.0% within the monocyte compartment and iMo and TiMas percentages lower than 5.7% and 8.6%, respectively, were associated with increased 90-day mortality. Monocytes and dendritic cells are deeply altered in cirrhotic patients, and subset profiles differ between stable and advanced liver disease. High cMo and low TiMas frequencies may be useful biomarkers of disease severity and mortality in liver cirrhosis.

Hyperglycemia and dyslipidemia: Reduced HLA-DR expression in monocyte subpopulations from diabetes patients

Immune dysfunction contributes to the higher risk of communicable and non-communicable diseases among diabetics. HLA-DR expression is a robust marker of immune competence in mononuclear cells, including antigen presentation to CD4 lymphocytes. Given the high prevalence of obesity among diabetics, we evaluated the independent association between hyperglycemia and dyslipidemias with respect to HLA-DR expression in blood monocytes from type 2 diabetes patients. The monocytes from individuals with (n = 16) or without diabetes (n = 25) were phenotyped by flow cytometry to assess the differential expression of HLA-DR on their three subpopulations (classical, intermediate and non-classical monocytes). Diabetes was independently associated with lower HLA-DR expression across all monocyte subpopulations (p < 0.05). Blood triglycerides were associated with further HLA-DR depression (interaction p < 0.002). Cholesterols counterbalanced the reductive effect, with CD36, a receptor for oxidized cholesterol, correlating with HLA-DR (rho = 0.373; p = 0.016). Future studies are warranted to elucidate the complex interactions between hyperglycemia and dyslipidemias on antigen presentation in diabetic monocytes.

Zoledronate rescues immunosuppressed monocytes in sepsis patients.

SummarySevere sepsis is often accompanied by a transient immune paralysis, which is associated with enhanced susceptibility to secondary infections and poor clinical outcomes. The functional impairment of antigen‐presenting cells is considered to be a major hallmark of this septic immunosuppression, with reduced HLA‐DR expression on circulating monocytes serving as predictor of mortality. Unconventional lymphocytes like γδ T‐cells have the potential to restore immune defects in a variety of pathologies including cancer, but their use to rescue sepsis‐induced immunosuppression has not been investigated. Our own previous work showed that Vγ9/Vδ2+ γδ T‐cells are potent activators of monocytes from healthy volunteers in vitro, and in individuals with osteoporosis after first‐time administration of the anti‐bone resorption drug zoledronate in vivo. We show here that zoledronate readily induces upregulation of HLA‐DR, CD40 and CD64 on monocytes from both healthy controls and sepsis patients, which could be abrogated by neutralising the pro‐inflammatory cytokines interferon (IFN)‐γ and tumour necrosis factor (TNF)‐α in the cultures. In healthy controls, the upregulation of HLA‐DR on monocytes was proportional to the baseline percentage of Vγ9/Vδ2 T‐cells in the peripheral blood mononuclear cell population. Of note, a proportion of sepsis patients studied here did not show a demonstrable response to zoledronate, predominantly patients with microbiologically confirmed bloodstream infections, compared with sepsis patients with more localised infections marked by negative blood cultures. Taken together, our results suggest that zoledronate can, at least in some individuals, rescue immunosuppressed monocytes during acute sepsis and thus may help improve clinical outcomes during severe infection.

Pseudomonas aeruginosa colonization causes PD-L1 overexpression on monocytes, impairing the adaptive immune response in patients with cystic fibrosis

