Erythrocytes and their role as health indicator: Using structure in a patient-orientated precision medicine approach

Pretorius, Etheresia; Olumuyiwa-Akeredolu, Oore-ofe O.; Mbotwe, Sthembile; Bester, Janette

doi:10.1016/j.blre.2016.01.001

Cited by 80 publications

(77 citation statements)

References 91 publications

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“…We and others have shown in a series of studies [e.g., Ref. (134–136, 1103–1106)] that erythrocyte morphology diverges very considerably from that “classical” discoid shape adopted by normal healthy cells, and that this can be a strong indicator of disease (137). In extreme cases [e.g., Ref.…”

Section: Clotting Coagulopathies and Fibrinogen In Pementioning

confidence: 90%

A Dormant Microbial Component in the Development of Preeclampsia

Kell

Kenny

2016

Front. Med.

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Preeclampsia (PE) is a complex, multisystem disorder that remains a leading cause of morbidity and mortality in pregnancy. Four main classes of dysregulation accompany PE and are widely considered to contribute to its severity. These are abnormal trophoblast invasion of the placenta, anti-angiogenic responses, oxidative stress, and inflammation. What is lacking, however, is an explanation of how these themselves are caused. We here develop the unifying idea, and the considerable evidence for it, that the originating cause of PE (and of the four classes of dysregulation) is, in fact, microbial infection, that most such microbes are dormant and hence resist detection by conventional (replication-dependent) microbiology, and that by occasional resuscitation and growth it is they that are responsible for all the observable sequelae, including the continuing, chronic inflammation. In particular, bacterial products such as lipopolysaccharide (LPS), also known as endotoxin, are well known as highly inflammagenic and stimulate an innate (and possibly trained) immune response that exacerbates the inflammation further. The known need of microbes for free iron can explain the iron dysregulation that accompanies PE. We describe the main routes of infection (gut, oral, and urinary tract infection) and the regularly observed presence of microbes in placental and other tissues in PE. Every known proteomic biomarker of “preeclampsia” that we assessed has, in fact, also been shown to be raised in response to infection. An infectious component to PE fulfills the Bradford Hill criteria for ascribing a disease to an environmental cause and suggests a number of treatments, some of which have, in fact, been shown to be successful. PE was classically referred to as endotoxemia or toxemia of pregnancy, and it is ironic that it seems that LPS and other microbial endotoxins really are involved. Overall, the recognition of an infectious component in the etiology of PE mirrors that for ulcers and other diseases that were previously considered to lack one.

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Section: Clotting Coagulopathies and Fibrinogen In Pementioning

confidence: 90%

A Dormant Microbial Component in the Development of Preeclampsia

Kell

Kenny

2016

Front. Med.

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“…One of the hallmarks of inflammation is a pathological coagulation system, and this is the direct result of upregulated circulating inflammatory molecules. During inflammation, platelets become aggregated and activated, with microparticle formation; RBCs become eryptotic and also produce microparticles (Van Der Spuy & Pretorius, ; Gasparyan et al , ; Pretorius & Kell, ; Bester & Pretorius, ; Pretorius et al , ,c; Soma et al , ); and pathological plasma clots form, mainly due to pathological changes in the healthy fibrin(ogen) protein structure (Kell & Pretorius, ; Pretorius et al , ). Therefore, by studying the effect of individual inflammatory molecules on RBCs, platelets and fibrin(ogen) we may improve our understanding of the inflammatory response and provide important advances in understanding both inflammation regulation and the resulting pathophysiological coagulation.…”

mentioning

confidence: 99%

Interleukin‐12 and its procoagulant effect on erythrocytes, platelets and fibrin(ogen): the lesser known side of inflammation

2017

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SummaryInflammation, with its associated inflammatory molecules, is integral to most chronic diseases, including the various cardiovascular diseases. Interleukin 12 (IL12) is one of the inflammatory cytokines that is upregulated during inflammation; however, we know very little about its exact effect on red blood cells (RBCs), platelets and fibrin(ogen). IL12 is an important pleiotropic cytokine in early inflammatory responses and has potent immunomodulatory, antitumour and anti-infection activity. Here we investigate how low levels of circulating IL12, comparable to levels found during chronic inflammation, affect coagulation parameters, platelets and RBCs. We used thromboelastography, scanning electron microscopy, refractometery and wide-field microscopy. Our results show that IL12 caused hypercoagulation, platelet activation and spreading, as well as RBC agglutination. This phenomenon has far-reaching implications for treatment of the plethora of conditions where IL12 is upregulated, since it suggests aberrant haemorheology as agglutination affects blood flow. This information might be used in future to target the lowering of IL12 in inflammatory conditions, as well as address RBC agglutination.

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“…End‐stage renal disease RBCs undergo certain pathophysiological modifications in structure, composition, and signaling potential. Severe shape distortions (IRR), which render RBCs susceptible to clearance, reflect a systemic inflammatory profile in almost all pathologies characterized by oxidative stress, including ESRD . We currently show for the first time that the percentage of irreversibly modified RBCs is a function of baseline Hb concentration, highlighting the close relationship between severe RBC shape distortions, inflammation, and anemia in ESRD.…”

Section: Discussionmentioning

confidence: 77%