[Application of serum SAA, CRP, PCT, WBC and N% in the diagnosis of neonatal septicemia].
Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine]
To explore the application value of SAA (serum amyloid A), CRP (C reactive protein), PCT (procalcitonin), WBC (white blood cell) and N% (neutrophil %) in the diagnosis of neonatal septicemia. This study was a retrospective study. 173 children with clinically diagnosed septicemia and 66 children with definitely diagnosed septicemia admitted to the Department of Neonatology, the Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China,from January 2022 to January 2024 were selected as the case group, and 148 children with neonatal jaundice who were hospitalized during the same period were selected as the control group. Fasting venous blood was collected within 24 hours after the children's admission to detect the levels of serum WBC, N%, SAA, CRP and PCT. One-way analysis of variance and Kruskal-Wallis test were used to compare the general data and inflammatory index levels of the three groups of children. The correlation analysis between SAA and other inflammatory indicators was conducted using Spearman correlation analysis. The receiver operating characteristic (ROC) curve was used to determine the diagnostic efficacy of different inflammatory indicators for patients with definitely diagnosed septicemia and those with clinically diagnosed septicemia, and for those with clinically diagnosed septicemia and those without infection. The results showed that the levels of WBC [(16.88±5.64)×10/L], N% [70.00 (63.00, 75.00)], PCT [2.22 (1.20, 5.55) mg/L], CRP [3.00 (0.50, 10.30) mg/L], SAA [19.70 (10.82, 49.90) mg/L] in the clinically diagnosed septicemia group and WBC [(16.10±7.48)×10/L], N% [73.50 (61.50, 80.93)], PCT [5.35 (0.69, 20.07) mg/L], CRP [15.52 (4.98, 30.50) mg/L], SAA [43.95 (14.00, 175.98) mg/L] in the definitely diagnosed septicemia group were all higher than those in the control group (11.17±3.38)×10/L, 49.81 (36.93, 62.75), 0.20 (0.07, 0.99) mg/L, 0.54 (0.20, 1.40) mg/L, 5.15 (3.60, 8.68) mg/L, and the differences were all statistically significant (all 0.05). Spearman correlation analysis showed that the level of SAA was positively correlated with WBC, N%, PCT and CRP (=0.453, 0.540, 0.343, 0.550, all <0.05). ROC curve analysis showed that the area under ROC curve(AUC) of SAA for the definitely diagnosed septicemia group and the clinically diagnosed septicemia group was higher than that of other inflammatory indicators, among them, the AUC of SAA for diagnosing the definitely diagnosed neonatal septicemia group was 0.933 (95%: 0.809-1.000, <0.05), with a sensitivity of 92.90% and a specificity of 99.30%. The AUC of SAA for diagnosing the clinically diagnosed septicemia group was 0.861 (95%: 0.818-0.904, <0.05), with a sensitivity of 83.20% and a specificity of 81.80%. In conclusion, compared with CRP, PCT, WBC and N%, SAA has higher sensitivity and specificity for distinguishing neonatal septicemia (including definitely diagnosed septicemia and clinically diagnosed septicemia), and has certain auxiliary diagnostic value for neonatal septicemia.
10.3760/cma.j.cn112150-20240709-00550
Partial SAA patients benefit from delayed response of IST.
Frontiers in immunology
Introduction:Severe aplastic anemia(SAA)is a severe disease characterized by immune-mediated bone marrow failure and pancytopenia. Immunosuppressive therapy (ATG plus CsA, IST) is the standard treatment for patients who are not suitable for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Some patients have a delayed response after 6 months of ATG, and unnecessary to be given secondary ATG or allo-HSCT. We attempted to distinguish patients who may get potential delayed response from those who were really not responsive to IST. Methods:We collected data from 45 SAA patients who were assessed no-response to IST at 6 months after rATG and failed to receive secondary ATG or allo-HSCT. Results:CsA plus eltrombopag (EPAG) group has an extra 75% response rate while CsA maintenance group has an extra 44% response rate at 12 months. ATG was applied within 30 days after diagnosis, ATG dosage was suffificient (ATG/lymphocyte ≥2), and absolute reticulocyte count (ARC) was ≥30×109 /L at 6 months, indicated patients could get delayed response and benefifit from CsA maintenance. Addition of EPAG could give an even better response. Otherwise, secondary ATG or allo-HSCT treatment were recommended to be given immediately. Clinical Trial Registration:https://www.chictr.org.cn/searchproj.aspx, identifier ChiCTR2300067615.
