Erythrocyte: A systems model of the control of aggregation and deformability.

Authors: Bazanovas AN, Evstifeev AI, Khaiboullina SF, Sadreev II, Skorinkin AI, Kotov NV.
Publication: Biosystems. 2015 May;131:1-8. doi: 10.1016/j.biosystems.2015.03.003. Epub 2015 Mar 21.

Human erythrocytes are highly specialized enucleate cells that are involved in providing efficient gas transport. Erythrocytes have been extensively studied both experimentally and by mathematical modeling in recent years. However, understanding of how aggregation and deformability are regulated is limited. These properties of the erythrocyte are essential for the physiological functioning of the cell. In this work, we propose a novel mathematical model of the molecular system that controls the aggregation and deformability of the erythrocyte. This model is based on the experimental results of previously published studies. Our model suggests fundamentally new mechanisms that regulate aggregation and deformability in a latch-like manner. The results of this work could be used as a general explanation of how the erythrocytes regulate their aggregation and deformability, and are essential in understanding erythrocyte disorders and aging.

Inflammatory cytokines kinetics define the severity and phase of nephropathia epidemica.

Authors: Baigildina AA, Khaiboullina SF, Martynova EV, Anokhin VA, Lombardi VC, Rizvanov AA.
Publication: Biomark Med. 2015;9(2):99-107. doi: 10.2217/bmm.14.88. Epub 2014 Oct 14.

AIMS: Nephropathia epidemica (NE) is a form of hemorrhagic fever with renal syndrome associated with the Puumala virus species of Hantavirus. The pathogenesis of NE is not well understood; therefore, investigating the inflammatory cytokine response to infection may provide useful knowledge in deciphering the pathophysiology of NE.
MATERIALS & METHODS: Using Luminex and ELISA, we analyzed the serum of 137 NE cases and 44 controls to investigate if serum cytokines associate with different clinical presentations.
RESULTS: Serum levels of TNF-α and IL-1β are associated with disease severity while upregulation of IL-6, CXCL10, CCL2 and CCL3 are associated with clinical presentation.
CONCLUSION: Inflammatory cytokine kinetics associate with the severity and phase of NE. Our data support a role for inflammatory cytokines in the pathophysiology of NE.

Upregulation of IFN-γ and IL-12 is associated with a milder form of hantavirus hemorrhagic fever with renal syndrome.

Authors: Khaiboullina SF, Martynova EV, Khamidullina ZL, Lapteva EV, Nikolaeva IV, Anokhin VV, Lombardi VC, Rizvanov AA.
Publication: Eur J Clin Microbiol Infect Dis. 2014 Dec;33(12):2149-56. doi: 10.1007/s10096-014-2176-x. Epub 2014 Jun 19.

Hantavirus hemorrhagic fever with renal syndrome (HFRS) is a zoonotic disease characterized by acute onset, fever, malaise, and back pain. As the disease progresses, hemorrhagic disturbances and kidney dysfunctions predominate. The examination of tissue collected postmortem supports the premise that virus replication is not responsible for this pathology; therefore, it is widely believed that virus-induced immune responses lead to the clinical manifestations associated with HFRS. The overproduction of inflammatory cytokines is commonly reported in subjects with HFRS and has given rise to the hypothesis that a so-called “cytokine storm” may play a pivotal role in the pathogenesis of this disease. Currently, supportive care remains the only effective treatment for HFRS. Our data show that serum levels of interferon (IFN)-γ, interleukin (IL)-10, CCL2, and IL-12 are upregulated in HFRS cases when compared to healthy controls and the level of upregulation is dependent on the phase and severity of the disease. Furthermore, we observed an association between the mild form of the disease and elevated serum levels of IFN-γ and IL-12. Collectively, these observations suggest that the administration of exogenous IFN-γ and IL-12 may provide antiviral benefits for the treatment of HFRS and, thus, warrants further investigations.

