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Alkaptonuria (AKU) is a rare autosomal recessive metabolic disorder caused by mutations in the homogentisate 1,2-dioxygenase (HGD) gene, leading to the accumulation of homogentisic acid (HGA), causing severe inflammatory conditions. Recently, the presence of serum amyloid A (SAA) has been reported in AKU tissues, classifying AKU as novel secondary amyloidosis; AA amyloidosis is characterized by the extracellular tissue deposition of fibrils composed of fragments of SAA. AA amyloidosis may complicate several chronic inflammatory conditions, like rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, chronic infections, neoplasms, etc. Treatments of AA amyloidosis relieve inflammatory disorders by reducing SAA concentrations; however, no definitive therapy is currently available. SAA regulation is a crucial step to improve AA secondary amyloidosis treatments. Here, applying a comprehensive in vitro and in silico approach, we provided evidence that HGA is a disruptor modulator of SAA, able to enhance its polymerization, fibril formation, and aggregation upon SAA/SAP colocalization. In silico studies deeply dissected the SAA misfolding molecular pathway and SAA/HGA binding, suggesting novel molecular insights about it. Our results could represent an important starting point for identifying novel therapeutic strategies in AKU and AA secondary amyloidosis-related diseases. [ABSTRACT FROM AUTHOR]

OBJECTIVE Comparing the utility of the anti-human serum amyloid A (SAA)-specific monoclonal and polyclonal antibodies assays (LZ-SAA) with the pure monoclonal anti-human antibody assays (VET-SAA) during clinical practice in primary care hospital populations by measuring SAA measurement in healthy and diseased domestic cats. ANIMALS 52 healthy and 185 diseased client-owned cats. METHODS SAA concentration was measured using different LZ-SAA and VET-SAA measurements for healthy and various diseased cats. Sensitivity, specificity, and accuracy were calculated for each disease. RESULTS VET-SAA has higher sensitivity than LZ-SAA for the most common diseases presenting to primary care veterinary hospitals, including chronic kidney disease, tumors, and gingivostomatitis. Our results reveal the capability of detecting low SAA concentrations in healthy and diseased cats using VET-SAA in contrast to LZ-SAA, which found elevations of SAA concentrations only in diseased cats. CLINICAL RELEVANCE Our findings indicate that switching to the new VET-SAA instead of the conventional LZ-SAA will likely enhance the diagnostic performance in primary care veterinary hospitals. [ABSTRACT FROM AUTHOR]

• CRP and SAA are good biomarkers to discriminate crises in FMF and USAID patients. • Serum calprotectin is not a suitable biomarker to discriminate crises in SAID. • Contrary to SAA, CRP diagnostic performances were not affected by the BMI. • CRP is a suitable, not expensive and easily available biomarker to monitor SAID. With their broad presentations and no global biomarker to discriminate crises and attack-free periods, Systemic Auto-Inflammatory Diseases (SAID) are difficult to manage. This study assessed Serum Amyloid A (SAA), C-reactive protein (CRP) and serum calprotectin as potential biomarkers to monitor patients with SAID. SAA (already studied in Familial Mediterranean Fever (FMF)), CRP and serum calprotectin were measured on SAID adult patients from Juvenile Inflammatory Rheumatism (JIR) cohort during their follow-up visits between 2020 and 2022. Crises and attack-free periods were clinically determined. 96 measures, mainly from FMF (43 %) and Unclassified SAID (USAID) (37 %) patients were included. Using ROC curves, a threshold with sensitivity and specificity of/over 75 % was determined for SAA (9 mg/L) and CRP (9 mg/L) but not for serum calprotectin, not investigated further. With this threshold, the results were similar in FMF and USAID patients' subgroups. SAA and CRP showed a positive correlation with crises and attack-free periods in SAID patients (r = 0.4796, p < 0.001 and r = 0.5525, p < 0.001, respectively) as in FMF and USAID patients, with no significant difference between both markers in diagnosis value and ROC curves Area Under Curve (AUC) (p = 0.32). Only the CRP results were not influenced by obesity. SAA and CRP can discriminate crisis and attack-free periods in our cohort of SAID patients mainly composed of FMF and USAID patients. However, only CRP can be used regardless of body mass index. It is the first report of common biomarkers for all SAID, including USAID patients, with CRP widely accessible in routine worldwide. [ABSTRACT FROM AUTHOR]

Close monitoring of disease activity in IBD patients is essential to avoid long term complications. Although endoscopic assessment is the ideal monitoring tool, the usage of noninvasive biomarkers is more practical and patient friendly. We aimed to study the performance of Interleukin-6(IL-6) and Serum Amyloid A(SAA) as serum biomarkers in assessment of the disease activity of IBD patients in correlation to C-reactive protein (CRP), Fecal Calprotectin (FC) and endoscopic indices. 83 IBD (26 CD and 57 UC) patients on stable treatment regimen were recruited. Serum markers included CRP, CBC, IL-6, SAA were analyzed, together with FC. These markers were compared with the endoscopic and clinical disease parameters. Harvey-Bradshaw Index (HBI) and the Simple Clinical Colitis Activity Index (SCCAI) were used to assess clinical activity in CD and UC patients, respectively. Endoscopic activity was recorded using the Simple Endoscopic Score (SES) for Crohn's disease or the Mayo Endoscopic Score (MES) for ulcerative colitis. In prediction of disease activity, IL-6, SAA and CRP demonstrated good area under receiver operating characteristics (AUC) (>0.7), with FC being the best (0.94) for endoscopically active disease (P < 0.01). Combining FC and IL-6 or SAA improved its discriminative accuracy with an AUC (∼0.96). FC most accurately predicts endoscopic disease activity in IBD patients, in comparison to other studied serological biomarkers. The serum IL-6 and SAA are potential predictors of endoscopic disease activity, and they might be valuable for assessment of disease activity. Finally, a composite score of FC and SAA or IL-6 can increased its diagnostic accuracy. [ABSTRACT FROM AUTHOR]

This study investigated the longitudinal trajectory of changes in antioxidative and anti-inflammatory high-density lipoprotein (HDL) components during healthy pregnancy and pregnancy with cardiometabolic complications. We recruited and longitudinally followed 84 women with healthy pregnancies and 46 pregnant women who developed cardiometabolic pregnancy complications (gestational diabetes mellitus and hypertensive disorders of pregnancy). Their general lipid profiles, oxidative stress status, inflammatory status, and antioxidative and anti-inflammatory HDL components were analyzed. The results of our study confirmed the expected trajectory for the routine lipid parameters. Our study results indicate more intensive oxidative stress and a higher level of inflammation in the group with complications compared with the control group. Sphingosine-1-phosphate (S1P) was significantly lower in the first trimester in the group with complications compared with the control group (p < 0.05). We did not find significant differences in the apolipoprotein A1 (Apo A1) concentrations in the first trimester between the control group and the group with complications, but in the second and third trimesters, the group with complications had significantly higher concentrations (p < 0.001, p < 0.05, respectively). The S1P, paraoxonase 1 (PON1), and serum amyloid A (SAA) concentrations were significantly lower in the group with complications in the first trimester. During the second trimester, only the SAA concentrations were identified as significantly lower in the group with complications compared with the control group, while in the third trimester, the PON1, apolipoprotein M (Apo M), and SAA concentrations were all significantly lower in the group with complications. Through a multivariate binary logistic regression analysis, the S1P concentration in the first trimester was distinguished as an HDL-associated marker independently associated with cardiometabolic pregnancy complications. In conclusion, our study results showed that HDL remodeling differs between healthy pregnancies and pregnancies with maternal cardiometabolic complications, with changed HDL composition and functionality consequently impacting its biological functionality in the latter case. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the early diagnosis effect and clinical predictive value of serum amyloid A and C reactive protein in children with acute upper respiratory tract infection. A total of 324 children with acute upper respiratory tract infection (ARTI) who were treated in our hospital from October 2020 to April 2022 were selected as the research subjects. The variation of C-reactive protein concentration was tested by sphericity hypothesis, and the Greenhouse-Geisser method was used for in-depth analysis. The Receiver-Operating Characteristic (ROC) curve was drawn to evaluate the early predictive value of serum amyloid A and C reactive protein in children with acute upper respiratory tract. The concentrations of serum amyloid A and C reactive protein in children with ARTI changed significantly, with the increase of time, the concentration decreased, and the difference was statistically significant (P<0.05). The concentrations of amyloid A and C-reactive protein were significantly different, and the difference was statistically significant (P<0.05). Finally, the predictive effect of serum amyloid A and C reactive protein changes in children with ARTI was analyzed. From the ROC curve, it can be known that for both viral and bacterial upper respiratory tract infections, serum amyloid A and C reactive protein Proteins all have higher area under the line, and the ratio of the two is larger than the area under the line, both above 0.8. The serum amyloid A and C-reactive protein in the blood routine test of children with ARTI showed a changing trend. It was concluded that the changes of serum amyloid A and C-reactive protein can be used for early prediction of children with ARTI. It is of great value to improve the clinical treatment of ARTI. [ABSTRACT FROM AUTHOR]