10.3389/fimmu.2023.1067977
SAA suppresses α-PD-1 induced anti-tumor immunity by driving T2 polarization in lung adenocarcinoma.
Cell death & disease
Cancer stem cells (CSCs) are believed to be crucial in the initiation, progression, and recurrence of cancer. CSCs are also known to be more resistant to cancer treatments. However, the interaction between CSCs and the immune microenvironment is complex and not fully understood. In current study we used single cell RNA sequence (scRNA-Seq, public dataset) technology to identify the characteristic of CSCs. We found that the lung adenocarcinoma cancer stem population is highly inflammatory and remodels the tumor microenvironment by secreting inflammatory factors, specifically the acute phase protein serum amyloid A (SAA). Next, we developed an ex-vivo autologous patient-derived organoids (PDOs) and peripheral blood mononuclear cells (PBMCs) co-culture model to evaluate the immune biological impact of SAA. We found that SAA not only promotes chemoresistance by inducing cancer stem transformation, but also restricts anti-tumor immunity and promotes tumor fibrosis by driving type 2 immunity, and α-SAA neutralization antibody could restrict treatment resistant and tumor fibrosis. Mechanically, we found that the malignant phenotype induced by SAA is dependent on P2X7 receptor. Our data indicate that cancer stem cells secreted SAA have significant biological impact to promote treatment resistant and tumor fibrosis by driving cancer stemness transformation and type 2 immunity polarization via P2X7 receptor. Notably, α-SAA neutralization antibody shows therapeutic potential by restricting these malignant phenotypes.
10.1038/s41419-023-06198-w
Inflammation and Tumor Progression: The Differential Impact of SAA in Breast Cancer Models.
Biology
Previous research has shown that the Serum Amyloid A (SAA) protein family is intricately involved in inflammatory signaling and various disease pathologies. We have previously demonstrated that SAA is associated with increased colitis disease severity and the promotion of tumorigenesis. However, the specific role of SAA proteins in breast cancer pathology remains unclear. Therefore, we investigated the role of systemic SAA1 and SAA2 (SAA1/2) in a triple-negative breast cancer mouse model. Syngeneic breast tumors were established in wild-type mice, and mice lacking the SAA1/2 (SAADKO). Subsequently, tumor volume was monitored, species survival determined, the inflammatory profiles of mice assessed with a multiplex assay, and tumor molecular biology and histology characterized with Western blotting and H&E histological staining. WT tumor-bearing mice had increased levels of plasma SAA compared to wild-type control mice, while SAADKO control and tumor-bearing mice presented with lower levels of SAA in their plasma. SAADKO tumor-bearing mice also displayed significantly lower concentrations of systemic inflammatory markers. Tumors from SAADKO mice overall had lower levels of SAA compared to tumors from wild-type mice, decreased apoptosis and inflammasome signaling, and little to no tumor necrosis. We demonstrated that systemic SAA1/2 stimulates the activation of the NLRP3 inflammasome in breast tumors, leading to the production of pro-inflammatory cytokines. This, in turn, promoted apoptosis and tumor necrosis but did not significantly impact tumor growth or histological grading.
10.3390/biology13090654
Clinical diagnostic value of IL-14, 1L-16 and SAA in periodontitis.