BackgroundCystic fibrosis (CF) is an endotoxin tolerance (ET)-related disease. Given that increased PD-L1 has been reported in ET, its expression and physiological effects on cystic fibrosis monocytes should be studied. MethodsWe analyzed the phenotype and ex vivo response of immune system cells in 32 patients with CF, 19 of them colonized by Pseudomonas aeruginosa. An in vitro model was developed of Pseudomonas aeruginosa colonization using purified lipopolysaccharides (LPS) from one of the most prevalent strains in patients with CF (a CF-adapted Pseudomonas aeruginosa ST395 clone). Changes in the immune response, including cytokine production and T-lymphocyte proliferation, as well as expression of PD-L1, were evaluated. ResultsPD-L1 was overexpressed in the monocytes of patients with CF compared with healthy volunteers, and levels of this immune checkpoint were associated with Pseudomonas aeruginosa colonization. In addition, patients with Pseudomonas aeruginosa colonization showed a patent ET status, including poor inflammatory response, reduced HLA-DR expression and T-lymphocyte proliferation impairment. PD-L1/PD-1 blocking assays reverted the impaired adaptive response. Ultimately, monocytes from healthy volunteers cultured in the presence of the clinically relevant strain of Pseudomonas aeruginosa or serum collected from patients with CF colonized by Pseudomonas aeruginosa reproduced the previous observed features. ConclusionsPseudomonas aeruginosa colonization in patients with CF was associated with PD-L1 overexpression and impaired T cell response, and LPS from this pathogen induced the observed phenotype. Our findings open new avenues for the use of anti-PD-1/PD-L1 immunotherapy in patients with CF who are colonized by Pseudomonas aeruginosa.

Anti-angiogenic effect of hexahydrocurcumin in rat corneal neovascularization.

This study was to investigate the anti-angiogenic effect of hexahydrocurcumin (HHC) to evaluate gene (p-basic fibroblast growth factor (bFGF)-SAINT-18 & p-vascular endothelial growth factor (VEGF)-SAINT-18 complex)-induced corneal neovascularization (CorNV) in rats. CorNV was induced in 24 eyes of 24 rats. Four groups (Group A: 0μg, B: 0.01μg, C: 0.1μg, and D: 1μg) of HHC were prepared and implanted into the rat subconjunctival substantia propria 1.5mm from the limbus at temporal side. The 1μg of p-bFGF-SAINT-18 & p-VEGF-SAINT-18 complex were prepared and implanted into the rat corneal stroma 1.5mm from the limbus at the same side. Inhibition of CorNV was observed and quantified from day 1 to day 60. bFGF and VEGF protein expression were analyzed by biomicroscopic examination, western blot analysis, and immunohistochemistry. Subconjunctival injection by 1μg HHC successfully inhibited gene-induced CorNV in rats. bFGF and VEGF protein expression were reduced after 6days. Meanwhile, the reduction of HLA-DR expression was detected. Our study showed that the HHC might provide an important anti-angiogenesis factor to inhibit CorNV development at the corneal experimental angiogenesis model.

Potential specific immunological indicators for stroke associated infection are partly modulated by sympathetic pathway activation.

BackgroundEvidence has led to the consideration of immunodepression after stroke as an important contributor to stroke associated infection (SAI). However, so far no specific immunological indicator has been identified for SAI, and the underlying mechanism remains poorly understood.ResultsSAI patients had significantly higher IL-6 and IL-10 levels and lower HLA-DR levels than no-infection patients within 48h after stroke onset. NA significantly increased IL-10 levels, reduced HLA-DR expression, and decreased IL-6 expression by increasing β-arrestin2 expression which reduced the activation of the NF-κB pathway. Propranolol reversed this effect of NA by reducing β-arrestin2 expression.Materials and MethodsA systematic search for eligible clinical studies was applied to pool the differences in peripheral cytokine levels between infection and no-infection stroke patients. The underlying mechanism behind these differences was investigated in vitro by applying norepinephrine (NA) and lipopolysaccharide (LPS) to simulate sympathetic pathway activation and sepsis respectively in THP-1 cells. Propranolol was applied to determine the effect of reversing the activation of the sympathetic pathway. Immunological indicators were also detected to assess the immune activation of THP-1 cells and measurements of the expression of β-arrestin2, NF-κB, IκBα and phosphor-IκBα were performed to assess the activation of the sympathetic pathway.ConclusionIL-6, IL-10 and HLA-DR are good candidate biomarkers for SAI. The activation of the sympathetic pathway could partly account for the specific immunological alterations found in SAI patients including HLA-DR decrease and IL-10 increase, which both could be reversed by propranolol. However, the mechanism underlying IL-6 increase still needs further exploration.

Reduced Expression of HLA-DR on Monocytes During Severe Respiratory Syncytial Virus Infections.

