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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: This meta-analysis provided evidence that SAA levels are positively and linearly associated with risks of all-cause and cardiovascular mortality among CKD patients.

Obesity is a chronic inflammatory condition and this meta-analysis evaluated the impact of bariatric surgery on SAA.
Studies included all types of bariatric surgery where SAA was measured before and after the surgical procedure.
Meta-analysis of 11 clinical studies (n = 394 individuals) confirmed a significant reduction in SAA following bariatric surgery (SMD: - 0.971, 95% CI: - 2.721, 0.779, p < 0.001). Meta-regression did not show any association between the changes in BMI and the absolute difference in SAA levels. No relationship between the changes in SAA and the length of follow-up was found.
Bariatric surgery significantly improved SAA. The decrease in SAA was not related to time after surgery or changes in BMI. Bariatric surgery may thus have an independent effect on SAA.

Background and Objectives: Preterm birth, one of the leading causes of neonatal mortality, occurs in between 5 and 18% of births. Premature birth can be induced by a variety of triggers, including infection or inflammation. Serum amyloid A, a family of apolipoproteins, increases significantly and rapidly at the onset of inflammation. This study aims to systematically review the results of studies in the literature that have examined the correlation between SAA and PTB/PROM. Materials and Methods: To examine the correlation between serum amyloid A levels in women who gave birth prematurely, a systematic analysis was performed according to PRISMA guidelines. Studies were retrieved by searching the electronic databases PubMed and Google Scholar. The primary outcome measure was the standardized mean difference in serum amyloid A level comparing the preterm birth or premature rupture of membranes groups and the term birth group. Results: Based on the inclusion criteria, a total of 5 manuscripts adequately addressed the desired outcome and were thus included in the analysis. All included studies showed a statistically significant difference in serum SAA levels between the preterm birth or preterm rupture of membranes groups and the term birth group. The pooled effect, according to the random effects model, is SMD = 2.70. However, the effect is not significant (p = 0.097). In addition, the analysis reveals an increased heterogeneity with an I2 = 96%. Further, the analysis of the influence on heterogeneity found a study that has a significant influence on heterogeneity. However, even after outline exclusion, heterogeneity remained high I2 = 90.7%. Conclusions: There is an association between increased levels of SAA and preterm birth/PROM, but studies have shown great heterogeneity.

The major acute phase proteins (APPs) in cattle are haptoglobin (Hp) and serum amyloid A (SAA), and in swine, are Hp, SAA, C-reactive protein (CRP), and Pig major acute phase protein (Pig-MAP). Many methodologic assays are presently available to measure these parameters, which are still being improved to increase their specificity, sensitivity, user-friendliness, and economic availability. In cattle, the main applications are the diagnosis and monitoring of frequent diseases such as mastitis and metritis in dairy cows and respiratory problems in young calves. In pigs, APPs are useful in the control of bacterial and viral infections, and they may be used at the slaughterhouse to monitor subclinical pathologies and improve food safety. The utility of APP in animal production must not be forgotten; optimization of protocols to improve performance, welfare, and nutrition may benefit from the use of APPs. Other sample types besides serum or plasma have potential uses; APP determination in milk is a powerful tool in the control of mastitis, saliva is a non-invasive sample type, and meat juice is easily obtained at the slaughterhouse. Increasing our knowledge of reference intervals and the influence of variables such as age, breed, sex, and the season is important. Finally, worldwide harmonization and standardization of analytical procedures will help to expand the use of APPs.

Heme oxygenase-1 (HMOX-1) is an enzyme that regulates heme degradation. Antiinflammatory, antioxidant, and cytoprotective effects of HMOX-1 were also described. It is encoded by the HMOX1 gene, and biallelic mutations cause HMOX-1 deficiency, which is a rare chronic multisystemic inflammatory disorder. This inflammatory status could lead to the development of secondary AA-type amyloidosis theoretically. Here, we report a 30-year-old male with AA-type renal amyloidosis due to a chronic inflammatory condition of unknown origin. Paternal consanguinity and dysmorphic features raised suspicion of a rare genetic disorder. Clinical exome sequencing (CES) confirmed the HMOX-1 deficiency diagnosis related to homozygous missense G139V mutation. To the best of our knowledge, our patient is the eleventh HMOX-1 deficiency case in the literature. Also, HMOX-1 deficiency-related systemic AA-type amyloidosis has not been reported before.

