Decreased response to recall antigens is associated with depressed costimulatory receptor expression in septic critically ill patients

Manjuck, Janice; Saha, Dhanonjoy C.; Astiz, Mark E.; Eales, L J; Rackow, Eric C.

doi:10.1067/mlc.2000.104306

Cited by 104 publications

(94 citation statements)

References 32 publications

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“…Given the link between severity of acute hepatic dysfunction and monocyte HLA-DR expression in AALF, the question arises as to whether the reduced surface expression of this molecule is of pathogenic significance. Functional analyses of monocyte function in ALF 11,14 and conditions characterized by reduced monocyte HLA-DR surface expression clearly demonstrate that these cells with reduced HLA-DR expression are "dysfunctional" as a consequence of their impaired ability at presenting antigen and at producing TNF-␣ following lipopolysaccharide stimulation, 21,32,33 the latter defect being directly linked to the development of recurrent bacterial and opportunistic infections. 21 Because cytokines are known to directly influence the expression of monocyte HLA-DR, we measured both proinflammatory (TNF-␣, IL-6) and anti-inflammatory (IL-10) cytokines in the circulation of our AALF patients and found elevated serum levels of both.…”

Section: Discussionmentioning

confidence: 99%

Reduced monocyte HLA-DR expression: A novel biomarker of disease severity and outcome in acetaminophen-induced acute liver failure

et al. 2006

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Acute liver failure (ALF) shares striking similarities with septic shock where a decrease in HLA-DR expression on monocytes is associated with disease severity and predicts outcome. We investigated monocyte HLA-DR expression in ALF in relation to inflammatory mediator levels and clinical outcome. Monocyte HLA-DR expression was determined in 50 patients with acetaminophen-induced ALF (AALF) and 20 non-acetaminophen-induced ALF (NAALF). AALF patients were divided into dead/transplanted (AALF-NS, n ‫؍‬ 26) and spontaneous survivors (AALF-S, n ‫؍‬ 24). Fifty patients with chronic liver disease (CLD) and 50 healthy volunteers served as controls. Monocyte HLA-DR expression was determined by double-color flow-cytometry with monoclonal antibodies detecting HLA-DR and monocyte specific CD14. Serum levels of interleukin (IL) -4, -6, -10, tumor necrosis factor (TNF)-␣ and interferon (IFN)-␥ were concomitantly measured by ELISA. Compared to healthy volunteers (75%) and CLD (67%) monocyte HLA-DR percentage expression was lower in AALF (15%, P < .001) and NAALF (22 %, P < .001). Compared to AALF-S, AALF-NS had lower monocyte HLA-DR % (11% vs. 36%, P < .001) and higher levels of IL-4, IL-6, IL-10 and TNF-␣ (P < .001). HLA-DR percentage negatively correlated with INR, blood lactate, pH and levels of encephalopathy (r ‫؍‬ ؊0.8 to ؊0.5, P < .01), IL-10 (r ‫؍‬ ؊0.8, P < .0001), TNF-␣ (r ‫؍‬ ؊0.4, P ‫؍‬ .02). HLA-DR percentage level <15% has a 96% sensitivity and 100% specificity and 98% accuracy in predicting poor prognosis. In conclusion, the strong relationship of monocyte HLA-DR expression with indices of disease severity, mediators of inflammation and outcome indicates a key role for this molecule as a biomarker of disease severity and prognosis. (HEPATOLOGY 2006;44:34-43.)

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Section: Discussionmentioning

confidence: 99%

Reduced monocyte HLA-DR expression: A novel biomarker of disease severity and outcome in acetaminophen-induced acute liver failure

et al. 2006

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“…However, this would first require modification and optimization of the methodologies used, in order to ensure they are compatible with the very small postnatal blood volumes available from extremely preterm infants. The activation markers HLA-DR, CD64, and CD86 have previously been associated with early diagnosis and/or prognosis of sepsis and bacterial infection (34)(35)(36). Although this is the focus of much of the investigation into HLA-DR expression, this is the first study to correlate expression with phagocytosis.…”

Section: Phagocytosis In Newborn Whole Bloodmentioning

confidence: 99%

Phagocytosis of neonatal pathogens by peripheral blood neutrophils and monocytes from newborn preterm and term infants

et al. 2013

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“…Levels of class II gene expression also vary in antigen-presenting cells dependent on particular stimuli. MHC class II gene expression may become markedly downregulated in particular physiological or disease states, for example, during severe or prolonged infection [26][27][28] or B-cell lymphoma 29 in which it is associated with poor outcome.…”

Section: Mhc Class II Genes and Their Expressionmentioning

confidence: 99%

Regulation of major histocompatibility complex class II gene expression, genetic variation and disease

et al. 2009

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Major histocompatibility complex (MHC) class II molecules are central to adaptive immune responses and maintenance of selftolerance. Since the early 1970s, the MHC class II region at chromosome 6p21 has been shown to be associated with a remarkable number of autoimmune, inflammatory and infectious diseases. Given that a full explanation for most MHC class II disease associations has not been reached through analysis of structural variation alone, in this review we examine the role of genetic variation in modulating gene expression. We describe the intricate architecture of the MHC class II regulatory system, indicating how its unique characteristics may relate to observed associations with disease. There is evidence that haplotypespecific variation involving proximal promoter sequences can alter the level of gene expression, potentially modifying the emergence and expression of key phenotypic traits. Although much emphasis has been placed on cis-regulatory elements, we also examine the role of more distant enhancer elements together with the evidence of dynamic inter-and intra-chromosomal interactions and epigenetic processes. The role of genetic variation in such mechanisms may hold profound implications for susceptibility to common disease.

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Decreased response to recall antigens is associated with depressed costimulatory receptor expression in septic critically ill patients

Cited by 104 publications

References 32 publications

Reduced monocyte HLA-DR expression: A novel biomarker of disease severity and outcome in acetaminophen-induced acute liver failure

Reduced monocyte HLA-DR expression: A novel biomarker of disease severity and outcome in acetaminophen-induced acute liver failure

Phagocytosis of neonatal pathogens by peripheral blood neutrophils and monocytes from newborn preterm and term infants

Regulation of major histocompatibility complex class II gene expression, genetic variation and disease

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