Differential immuno-reactivity to genomic DNA, RNA and mitochondrial DNA is associated with auto-immunity.

Authors: Ivanova VV, Khaiboullina SF, Cherenkova EE, Martynova EV, Nevzorova TA, Kunst MA, Sibgatullin TB, Maksudova AN, Oliveira PJ, Lombardi VC, Palotás A, Rizvanov AA.
Publication: Cell Physiol Biochem. 2014;34(6):2200-8. doi: 10.1159/000369663. Epub 2014 Dec 4.

BACKGROUND: Circulating auto-reactive antibodies are hallmark features of auto-immune diseases, however little is known with respect to the specificity of such bio-markers. In the present study, we investigated the specificity of anti-nucleic acid antibodies in the blood of subjects with systemic lupus erythematosus (SLE) and healthy controls.
METHODS: Sera from 12 SLE cases and 8 controls were evaluated for immuno-reactivity to purified RNA, DNA and mitochondrial DNA (mtDNA) by enzyme-linked immuno-sorbent assay (ELISA).
RESULTS: As expected, immuno-reactivity to total nucleic acids was significantly higher in subjects with SLE when compared to healthy controls, however a clear distinction was observed among the various nucleic acid sub-types, with sera from SLE subjects displaying the greatest immuno-reactivity to RNA followed by mtDNA and then total DNA.
CONCLUSION: The identification of auto-reactive antibodies can serve as highly sensitive biomarkers, although their specificity may not always allow diagnostic certainty. The knowledge that auto-antibodies in subjects with SLE display differential immuno-reactivity may help to improve existing diagnostics and may lead to a better understanding of the pathogenesis of auto-immune disorders.

CCL27: Novel Cytokine with Potential Role in Pathogenesis of Multiple Sclerosis

Authors: Svetlana F. Khaiboullina, Aigul R. Gumerova, Irina F. Khafizova, Ekaterina V. Martynova, Vincent C. Lombardi, Saverio Bellusci, and Albert A. Rizvanov
Publication: BioMed Research International Article ID 189638 Received 7 November 2014; Accepted 11 December 2014

Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease of unknown etiology. Leukocyte infiltration of brain tissue and the subsequent inflammation, demyelination, axonal damage, and formation of sclerotic plaques is a hallmark of MS. Upregulation of proinflammatory cytokines has been suggested to play an essential role in regulating lymphocyte migration in MS. Here we present data on serum cytokine expression in MS cases. Increased serum levels of IL-17 and IL-23 were observed, suggesting activation of the Th17 population of immune effector cells. Additionally, increased levels of IL-22 were observed in the serum of those with acute phase MS. Unexpectedly, we observed an upregulation of the serum chemokine CCL27 in newly diagnosed and acute MS cases. CCL27 is an inflammatory chemokine associated with homing of memory T cells to sites of inflammation. Therefore, its upregulation in association with MS suggests a potential role in disease pathogenesis. Our data supports previous reports showing IL-17 and -23 upregulation in association with MS and potentially identify a previously unknown involvement for CCL27.

Plasmacytoid dendritic cells of the gut: Relevance to immunity and pathology

Authors: Vincent C. Lombardi, Svetlana F. Khaiboullina
Publication: Clinical Immunology Volume 153, Issue 1, July 2014, Pages 165–177

Plasmacytoid dendritic cells (pDCs) are bone marrow-derived immune cells with the ability to express copious amounts of type I and III interferon (IFN) and can differentiate into antigen-presenting dendritic cells as a result of stimulation by pathogen-derived nucleic acid. These powerful combined functionalities allow pDCs to bridge the innate and adaptive immune systems resulting in a concerted pathogen response. The contribution of pDCs to gastrointestinal immunity is only now being elucidated and is proving to be a critical component in systemic immunity. This review will explore the immunology of pDCs and will discuss their involvement in human disease and tolerance with an emphasis on those in the gastrointestinal lymphoid tissue.