Importantly, eosinophils can also release eosinophilic cationic proteins and major basic proteins which are largely described during tissue damage in several conditions. ...in association with ...cellular components, the production and entrance of AHA in the heart may promote myocarditis in the spectrum of post-COVID manifestations. ...IFN-α inhibition by auto-Abs may unbalance self-tolerance, which in turn may promote auto-Abs generation. 5 Finally, there was a positive correlation between multiple inflammatory markers (e.g.: IFN-γ, C-Reactive Protein, and IL-6) detected in the acute stage, and auto-Abs identified at the convalescent phase. 3 Altogether, these findings suggest that the emergence of inflammatory markers during the acute phase of COVID-19 may reduce self-tolerogenic immune mechanisms implicating in eventual cardiac and other, autoimmune reactions. The early production of auto-Abs during the acute infection may be related to the physiopathology of distinct manifestations associated with SARS-CoV-2 infection. 1,3 Further, longitudinal immunological evaluation of postinfected individuals may clarify underpinning pathological mechanisms associated with post-COVID symptoms.
Emerging evidence of antibody-independent functions, as well as the clinical efficacy of anti-CD20 depleting therapies, helped to reassess the contribution of B cells during multiple sclerosis (MS) ...pathogenesis.
To investigate whether CD19
B cells may share expression of the serine-protease granzyme-B (GzmB), resembling classical cytotoxic CD8
T lymphocytes, in the peripheral blood from relapsing-remitting MS (RRMS) patients.
In this study, 104 RRMS patients during different treatments and 58 healthy donors were included. CD8, CD19, Runx3, and GzmB expression was assessed by flow cytometry analyses.
RRMS patients during fingolimod (FTY) and natalizumab (NTZ) treatment showed increased percentage of circulating CD8
GzmB
T lymphocytes when compared to healthy volunteers. An increase in circulating CD19
GzmB
B cells was observed in RRMS patients during FTY and NTZ therapies when compared to glatiramer (GA), untreated RRMS patients, and healthy donors but not when compared to interferon-β (IFN). Moreover, regarding Runx3, the transcriptional factor classically associated with cytotoxicity in CD8
T lymphocytes, the expression of GzmB was significantly higher in CD19
Runx3
-expressing B cells when compared to CD19
Runx3
counterparts in RRMS patients.
CD19
B cells may exhibit cytotoxic behavior resembling CD8
T lymphocytes in MS patients during different treatments. In the future, monitoring "cytotoxic" subsets might become an accessible marker for investigating MS pathophysiology and even for the development of new therapeutic interventions.
Our group is interested in the cytotoxic mechanism during autoimmune neuroinflammation. Unexpectedly, we come across a case that presents a massive enhancement of cytotoxic behavior in lymphocytes, ...either in peripheral blood and cerebrospinal fluid. Interestingly, this specific patient was refractory to Methylprednisolone treatment. Hypothetically, the cytotoxic activity could represent a novel and complementary effector mechanism to NMOSD pathogenesis. Nevertheless, further investigation is needed to evaluate the extension and the clinical relevance of our finds.
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•Peripheral blood and cerebrospinal fluid from a NMOSD patient refractory to methylprednisolone during relapses were analyzed.•Cytotoxic activity of CD8+ T lymphocytes was previous associated to methylprednisolone resistance.•CD8+ and CD4+ T lymphocytes massively express GzmB in the peripheral blood and CSF during NMOSD.•B cells also express larger amounts of GzmB during refractory NMOSD.•Cytotoxic mechanisms by classical and non-classical subsets need further investigation in the context of NMOSD.