Acute-phase serum amyloid A (SAA) can disrupt vascular homeostasis and is elevated in subjects with diabetes, cardiovascular disease, and rheumatoid arthritis. Cyclic nitroxides (e.g., Tempo) are a class of piperidines that inhibit oxidative stress and inflammation. This study examined whether 4-methoxy-Tempo (4-MetT) inhibits SAA-mediated vascular and renal dysfunction. Acetylcholine-mediated vascular relaxation and aortic guanosine-3′,5′-cyclic monophosphate (cGMP) levels both diminished in the presence of SAA. 4-MetT dose-dependently restored vascular function with corresponding increases in cGMP. Next, male ApoE-deficient mice were administered a vehicle (control, 100 µL PBS) or recombinant SAA (100 µL, 120 µg/mL) ± 4-MetT (at 15 mg/kg body weight via i.p. injection) with the nitroxide administered before (prophylaxis) or after (therapeutic) SAA. Kidney and hearts were harvested at 4 or 16 weeks post SAA administration. Renal inflammation increased 4 weeks after SAA treatment, as judged by the upregulation of IFN-γ and concomitant increases in iNOS, p38MAPK, and matrix metalloproteinase (MMP) activities and increased renal fibrosis (Picrosirius red staining) in the same kidneys. Aortic root lesions assessed at 16 weeks revealed that SAA enhanced lesion size (vs. control; p < 0.05), with plaque presenting with a diffuse fibrous cap (compared to the corresponding aortic root from control and 4-MetT groups). The extent of renal dysfunction and aortic lesion size was largely unchanged in 4-MetT-supplemented mice, although renal fibrosis diminished at 16 weeks, and aortic lesions presented with redistributed collagen networks. These outcomes indicate that SAA stimulates renal dysfunction through promoting the IFN-γ–iNOS–p38MAPK axis, manifesting as renal damage and enhanced atherosclerotic lesions, while supplementation with 4-MetT only affected some of these pathological changes. [ABSTRACT FROM AUTHOR]

Serum amyloid A (SAA) is a cardiovascular risk factor and may serve as a predictor of infarct-related artery (IRA) patency in patients with ST-segment elevation myocardial infarction (STEMI). We measured SAA levels in STEMI patients who underwent percutaneous coronary intervention (PCI) and investigated their association with IRA patency. According to the Thrombolysis in Myocardial Infarction (TIMI) flow grade, 363 STEMI patients undergoing PCI in our hospital were divided into an occlusion group (TIMI 0-2) and a patency group (TIMI 3). The SAA level before PCI was significantly higher in STEMI patients with IRA occluded than in those with patent ones. At a cutoff value of 36.9 mg/L, SAA had a sensitivity of 63.0% and a specificity of 90.6% (area under the ROC curve [AUC] =.833, 95% CI:.793-.873, P <.001). Multivariate logistic regression analysis showed that SAA was an independent predictor of IRA patency in STEMI patients before PCI (odds ratio [OR] = 1.041, 95% CI: 1.020-1.062, P <.001). SAA can be used as a potential predictor of IRA patency in STEMI patients before PCI. [ABSTRACT FROM AUTHOR]

Objective: In this study, we aimed to evaluate the combined diagnostic value of procalcitonin (PCT), C-reactive protein (CRP), and serum amyloid A (SAA) in sepsis caused by urinary tract infection. Method: A total of 80 patients with urosepsis who were hospitalized were included in the study group, and 80 patients with urinary tract infection without sepsis were included in the control group. We collected the PCT, SAA, and CRP levels of patients following admission. Subsequently, we conducted a comparative analysis to assess the specificity, accuracy, and sensitivity of combined diagnostic approaches in contrast to individual diagnostic methods for blood PCT, SAA, and CRP. Results: The levels of PCT, SAA, and CRP in the study group were significantly higher than those in the control group, and the differences were statistically significant (P < 0.01). Multi-factor logistic regression analysis revealed that the levels of PCT (P = 0.003) and SAA (P = 0.014) were associated with urosepsis. The sensitivity of PCT was 87.133% and the specificity was 93.066%, which were higher than that of SAA and CRP. The specificity of the combined detection of the three was 95.670%, which was higher than that of PCT, SAA, and CRP alone. Correlation analysis revealed that PCT had a significant positive correlation with CRP and SAA (P < 0.01), and a weak correlation with white blood cell count (WBC) and fibrinogen (FIB) (P = 0.03 for WBC, P = 0.04 for FIB). Conclusion: PCT, SAA, and CRP indicators in patients with urosepsis are significantly elevated, and all three are valuable in the diagnosis of urosepsis. PCT alone has good diagnostic efficiency for urosepsis, and a certain correlation with other inflammatory factors. The diagnostic efficacy of the three indicators in combination is better than that of any one of the three, and is worthy of widespread clinical application. [ABSTRACT FROM AUTHOR]

Background: Hereditary angioedema (HAE) is a rare disease characterized by localized and self-limited angioedema (AE) attacks. A local increase of bradykinin (BK) mediates AE attacks in HAE, however the role of inflammation in HAE has been poorly explored We aim to analyze the role of inflammatory mediators in HAE patients during AE attacks. Methods: Patients with a confirmed HAE diagnosis due to C1 inhibitor deficiency (HAE-C1INH) or patients F12 gene mutations (HAE-FXII) attending to our outpatient clinic between November-2019 and May-2022 were included. Demographic and clinical characteristics were analyzed. Blood samples were collected both during symptom-free periods (baseline) and during HAE attacks, and acute phase reactants (APR), such as serum amyloid A (SAA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), D-Dimer and white blood cells were measured. Results: Seventy-eight patients were enrolled in the study, with a predominant representation of women (76%, n=59), and a mean age of 47.8 years (range 6-88). Among them, 67% (n=52) of patients had HAE-C1INH (46 classified as type 1 and 6 as type 2) while 33% (n=26) had HAE-FXII. During attack-free periods, the majority of patients exhibited normal levels of SAA, ESR, D-dimer, ACE and WCC. However, in a subset of patients (16% for SAA, 18% for ESR, and 14.5% for Ddimer), elevations were noted at baseline. Importantly, during HAE attacks, significant increases were observed in SAA in 88% of patients (p< 0.0001 vs. baseline), in ESR in 65% (p= 0.003 vs. baseline) and D-dimer in 71% (p=0.001 vs. baseline) of the patients. A comparison between baseline and acute attack levels in 17 patients revealed significant differences in SAA AA (p<0. 0001), ESR (p<0.0001) and D-dimer (p= 0.004). No significant differences were observed in CRP (p=0.7), ACE (p=0.67) and WCC (p=0.54). These findings remained consistent regardless of HAE type, disease activity or location of angioedema. Conclusion: The systemic increase in APR observed during HAE attacks suggests that inflammation extends beyond the localized edematous area. This finding underscores the potential involvement of inflammatory pathways in HAE and highlights the need for further investigation into their role in the pathophysiology of HAE. [ABSTRACT FROM AUTHOR]

Introduction: The glutaraldehyde test (GAT) allows for animal-side semiquantitative estimation of fibrinogen and gamma-globulin concentrations in blood samples of adult cattle and therefore detection of inflammatory disease conditions. However, the test has potential limitations, especially due to the latency period until sufficiently high fibrinogen and/or gamma-globulin concentrations are reached. The aim of the present study was therefore to assess the association between results of GAT with other inflammatory markers including hematologic variables, fibrinogen, plasma haptoglobin and serum amyloid A (SAA) concentrations. Methods: For the purpose of this prospective observational study, a convenience sample of 202 cows with a broad range of inflammatory and noninflammatory clinical conditions was included. The GAT was run on EDTA blood, fibrinogen was measured using the Clauss and the heat precipitation method, and commercially available ELISA tests were used for determination of plasma haptoglobin and SAA concentrations. Results: Shortened GAT coagulation times were more closely correlated to serum globulin (rs = -0.72) than to plasma fibrinogen concentrations measured with the heat precipitation (rs = -0.64) and the Clauss method (rs = -0.70). Cows with a markedly (=3 min) or moderately (4-6 min) shortened coagulation time had higher (p < 0.001) plasma haptoglobin and SAA concentrations than cows with a negative test result. Total leukocyte, monocyte and neutrophil concentrations did not differ significantly between groups. An identified cut-off for the GAT coagulation time of =14 min had a sensitivity and specificity of 54.4 and 100%, respectively, for the prediction of an inflammatory state based on clinical findings and/or increased plasma haptoglobin or SAA concentrations. Discussion: In conclusion, this study demonstrates considerable diagnostic agreement between positive GAT results and increased plasma concentrations of haptoglobin and SAA. Despite high specificity, the test lacks sensitivity in case of acute inflammatory conditions indicating that plasma acute phase protein concentrations and hematologic findings can provide additional diagnostic information if the GAT is negative. [ABSTRACT FROM AUTHOR]

Purpose of Review: Amyloid A (AA) amyloidosis is an organ- or life-threatening complication of chronic inflammatory disorders. Here, we review the epidemiology, causes, pathogenesis, clinical features, and diagnostic and therapeutic strategies of AA amyloidosis. Recent Findings: The incidence of AA amyloidosis has declined due to better treatment of the underlying diseases. Histopathological examination is the gold standard of diagnosis, but magnetic resonance imaging can be used to detect cardiac involvement. There is yet no treatment option for the clearance of amyloid fibril deposits; therefore, the management strategy primarily aims to reduce serum amyloid A protein. Anti-inflammatory biologic agents have drastically expanded our therapeutic armamentarium. Kidney transplantation is preferred in patients with kidney failure, and the recurrence of amyloidosis in the allograft has become rare as transplant recipients have started to benefit from the new agents. Summary: The management of AA amyloidosis has been considerably changed over the recent years due to the novel therapeutic options aiming to control inflammatory activity. New agents capable of clearing amyloid deposits from the tissues are still needed. [ABSTRACT FROM AUTHOR]