Clinical oral investigations
OBJECTIVES:Periodontitis is a chronic infectious disease, which leads to inflammatory destruction of periodontal supporting tissues. Interleukin 14 (IL-14), Interleukin 16 (IL-16) and serum amyloid A (SAA) have been demonstrated to be abnormally expressed in inflammatory diseases. Therefore, this study was performed to analyzed the expression and potential clinical values of IL-14, 1L-16 and SAA in periodontitis. MATERIALS AND METHODS:A total of 100 periodontitis patients and 100 healthy volunteers were recruited and the saliva and serum samples were collected. Then the C-reactive protein (CRP), procalcitonin (PCT), IL-14, 1L-16 and SAA levels in the saliva and serum of periodontitis patients were measured by Elisa kits. Besides, the significance of CRP, PCT, IL-14, 1L-16 and SAA in periodontitis patients were analyzed by receiver operating characteristic (ROC) analysis. RESULTS:The results showed that CRP, PCT, IL-14, 1L-16 and SAA levels were significantly increased in the the saliva and serum of the periodontitis patients. Additionally, the area under the curve (AUC) of saliva CRP, PCT, IL-14, 1L-16 and SAA for the diagnosis of periodontitis were 0.9035, 0.9435, 0.9508, 0.9500 and 0.9467, respectively. The AUC of serum CRP, PCT, IL-14, 1L-16 and SAA for the diagnosis of periodontitis were 0.9035, 0.9435, 0.9508, 0.9500 and 0.9467, respectively. What's more, the diagnostic value of IL-14, 1L-16 and SAA were enhanced when combining with CRP and PCT. CONCLUSION AND CLINICAL RELEVANCE:This study demonstrated that IL-14, IL-16 and SAA expressions were upregulated in periodontitis patients and exhibited a significant significance for periodontitis diagnosis.
10.1007/s00784-023-05269-8
The ASC inflammasome adapter governs SAA-derived protein aggregation in inflammatory amyloidosis.
EMBO molecular medicine
Extracellularly released molecular inflammasome assemblies -ASC specks- cross-seed Aβ amyloid in Alzheimer's disease. Here we show that ASC governs the extent of inflammation-induced amyloid A (AA) amyloidosis, a systemic disease caused by the aggregation and peripheral deposition of the acute-phase reactant serum amyloid A (SAA) in chronic inflammatory conditions. Using super-resolution microscopy, we found that ASC colocalized tightly with SAA in human AA amyloidosis. Recombinant ASC specks accelerated SAA fibril formation and mass spectrometry after limited proteolysis showed that ASC interacts with SAA via its pyrin domain (PYD). In a murine model of inflammatory AA amyloidosis, splenic amyloid load was conspicuously decreased in Pycard mice which lack ASC. Treatment with anti-ASC antibodies decreased amyloid loads in wild-type mice suffering from AA amyloidosis. The prevalence of natural anti-ASC IgG (-logEC ≥ 2) in 19,334 hospital patients was <0.01%, suggesting that anti-ASC antibody treatment modalities would not be confounded by natural autoimmunity. These findings expand the role played by ASC and IL-1 independent inflammasome employments to extraneural proteinopathies and suggest that anti-ASC immunotherapy may contribute to resolving such diseases.
10.1038/s44321-024-00107-0
CRP Versus SAA for Identification of Inflammatory Hepatic Adenomas.
Applied immunohistochemistry & molecular morphology : AIMM
Subtyping hepatic adenomas is important for patient management due to differing complication risks. Immunohistochemical staining with C-reactive protein (CRP) and serum amyloid-A (SAA) is widely accepted as a surrogate for molecular classification to identify inflammatory hepatocellular adenomas. Limited data, however, has been published on how these 2 stains compare for sensitivity. We conducted a large, multicenter, retrospective study to examine the sensitivity and staining characteristics of CRP and SAA in inflammatory hepatic adenomas, with focal nodular hyperplasia (FNHs) as a control group. Inflammatory adenomas were identified in 133 patients (average age 37 years, 109 were female). In all, 69.9% of cases were resection specimens and 90.2% of all cases showed positive staining for both CRP and SAA; 10 (7.5%) were positive for CRP only and 3 (2.3%) were positive for SAA only. CRP was more sensitive than SAA (97.74% vs. 92.48%, P -value = 0.0961) and showed more extensive and intense staining, with a significantly higher modified H-score ( P <0.001). Focal nodular hyperplasia can also show positive CRP and SAA staining but with a lower modified H-score ( P <0.0001). Based on beta-catenin and glutamine synthetase staining, 26 of inflammatory adenomas also had beta-catenin activation (19.5%). All 3 cases with positive SAA and negative CRP staining were beta-catenin activated. In contrast, the proportion of cases that were CRP positive and SAA negative was similar regardless of beta-catenin activation. The data affirms the strategy of using both CRP and SAA immunostains for hepatic adenoma subtyping and raises the awareness of the highly variable nature of SAA staining characteristics.
