Neutrophil CD64 expression: distinguishing acute inflammatory autoimmune disease from systemic infections

Allen, Elyse M.; Bakke, Antony C.; Purtzer, M Z; Deodhar, Atul

doi:10.1136/ard.61.6.522

Cited by 81 publications

(37 citation statements)

References 9 publications

(5 reference statements)

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“…57 However, our studies have used healthy donors for isolating PMNs, on which Fc␥RIIa and Fc␥RIIIb are the principal Fc␥ receptors, and it should be borne in mind that Fc␥RI (CD64) can be detected on circulating PMNs during sepsis. 58 Whether or not Fc␥RI makes an additional contribution to leukocyte-EC interactions during infections in SLE awaits investigation. A further consideration is whether AECAmediated adhesion of SLE PMNs to ECs is influenced by the Fc␥RIIa 131H/R polymorphism, with the R/R131 allotype being linked to lupus nephritis.…”

Section: Discussionmentioning

confidence: 99%

Antiendothelial cell antibodies mediate enhanced leukocyte adhesion to cytokine-activated endothelial cells through a novel mechanism requiring cooperation between FcγRIIa and CXCR1/2

Florey

Johns

Esho

et al. 2007

Blood

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Antiendothelial cell antibodies (AECAs) are commonly detectable in diseases associated with vascular injury, including systemic lupus erythematosus (SLE), systemic sclerosis, Takayasu arteritis, Wegener granulomatosis, Behç et syndrome, and transplant arteriosclerosis. Here, we explore the hypothesis that these antibodies might augment polymorphonuclear leukocyte (PMN) adhesion to endothelium in inflammation. Initially, we established that a mouse IgG mAb bound to endothelial cells (ECs) significantly increased PMN adhesion to cytokine-stimulated endothelium in an Fc␥RIIa-dependent manner. Neutralizing antibodies, and adenoviral transduction of resting ECs, demonstrated that the combination of Eselectin, CXCR1/2, and ␤ 2 integrins is both necessary and sufficient for this process. We observed an identical mechanism using AECA IgG isolated directly from patients with SLE. Assembled immune complexes also enhanced PMN adhesion to endothelium, but, in contrast to adhesion because of AECAs, this process did not require CXCR1/2, was not inhibited by pertussis toxin, and was Fc␥RIIIb rather than Fc␥RIIa dependent. IntroductionThe recruitment of circulating polymorphonuclear leukocytes (PMNs) to sites of inflammation is mediated by a series of adhesion and activation steps, known as the "adhesion cascade." 1 Thus, selectins are largely responsible for initial tethering of flowing PMNs to endothelium and also mediate subsequent PMN rolling on the endothelial surface. Activation of rolling PMNs leads to leukocyte arrest via modulation of the affinity and avidity of ␤ 2 integrins, with LFA-1 (CD11a/CD18) acting primarily to slow rolling and to promote arrest, and Mac-1 (CD11b/CD18) acting to stabilize adhesion. [2][3][4][5] The capacity of endothelial cells (ECs) to support these interactions with PMNs is stimulated by cytokines such as TNF␣ and IL-1␤, which induce expression of a large number of adhesion molecules, chemottractant, and other proinflammatory genes, including E-selectin, chemokines (eg, IL-8), and ICAM-1. 6,7 Antibodies that react with the surface of vascular endothelial cells (antiendothelial cell antibodies, AECAs) are found in a variety of diseases associated with vascular injury, including systemic lupus erythematosus (SLE), systemic sclerosis, Takayasu arteritis, Wegener granulomatosis, Behçets syndrome, and transplant arteriosclerosis, 8,9 A number of mechanisms have been proposed whereby IgG binding to ECs may exert pathogenic effects, including the induction of EC inflammatory activation and thrombogenicity, the stimulation of leukocyte free-radical production and cellular cytotoxicity, and the induction of EC apoptosis. [10][11][12][13][14] Interactions between circulating human PMNs and immune complexes are mediated via 2 low-affinity Fc␥ receptors, Fc␥RIIa (CD32a) and Fc␥RIIIb (CD16b), which are both thought to form homodimers and have distinct membrane-anchoring and -signaling capacities. [15][16][17][18][19] The cytoplasmic domain of Fc␥RIIa has a specialized immunoreceptor tyrosine-based activ...