Yi Wang,1,2 Wenhui Zhang,1,3 Shourong Liu,1 Fei Wang,1 Qian Huang,1 Er Li,3 Mingli Zhu,4 Jianhua Yu,1,&ast; Jinchuan Shi1,&ast; 1Department of Infection, Affiliated Hangzhou Xixi Hospital, Zhejiang University of Traditional Chinese Medicine, Hangzhou, People’s Republic of China; 2Institute of Hepatology and Epidemiology, Affiliated Hangzhou Xixi Hospital, Zhejiang University of Traditional Chinese Medicine, Hangzhou, People’s Republic of China; 3Department of Nursing, Affiliated Hangzhou Xixi Hospital, Zhejiang University of Traditional Chinese Medicine, Hangzhou, People’s Republic of China; 4Medical Laboratory, Affiliated Hangzhou Xixi Hospital, Zhejiang University of Traditional Chinese Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianhua Yu; Jinchuan Shi, Department of Infection, Affiliated Hangzhou Xixi Hospital, Zhejiang University of Traditional Chinese Medicine, Hangzhou, People’s Republic of China, Email yujhmc@126.com; shijinchuan2008@126.comObjective: Precise prediction of the occurrence of complicated perianal abscesses (PAs) in monkeypox (mpox)-infected patients is important for therapeutic optimization. This study sought to identify risk factors of complicated PA.Methods: A total of 48 patients with mpox infection (PA group, n = 10; non-PA (NPA) group, n = 38) were enrolled in our study, who were hospitalized in Hangzhou Xixi Hospital, China from 29 June to 3 September 2023. The data of demographic characteristics, and clinical symptoms, serum SAA, PCT, CRP, and IL-6 levels were collected by the Electronic Medical Record. The diagnostic values of these biomarkers were assessed using multivariate logistic regression and ROC curve analyses.Results: A decrease in serum IL-6, SAA, and CRP levels (all p-value < 0.05), but not PCT, was observed in all mpox-infected patients. A significant positive correlation was also noted between IL-6, SAA, CRP, and PCT levels (all p-value < 0.05). There was a significant increase in IL-6 and SAA levels and the SAA/CRP ratio in serum samples from patients in the PA group. Multivariate logistic regression and ROC curve analyses identified that the combined use of perianal symptoms and SAA was more sensitive than perianal symptoms or SAA alone as predictors of complicated PA. This combination had the highest predictive value for disease progression, with an AUC of 0.920 (p-value < 0.001).Conclusion: The combination of perianal symptoms and SAA levels was strongly linked to the occurrence of complicated PA in mpox-infected patients. These findings may inform the early diagnosis of this patient population.Keywords: serum amyloid A, perianal symptoms, perianal abscess, mpox-infected patients

Community-acquired pneumonia (CAP) poses a significant global health threat, particularly affecting vulnerable populations. Biomarkers and scoring systems play a crucial role in diagnosing, assessing severity, and guiding treatment decisions for CAP patients. Biomarkers like C reactive protein, procalcitonin, and the neutrophil-to-lymphocyte ratio aid in diagnosis and severity assessment, while scoring systems such as CURB-65 and Pneumonia Severity Index classify patients into risk categories. Emerging biomarkers (uremia, elevated respiratory rate, hypotension, and age ≥ 65) like serum amyloid A and S100 proteins show promise in predicting disease severity and prognosis. However, further research is needed to determine their precise roles and clinical utility in CAP management.

Abstract Background The chicken’s inflammatory response is an essential part of the bird’s response to infection. A single dose of Escherichia coli (E. coli) lipopolysaccharide (LPS) endotoxin can activate the acute phase response (APR) and lead to the production of acute phase proteins (APPs). In this study, the responses of established chicken APPs, Serum amyloid A (SAA) and Alpha-1-acid-glycoprotein (AGP), were compared to two novel APPs, Hemopexin (Hpx) and Extracellular fatty acid binding protein (Ex-FABP), in 15-day old broilers over a time course of 48 h post E.coli LPS challenge. We aimed to investigate and validate their role as biomarkers of an APR. Novel plant extracts, Citrus (CTS) and cucumber (CMB), were used as dietary supplements to investigate their ability to reduce the inflammatory response initiated by the endotoxin. Results A significant increase of established (SAA, AGP) and novel (Ex-FABP, Hpx) APPs was detected post E.coli LPS challenge. Extracellular fatty acid binding protein (Ex-FABP) showed a similar early response to SAA post LPS challenge by increasing ~ 20-fold at 12 h post challenge (P

Summary The inflammatory response to a truly closed castration procedure in 51 horses using an inguinal approach was quantified by serum amyloid A (SAA) measurements to be on average 94 mg/L on day three after surgery. The average SAA value after field castrations, using a scrotal approach, was reported by four different investigations to be between 480 and 708 mg/L on day three post‐operatively. The discrepancy in SAA levels between these different approaches proved to be significant (p < 0.001), quantifying a substantially lower inflammatory response of the closed inguinal technique over regular field castrations using a scrotal approach. [ABSTRACT FROM AUTHOR]

The identification of novel, robust biomarkers for the diagnosis of rheumatic diseases (RDs) and the presence of active disease might facilitate early treatment and the achievement of favourable long-term outcomes. We conducted a systematic review and meta-analysis of studies investigating the acute phase reactant, serum amyloid A (SAA), in RD patients and healthy controls to appraise its potential as diagnostic biomarker. We searched PubMed, Scopus, and Web of Science from inception to 10 April 2024 for relevant studies. We evaluated the risk of bias and the certainty of evidence using the JBI Critical Appraisal Checklist and GRADE, respectively (PROSPERO registration number: CRD42024537418). In 32 studies selected for analysis, SAA concentrations were significantly higher in RD patients compared to controls (SMD = 1.61, 95% CI 1.24–1.98, p < 0.001) and in RD patients with active disease compared to those in remission (SMD = 2.17, 95% CI 1.21–3.13, p < 0.001). Summary receiving characteristics curve analysis showed a good diagnostic accuracy of SAA for the presence of RDs (area under the curve = 0.81, 95% CI 0.78–0.84). The effect size of the differences in SAA concentrations between RD patients and controls was significantly associated with sex, body mass index, type of RD, and study country. Pending the conduct of prospective studies in different types of RDs, the results of this systematic review and meta-analysis suggest that SAA is a promising biomarker for the diagnosis of RDs and active disease. [ABSTRACT FROM AUTHOR]

Serum amyloid A (SAA) proteins are highly conserved lipoproteins that are notoriously involved in the acute phase response and systemic amyloidosis, but their biological functions are incompletely understood. Recent work has shown that SAA proteins can enter the brain by crossing the intact blood–brain barrier (BBB), and that they can impair BBB functions. Once in the central nervous system (CNS), SAA proteins can have both protective and harmful effects, which have important implications for CNS disease. In this review of the thematic series on SAA, we discuss the existing literature that relates SAA to neuroinflammation and CNS disease, and the possible roles of the BBB in these relations. [ABSTRACT FROM AUTHOR]

In older horses, basal metabolic rate decreases, and plasma metabolite and hormone concentrations related to energy metabolism change. The occurrence of age-related diseases, which increases in old animals, may enhance inflammatory reactivity (inflammaging). Finding the appropriate treatment for inflammaging at an early stage may prevent various age-related diseases. Changes in metabolite and hormone concentrations and enzyme activities involved in energy metabolism in the plasma of clinically healthy riding horses of various ages were measured to identify biomarkers of inflammaging (persistent low-grade inflammation that occurs with aging). All horses were clinically healthy, and their body condition scores (BCSs) were 4 or 5 (9-point scale). Plasma triglyceride (TG), total cholesterol (T-Cho), blood urea nitrogen (BUN), insulin concentrations, malondialdehyde (MDA), and serum amyloid A (SAA) concentrations generally increased with age. Adiponectin concentrations, plasma superoxide dismutase (SOD), and leukocyte AMP-activated protein kinase (AMPK) activities decreased, while plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), and glutathione peroxidase (GPx) remained unchanged as horses aged. Although riding horses that partake in continuous exercise seems to be less likely to develop inflammaging, horses over 17 years of age tend to show proinflammatory signs with disordered lipid metabolism. In riding horses, SAA, in combination with other markers, may be a useful biomarker for inflammaging and dysregulated lipid metabolism in aging horses. [ABSTRACT FROM AUTHOR]

Objective: Our previous study revealed that serum amyloid A (SAA) levels in polyp tissues could serve as a biomarker for the prediction of corticosteroid insensitivity in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). However, their association with disease control status in the patients after endoscopic sinus surgery remains to be assessed. Methods: Polyp tissues and control uncinate process mucosa were collected from 48 patients with CRSwNP and 10 healthy control subjects. SAA expression was examined using immunohistochemistry and enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) curves were performed to determine the predictive value of SAA in nasal polyps. The clinical characteristics of 2 CRSwNP subtypes (SAAhigh and SAAlow) were evaluated. Results: The SAA expression levels in polyp tissues were significantly elevated both in non-eosinophilic and eosinophilic CRSwNP as compared to the healthy controls. In patients with CRSwNP, the tissue SAA level was significantly higher in the disease-controlled patients than those of the partly controlled and uncontrolled. ROC curve analysis revealed that a cut-off value of 114.9 ng/mL for the tissue SAA level predicted the patients with disease-controlled status with 93.33% sensitivity and 63.64% specificity (AUC =.8727, P <.001). Furthermore, The SAAhigh subgroup showed higher tissue eosinophil numbers and percentage of the disease-controlled patients compared to the SAAlow subgroup. Conclusions: Our findings suggest that measurements of SAA in polyp tissues may provide useful information for evaluating CRSwNP conditions, especially identifying the CRSwNP patients with disease-controlled status after endoscopic sinus surgery. [ABSTRACT FROM AUTHOR]