10.1097/PAI.0000000000001155
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
Decrease of circulating SAA is correlated with reduction of abdominal SAA secretion during weight loss.
Obesity (Silver Spring, Md.)
OBJECTIVE:The study goal was to determine the effect of weight loss (WL) alone and with aerobic exercise (WL + AEX) on serum amyloid A (SAA) levels and adipose SAA secretion from gluteal and abdominal depots. METHODS:Ninety-six overweight or obese postmenopausal women undertook a 6-month WL alone (n = 47) or with AEX training (n = 49) (6 months WL and WL + AEX are considered WL when groups were combined). Their serum SAA levels, body weight, and adipose SAA secretion ex vivo from gluteal and abdominal depot were measured before and after WL interventions. RESULTS:The participants lost an average of 8% body weight with a 10% decrease of serum SAA. Serum SAA levels remained significantly correlated with body weight before and after WL. However, the changes of serum SAA level did not correlate with changes of body weight. The gluteal adipose tissue secreted ∼50% more SAA than the abdominal tissue, but the changes of abdominal, but not gluteal, SAA secretion correlated (R(2) = 0.19, p < 0.01) with those of serum SAA levels during WL. CONCLUSIONS:No linear correlation between the decrease in systemic SAA and WL was found. There is a depot-dependent difference in adipose SAA secretion and abdominal SAA secretion, which may partially account for the systemic SAA reduction during WL.
10.1002/oby.20657
Paradoxical effects of SAA on lipoprotein oxidation suggest a new antioxidant function for SAA.
Jayaraman Shobini,Haupt Christian,Gursky Olga
Journal of lipid research
Oxidative stress and inflammation, which involve a dramatic increase in serum amyloid A (SAA) levels, are critical in the development of atherosclerosis. Most SAA circulates on plasma HDL particles, altering their cardioprotective properties. SAA-enriched HDL has diminished anti-oxidant effects on LDL, which may contribute to atherogenesis. We determined combined effects of SAA enrichment and oxidation on biochemical changes in HDL. Normal human HDLs were incubated with SAA, oxidized by various factors (Cu, myeloperoxidase, HO, OCl), and analyzed for lipid and protein modifications and biophysical remodeling. Three novel findings are reported: addition of SAA reduces oxidation of HDL and LDL lipids; oxidation of SAA-containing HDL in the presence of OCl generates a covalent heterodimer of SAA and apoA-I that resists the release from HDL; and mild oxidation promotes spontaneous release of proteins (SAA and apoA-I) from SAA-enriched HDL. We show that the anti-oxidant effects of SAA extend to various oxidants and are mediated mainly by the unbound protein. We propose that free SAA sequesters lipid hydroperoxides and delays lipoprotein oxidation, though much less efficiently than other anti-oxidant proteins, such as apoA-I, that SAA displaces from HDL. These findings prompt us to reconsider the role of SAA in lipid oxidation in vivo.
10.1194/jlr.M071191
Human SR-BII mediates SAA uptake and contributes to SAA pro-inflammatory signaling in vitro and in vivo.