Respiratory syncytial virus (RSV) is a common cause of bronchiolitis in infants with a wide spectrum of disease severity. Besides environmental and genetic factors, it is thought that the innate immune system plays a pivotal role. The aim of this study was to investigate the expression of immune receptors on monocytes and the in vitro responsiveness from infants with severe RSV infections. Peripheral blood mononuclear cells (PBMCs) from infants with RSV infections were isolated. Classical, intermediate and nonclassical monocytes were immunophenotyped for the expression of CD14, CD16, human leukocyte antigen (HLA)-ABC and HLA-DR. PBMCs were stimulated with lipopolysaccharide to determine the secretion of tumor necrosis factor and interleukin (IL)-10 with enzyme-linked immunosorbent assay. During RSV infection, intermediate monocytes are increased in the peripheral blood, whereas classical and nonclassical monocytes are reduced. The expression of CD14 and HLA-ABC is increased on monocytes, whereas the expression of HLA-DR is suppressed. Low HLA-DR expression is correlated with increased disease severity. PBMCs from infants with severe RSV infections show an impaired IL-10 response in vitro. Phenotyping subpopulations of monocytes combined with in vitro responsiveness reveals significant differences between nonsevere and severe RSV infections. Reduced HLA-DR expression and impaired IL-10 production in vitro during severe RSV infections indicate that an imbalanced innate immune response may play an important role in disease severity.

Profoundly Reduced CD1c+ Myeloid Dendritic Cell HLA-DR and CD86 Expression and Increased Tumor Necrosis Factor Production in Experimental Human Blood-Stage Malaria Infection.

Dendritic cells (DCs) are sentinels of the immune system that uniquely prime naive cells and initiate adaptive immune responses. CD1c (BDCA-1) myeloid DCs (CD1c(+) mDCs) highly express HLA-DR, have a broad Toll-like receptor (TLR) repertoire, and secrete immune modulatory cytokines. To better understand immune responses to malaria, CD1c(+) mDC maturation and cytokine production were examined in healthy volunteers before and after experimental intravenous Plasmodium falciparum infection with 150- or 1,800-parasite-infected red blood cells (pRBCs). After either dose, CD1c(+) mDCs significantly reduced HLA-DR expression in prepatent infections. Circulating CD1c(+) mDCs did not upregulate HLA-DR after pRBC or TLR ligand stimulation and exhibited reduced CD86 expression. At peak parasitemia, CD1c(+) mDCs produced significantly more tumor necrosis factor (TNF), whereas interleukin-12 (IL-12) production was unchanged. Interestingly, only the 1,800-pRBC dose caused a reduction in the circulating CD1c(+) mDC count with evidence of apoptosis. The 1,800-pRBC dose produced no change in T cell IFN-γ or IL-2 production at peak parasitemia or at 3 weeks posttreatment. Overall, CD1c(+) mDCs are compromised by P. falciparum exposure, with impaired HLA-DR and CD86 expression, and have an increased capacity for TNF but not IL-12 production. A first prepatent P. falciparum infection is sufficient to modulate CD1c(+) mDC responsiveness, likely contributing to hampered effector T cell cytokine responses and assisting parasite immune evasion.

A Glucuronoxylomannan-Associated Immune Signature, Characterized by Monocyte Deactivation and an Increased Interleukin 10 Level, Is a Predictor of Death in Cryptococcal Meningitis.

Background. Cryptococcal meningitis remains a significant cause of death among human immunodeficiency virus type 1 (HIV)–infected persons in Africa. We aimed to better understand the pathogenesis and identify immune correlates of mortality, particularly the role of monocyte activation.Methods. A prospective cohort study was conducted in Cape Town, South Africa. Patients with a first episode of cryptococcal meningitis were enrolled, and their immune responses were assessed in unstimulated and stimulated blood specimens, using flow cytometry and cytokine analysis.Results. Sixty participants were enrolled (median CD4+ T-cell count, 34 cells/µL). Mortality was 23% (14 of 60 participants) at 14 days and 39% (22 of 57) at 12 weeks. Nonsurvivors were more likely to have an altered consciousness and higher cerebrospinal fluid fungal burden at presentation. Principal component analysis identified an immune signature associated with early mortality, characterized by monocyte deactivation (reduced HLA-DR expression and tumor necrosis factor α response to lipopolysaccharide); increased serum interleukin 6, CXCL10, and interleukin 10 levels; increased neutrophil counts; and decreased T-helper cell type 1 responses. This immune signature remained an independent predictor of early mortality after adjustment for consciousness level and fungal burden and was associated with higher serum titers of cryptococcal glucuronoxylomannan.Conclusions. Cryptococcal-related mortality is associated with monocyte deactivation and an antiinflammatory blood immune signature, possibly due to Cryptococcus modulation of the host immune response. Validation in other cohorts is required.

