SAA (Serum Amyloid A): A Novel Predictor of Stroke-Associated Infections. Schweizer Juliane,Bustamante Alejandro,Lapierre-Fétaud Vanessa,Faura Júlia,Scherrer Natalie,Azurmendi Gil Leire,Fluri Felix,Schütz Valerie,Luft Andreas,Boned Sandra,Sanchez Jean-Charles,Montaner Joan,Katan Mira Stroke BACKGROUND AND PURPOSE:The aim of this study was to evaluate and independently validate SAA (serum amyloid A)-a recently discovered blood biomarker-to predict poststroke infections. METHODS:The derivation cohort (A) was composed of 283 acute ischemic stroke patients and the independent validation cohort (B), of 367 patients. The primary outcome measure was any stroke-associated infection, defined by the criteria of the US Centers for Disease Control and Prevention, occurring during hospitalization. To determine the association of SAA levels on admission with the development of infections, logistic regression models were calculated. The discriminatory ability of SAA was assessed, by calculating the area under the receiver operating characteristic curve. RESULTS:After adjusting for all predictors that were significantly associated with any infection in the univariate analysis, SAA remained an independent predictor in study A (adjusted odds ratio, 1.44 [95% CI, 1.16-1.79]; =0.001) and in study B (adjusted odds ratio, 1.52 [1.05-2.22]; =0.028). Adding SAA to the best regression model without the biomarker, the discriminatory accuracy improved from 0.76 (0.69-0.83) to 0.79 (0.72-0.86; <0.001; likelihood ratio test) in study A. These results were externally validated in study B with an improvement in the area under the receiver operating characteristic curve, from 0.75 (0.70-0.81) to 0.76 (0.71-0.82; <0.038). CONCLUSIONS:Among patients with ischemic stroke, blood SAA measured on admission is a novel independent predictor of infection after stroke. SAA improved the discrimination between patients who developed an infection compared with those who did not in both derivation and validation cohorts. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00390962. 10.1161/STROKEAHA.120.030064

Serum Amyloid A (SAA) Proteins. Sack George H Sub-cellular biochemistry As normal constituents of blood serum, the Serum Amyloid A (SAA) proteins are small (104 amino acids in humans) and remarkably well-conserved in mammalian evolution. They are synthesized prominently, but not exclusively, in the liver. Fragments of SAA can associate into insoluble fibrils (called "amyloid") characteristic of "secondary" amyloid disease in which they can interrupt normal physiology and lead to organ failure. SAA proteins comprise a family of molecules, two members of which (SAA1 and SAA2) are (along with C-reactive protein, CRP) the most prominent members of the acute phase response (APR) during which their serum levels rise dramatically after trauma, infection and other stimuli. Biologic function (s) of SAA are unresolved but features are consistent with a prominent role in primordial host defense (including the APR ). SAA proteins are lipophilic and contribute to high density lipoproteins (HDL) and cholesterol transport. SAA proteins interact with specific receptors and have been implicated in tissue remodeling through metalloproteinases, local tissue changes in atherosclerosis, cancer metastasis, lung inflammation, maternal-fetal health and intestinal physiology. Molecular details of some of these are emerging. 10.1007/978-3-030-41769-7_17

Low serum amylase, lipase, and trypsin as biomarkers of metabolic disorders: A systematic review and meta-analysis. Ko Juyeon,Cho Jaelim,Petrov Maxim S Diabetes research and clinical practice AIMS:While there is plentiful evidence on elevated serum levels of amylase, lipase, and trypsin in acute illness, low serum levels of these digestive enzymes have been studied infrequently. The aim was to systematically review published studies on the relationship between low serum levels of amylase, lipase, or trypsin and metabolic disorders. METHODS:The search was conducted in MEDLINE and Scopus databases. Studies in humans were included if they reported on the association between serum levels of amylase, lipase, or trypsin within normal range and metabolic disorders. Random-effects meta-analysis was conducted. RESULTS:A total of 20 studies encompassing 20,916 participants were included. Compared with healthy individuals, individuals with type 2 diabetes mellitus (mean difference = -5.3; p < 0.001), metabolic syndrome (mean difference = -5.1; p < 0.001), and overweight/obesity (mean difference = -0.8; p = 0.02) had significantly lower serum levels of amylase. Both individuals with type 1 diabetes mellitus (mean difference = -1.8; p < 0.001) and type 2 diabetes mellitus (mean difference = -0.8; p < 0.001) had significantly lower serum levels of lipase compared with healthy individuals. Data on serum trypsin were not suitable for meta-analysis. In the pooled analysis, individuals with type 2 diabetes mellitus had 3.1-times lower serum levels of amylase, 2.9-times lower serum levels of lipase, and 2.5-times lower serum levels of trypsin levels than the upper limits of normal for the three digestive enzymes. CONCLUSION:Low serum levels of amylase and lipase are significantly associated with type 2 diabetes mellitus, type 1 diabetes mellitus, excess adiposity, and metabolic syndrome. The role of digestive enzymes in the pathogenesis of metabolic disorders warrants further investigations. 10.1016/j.diabres.2019.107974

Serum amyloid A: A potential biomarker of lung disorders. Vietri Lucia,Fui Annalisa,Bergantini Laura,d'Alessandro Miriana,Cameli Paolo,Sestini Piersante,Rottoli Paola,Bargagli Elena Respiratory investigation Serum amyloid A is an acute-phase protein with multiple immunological functions. Serum amyloid A is involved in lipid metabolism, inflammatory reactions, granuloma formation, and cancerogenesis. Additionally, serum amyloid A is involved in the pathogenesis of different autoimmune lung diseases. The levels of serum amyloid A has been evaluated in biological fluids of patients with different lung diseases, including autoimmune disorders, chronic obstructive pulmonary diseases, obstructive sleep apnea syndrome, sarcoidosis, asthma, lung cancer, and other lung disorders, such as idiopathic pulmonary fibrosis, tuberculosis, radiation pneumonitis, and cystic fibrosis. This review focuses on the cellular and molecular interactions of serum amyloid A in different lung diseases and suggests this acute-phase protein as a prognostic marker. 10.1016/j.resinv.2019.09.005

Serum Amyloid A3 is required for normal lung development and survival following influenza infection. Scientific reports Serum amyloid A (SAA) proteins are a family of acute phase apolipoproteins implicated to directly modulate innate and adaptive immune responses. However, new studies comparing endogenous SAAs and recombinant forms of these proteins have questioned the function of SAA in inflammation and immunity. We generated SAA3 knockout mice to evaluate the contribution of SAA3 to lung development and immune-mediated lung disease. While SAA3 deficiency does not affect the generation of house dust mite-induced allergic asthma, mice lacking SAA3 develop adult-onset obesity, intrinsic airway hyperresponsiveness, increased inflammatory and fibrotic gene expression in the lung, and elevated levels of lung citrullinated proteins. Polyclonally stimulated CD4 T cells from SAA3-/- mice exhibit impaired glycolytic activity, decreased T2 and T1 cytokine secretion, and elevated IL-17A production compared to wild type cells. Polyclonally stimulated CD8 T cells from SAA3-/- mice also exhibit impaired glycolytic activity as well as a diminished capacity to produce IL-2 and IFNγ. Finally, SAA3-/- mice demonstrate increased mortality in response to H1N1 influenza infection, along with higher copy number of viral RNAs in the lung, a lack of CD8 T cell IFNγ secretion, and decreased flu-specific antibodies. Our findings indicate that endogenous SAA3 regulates lung development and homeostasis, and is required for protection against H1N1 influenza infection. 10.1038/s41598-018-34901-x