PloS one
Serum amyloid A (SAA) is an acute phase protein with cytokine-like and chemotactic properties, that is markedly up-regulated during various inflammatory conditions. Several receptors, including FPRL-1, TLR2, TLR4, RAGE, class B scavenger receptors, SR-BI and CD36, have been identified as SAA receptors. This study provides new evidence that SR-BII, splice variant of SR-BI, could function as an SAA receptor mediating its uptake and pro-inflammatory signaling. The uptake of Alexa Fluor488 SAA was markedly (~3 fold) increased in hSR-BII-expressing HeLa cells when compared with mock-transfected cells. The levels of SAA-induced interleukin-8 secretion by hSR-BII-expressing HEK293 cells were also significantly (~3-3.5 fold) higher than those detected in control cells. Moderately enhanced levels of phosphorylation of all three mitogen-activated protein kinases, ERK1/2, and p38 and JNK, were observed in hSR-BII-expressing cells following SAA stimulation when compared with control wild type cells. Transgenic mice with pLiv-11-directed liver/kidney overexpression of hSR-BI or hSR-BII were used to assess the in vivo role of each receptor in SAA-induced pro-inflammatory response in these organs. Six hours after intraperitoneal SAA injection both groups of transgenic mice demonstrated markedly higher (~2-5-fold) expression levels of inflammatory mediators in the liver and kidney compared to wild type mice. Histological examinations of hepatic and renal tissue from SAA-treated mice revealed moderate level of damage in the liver of both transgenic but not in the wild type mice. Activities of plasma transaminases, biomarkers of liver injury, were also moderately higher in hSR-B transgenic mice when compared to wild type mice. Our findings identify hSR-BII as a functional SAA receptor that mediates SAA uptake and contributes to its pro-inflammatory signaling via the MAPKs-mediated signaling pathways.
10.1371/journal.pone.0175824
High-Density Lipoproteins and Serum Amyloid A (SAA).
Webb Nancy R
Current atherosclerosis reports
PURPOSE OF REVIEW:Serum amyloid A (SAA) is a highly sensitive acute phase reactant that has been linked to a number of chronic inflammatory diseases. During a systemic inflammatory response, liver-derived SAA is primarily found on high-density lipoprotein (HDL). The purpose of this review is to discuss recent literature addressing the pathophysiological functions of SAA and the significance of its association with HDL. RECENT FINDINGS:Studies in gene-targeted mice establish that SAA contributes to atherosclerosis and some metastatic cancers. Accumulating evidence indicates that the lipidation state of SAA profoundly affects its bioactivities, with lipid-poor, but not HDL-associated, SAA capable of inducing inflammatory responses in vitro and in vivo. Factors that modulate the equilibrium between lipid-free and HDL-associated SAA have been identified. HDL may serve to limit SAA's bioactivities in vivo. Understanding the factors leading to the release of systemic SAA from HDL may provide insights into chronic disease mechanisms.
10.1007/s11883-020-00901-4
A Reference chart for clinical biochemical tests of hemolyzed serum samples.
Ni Jun,Zhu Wenbo,Wang Yanyang,Wei Xuefei,Li Jingjing,Peng Lu,Zhang Kui,Bai Bing
Journal of clinical laboratory analysis
BACKGROUND:Although the effect of hemolysis has been extensively evaluated on clinical biochemical tests, a practical guidance for laboratory staff to rapidly determine whether a hemolyzed blood sample is acceptable and how to interpret the results is lacking. Here, we introduce a chart as a convenient reference for dealing with such samples. METHODS:Serum samples with 0.1%, 0.3%, 1%, 3%, and 10% hemolysis were prepared from sonicated endogenous red blood cells and received 35 wet and 22 dry clinical biochemical tests, respectively. The contributing part in the biochemical test result at each hemolysis condition was derived by subtracting the original test result of this sample with no hemolysis. The net results were used for analyses and preparation of the reference chart. RESULTS:The reference chart displayed the analytically calculated hemolysis interference and related statistical analyses. The chart also provided the color appearance of serum samples at each hemolysis condition for clinical staffs to determine whether a hemolyzed sample could be accepted. CONCLUSION:In clinical laboratories, preparation of such a reference chart is extremely useful in dealing with hemolyzed blood samples for clinical biochemical tests.
10.1002/jcla.23561