Human Mesenchymal Stem Cells Alter the Gene Profile of Monocytes from Patients with Type 2 Diabetes and End-Stage Renal Disease

Macrophage infiltration contributes to the pathogenesis of Type 2 diabetes. Mesenchymal stem cells (MSCs) possess immunomodulatory properties, making them an ideal candidate for therapeutic intervention. This study investigated whether MSCs can modulate the phenotype of monocytes isolated from Type 2 diabetic patients with end-stage renal disease. Monocytes from control (n = 4) and Type 2 diabetic patients with end-stage renal disease (n = 5) were assessed using flow cytometry and microarray profiling, following 48 h of co-culture with MSCs. Control subjects had a greater proportion of CD14(++)CD16(-) monocytes while diabetic patients had a higher proportion of CD14(++)CD16(+) and CD14(+)CD16(++) monocytes. MSCs promoted the proliferation of monocytes isolated from diabetic patients, reduced HLA-DR expression in both groups and promoted the expression of anti-inflammatory genes. MSC-derived factors alter the polarization of monocytes isolated from healthy and diabetic subjects toward an M2 phenotype.

Modulation of HLA-DR in dry eye patients following 30 days of treatment with a lubricant eyedrop solution.

PurposeTo determine the changes in dry eye disease (DED) severity and the percentage of cells expressing HLA-DR on the ocular surface following treatment with lubricant eyedrops containing polyethylene glycol and propylene glycol (PEG/PG) and the gelling agent hydroxypropyl guar (HP-Guar).Patients and methodsNineteen patients with DED used PEG/PG + HP-Guar eyedrops four times per day for 30 days. Assessments included DED severity (Ocular Surface Disease Index [OSDI], corneal staining, conjunctival staining, tear film break-up time [TFBUT], and Schirmer testing) and impression cytology of the conjunctiva with masked flow cytometry at baseline and at 30 days.ResultsThere was a significant decrease in corneal staining (P<0.01), OSDI (P=0.02), and TFBUT (P<0.01) following treatment with PEG/PG + HP-Guar. Results from flow cytometry revealed a significant decrease in cells expressing HLA-DR (P=0.02).ConclusionTreatment with PEG/PG + HP-Guar eyedrops showed improvement in dry eye severity and reduction in surface inflammation as indicated by a reduction in HLA-DR expression.

Decreased Tim-3 expression is associated with functional abnormalities of monocytes in decompensated cirrhosis without overt bacterial infection

Patients with advanced cirrhosis usually exhibit altered monocyte function. However, the molecular mechanisms underlying the functional changes of monocytes are poorly understood. We investigated the role of T-cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3) in regulating monocyte function in 94 patients with decompensated liver cirrhosis (DC-LC) (decompensation was defined by ascites, hepatic encephalopathy or upper gastrointestinal bleeding), 58 with compensated liver cirrhosis (C-LC) and 52 healthy controls (HC) by characterizing the frequency of Tim-3(+) monocytes, their phagocytosis capacity, HLA-DR expression, cytokine secretion and MAP kinase activation induced by lipopolysaccharide (LPS). Tim-3 expression on CD14(+) monocytes in DC-LC group were significantly lower than that in C-LC and HC and were associated with increased levels of plasma endotoxin, enhanced cytokine production, decreased phagocytic capacity, and reduced HLA-DR expression. Tim-3 expression on monocytes and monocyte function did not differ between C-LC and HC group. Tim-3(+)CD14(+) cells had more potent phagocytic capacity, higher levels of HLA-DR, CD86, CD80, CD163, and CD206 expression, but lower levels of CD1a and CD83, related to that of Tim-3(-)CD14(+) monocytes. In addition, Tim-3(+)CD14(+) cells produced less TNF-α but higher levels of IL-10 in response to LPS. Treatment with anti-Tim-3 antibody significantly reduced phagocytic capacity, but enhanced LPS-stimulated TNF-α, IL-6, and IL-10 secretion. Furthermore, blocking Tim-3 signaling increased p38 MAP kinase phosphorylation in monocytes upon LPS stimulation. Downregulation of Tim-3 expression was associated with endotoxemia and functional alterations of monocytes in patients with decompensated cirrhosis.

