Therapeutic Modulation of the Host Defense by Hemoadsorption with CytoSorb®—Basics, Indications and Perspectives—A Scoping Review

The “normal” immune response to an insult triggers a highly regulated response determined by the interaction of various immunocompetent cells with pro- and anti-inflammatory cytokines. Under pathologic conditions, the massive elevation of cytokine levels (“cytokine storm”) could not be controlled until the recent development of hemoadsorption devices that are able to extract a variety of different DAMPs, PAMPs, and metabolic products from the blood. CytoSorb® has been approved for adjunctive sepsis therapy since 2011. This review aims to summarize theoretical knowledge, in vitro results, and clinical findings to provide the clinician with pragmatic guidance for daily practice. English-language and peer-reviewed literature identified by a selective literature search in PubMed and published between January 2016 and May 2021 was included. Hemoadsorption can be used successfully as adjunct to a complex therapeutic regimen for various conditions. To the contrary, this nonspecific intervention may potentially worsen patient outcomes in complex immunological processes. CytoSorb® therapy appears to be safe and useful in various diseases (e.g., rhabdomyolysis, liver failure, or intoxications) as well as in septic shock or cytokine release syndrome, although a conclusive assessment of treatment benefit is not possible and no survival benefit has yet been demonstrated in randomized controlled trials.

Endogenous control of inflammation characterizes pregnant women with asymptomatic or paucisymptomatic SARS-CoV-2 infection

In 14 pregnant women who had asymptomatic or paucisymptomatic SARS-CoV-2 infection, we performed a detailed 38-parameter analysis of peripheral blood mononuclear cells by mass cytometry, studied the expression of T-cell master regular genes, investigated cell proliferation and cytokine production, and measured plasma levels of 62 cytokines. No patient showed lymphopenia or gross alterations of white blood cells. Unsupervised analyses revealed that most immune parameters were similar in patients and uninfected controls, apart from an increase in low density neutrophils in SARS-CoV-2 positive women. Also, patients did not show altered plasma levels of interleukin-6 or other main inflammatory molecules, but displayed significant increases of anti-inflammatory cytokines such as IL-1RA, IL-10 and IL-19, and decreased levels of IL-17, PD-L1 and D-dimer. The endogenous control of inflammation, as evidenced by plasma levels of soluble molecules, could be a strategy used during pregnancy to avoid virus-induced damages and maintain a normal immune response.

Early Detection of Sepsis using Machine Learning

Sepsis is a global cause of the death due to infection and subsequent overreaction of the immune system. Mortality rates are highest in developed and developing countries in cases of septic shock. Sepsis is a clinical condition with an emergency referral that can be avoided by advance warning. SIRS is a normal immune response to any infection, and hospitals or antibiotics are not required by most people. Early sepsis prediction is possibly life-saving, and we are planning to predict sepsis 6 hours before clinical sepsis diagnosis. We used two types of Standard Scalar and Min Max Scalar pre-treatment methods to pre-treat the data. The Recursive Feature Elimination (RFE) method is used to pick the features most closely related to the predictive or efficiency factor. The ML algorithms used are the Logistic Regression algorithm and XGboost. Cross-validation 10 times with the train splitting method is used to validate attributes. we selected the best model from these two trained models.

Immunotherapy of renal cell carcinoma: Current state of the problem and promising areas of research

This review considers current variants of immunotherapy in patients with disseminated renal cell carcinoma. Data from experimental studies concerning defects in immunocompetent cells and mechanisms that block the normal immune response in patients with tumors are presented. Data of completed clinical trials of blockers of co-inhibiting molecules and cytokines in patients with renal cell carcinoma are analyzed.

