Neutrophil Subsets, Platelets, and Vascular Disease in Psoriasis

Teague, Heather; Varghese, Nevin; Tsoi, Lam C.; Dey, Amit; Garshick, Michael; Silverman, Joanna I; Baumer, Yvonne; Harrington, Charlotte; Stempinski, Erin; Elnabawi, Youssef; Dagur, Pradeep K.; Cui, Kairong; Tunc, Ilker; Seifuddin, Fayaz; Joshi, Aditya; Stansky, Elena; Purmalek, Monica; Rodante, Justin; Keel, Andrew; Aridi, Tarek; Carmona‐Rivera, Carmelo; Sanda, Gregory E.; Chen, Marcus Y; Pirooznia, Mehdi; McCoy, J. Philip; Gelfand, Joel M.; Zhao, Keji; Guðjónsson, Jóhann E.; Playford, Martin P.; Kaplan, Mariana J.; Berger, Jeffrey S.; Mehta, Nehal N.

doi:10.1016/j.jacbts.2018.10.008

Cited by 63 publications

(77 citation statements)

References 50 publications

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“…LDNs in autoimmune disease are CD10 + [25] and LDNs identified in cardiovascular risk associated with psoriasis are identified by CD10 hi expression. [14] As CD10 expression was equal in LDNs and NDNs from healthy individuals and T cell suppression was seen in both neutrophil densities, we would propose that the T cell suppression is disease specific, and perhaps CD10 -LDNs seen in disease may be a result of emergency granulopoesis [40] and are therefore not present in healthy individuals.…”

Section: Discussionmentioning

confidence: 93%

“…LDNs from healthy individuals produced fewer NETs than NDN, in direct contrast to LDNs isolated from chronic inflammatory conditions such as psoriasis and idiopathic inflammatory myopathy, where LDNs produce increased numbers of NETs. [14,15] It is difficult to reconcile many of the features of LDNs as healthy LDNs have normal expression of CD10 and CD16 characteristic of mature neutrophils and no reduction in ROS production in spite of having an immature nuclear morphology.…”

Section: Discussionmentioning

confidence: 99%

“…LDNs have a similar density to peripheral blood mononuclear cells (PBMCs) and are isolated alongside these cells, in contrast to normal density neutrophils (NDNs) which segregate with other polymorphonuclear (PMN) cells during density exclusion. [3,4] LDNs have been described in pregnancy, [5] autoimmune disease, [6,7] cancer, [8,9] infection [10][11][12][13] and inflammation, [14,15] and speculated to contribute to pathophysiology. Across these studies, LDNs do not represent one discrete neutrophil sub-population, but rather a spectrum of multiple neutrophil phenotypes which vary in morphology, maturation and activation dependant on the underlying disease process.…”

Section: Graphical Abstract: Introductionmentioning

confidence: 99%

“…These studies are limited to characterising neutrophil phenotype without assessing the function of pure LDNs. [3,5,13,14,[17][18][19][20][21] In addition, isolation of neutrophils within the PBMC and in the presence of monocytes can result in their activation. [22] For functional assays, further isolation of LDNs from PBMC is performed by FACS [10,12] which can also cause artefactual activation or by magnetic selection which is also problematic if the NDNs do not undergo the same protocol [7,[23][24][25][26][27] and are instead subject to second density gradient or RBC lysis treatment.…”

Section: Graphical Abstract: Introductionmentioning

confidence: 99%

“…[26,27] The ability of LDNs to generate neutrophil extracellular traps (NETs) also varies between conditions. In SLE and Psoriasis, LDNs produce increased NETs compared with NDNs from the same donor, [14,23] while in Rheumatoid Arthritis, NET formation did not appear to differ, [30] but importantly healthy LDNs were not included as a comparator. Together, these data suggest that low neutrophil density may represent 'disease specific' neutrophil populations rather than a distinct class of neutrophils common to all conditions.…”

Section: Graphical Abstract: Introductionmentioning

confidence: 99%

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Ultra-pure isolation of low density neutrophils casts doubt on their exceptionality in health and disease

Hardisty

Llanwarne

Minns

et al. 2020

Preprint

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Low density neutrophils (LDNs) are described in a number of inflammatory conditions, cancers and infections and associated with immunopathology, and a mechanistic role in disease. The role of LDNs at homeostasis in healthy individuals has not been investigated. We have developed an isolation protocol that generates high purity LDNs from healthy donors. Healthy LDNs were identical to healthy NDNs, aside from reduced neutrophil extracellular trap formation. CD66b, CD16, CD15, CD10, CD54, CD62L, CXCR2, CD47 and CD11b were expressed at equivalent levels in LDNs and normal density neutrophils (NDNs) and underwent apoptosis and ROS production interchangeably. Healthy LDNs had no differential effect on CD4 + or CD8 + T cell proliferation or IFNγ production compared with NDNs.LDNs were generated from healthy NDNs in vitro by activation with TNF, LPS or fMLF, suggesting a mechanism of LDN generation in disease however, we show neutrophilia in people with Cystic Fibrosis (CF) was not due to increased LDNs. LDNs are present in the neutrophil pool at homeostasis and have limited functional differences to NDNs. We conclude that increased LDN numbers in disease reflect the specific pathology or inflammatory environment and that neutrophil density alone is inadequate to classify discrete functional populations of neutrophils.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Graphical Abstract: Introductionmentioning

confidence: 99%

Section: Graphical Abstract: Introductionmentioning

confidence: 99%

Section: Graphical Abstract: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Ultra-pure isolation of low density neutrophils casts doubt on their exceptionality in health and disease