Senescent cells have a profound impact on the surrounding microenvironment through the secretion of numerous bioactive molecules and inflammatory factors. The induction of therapy-induced senescence by anticancer drugs is known, but how senescent tumor cells influence the tumor immune landscape, particularly neutrophil activity, is still unclear. In this study, we investigate the induction of cellular senescence in breast cancer cells and the subsequent immunomodulatory effects on neutrophils using the CDK4/6 inhibitor palbociclib, which is approved for the treatment of breast cancer and is under intense investigation for additional malignancies. Our research demonstrates that palbociclib induces a reversible form of senescence endowed with an inflammatory secretome capable of recruiting and activating neutrophils, in part through the action of interleukin-8 and acute-phase serum amyloid A1. The activation of neutrophils is accompanied by the release of neutrophil extracellular trap and the phagocytic removal of senescent tumor cells. These findings may be relevant for the success of cancer therapy as neutrophils, and neutrophil-driven inflammation can differently affect tumor progression. Our results reveal that neutrophils, as already demonstrated for macrophages and natural killer cells, can be recruited and engaged by senescent tumor cells to participate in their clearance. Understanding the interplay between senescent cells and neutrophils may lead to innovative strategies to cope with chronic or tumor-associated inflammation. [ABSTRACT FROM AUTHOR]

Background: The chicken's inflammatory response is an essential part of the bird's response to infection. A single dose of Escherichia coli (E. coli) lipopolysaccharide (LPS) endotoxin can activate the acute phase response (APR) and lead to the production of acute phase proteins (APPs). In this study, the responses of established chicken APPs, Serum amyloid A (SAA) and Alpha-1-acid-glycoprotein (AGP), were compared to two novel APPs, Hemopexin (Hpx) and Extracellular fatty acid binding protein (Ex-FABP), in 15-day old broilers over a time course of 48 h post E.coli LPS challenge. We aimed to investigate and validate their role as biomarkers of an APR. Novel plant extracts, Citrus (CTS) and cucumber (CMB), were used as dietary supplements to investigate their ability to reduce the inflammatory response initiated by the endotoxin. Results: A significant increase of established (SAA, AGP) and novel (Ex-FABP, Hpx) APPs was detected post E.coli LPS challenge. Extracellular fatty acid binding protein (Ex-FABP) showed a similar early response to SAA post LPS challenge by increasing ~ 20-fold at 12 h post challenge (P < 0.001). Hemopexin (Hpx) showed a later response by increasing ∼5-fold at 24 h post challenge (P < 0.001) with a similar trend to AGP. No differences in APP responses were identified between diets (CTS and CMB) using any of the established or novel biomarkers. Conclusions: Hpx and Ex-FABP were confirmed as potential biomarkers of APR in broilers when using an E. coli LPS model along with SAA and AGP. However, no clear advantage for using either of dietary supplements to modulate the APR was identified at the dosage used. [ABSTRACT FROM AUTHOR]

In this study, the changes in concentrations of serum amyloid A (SAA) induced by orchidectomy, Burdizzo castration, and in-situ spermatic cord ligation in Red Sokoto bucks were evaluated. Sixteen (16) Red Sokoto bucks, 6 months to one year old and weighing between 11kg and 12 kg, were randomly divided into 4 groups (A-D), each comprising 4 bucks. Bucks in group A were castrated using the Burdizzo method, B in-situ spermatic cord ligation, and C orchidectomy while group D served as control. Blood was collected from each buck, serum was harvested and analyzed for SAA at 0, 4, 8, 12, 15, 20, 24, 36, 48 and 72 hours post-castration. Results revealed significant increase (p=0.028) in the levels of SAA in all castrated goats from 4 hours post-castration, reaching peak concentration at 20 hours post-castration with the highest recorded in goats castrated by orchidectomy (63.34 ± 1.49 pg/mL; 120.44 ± 3.74 pg/mL), followed by in-situ spermatic cord ligation (25.08 ± 2.19 pg/mL; 109.77 ± 2.97 pg/mL) and then Burdizzo (61.36 ± 2.63 pg/mL; 87.29 ± 3.92 pg/mL). This was followed by a significant (p=0.041) decrease by 24 hours post-castration and non-significant (p=0.101) fluctuations up to 72 hours post-castration in all castrated bucks. In conclusion, all the castration methods induced changes in serum concentration of SAA, which was less marked in Burdizzo and in-situ spermatic cord ligation compared to orchidectomy. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate diagnostic accuracy of point-of-care Serum Amyloid A (POC-SAA) and its comparison with procalcitonin for diagnosis of neonatal sepsis. Methods: The present diagnostic accuracy study consecutively recruited neonates with suspected sepsis. Blood samples for sepsis screen, culture, high sensitivity C-reactive protein (CRP) (hs-CRP, as a part of sepsis screen), procalcitonin and POC-SAA were collected before starting antibiotics. The optimum cut-off level of biomarkers (POC-SAA and procalcitonin) was determined by receiver-operating-characteristics curve (ROC) analysis. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of POC-SAA and procalcitonin were derived for 'clinical sepsis (neonates with suspected sepsis and either positive sepsis screen and/or blood culture)' and 'culture positive sepsis' (neonates with suspected sepsis and positive blood culture). Results: Seventy-four neonates with mean±SD gestational age of 32.8±3.7 wk were evaluated for suspected sepsis, of which the proportion of 'clinical sepsis' and 'culture positive sepsis' was 37.8% had 16.2%, respectively. At a cut-off of 25.4 mg/L, POC-SAA had sensitivity, specificity, PPV and NPV of 53.6%, 80.4%, 62.5% and 74.0%, respectively for diagnosis of clinical sepsis. The sensitivity, specificity, PPV and NPV of POC-SAA for detection of culture positive sepsis were 83.3%, 61.3%, 29.4% and 95.0%, respectively at a cut-off of 10.3 mg/L. There was no significant difference in the diagnostic accuracy of biomarkers for detection of culture positive sepsis (area under the curve, AUC of POC-SAA vs. procalcitonin vs. hs-CRP: 0.72 vs. 0.85 vs. 0.85; p = 0.21). Conclusions: POC-SAA is comparable to procalcitonin and hs-CRP for diagnosis of neonatal sepsis. [ABSTRACT FROM AUTHOR]

Simple Summary: Pregnancy-associated glycoproteins (PAG) secreted from fetoplacental binucleate cells are used in clinical practice for the early detection of bovine pregnancy. This study examined the postpartum PAG concentration to monitor binucleated cell clearance during postpartum uterine repair. PAG concentration was correlated with inflammatory parameters (serum amyloid A and milk amyloid A), postpartum inflammatory conditions (mastitis, ketosis, and follicular cysts), and FOXP3 gene-related repeat breeders. Excessive inflammation occurring during the postpartum period may reduce PAG concentration gradually. Clarifying the mechanism of decreased PAG concentration during the postpartum period has a beneficial effect on improving reproductive efficiency, performance, and reproduction aspects. We evaluated the relationship between decreased pregnancy-associated glycoprotein (PAG) levels, inflammatory parameters (serum amyloid A [SAA] and milk amyloid A [MAA]), postpartum inflammatory conditions (mastitis, ketosis, and follicular cysts), and the FOXP3 gene. Nineteen Holstein-Friesian cows were included in this study. Up to approximately eight weeks after delivery, weekly health examinations were performed for mastitis and ketosis, and reproductive organ ultrasonography was performed. The decreasing PAG rate was negatively correlated with SAA concentration (r = −0.493, p = 0.032). Cows with mastitis exhibited a slower trend of PAG decrease (p = 0.095), and a greater percentage of these cows had MAA concentrations above 12 µg/mL (p = 0.074) compared with those without mastitis. A negative correlation, although nonsignificant (r = −0.263, p = 0.385), was observed between the day-open period and decreased PAG rate. The day-open period was correlated with the presence or absence of follicular cysts (p = 0.046). Four cows that developed follicular cysts were homozygous for the G allele of the FOXP3 gene related to repeat breeders. These results indicate a relationship between a decreased PAG rate and inflammatory status during the postpartum period. Thus, suppressing inflammation during the perinatal period may improve reproductive efficiency in the dairy industry. [ABSTRACT FROM AUTHOR]