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Section: Discussionmentioning

confidence: 99%

Antiendothelial cell antibodies mediate enhanced leukocyte adhesion to cytokine-activated endothelial cells through a novel mechanism requiring cooperation between FcγRIIa and CXCR1/2

Florey

Johns

Esho

et al. 2007

Blood

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“…Up-regulation and increased expression of nCD64 appears to be a sensitive marker for early-onset clinical infection in newborn children. 25,31 In adults, its use has been suggested for differentiating systemic infection from active inflammatory disease, 32 monitoring IFN-γ therapy 21 and as an indicator for initiating or discontinuing antibiotic treatment. 25 Our observation that nCD64 expression correlates with a rise in proinflammatory cytokines 20 h earlier, further substantiates the notion that nCD64 expression is a reliable and quantitative measure of the innate immune response.…”

Section: Discussionmentioning

confidence: 99%

Hematological indices, inflammatory markers and neutrophil CD64 expression: comparative trends during experimental human endotoxemia

Meer

Pickkers

Scott

et al. 2007

Journal of Endotoxin Research

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CD64 is a high-affinity FcγRI receptor expressed by activated neutrophils that has been recently evaluated as a potential sepsis parameter. In the present study, the kinetics of neutrophil membrane CD64 expression were examined during a standardized inflammatory response, using a human endotoxemia model, and compared with hematological indices, CRP, cytokines and interleukins. Ten healthy subjects received 2 ng/kg intravenous Escherichia coli lipopolysaccharide (LPS). After administration of LPS, neutrophil CD64 showed a biphasic response, characterized by a first increase from 108.5 ± 7.5 to 133 ± 6 AFU after 1 h ( P = 0.047) and a second increase that started at 6 h and reached its maximum of 167 ± 13 AFU at 22 h ( P < 0.0001). CRP concentrations increased to 40 ± 5 mg/dl 22 h after the administration of LPS. The cytokines and interleukins reached their maximum response within 1—2 h. The maximum values of pro-inflammatory cytokines (TNF-α, IFN-γ and IL-6) correlated with the CD64 expression at 22 h after LPS administration ( r2 = 0.76, r2 = 0.78, r2 = 0.81, respectively, all P < 0.05), whereas this correlation was not found for the anti-inflammatory IL-10 ( r2 = 0.058, P = 0.54), suggesting that neutrophil CD64 expression might be a quantitative marker for innate immunity that could easily be used in the clinical setting.

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“…þ T-cell levels in HIV-positive patients, 16 using CD34 þ (note: the superscript ' þ ' denotes that the cell expresses that antigen) cell counts for predicting harvest yield in haematopoietic stem-cell transplantation, 21 evaluating neutrophil CD64 expression in sepsis 22 and foetomaternal haemorrhage quantitation. 23 Although 'broad-brush' quantitative leukaemia panels are yet to find a role, quantitation has been shown to be of value in specific prognostic situations such as CD38 and ZAP-70 expression in CLL.…”

Section: Reporting Resultsmentioning

confidence: 99%

Flow cytometry in clinical pathology

Virgo

Gibbs

2011

Ann Clin Biochem

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Flow cytometry has had an impact upon all areas of clinical pathology and now, in the 21st century, it is truly coming of age. This study reviews the application of flow cytometry within clinical pathology with an emphasis upon haematology and immunology. The basic principles of flow cytometry are discussed, including the principles and considerations of the flow-cell and hydrodynamic focusing, detector layout and function, use of fluorochromes and multicolour flow cytometry (spectral overlap and colour compensation), alongside the strategies available for sample preparation, data acquisition and analysis, reporting of results, internal quality control, external quality assessment and flow sorting. The practice of flow cytometry is discussed, including the principles and pitfalls associated with leukocyte immunophenotyping for leukaemia and lymphoma diagnosis, immune deficiency, predicting and monitoring response to monoclonal antibody therapy, rare event detection and screening for genetic disease. Each section is illustrated with a case study. Future directions are also discussed.

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Neutrophil CD64 expression: distinguishing acute inflammatory autoimmune disease from systemic infections

Cited by 81 publications

References 9 publications

Antiendothelial cell antibodies mediate enhanced leukocyte adhesion to cytokine-activated endothelial cells through a novel mechanism requiring cooperation between FcγRIIa and CXCR1/2

Antiendothelial cell antibodies mediate enhanced leukocyte adhesion to cytokine-activated endothelial cells through a novel mechanism requiring cooperation between FcγRIIa and CXCR1/2

Hematological indices, inflammatory markers and neutrophil CD64 expression: comparative trends during experimental human endotoxemia

Flow cytometry in clinical pathology

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