Hardisty

Llanwarne

Minns

et al. 2020

Preprint

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Association of Psoriasis With Incident Venous Thromboembolism and Peripheral Vascular Disease

Chen¹,

Lee

Huang

et al. 2022

JAMA Dermatol

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IMPORTANCE Psoriasis, venous thromboembolism (VTE), and peripheral vascular disease (PVD) share similar mechanisms involving chronic inflammation. However, the associations between psoriasis and VTE or PVD are unclear.OBJECTIVE To determine the association of psoriasis with incident VTE and PVD.DATA SOURCES MEDLINE, Embase, Cochrane Library, Web of Science, and Cumulative Index to Nursing and Allied Health Literature were systematically searched for relevant publications from their respective inception through May 21, 2021. No restrictions on language or geographic locations were imposed.STUDY SELECTION Two authors independently selected cohort studies that investigated the risk for incident VTE or PVD in patients with psoriasis. Any discrepancy was resolved through discussion with 2 senior authors until reaching consensus. Only 13 initially identified studies met the selection criteria for qualitative review, and only 9 of these for quantitative analysis. DATA EXTRACTION AND SYNTHESISThe Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline was followed. Two authors independently extracted data and assessed the risk of bias of included studies by using the Newcastle-Ottawa Scale. Disagreements were resolved by discussion with 2 other authors. A random-effects model meta-analysis was conducted to calculate the pooled hazard ratios (HRs) with the corresponding confidence intervals for incident VTE and PVD. Subgroup analyses based on arthritis status, psoriasis severity, sex, and geographic location were also performed. MAIN OUTCOMES AND MEASURES Hazard ratios for incident VTE and PVD associated with psoriasis.RESULTS A total of 13 cohort studies with 12 435 982 participants were included. The meta-analysis demonstrated a significantly increased risk for incident VTE (pooled HR, 1.26; 95% CI, 1.08-1.48) and PVD (pooled HR, 1.27; 95% CI, 1.16-1.40) among patients with psoriasis. Subgroup analyses illustrated increased risk for incident VTE among participants with psoriatic arthritis (pooled HR, 1.24; 95% CI, 1.01-1.53), women (pooled HR, 1.89; 95% CI, 1.36-2.61), and those in Asia (pooled HR, 2.02; 95% CI, 1.42-2.88) and Europe (pooled HR, 1.28; 95% CI, 1.06-1.53).CONCLUSIONS AND RELEVANCE This systematic review and meta-analysis found an increased risk for incident VTE and PVD among patients with psoriatic disease. Typical presentations of VTE or PVD should not be overlooked in patients with psoriasis. Risk factors, such as obesity, physical inactivity, smoking, and varicose veins, should be identified and treated in patients with psoriasis, and medications like hormone-related therapies should be prescribed with caution.

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Low‐Density Neutrophils in Systemic Lupus Erythematosus

Tay

Celhar

Fairhurst

2020

Arthritis & Rheumatology

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Patients with systemic lupus erythematosus ( SLE ) display increased numbers of immature neutrophils in the blood, but the exact role of these immature neutrophils is unclear. Neutrophils that sediment within the peripheral blood mononuclear cell fraction after density centrifugation of blood are generally defined as low‐density neutrophils ( LDN s). Far beyond antimicrobial functions, LDN s are emerging as decision‐shapers during innate and adaptive immune responses. Traditionally, neutrophils have been viewed as a homogeneous population. However, the various LDN populations identified in SLE to date are heterogeneously composed of mixed populations of activated mature neutrophils and immature neutrophils at various stages of differentiation. Controversy also surrounds the role of LDN s in SLE in terms of whether they are proinflammatory or polymorphonuclear myeloid‐derived suppressor cells. It is clear that LDN s in SLE can secrete increased levels of type I interferon ( IFN ) and that they contribute to the cycle of inflammation and tissue damage. They readily form neutrophil extracellular traps, exposing modified autoantigens and oxidized mitochondrial DNA , which contribute to autoantibody production and type I IFN signaling, respectively. Importantly, the ability of LDN s in SLE to perform canonical neutrophil functions is polarized, based on mature CD 10+ and immature CD 10− neutrophils. Although this field is still relatively new, multiomic approaches have advanced our understanding of the diverse origins, phenotype, and function of LDN s in SLE . This review updates the literature on the origin and nature of LDN s, their distinctive features, and their biologic roles in the immunopathogenesis and end‐organ damage in SLE .

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Neutrophil Subsets, Platelets, and Vascular Disease in Psoriasis

Abstract: Visual Abstract

Cited by 63 publications

References 50 publications

Ultra-pure isolation of low density neutrophils casts doubt on their exceptionality in health and disease

Ultra-pure isolation of low density neutrophils casts doubt on their exceptionality in health and disease

Association of Psoriasis With Incident Venous Thromboembolism and Peripheral Vascular Disease

Low‐Density Neutrophils in Systemic Lupus Erythematosus

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