Serum amyloid A (SAA) is a highly conserved acute‐phase protein that plays roles in activating multiple pro‐inflammatory pathways during the acute inflammatory response and is commonly used as a biomarker of inflammation. It has been linked to beneficial roles in tissue repair through improved clearance of lipids and cholesterol from sites of damage. In patients with chronic inflammatory diseases, elevated levels of SAA may contribute to increased severity of the underlying condition. The majority of circulating SAA is bound to lipoproteins, primarily high‐density lipoprotein (HDL). Interaction with HDL not only stabilizes SAA but also alters its functional properties, likely through altered accessibility of protein–protein interaction sites on SAA. While high‐resolution structures for lipid‐free, or apo‐, forms of SAA have been reported, their relationship with the HDL‐bound form of the protein, and with other possible mechanisms of SAA binding to lipids, has not been established. Here, we have used multiple biophysical techniques, including SAXS, TEM, SEC‐MALS, native gel electrophoresis, glutaraldehyde crosslinking, and trypsin digestion to characterize the lipid‐free and lipid‐bound forms of SAA. The SAXS and TEM data show the presence of soluble octamers of SAA with structural similarity to the ring‐like structures reported for lipid‐free ApoA‐I. These SAA octamers represent a previously uncharacterized structure for lipid‐free SAA and are capable of scaffolding lipid nanodiscs with similar morphology to those formed by ApoA‐I. The SAA–lipid nanodiscs contain four SAA molecules and have similar exterior dimensions as the lipid‐free SAA octamer, suggesting that relatively few conformational rearrangements may be required to allow SAA interactions with lipid‐containing particles such as HDL. This study suggests a new model for SAA–lipid interactions and provides new insight into how SAA might stabilize protein‐lipid nanodiscs or even replace ApoA‐I as a scaffold for HDL particles during inflammation. [ABSTRACT FROM AUTHOR]

Bovine ephemeral fever is an arthropod-borne viral disease that primarily affects cattle and causes economic losses mainly due to the sudden decrease in milk yield. We aimed to reveal the biochemical reflection of the acute phase response by detecting the changes in serum acute phase proteins in cattle naturally infected with the bovine ephemeral fever virus. The material of this study consisted of 21 Simmental dairy cows (4-6 years old) naturally infected with bovine ephemeral fever virus (infected group) and 10 clinically and serologically healthy Simmental dairy cows (control group). The prevalence of the disease in suspected cattle was 52 per 100. It was determined that in infected cows levels of serum haptoglobin, serum amyloid A (P = 0.001), and ceruloplasmin increased significantly (P = 0.05), whereas levels of albumin decreased significantly (P = 0.05). It is thought that the acute phase proteins variation pattern for bovine ephemeral fever would be beneficial both in better understanding the pathogenesis of the disease and in determining the diagnosis and prognosis correctly. [ABSTRACT FROM AUTHOR]

Abstract Background Anemia is a common complication of total hip arthroplasty (THA). In this study, we evaluated the preoperative risk factors for postoperative anemia after THA and developed a nomogram model based on related preoperative and intraoperative factors. Methods From January 2020 to May 2023, 927 THA patients at the same medical center were randomly assigned to either the training or validation cohort. The correlation between preoperative and intraoperative risk factors and postoperative anemia after THA was evaluated using univariate and multivariate logistic regression analysis. A nomogram was developed using these predictive variables. The effectiveness and validation for the clinical application of this nomogram were evaluated using the concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Results Through univariate and multivariate logistic regression analysis, 7 independent predictive factors were identified in the training cohort: Lower body mass index (BMI), extended operation time, greater intraoperative bleeding, lower preoperative hemoglobin level, abnormally high preoperative serum amyloid A (SAA) level, history of cerebrovascular disease, and history of osteoporosis. The C-index of the model was 0.871, while the AUC indices for the training and validation cohorts were 84.4% and 87.1%, respectively. In addition, the calibration curves of both cohorts showed excellent consistency between the observed and predicted probabilities. The DCA curves of the training and validation cohorts were high, indicating the high clinical applicability of the model. Conclusions Lower BMI, extended operation time, increased intraoperative bleeding, reduced preoperative hemoglobin level, elevated preoperative SAA level, history of cerebrovascular disease, and history of osteoporosis were seven independent preoperative risk factors associated with postoperative anemia after THA. The nomogram developed could aid in predicting postoperative anemia, facilitating advanced preparation, and enhancing blood management. Furthermore, the nomogram could assist clinicians in identifying patients most at risk for postoperative anemia.

Abstract Aims/Introduction Serum amyloid A (SAA) is an acute phase reactive protein that plays a vital role in the early diagnosis, risk prediction, efficacy observation and prognosis evaluation of infectious diseases. This study aimed to assess the association between SAA levels and the prognosis of patients with coronavirus disease 2019 (COVID‐19) and diabetes. Materials and Methods We carried out this retrospective cohort study from March 2022 to May 2022. The population was stratified by tertiles of SAA levels: low (36 mg/L). The primary outcome was whether the patient developed severe COVID‐19, and secondary outcomes included the need for invasive mechanical ventilation and length of hospital stay. Logistic regression analyses were carried out to identify risk factors affecting the prognosis of patients with COVID‐19 and diabetes. Results We analyzed 910 diabetes patients with COVID‐19. The median age of the patients was 69 years, and 52.3% were men. As SAA levels increased, the proportion of severe COVID‐19 (6.3% vs 7.3% vs 22.8%, P 36 mg/L further increased the odds ratio to 4.423 (P 36 mg/L remained an independent risk factor for the development of severe COVID‐19 (adjusted odds ratio 3.038, P

Serum amyloid A (SAA) is a clinically useful inflammatory marker involved in the pathogenesis of autoimmune diseases. This study aimed to explore the SAA levels in a cohort of patients with myasthenia gravis (MG) in relation to disease‐related clinical parameters and myasthenic crisis (MC) and elucidate the effects of SAA on immune response. A total of 82 MG patients including 50 new‐onset MG patients and 32 MC patients were enrolled in this study. Baseline data and laboratory parameters of all enrolled MG patients were routinely recorded through electronic medical systems. SAA levels were measured by enzyme‐linked immunosorbent assay (ELISA) kit. CD4+ T and CD19+ B cell subsets were analyzed by flow cytometry. In vitro, human recombinant SAA (Apo‐SAA) was applied to stimulate peripheral blood mononuclear cells (PBMCs) from MG patients to observe the effect on T and B cell differentiation. Our results indicated that SAA levels in new‐onset MG patients were higher than those in controls and were positively correlated with QMG score, MGFA classification, plasmablast cells, IL‐6, and IL‐17 levels. Subgroup analysis revealed that SAA levels were increased in generalized MG (GMG) patients than in ocular MG (OMG), as well as elevated in late‐onset MG (LOMG) than in early‐onset MG (EOMG) and higher in MGFA III/IV compared with MGFA I/II. The ROC curve demonstrated that SAA showed good diagnostic value for MC, especially when combined with NLR. In vitro, Apo‐SAA promoted the Th1 cells, Th17 cells, plasmablast cells, and plasma cells differentiation in MG PBMCs. The present findings suggested that SAA was increased in MG patients and promoted expansion of CD4+ T cell and CD19+ B cell subsets, which implicated in the severity of MG patients. [ABSTRACT FROM AUTHOR]

The prevailing hypotheses for the persistent symptoms of Long COVID have been narrowed down to immune dysregulation and autoantibodies, widespread organ damage, viral persistence, and fibrinaloid microclots (entrapping numerous inflammatory molecules) together with platelet hyperactivation. Here we demonstrate significantly increased concentrations of von Willebrand factor (VWF), platelet factor 4 (PF4), serum amyloid A (SAA), α-2 antiplasmin (α-2AP), endothelial-leukocyte adhesion molecule 1 (E-selectin), and platelet endothelial cell adhesion molecule (PECAM-1) in the soluble part of the blood. It was noteworthy that the mean level of α-2 antiplasmin exceeded the upper limit of the laboratory reference range in Long COVID patients, and the other 5 were significantly elevated in Long COVID patients as compared to the controls. This is alarming if we take into consideration that a significant amount of the total burden of these inflammatory molecules has previously been shown to be entrapped inside fibrinolysis-resistant microclots (thus decreasing the apparent level of the soluble molecules). We conclude that presence of microclotting, together with relatively high levels of six biomarkers known to be key drivers of endothelial and clotting pathology, points to thrombotic endothelialitis as a key pathological process in Long COVID. [ABSTRACT FROM AUTHOR]

The effect of persistent skin inflammation on extracutaneous organs and blood is not well studied. Patients with recessive dystrophic epidermolysis bullosa (RDEB), a severe form of the inherited blistering skin disorder, have widespread and persistent skin ulcers, and they develop various complications including anaemia, hyperglobulinaemia, hypoalbuminaemia and secondary amyloidosis. These complications are associated with the bioactivities of IL‐6, and the development of secondary amyloidosis requires the persistent elevation of serum amyloid A (SAA) level. We found that patients with RDEB had significantly higher serum levels of IL‐6 and SAA compared to healthy volunteers and patients with psoriasis or atopic dermatitis. Both IL‐6 and SAA were highly expressed in epidermal keratinocytes and dermal fibroblasts of the skin ulcer lesions. Keratinocytes and fibroblasts surrounding the ulcer lesions are continuously exposed to Toll‐like receptor (TLR) ligands, pathogen‐associated and damage‐associated molecular pattern molecules. In vitro, TLR ligands induced IL‐6 expression via NF‐κB in normal human epidermal keratinocytes (NHEKs) and dermal fibroblasts (NHDFs). SAA further induced the expression of IL‐6 via TLR1/2 and NF‐κB in NHEKs and NHDFs. The limitation of this study is that NHEKs and NHDFs were not derived from RDEB patients. These observations suggest that TLR‐mediated persistent skin inflammation might increase the risk of IL‐6‐related systemic complications, including RDEB. [ABSTRACT FROM AUTHOR]