Effect of Immunosuppression on T-Helper 2 and B-Cell Responses to Influenza Vaccination.

Influenza vaccine immunogenicity is suboptimal in immunocompromised patients. However, there are limited data on the interplay of T- and B- cell responses to vaccination with simultaneous immunosuppression. We collected peripheral blood mononuclear cells from transplant recipients before and 1 month after seasonal influenza vaccination. Before and after vaccination, H1N1-specific T- and B-cell activation were quantified with flow cytometry. We also developed a mathematical model using T- and B-cell markers and mycophenolate mofetil (MMF) dosage. In the 47 patients analyzed, seroconversion to H1N1 antigen was demonstrated in 34%. H1N1-specific interleukin 4 (IL-4)-producing CD4(+) T-cell frequencies increased significantly after vaccination in 53% of patients. Prevaccine expression of H1N1-induced HLA-DR and CD86 on B cells was high in patients who seroconverted. Seroconversion against H1N1 was strongly associated with HLA-DR expression on B cells, which was dependent on the increase between prevaccine and postvaccine H1N1-specific IL-4(+)CD4(+) T cells (R(2) = 0.35). High doses of MMF (≥ 2 g/d) led to lower seroconversion rates, smaller increase in H1N1-specific IL-4(+)CD4(+) T cells, and reduced HLA-DR expression on B cells. The mathematical model incorporating a MMF-inhibited positive feedback loop between H1N1-specific IL-4(+)CD4(+) T cells and HLA-DR expression on B cells captured seroconversion with high specificity. Seroconversion is associated with influenza-specific T-helper 2 and B-cell activation and seems to be modulated by MMF.

0094. Monocyte tace activity profile during sepsis and systemic inflammatory response syndrome

To date, immune-modulatory treatments in sepsis have proved unsuccessful. Better understanding of inflammatory processes might help tailor such therapies more effectively and improve their efficacy. It is now recognised that some patients may require immune stimulating therapies. Monocytes display altered behaviour in response to systemic inflammation; this has been called “deactivation” and is characterised by reduced HLA-DR expression and attenuated tumour necrosis factor-α (TNF) release in response to lipopolysaccharide (LPS) stimulus1. TNF converting enzyme (TACE), activated via p38-mitogen activated protein kinase (MAPK) mediated pathway2, is essential for the shedding of TNF and TNF receptors (TNFRs)-1&2. Altered TACE behaviour may be mechanistically important in deactivation.

Innate Immune Dysfunction in Trauma Patients

Innate Immune Dysfunction in Trauma Patients

PECULIAR IMMUNOLOGICAL PROPERTIES OF CHRONIC POSTTRAUMATIC OSTEOMYELITIS

A comparative study of cellular immunity parameters was performed in patients with long bone chronic posttraumatic osteomyelitis in regard to osteomyelitis stages. Thirty patients with the fistulous form of long bone chronic posttraumatic osteomyelitis and 13 patients with long bone chronic posttraumatic osteomyelitis in the remission stage were examined using laser flow citometry. It was revealed that a moderate leukocytosis, increased monocyte and neutrophile absolute number as well as increased CD25 and HLA-DR-positive T-lymphocyte number are typical for chronic osteomyelitis regardless of the pathological process stages. The remission stage in patients with chronic posttraumatic osteomyelitis is accompanied by moderate activation of humoral immunity (increased B-lymphocyte (CD19+) number and increased production of IgG). The decrease in the peripheral blood lymphocyte number and well as reduction of HLA-DR expression on monocytes creates prerequisites for the development of fistulous osteomyelitis form and can be an indication for administering the preparations of immunomodulating action.

Association of an increased frequency of CD14+HLA‐DRlo/neg monocytes with decreased time to progression in chronic lymphocytic leukaemia (CLL)

Association of an increased frequency of CD14⁺HLA‐DR^lo/neg monocytes with decreased time to progression in chronic lymphocytic leukaemia (CLL)