Tolerance of monocytes and macrophages in response to bacterial endotoxin

Monocytes belong to myeloid effector cells, which constitute the first line of defense against pathogens, also called the nonspecific immune system and play an important role in the maintenance of tissue homeostasis. In response to stimulation, monocytes differentiate into macrophages capable of microorganism phagocytosis and secrete factors that play a key role in the regulation of immune responses. However excessive exposure of monocytes/macrophages to the lipopolysaccharide (LPS) of Gram negative bacteria leads to the acquisition of immune tolerance by these cells. Such state results from disruption of different biological processes, for example intracellular signaling pathways and is accompanied by a number of disease states (immune, inflammatory or neoplastic conditions). Regulation of monocytes/macrophages activity is controlled by miRNAs, which are involved in the modulation of immune tolerance acquired by these cells. Moreover, the tolerance to endotoxin is conditioned by the posttranscriptional processes and posttranslational epigenetic modifications leading to the impairment of normal immune response for example by alterations in the expression of many genes encoding immune signaling mediators. The aim of this paper is to provide an overview existing knowledge on the modulation of activity of monocytes/macrophages in response to bacterial endotoxin and impaired immune responses.

Immunocompetence in adults: more than HIV negative

I read a case report about Tuberculosis and fungal co-infection in a previously healthy patient published in Colomb Med (Cali) by Fontalvo et al., and I would like to address some related comments. Frequently clinicians report adult cases of patients with opportunistic infections as disseminated tuberculosis and/or fungal infections in patients consider as immunocompetent based mainly in the absence of human immunodeficiency virus infection (HIV negative). Immunocompetence is more complex than absence of HIV infection and involves a normal capacity to develop an immune response following the exposure to an antigen or broadly a normal immune response, but usually immunocompetent is define as the opposite of immunodeficiency. In the report authors said “Our aim is to report the case of an immunocompetent patient diagnosed with Mycobacterium tuberculosis and Candida albicans co-infections” but my deliberation is Do we make in the clinical practice all the efforts to consider a patient as immunocompetent? Mycobacterial, fungal and other opportunistic infections force the clinician to rule out a large list of conditions associated with secondary immunodeficiency as infectious agents (HIV, Herpesvirus, HTLV), drugs (steroids, immunosuppressants, biologics, chemotherapy) , metabolic diseases (diabetes, renal failure, cirrhosis), malignancies (leukemia, lymphomas and solid tumors) and environmental conditions (radiation, heavy metals) but even adult patients can have late onset primary genetic immunodeficiency

Combination with Methotrexate and Cyclophosphamide Attenuated Maturation of Dendritic Cells: Inducing Treg Skewing and Th17 SuppressionIn Vivo

Immune disorder is considered the main pathogenesis of autoimmune diseases, such as rheumatoid arthritis (RA). The balance of the two special subsets of CD4+T cells, T helper cell 17 (Th17), and Regulator T cell (Treg) is the key factor of maintaining a normal immune response. Dendritic cells (DCs), which are the most powerful antigen-presenting cells, play an important role in regulating the balance of Th17 and Treg. The combination of disease modifying antirheumatic drugs (DMARDs) is an important strategy of RA therapy. In this study, we investigated the effect of MTX and CTX on DC maturation in ovalbumin (OVA) immunized mice. Th17 inflammatory response is stronger, while the level of DCs maturity is higher. In contrast, the immunosuppression of Treg is stronger. We found that MTX combined with CTX significantly inhibited the DCs maturity and downregulated the antigen presenting capacity of DCs. As a result, it reestablished a balance of Th17 and Treg. Our study adds a novel mechanism and therapeutic target of MTX combined with CTX for autoimmune disease treatment.

Immune response

2.1 Normal, 497 2.2 Abnormal, 499 • The normal immune response is divided into a layered response: ▪ A physical barrier ▪ Innate responses ▪ Adaptive responses • A number of physical and mechanical barriers protect the body from invasion of foreign organisms: ▪...

Dampening Host Sensing and Avoiding Recognition inPseudomonas aeruginosaPneumonia

Pseudomonas aeruginosais an opportunistic pathogen and causes a wide range of acute and chronic infections.P. aeruginosainfections are kept in check by an effective immune surveillance in the healthy host, while any imbalance or defect in the normal immune response can manifest in disease. Invasive acute infection in the immunocompromised patients is mediated by potent extracellular and cell bound bacterial virulence factors. Life-threatening chronic infection in cystic fibrosis patients is maintained by pathogenic variants that contribute to evade detection and clearance by the immune system. Here, we reviewed the molecular basis of receptor-mediated recognition ofP. aeruginosaand their role in initiating inflammation and the colonization. In addition, the consequence of theP. aeruginosagenetic adaptation for the antibacterial defence and the maintaining of chronic infection are discussed.