Objective: This study investigated whether serum amyloid A (AA) levels can be used as a biomarker in patients with threatened abortion. Material and Methods: This prospective cohort study was conducted at the Antalya Training and Research Hospital, Department of Obstetrics and Gynecology, Türkiye, between April and October 2023. Eighty‐eight pregnant women, 44 diagnosed with threatened miscarriage (Group 1) and 44 healthy individuals (Group 2), were included in the study. Sociodemographic, obstetric, and laboratory parameters were compared between the groups. Results: No statistically significant differences were observed between the groups in terms of sociodemographic data (age, body mass index, education level, economic status, occupation status, smoking, and alcohol consumption). However, obstetric characteristics (number of pregnancies, living children, miscarriages, dilatation and curettage, gestational age on admission, and fetal crown‐rump length) and laboratory values including complete blood count, hematocrit, leukocyte, neutrophil, lymphocytes, platelet, hs‐C‐reactive protein, neutrophil‐lymphocyte and platelet‐lymphocyte ratio (p >.05), and serum AA values (7.49 ± 3.07 in Group 1 vs. 9.46 ± 4.80 in Group 2, p =.024) differed significantly. Receiver operating characteristic analysis showed that the area under the curve (AUC: 0.662) was statistically significant for serum AA (p =.032), with a cut‐off value of ≥7.51 (95% [confidence interval] 0.516−0.749, sensitivity 65%, specificity 51%). The positive predictive value of serum AA for threatened miscarriage was 56.8%, and the negative predictive value 59.4%. Conclusion: This study shows that serum AA can be used as a biomarker in the diagnosis of threatened miscarriage. Prospective studies involving more participants are now needed to confirm our results. [ABSTRACT FROM AUTHOR]

Background: Anemia is a common complication of total hip arthroplasty (THA). In this study, we evaluated the preoperative risk factors for postoperative anemia after THA and developed a nomogram model based on related preoperative and intraoperative factors. Methods: From January 2020 to May 2023, 927 THA patients at the same medical center were randomly assigned to either the training or validation cohort. The correlation between preoperative and intraoperative risk factors and postoperative anemia after THA was evaluated using univariate and multivariate logistic regression analysis. A nomogram was developed using these predictive variables. The effectiveness and validation for the clinical application of this nomogram were evaluated using the concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Results: Through univariate and multivariate logistic regression analysis, 7 independent predictive factors were identified in the training cohort: Lower body mass index (BMI), extended operation time, greater intraoperative bleeding, lower preoperative hemoglobin level, abnormally high preoperative serum amyloid A (SAA) level, history of cerebrovascular disease, and history of osteoporosis. The C-index of the model was 0.871, while the AUC indices for the training and validation cohorts were 84.4% and 87.1%, respectively. In addition, the calibration curves of both cohorts showed excellent consistency between the observed and predicted probabilities. The DCA curves of the training and validation cohorts were high, indicating the high clinical applicability of the model. Conclusions: Lower BMI, extended operation time, increased intraoperative bleeding, reduced preoperative hemoglobin level, elevated preoperative SAA level, history of cerebrovascular disease, and history of osteoporosis were seven independent preoperative risk factors associated with postoperative anemia after THA. The nomogram developed could aid in predicting postoperative anemia, facilitating advanced preparation, and enhancing blood management. Furthermore, the nomogram could assist clinicians in identifying patients most at risk for postoperative anemia. [ABSTRACT FROM AUTHOR]

The acute phase protein Serum Amyloid A (SAA) is synthesised by the liver in response to inflammatory stimuli. Previous studies have revealed that SAA may be a better biomarker of disease activity in inflammatory bowel disease (IBD) compared to C-reactive protein (CRP). This retrospective monocentric study evaluated whether SAA correlates with biomarkers like faecal calprotectin (FC), CRP, the Neutrophil to Lymphocyte ratio (NLR), the platelet count and clinical disease activity of IBD patients. Serum samples from the IBD outpatient clinic of the University Hospital Heidelberg were analysed for SAA concentrations if an FC concentration measurement was available from ±14 days to collection of the serum sample. Three hundred and six serum samples from 265 patients (166 with Crohn's disease, 91 with ulcerative colitis and 8 with IBD unclassified) met the inclusion criteria. There was a significant positive correlation between SAA and FC, CRP, NLR, platelet count and the Simple Clinical Colitis Activity Index (SCCAI). The cut-off for SAA serum concentration at 4.55 mg/L achieved a sensitivity of 57.5% and a specificity of 69.7% for the detection of active inflammation in IBD. SAA may be used as an additional biomarker in the disease monitoring strategy of IBD patients, especially in patients with low CRP concentrations. [ABSTRACT FROM AUTHOR]

Amyloid deposition within stenotic aortic valves (AVs) also appears frequent in the absence of cardiac amyloidosis, but its clinical and pathophysiological relevance has not been investigated. We will elucidate the rate of isolated AV amyloid deposition and its potential clinical and pathophysiological significance in aortic stenosis (AS). In 130 patients without systemic and/or cardiac amyloidosis, we collected the explanted AVs during cardiac surgery: 57 patients with calcific AS and 73 patients with AV insufficiency (41 with AV sclerosis and 32 without, who were used as controls). Amyloid deposition was found in 21 AS valves (37%), 4 sclerotic AVs (10%), and none of the controls. Patients with and without isolated AV amyloid deposition had similar clinical and echocardiographic characteristics and survival rates. Isolated AV amyloid deposition was associated with higher degrees of AV fibrosis (p = 0.0082) and calcification (p < 0.0001). Immunohistochemistry analysis suggested serum amyloid A1 (SAA1), in addition to transthyretin (TTR), as the protein possibly involved in AV amyloid deposition. Circulating SAA1 levels were within the normal range in all groups, and no difference was observed in AS patients with and without AV amyloid deposition. In vitro, AV interstitial cells (VICs) were stimulated with interleukin (IL)-1β which induced increased SAA1-mRNA both in the control VICs (+6.4 ± 0.5, p = 0.02) and the AS VICs (+7.6 ± 0.5, p = 0.008). In conclusion, isolated AV amyloid deposition is frequent in the context of AS, but it does not appear to have potential clinical relevance. Conversely, amyloid deposition within AV leaflets, probably promoted by local inflammation, could play a role in AS pathophysiology. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to compare the clinical and laboratory characteristics of early-onset familial Mediterranean fever patients (EOFPs), adult-onset familial Mediterranean fever (FMF) patients (AOFPs), and late-onset FMF patients (LOFPs). Materials and Methods: This study included a total of 202 FMF patients aged 18 years and above. Mediterranean fever (MEFV) gene mutations, demographic data, clinical characteristics, medications patients are on, neutrophil to absolute lymphocyte ratio (NLR), and C-reactive protein (CRP) levels obtained during an attack period, and three weeks after the attack were recorded. Based on the age of symptom onset, patients were divided into three groups: <20 years (EOFPs), 20--39 years (AOFPs), and ≥40 years (LOFPs). Results: The most common symptom was abdominal pain, followed by fever. Fever was statistically significantly more common in EOFPs compared to LOFPs (p=0.001). Most patients with the M694V homozygous mutation had a disease onset below 20 years of age, whereas no compound heterozygous mutation was found in LOFPs. The body mass index (BMI) in EOFPs was lower than in AOFPs and LOFPs (p=0.002). In the attack-free group, patients with the M694V homozygous mutation had significantly higher NLRs (median, 2.36 vs. 2.01, p=0.042). Conclusion: LOFPs had a milder form of the disease with less frequent abdominal pain and fever. We would like to advise clinicians that the NLR can be used to detect acute and subacute inflammation, especially in patients with the M694V homozygous mutation among EOFPs [ABSTRACT FROM AUTHOR]

Aims/Introduction: Serum amyloid A (SAA) is an acute phase reactive protein that plays a vital role in the early diagnosis, risk prediction, efficacy observation and prognosis evaluation of infectious diseases. This study aimed to assess the association between SAA levels and the prognosis of patients with coronavirus disease 2019 (COVID‐19) and diabetes. Materials and Methods: We carried out this retrospective cohort study from March 2022 to May 2022. The population was stratified by tertiles of SAA levels: low (<8.5 mg/L), medium (8.5–36 mg/L) and high (>36 mg/L). The primary outcome was whether the patient developed severe COVID‐19, and secondary outcomes included the need for invasive mechanical ventilation and length of hospital stay. Logistic regression analyses were carried out to identify risk factors affecting the prognosis of patients with COVID‐19 and diabetes. Results: We analyzed 910 diabetes patients with COVID‐19. The median age of the patients was 69 years, and 52.3% were men. As SAA levels increased, the proportion of severe COVID‐19 (6.3% vs 7.3% vs 22.8%, P < 0.001) and the proportion of invasive mechanical ventilation also increased among the three groups. Patients with high SAA levels had a longer length of hospital stay compared with patients with medium SAA and low SAA levels. Univariate logistic regression analysis showed that SAA >36 mg/L further increased the odds ratio to 4.423 (P < 0.001) for the development of severe COVID‐19 compared with low SAA. Multivariate logistic regression analysis, adjusted for age and sex, confirmed that SAA >36 mg/L remained an independent risk factor for the development of severe COVID‐19 (adjusted odds ratio 3.038, P < 0.001). Conclusions: SAA levels are strongly associated with poor prognosis in patients with COVID‐19 and diabetes. [ABSTRACT FROM AUTHOR]