Photodynamic therapy is a minimally invasive health technology used to treat cancer and other non-malignant diseases, as well as inactivation of viruses, bacteria and fungi. In this work, we sought ...to combine the phototherapy technique using low intensity LED (660 nm) to induce ablation in melanoma tumor in mice treated with nanoparticles. In vitro and in vivo studies were conducted, and our results demonstrated that multi-walled carbon nanotubes (MWCNTs) do not destroy tumor cells in vivo, but stimulate the inflammatory process and angiogenesis. Reduced graphene oxide (rGO), has been shown to play a protective role associated with the LED ablation, inducing necrosis, stimulation of immune response by lymphoproliferation, and decreased tumor mass in vivo. We consider that LED alone can be very effective in controlling the growth of melanoma tumors and its association with rGO is potentiated.
The injection of reduced graphene oxide (rGO) near the tumor promotes its migration into the tumor mass. The treatment with 660 nm LED decreases the tumor mass and stimulates the immune response against B16F10 cells in vivo. Display omitted
Given the low detection rates of CSF IgG-Oligoclonal bands (IgG-OCB) in non-European Multiple Sclerosis (MS) patients and higher specificity of the MRZH-reaction, we evaluated whether associating ...MRZH-reaction to CSF IgG-OCB detection improved investigation of suspected MS. Paired CSF and sera were analyzed for IgG-OCB and polyspecific viral antibodies. IgG-OCB were detected in 72% of MS patients and an MRZH-reaction in 67%. Combining IgG-OCB and MRZH raised detection of IgG abnormalities to 97% of studied MS patients. Detection of IgG-OCB and/or ≥2 MRZH antibodies showed sensitivity of 88% and specificity of 92% for MS, versus 72% and 96% for IgG-OCB alone.
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•MRZH reaction was present in 67% MS patients and IgG-OCB in 72%.•Bispecific or higher MRZH reaction was present in 67% of IgG-OCB negative patients.•Analyzing IgG-OCB and MRZH, intrathecal IgG synthesis was seen in 97% MS patients.•Detection of either two viral antibodies or IgG-OCB had sensitivity of 88% for MS.•Detection of either two viral antibodies or IgG-OCB had specificity of 92% for MS.
COVID-19 can result in severe lung injury. It remained to be determined why diabetic individuals with uncontrolled glucose levels are more prone to develop the severe form of COVID-19. The molecular ...mechanism underlying SARS-CoV-2 infection and what determines the onset of the cytokine storm found in severe COVID-19 patients are unknown. Monocytes and macrophages are the most enriched immune cell types in the lungs of COVID-19 patients and appear to have a central role in the pathogenicity of the disease. These cells adapt their metabolism upon infection and become highly glycolytic, which facilitates SARS-CoV-2 replication. The infection triggers mitochondrial ROS production, which induces stabilization of hypoxia-inducible factor-1α (HIF-1α) and consequently promotes glycolysis. HIF-1α-induced changes in monocyte metabolism by SARS-CoV-2 infection directly inhibit T cell response and reduce epithelial cell survival. Targeting HIF-1ɑ may have great therapeutic potential for the development of novel drugs to treat COVID-19.
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•Elevated glucose levels regulate viral replication and cytokine production in monocytes•Glycolysis sustains CoV-2-induced monocyte response and viral replication•mtROS/HIF-1α is necessary for CoV-2 replication and monocyte cytokine production•Monocyte-derived cytokines drive T cell dysfunction and epithelial cell death
Diabetic people with uncontrolled blood glucose levels have a greater risk to develop severe COVID-19 disease. Codo et al. show that elevated glucose levels and glycolysis promote SARS-CoV-2 (CoV-2) replication and cytokine production in monocytes through a mitochondrial ROS/hypoxia-inducible factor-1α dependent pathway, resulting in T cell dysfunction and epithelial cell death.
