Does activation of the FcγRIIa play a role in the pathogenesis of the acute lung injury/acute respiratory distress syndrome?

ALI (acute lung injury) and its more severe form ARDS (acute respiratory distress syndrome) are inflammatory diseases of the lung characterized by hypoxaemia and diffuse bilateral infiltrates. Disruption of epithelial integrity and injury to endothelium are contributing factors of the development of ALI/ARDS, and alveolar damage is the most pronounced feature of ALI/ARDS. The resulting increase in lung microvascular permeability promotes influx of inflammatory cells to the alveolar spaces. Oedema fluid contains pro-nflammatory mediators and plasma proteins, including Igs (immunoglobulins). Moreover, several reports describe the presence of autoantibodies and immune complexes [anti-IL-8 (interleukin-8) autoantibody/IL-8 complexes] in lung fluids (oedema and bronchoalveolar lavage fluids) from patients with ALI/ARDS. These immune complexes associate with FcγRIIa (Fcγ IIa receptor) in lungs of patients with ARDS. Furthermore, the expression of FcγRIIa is substantially elevated in lungs of these patients. FcγRIIa appears on virtually all myeloid cells, platelets and endothelial cells. It is a low-affinity receptor for IgG that preferentially binds aggregated immunoglobulins and immune complexes. FcγRs regulate phagocytosis and cell-mediated cytotoxicity, and initiate the release of inflammatory mediators. It should be noted that immune complexes formed between either anti-neutrophil autoantibodies and their specific antigens or anti-HLA (human leucocyte antigen) antibodies and target antigens are implicated in the pathogenesis of TRALI (transfusion-related acute lung injury), and importantly, animal studies indicate that FcγRs are essential for these complexes to cause damage to the lungs. Therefore, we hypothesize that FcγRs such as FcγRIIa could contribute to the pathogenesis of ALI/ARDS

Rapid induction of autoantibodies during ARDS and septic shock

<p>Abstract</p> <p>Background</p> <p>Little is known about the induction of humoral responses directed against human autoantigens during acute inflammation. We utilized a highly sensitive antibody profiling technology to study autoantibodies in patients with acute respiratory distress syndrome (ARDS) and severe sepsis, conditions characterized by intensive immune activation leading to multiple organ dysfunction.</p> <p>Methods</p> <p>Using Luciferase Immunoprecipitation Systems (LIPS), a cohort of control, ARDS and sepsis patients were tested for antibodies to a panel of autoantigens. Autoantibody titers greater than the mean plus 3 SD of the 24 control samples were used to identify seropositive samples. Available longitudinal samples from different seropositive ARDS and sepsis patient samples, starting from within the first two days after admission to the intensive care, were then analyzed for changes in autoantibody over time.</p> <p>Results</p> <p>From screening patient plasma, 57% of ARDS and 46% of septic patients without ARDS demonstrated at least one statistically significant elevated autoantibody compared to the controls. Frequent high titer antibodies were detected against a spectrum of autoantigens including potassium channel regulator, gastric ATPase, glutamic decarboxylase-65 and several cytokines. Analysis of serial samples revealed that several seropositive patients had low autoantibodies at early time points that often rose precipitously and peaked between days 7-14. Further, the use of therapeutic doses of corticosteroids did not diminish the rise in autoantibody titers. In some cases, the patient autoantibody titers remained elevated through the last serum sample collected.</p> <p>Conclusion</p> <p>The rapid induction of autoantibodies in ARDS and severe sepsis suggests that ongoing systemic inflammation and associated tissue destruction mediate the break in tolerance against these self proteins.</p

Helicobacter pylori components increase the severity of metabolic syndrome and its hepatic manifestations induced by a high fat diet

Abstract The metabolic syndrome, often accompanied by hepatic manifestations, is a high-risk factor for developing cardiovascular disease. Patients with metabolic dysfunction associated with steatohepatic disease (MASDL) are at significant risk of developing coronary artery disease. Atherosclerosis is a systemic inflammatory disorder in which several factors, including dietary or infectious factors, can cause an inflammatory response. Helicobacter pylori (HP) bacteria have been implicated in the progression of proatherogenic vascular endothelial lesions, moreover, our previous study in an experimental in vivo model of Cavia porcellus showed that HP components and high-fat substances acted synergistically in promoting vascular endothelial inflammation, leading to an early onset of a proatherogenic environment. In the present study, our goal was to determine the contribution of HP components to the development of hepatic manifestations of metabolic syndrome in an experimental model. Our results showed that HP infection in animals exposed to a high-fat diet increased oxidative stress and lipid peroxidation, followed by endothelial lipid deposition, impaired endothelial apoptosis, cell lysis, and increased vascular stiffness. Finally, histopathological analysis of liver tissue showed signs of MASLD development in HP-infected animals fed a high-fat diet