Serum amyloid A (SAA) are major acute‐phase response proteins which actively participate in many inflammatory diseases. This study was designed to explore the function of SAA in acute ocular inflammation and the underlying mechanism. We found that SAA3 was upregulated in endotoxin‐induced uveitis (EIU) mouse model, and it was primarily expressed in microglia. Recombinant SAA protein augmented intraocular inflammation in EIU, while the inhibition of Saa3 by siRNA effectively alleviated the inflammatory responses and rescued the retina from EIU‐induced structural and functional damage. Further study showed that the recombinant SAA protein activated microglia, causing characteristic morphological changes and driving them further to pro‐inflammatory status. The downregulation of Saa3 halted the amoeboid change of microglia, reduced the secretion of pro‐inflammatory factors, and increased the expression of tissue‐reparative genes. SAA3 also regulated the autophagic activity of microglial cells. Finally, we showed that the above effect of SAA on microglial cells was at least partially mediated through the expression and signaling of Toll‐like receptor 4 (TLR4). Collectively, our study suggested that microglial cell‐expressed SAA could be a potential target in treating acute ocular inflammation. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study aimed to investigate the expression of acute phase proteins and plasma cytokines in cats with various tumor types and varying metastatic statuses. ANIMALS: 5 clinically healthy cats and 22 cats with neoplastic disease that underwent CT imaging before treatment were enrolled. Patients were grouped based on their tumor types and metastatic status. METHODS: Blood samples were collected from all cats for general blood analyses before they underwent CT imaging. The remaining plasma sample was frozen for subsequent alpha 1-acid glycoprotein (AGP), serum amyloid A (SAA), and feline cytokine panel measurements. These results were compared with those of healthy cats as well as between metastatic status and tumor types. RESULTS: Only 4 cats (18%) exhibited elevated SAA levels, whereas 16 (73%) showed elevated AGP levels. AGP was significantly increased in cats with tumors (P = .016), while SAA was not. Only IL-8 showed a significant difference (P = .002) between cats with primary tumors and those with radiologically suspected tumor metastasis. CLINICAL RELEVANCE: While AGP is a more prominent biomarker than SAA in cats with tumors, a significant elevation of AGP and SAA levels in association with metastasis and specific tumor types could not be identified. Alternatively, further investigation is warranted to evaluate the potential significance of IL-8 in tumor progression and metastasis. [ABSTRACT FROM AUTHOR]

Objective: In this study were investigated serum paraoxonase, haptoglobin, tumor necrosis factor-α, acetylcholinesterase, serum amyloid A, nonesterifie fatty acids, glucose, beta hydroxybutyric acid, total protein, aspartat aminotransferase, gama glutamil transferase, cholesterol and triglyceride in ewes with pregnancy toxemia. Materials and Methods: This study material consisted 10 control and 10 group with pregnancy toxemia, total 20 merino hybrid ewes at aged between 2-6 years. Results: The analysis of blood serum samples revealed that serum amyloid A (SAA), haptoglobin (HPT), tumor necrosis factor-α (TNF), paraoxonase (PON1), acetylcholinesterase (ACHE), aspartat aminotransferase (AST), gama glutamil transferase (GGT) and cholesterol did not differ statistically significant between two groups although SAA, HPT, TNF, PON1, ACHE, AST, GGT levels were higher in ewes with pregnancy toxemia when compared to healthy ewes. Beta hydroxybutyric acid (BHBA) and nonesterifie fatty acids (NEFA) (p<0.001), triglyceride and total protein (p<0.01) increased that glucose (p<0.001) levels decreased in sheep with pregnancy toxemia compared with healthy ewes. Conclusion: Acetylcholinesterase, paraoxonase, haptoglobin, tumor necrosis factor-α, serum amyloid A concentration researched may prove beneficial laboratory findings disease in sheep with pregnancy toxemia. [ABSTRACT FROM AUTHOR]

IntroductionThe glutaraldehyde test (GAT) allows for animal-side semi-quantitative estimation of fibrinogen and gamma-globulin concentrations in blood samples of adult cattle and therefore detection of inflammatory disease conditions. However, the test has potential limitations, especially due to the latency period until sufficiently high fibrinogen and/or gamma-globulin concentrations are reached. The aim of the present study was therefore to assess the association between results of GAT with other inflammatory markers including hematologic variables, fibrinogen, plasma haptoglobin and serum amyloid A (SAA) concentrations.MethodsFor the purpose of this prospective observational study, a convenience sample of 202 cows with a broad range of inflammatory and non-inflammatory clinical conditions was included. The GAT was run on EDTA blood, fibrinogen was measured using the Clauss and the heat precipitation method, and commercially available ELISA tests were used for determination of plasma haptoglobin and SAA concentrations.ResultsShortened GAT coagulation times were more closely correlated to serum globulin (rs = −0.72) than to plasma fibrinogen concentrations measured with the heat precipitation (rs = −0.64) and the Clauss method (rs = −0.70). Cows with a markedly (≤3 min) or moderately (4–6 min) shortened coagulation time had higher (p

Running Title: DDL inhibits the LPS-induced SAA3 gene expression in microglia Objective: Research on the mechanism of Dehydrocostus lactone (DDL) in microglial cells of the brain needs to be improved, despite its reported anti-inflammatory, anticancer, and anti-proliferation properties as a natural product of Eerdun Wurile The precise functions of the Serum amyloid A (SAA) genes are not yet defined. However, these genes are suggested to possess antibacterial properties and can attract monocytes and neutrophils. On the other hand, SAA genes can also induce inflammatory cytokines and metalloproteinases in smooth muscle cells and macrophages, thus promoting inflammation. This study aimed to investigate the impact of DDL on SAA3 gene expression in microglial cells stimulated by LPS. Methods: The anti-inflammatory effects of DDL were studied using LPS-stimulated murine BV2 microglia. BV2 was cultured in DMEM, and then 4µM DDL was added. Then BV2 was treated with one ng/ml LPS for 24 hours to stimulate. Results: LPS treatment increased the expression of SAA3 mRNA in BV2 microglial cells, while DDL pre-treatment inhibited LPS-induced SAA3 mRNA expression. Conclusion: Microglia cells treated with LPS display a significant reduction in the expression of SAA3 gene transcripts upon treatment with DDL.

Background and Aim: Our previous research suggested that heat-killed Lactobacillus sakei HS-1 (HK-LS HS-1) is potentially beneficial for improving intestinal microbes and reducing the number of medical treatments. This study aimed to investigate the effect of HK-LS HS-1 as a supplement in milk replacers (MRs) on clinical health during the 1-month preweaning period. Materials and Methods: Eighteen female calves were randomly assigned to either a group receiving the HK-LS HS-1 supplement (n = 9) or a control group without it (n = 9). We then investigated the effect of including supplementary HK-LS HS-1; 0.2% in MRs twice daily at 09:00 and 16:00 on the health, serum biochemical parameters (measured using an automated biochemical analyzer), and fecal bacteriological changes of preweaning Japanese Black calves at the day of the start of supplementation (before HK-LS HS-1 supplementation; day 0), at weaning (day 30), and at 2 weeks (day 45) and 4 weeks (day 60) after weaning. Results: During the supplementation period (0–30 days), (1) an increase (p = 0.023) was observed in albumin, and there was a tendency of increase in total cholesterol level in the HK-LS HS-1 group but not in the control group; (2) substantial differences were obtained after the weaning period (30–60 days), although no differences were observed from 0–30 days in both groups. The anti-Müllerian hormone (AMH) level was substantially increased after weaning in the control group. No differences were observed in the amounts of Coliform spp. and Staphylococcaceae spp. between the two groups; thus, HK-LS HS-1 supplementation had similar antibacterial effects. A significant reduction was observed in the time to weaning of the HK-LS HS-1 group in the field trial. Conclusion: Supplementation with HK-LS HS-1 from an early stage after birth to weaning is a cost-effective treatment to improve the growth rate of preweaning calves. However, supplementation during only preweaning periods appears to have no beneficial effects on preventing weaning stress, especially in terms of AMH levels.

Alkaptonuria (AKU) is a rare autosomal recessive metabolic disorder caused by mutations in the homogentisate 1,2-dioxygenase (HGD) gene, leading to the accumulation of homogentisic acid (HGA), causing severe inflammatory conditions. Recently, the presence of serum amyloid A (SAA) has been reported in AKU tissues, classifying AKU as novel secondary amyloidosis; AA amyloidosis is characterized by the extracellular tissue deposition of fibrils composed of fragments of SAA. AA amyloidosis may complicate several chronic inflammatory conditions, like rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, chronic infections, neoplasms, etc. Treatments of AA amyloidosis relieve inflammatory disorders by reducing SAA concentrations; however, no definitive therapy is currently available. SAA regulation is a crucial step to improve AA secondary amyloidosis treatments. Here, applying a comprehensive in vitro and in silico approach, we provided evidence that HGA is a disruptor modulator of SAA, able to enhance its polymerization, fibril formation, and aggregation upon SAA/SAP colocalization. In silico studies deeply dissected the SAA misfolding molecular pathway and SAA/HGA binding, suggesting novel molecular insights about it. Our results could represent an important starting point for identifying novel therapeutic strategies in AKU and AA secondary amyloidosis-related diseases.