Recently, it was shown that highly effective anti-CD20 therapies used for MS patients not only deplete CD20+ B cells, but also a small subset of T cells expressing CD20 surface marker (CD3+CD20+ T ...cells). Here we demonstrated that, in progressive MS patients, CD3+CD20+ T cells share the ability to express cytotoxic factors such as perforin and serine-protease granzyme-B (GzmB), classically associated with CD8+ T cells functionality. Beyond it, cluster analyses show that a set of activation markers and transcriptional factors related with CD8 effector program are also expressed in CD3+CD20+ T cells. Further characterization of surface and functional markers from CD3+CD20+ T subsets may be helpful for development of new therapeutic strategies mainly for progressive MS patients, as well as for assessing pathophysiological effects of highly effective anti-CD20 therapies.
•Neurofilament measurement has become a promising biomarker in MS.•In relapsing MS, predictors were cortical lesions and previous clinical activity.•In progressive MS, T1-hypointense lesion volume ...was the only predictor.
A major aim in MS field has been the search for biomarkers that enable accurate detection of neuronal damage. Besides MRI, recent studies have shown that neuroaxonal damage can also be tracked by neurofilament detection. Nevertheless, before widespread implementation, a better understanding of the principal contributors for this biomarker is of paramount importance. Therefore, we analyzed neurofilament light chain (NfL) in relapsing (RMS) and progressive MS (PMS), addressing which MRI and clinical variables are better related to this biomarker.
Forty-seven MS patients underwent MRI (3T) and cerebrospinal fluid (CSF) sampling. We measured NfL concentrations using ELISA (UmanDiagnostics) and performed multivariable regression analysis to assess the contribution of clinical and MRI metrics to NfL.
NfL correlated with previous clinical activity in RMS (p < 0.001). In RMS, NfL also correlated with Gad+ and cortical lesion volumes. However, after multivariable analysis, only cortical lesions and relapses in previous 12 months remained in the final model (R2 = 0.610; p = 0.009 and p = 0.00008, respectively). In PMS, T1-hypointense lesion volume was the only predictor after multivariate analysis (R2 = 0.564; p = 0.012).
CSF NfL levels are increased in RMS and associated with relapses and cortical lesions. Although NfL levels were correlated with Gad+ lesion volume, this association did not persist in multivariable analysis after controlling for previous clinical activity. We encourage controlling for previous clinical activity when testing the association of NfL with MRI. In PMS, the major contributor to NfL was T1-hypointense lesion volume.
Recently, it has been argued that obesity leads to a chronic pro-inflammatory state that can accelerate immunosenescence, predisposing to the early acquisition of an immune risk profile and health ...problems related to immunity in adulthood. In this sense, the present study aimed to verify, in circulating leukocytes, the gene expression of markers related to early immunosenescence associated with obesity and its possible relationships with the physical fitness in obese adults with type 2 diabetes or without associated comorbidities. The sample consisted of middle-aged obese individuals (body mass index (BMI) between 30-35 kg/m²) with type 2 diabetes mellitus (OBD; n = 17) or without associated comorbidity (OB; n = 18), and a control group of eutrophic healthy individuals (BMI: 20 - 25 kg/m²) of same ages (E; n = 18). All groups (OBD, OB and E) performed the functional analyses muscle strength (1RM) and cardiorespiratory fitness (VO
), anthropometry, body composition (Air Displacement Plethysmograph), blood collections for biochemical (anti-CMV) and molecular (gene expression of leptin, IL-2, IL-4, IL-6, IL-10, TNF-α, PD-1, P16
, CCR7, CD28 and CD27) analyses of markers related to immunosenescence. Increased gene expression of leptin, IL-2, IL-4, IL-10, TNF-α, PD-1, P16
, CCR7 and CD27 was found for the OBD and OB groups compared to the E group. Moreover, VO
for the OBD and OB groups was significantly lower compared to E. In conclusion, obesity, regardless of associated disease, induces increased gene expression of markers associated with inflammation and immunosenescence in circulating leukocytes in obese middle-aged individuals compared to a eutrophic group of the same age. Additionally, increased adipose tissue and markers of chronic inflammation and immunosenescence were associated to impairments in the cardiorespiratory capacity of obese middle-aged individuals.
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