This study investigated the longitudinal trajectory of changes in antioxidative and anti-inflammatory high-density lipoprotein (HDL) components during healthy pregnancy and pregnancy with cardiometabolic complications. We recruited and longitudinally followed 84 women with healthy pregnancies and 46 pregnant women who developed cardiometabolic pregnancy complications (gestational diabetes mellitus and hypertensive disorders of pregnancy). Their general lipid profiles, oxidative stress status, inflammatory status, and antioxidative and anti-inflammatory HDL components were analyzed. The results of our study confirmed the expected trajectory for the routine lipid parameters. Our study results indicate more intensive oxidative stress and a higher level of inflammation in the group with complications compared with the control group. Sphingosine-1-phosphate (S1P) was significantly lower in the first trimester in the group with complications compared with the control group (p < 0.05). We did not find significant differences in the apolipoprotein A1 (Apo A1) concentrations in the first trimester between the control group and the group with complications, but in the second and third trimesters, the group with complications had significantly higher concentrations (p < 0.001, p < 0.05, respectively). The S1P, paraoxonase 1 (PON1), and serum amyloid A (SAA) concentrations were significantly lower in the group with complications in the first trimester. During the second trimester, only the SAA concentrations were identified as significantly lower in the group with complications compared with the control group, while in the third trimester, the PON1, apolipoprotein M (Apo M), and SAA concentrations were all significantly lower in the group with complications. Through a multivariate binary logistic regression analysis, the S1P concentration in the first trimester was distinguished as an HDL-associated marker independently associated with cardiometabolic pregnancy complications. In conclusion, our study results showed that HDL remodeling differs between healthy pregnancies and pregnancies with maternal cardiometabolic complications, with changed HDL composition and functionality consequently impacting its biological functionality in the latter case.

Acute-phase serum amyloid A (SAA) can disrupt vascular homeostasis and is elevated in subjects with diabetes, cardiovascular disease, and rheumatoid arthritis. Cyclic nitroxides (e.g., Tempo) are a class of piperidines that inhibit oxidative stress and inflammation. This study examined whether 4-methoxy-Tempo (4-MetT) inhibits SAA-mediated vascular and renal dysfunction. Acetylcholine-mediated vascular relaxation and aortic guanosine-3′,5′-cyclic monophosphate (cGMP) levels both diminished in the presence of SAA. 4-MetT dose-dependently restored vascular function with corresponding increases in cGMP. Next, male ApoE-deficient mice were administered a vehicle (control, 100 µL PBS) or recombinant SAA (100 µL, 120 µg/mL) ± 4-MetT (at 15 mg/kg body weight via i.p. injection) with the nitroxide administered before (prophylaxis) or after (therapeutic) SAA. Kidney and hearts were harvested at 4 or 16 weeks post SAA administration. Renal inflammation increased 4 weeks after SAA treatment, as judged by the upregulation of IFN-γ and concomitant increases in iNOS, p38MAPK, and matrix metalloproteinase (MMP) activities and increased renal fibrosis (Picrosirius red staining) in the same kidneys. Aortic root lesions assessed at 16 weeks revealed that SAA enhanced lesion size (vs. control; p < 0.05), with plaque presenting with a diffuse fibrous cap (compared to the corresponding aortic root from control and 4-MetT groups). The extent of renal dysfunction and aortic lesion size was largely unchanged in 4-MetT-supplemented mice, although renal fibrosis diminished at 16 weeks, and aortic lesions presented with redistributed collagen networks. These outcomes indicate that SAA stimulates renal dysfunction through promoting the IFN-γ–iNOS–p38MAPK axis, manifesting as renal damage and enhanced atherosclerotic lesions, while supplementation with 4-MetT only affected some of these pathological changes.

Backgrounds: The available literature on the correlation between serum amyloid A (SAA) and prognosis of chronic kidney disease (CKD) are limited, and the findings from existing studies are inconclusive. This meta-analysis aimed to evaluate the available evidence regarding the link between SAA and risks of all-cause and cardiovascular mortality in CKD patients. Additionally, we aimed to investigate the potential dose-response relationships, provided that adequate data is accessible. Methods: Pubmed and Embase were searched for related literature (last update: 12 July 2023). The pooled effect estimates were calculated using random- or fixed-effects models depending on heterogeneity among studies. Results: This meta-analysis incorporated 8 studies encompassing 2331 CKD patients. The findings revealed an 85% increase in all-cause mortality risk [hazard risk (HR) 1.85, 95% confidence interval (CI) 1.29-2.65] and a 39% increase in cardiovascular mortality risk (HR 1.07, 95% CI 1.07-1.80) when comparing the highest tertile of baseline SAA levels to the lowest tertile. Furthermore, a positive linear relationship between SAA and all-cause mortality risk was observed (Pnon-linearity = 0.959), with a 17.7% increase in risk for each 10 mg/L SAA increase (HR 1.177, 95% CI 1.055-1.313). Similarly, a linear relationship between SAA and cardiovascular mortality risk was identified (Pnon-linearity = 0.477) with a 19.3% increase in risk for each 10 mg/L SAA increase (HR 1.193, 95% CI 1.025-1.388). Conclusions: This meta-analysis provided evidence that SAA levels are positively and linearly associated with risks of all-cause and cardiovascular mortality among CKD patients. [ABSTRACT FROM AUTHOR]

Serum amyloid A (SAA) is a family of proteins, the plasma levels of which may increase >1000-fold in acute inflammatory states. We investigated the role of SAA in sepsis using mice deficient in all three acute-phase SAA isoforms (SAA-TKO). SAA deficiency significantly increased mortality rates in the three experimental sepsis mouse models: cecal ligation and puncture (CLP), cecal slurry (CS) injection, and lipopolysaccharide (LPS) treatments. SAA-TKO mice had exacerbated lung pathology compared to wild-type (WT) mice after CLP. A bulk RNA sequencing performed on lung tissues excised 24 h after CLP indicated significant enrichment in the expression of genes associated with chemokine production, chemokine and cytokine-mediated signaling, neutrophil chemotaxis, and neutrophil migration in SAA-TKO compared to WT mice. Consistently, myeloperoxidase activity and neutrophil counts were significantly increased in the lungs of septic SAA-TKO mice compared to WT mice. The in vitro treatment of HL-60, neutrophil-like cells, with SAA or SAA bound to a high-density lipoprotein (SAA-HDL), significantly decreased cellular transmigration through laminin-coated membranes compared to untreated cells. Thus, SAA potentially prevents neutrophil transmigration into injured lungs, thus reducing exacerbated tissue injury and mortality. In conclusion, we demonstrate for the first time that endogenous SAA plays a protective role in sepsis, including ameliorating lung injury. [ABSTRACT FROM AUTHOR]

Intravenous immunoglobulin (IVIG) resistance is of prime importance in Kawasaki disease (KD). In this study, we examined the value and mechanism of serum amyloid A (SAA) level in predicting IVIG resistance in patients with KD. SAA levels were measured in 497 consecutive patients with KD before IVIG therapy in the training set. The patients were divided into two groups (IVIG-responsive and IVIG-resistant) according to the American Heart Association (AHA) definition of IVIG resistance. Demographic, echocardiographic, and laboratory data were also retrospectively analyzed and tabulated to predict IVIG resistance. The predictive value of SAA was validated on test sets of prospective data. Cytokine microarrays were analyzed from 4 patients with resistant to IVIG, 4 patients with responsive to IVIG and 4 healthy volunteers. During the training set, 409 patients with KD were enrolled, of whom 43 (10.5%) were resistant to initial IVIG treatment and 47 (11.49%) had coronary artery lesions (CALs). Serum levels of SAA were higher in the IVIG resistant group compared to the IVIG responsive group, (380.00 [204.40–547.25] vs 230.85 [105.40–490.00] mg/L; p =.008). The values of total bilirubin, C-reactive protein, neutrophils, alanine aminotransferase, aspartate aminotransferase, interleukin-6(IL-6), and procalcitonin were significantly higher in the IVIG-resistant group than in the IVIG-responsive group (p <.05); however, the lymphocytes, platelets, serum sodium levels, and duration of fever before IVIG therapy were significantly lower (p <.05). There was no significant difference in SAA levels between patients with KD with and without CALs. Binary logistic regression analysis showed that SAA (p =.008), neutrophils (p <.001), total bilirubin (p =.001), platelet count (p =.004), and serum sodium level (p =.019) were independent factors influencing IVIG resistance. The optimal cutoff value of SAA for IVIG resistance prediction was 252.45 mg/L, with a corresponding clinical sensitivity of 69.8% and specificity of 54.4%. Based on receiver operating characteristic (ROC) curve analyses, the area under the curve (AUC) of combined detection with these five indicators was 0.800, clinical sensitivity was 69.8%, and specificity was 76.2%. In the prospective data, the sensitivity, specificity, and accuracy of SAA for identifying IVIG resistance KD were 77.8%,69.0%, and 70.0%, respectively. Compared with IVIG- responsive group and healthy children, the levels of IL-6 was upregulated significantly in IVIG-resistant group through cytokine microarrays. SAA may be a potential biomarker for predicting IVIG responsiveness to KD, Combined detection of SAA levels, total bilirubin, neutrophil count, platelet count, and serum sodium levels is superior to that of any other single indicator for predicting IVIG resistance in KD. And elevated SAA may accompany with IL-6 in KD patients, its use in clinical practice may be helpful for treatment management. [ABSTRACT FROM AUTHOR]