Amyloidogenesis is the inherent ability of proteins to change their conformation from native state to cross β-sheet rich fibrillar structures called amyloids which result in a wide range of diseases like Parkinson\'s disease, Alzheimer\'s disease, Finnish familial amyloidosis, ATTR amyloidosis, British and Danish dementia, etc. COVID-19, on the other hand is seen to have many similarities in symptoms with other amyloidogenic diseases and the overlap of these morbidities and symptoms led to the proposition whether SARS-CoV-2 proteins are undergoing amyloidogenesis and whether it is resulting in or aggravating amyloidogenesis of any human host protein. Thus the SARS-CoV-2 proteins in infected cells, i.e., Spike (S) protein, Nucleocapsid (N) protein, and Envelope (E) protein were tested via different machinery and amyloidogenesis in them were proven. In this review, we will analyze the pathway of amyloid formation in S-protein, N-protein, E-protein along with the effect that SARS-CoV-2 is creating on various host proteins leading to the unexpected onset of many morbidities like COVID-induced Acute Respiratory Distress Syndrome (ARDS), Parkinsonism in young COVID patients, formation of fibrin microthrombi in heart, etc., and their future implications.

Background: Serum amyloid A has been widely reported as a useful biochemical marker in the diagnoses of acute appendicitis. The aim of this study was to appraise the diagnostic accuracy of serum amyloid A in the diagnosis of acute appendicitis. Methods: A systematic search of several databases was conducted. The search time was from the beginning of the databases creation to March 1, 2021, and the languages were restricted to English and Chinese. Clinical studies using serum amyloid A for the diagnosis of acute appendicitis were included. The overall sensitivity and specificity were calculated by using a bivariable mixed effects model. Heterogeneity was tested using I2 statistics. This study has been registered on the International Prospective Register of Systematic Reviews (PROSPERO; no. CRD42021241343). Results: Five studies comprising 668 participants were eligible for inclusion. The overall sensitivity and specificity of serum amyloid A in diagnosing acute appendicitis were 0.87 (95% confidence interval [CI], 0.79-0.92) and 0.74 (95% CI, 0.59-0.85), respectively. The positive and negative likelihood were 3.3 (95% CI, 2.1-5.4) and 0.18 (95% CI, 0.11-0.28), respectively. The area under the summary receiver operating characteristic curves was 0.89 (95% CI, 0.86-0.91). The heterogeneity was significant (I2 = 82%; 95% CI [63%-100%]). Conclusions: Serum amyloid A has good diagnostic accuracy for acute appendicitis. It is expected that serum amyloid A could be helpful in the early clinical diagnosis of acute appendicitis.

OBJECTIVE: An excessive inflammatory response in patients with coronavirus disease 2019 (COVID-19) is associated with high disease severity and mortality. Specific acute phase reactants might be useful for risk stratification. A systematic review and meta-analysis was conducted of studies on serum amyloid A (SAA) in patients with COVID-19.
METHODS: The PubMed, Web of Science, and Scopus databases were searched, covering the period January 2020 to December 2020, for studies reporting SAA concentrations, COVID-19 severity, and survival status.
RESULTS: Nineteen studies involving 5617 COVID-19 patients were included in the meta-analysis. Pooled results showed that SAA concentrations were significantly higher in patients with severe disease and non-survivors (standard mean difference (SMD) 1.20, 95% confidence interval 0.91-1.49, P < 0.001). Extreme between-study heterogeneity was observed (I2 = 92.4%, P < 0.001). In the sensitivity analysis, the effect size was not significantly affected when each study was removed in turn (range 1.10-1.29). The Begg test (P = 0.030), but not the Egger test (P = 0.385), revealed the presence of publication bias. Pooled SMD values were significantly and positively associated with sex (t = 2.20, P = 0.047) and aspartate aminotransferase (t = 3.44, P = 0.014).
CONCLUSIONS: SAA concentrations were significantly and positively associated with higher COVID-19 severity and mortality. This acute phase reactant might assist with risk stratification and monitoring in this group.

Serum amyloid A (SAA) is an acute phase protein with a significant importance for patients with inflammatory rheumatic diseases (IRD). The central role of SAA in pathogenesis of IRD has been confirmed by recent discoveries, including its involvement in the activation of the inflammasome cascade and recruitment of interleukin 17 producing T helper cells. Clinical utility of SAA in IRD was originally evaluated nearly half a century ago. From the first findings, it was clear that SAA could be used for evaluating disease severity and monitoring disease activity in patients with rheumatoid arthritis and secondary amyloidosis. However, cost-effective and more easily applicable markers, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), overwhelmed its use in clinical practice. In the light of emerging evidences, SAA has been discerned as a more sensitive biomarker in a wide spectrum of IRD, especially in case of subclinical inflammation. Furthermore, a growing number of studies are confirming the advantages of SAA over many other biomarkers in predicting and monitoring response to biological immunotherapy in IRD patients. Arising scientific discoveries regarding the role of SAA, as well as delineating SAA and its isoforms as the most sensitive biomarkers in various IRD by recently developing proteomic techniques are encouraging the revival of its clinical use. Finally, the most recent findings have shown that SAA is a biomarker of severe Coronavirus disease 2019 (COVID-19). The aim of this review is to discuss the SAA-involving immune system network with emphasis on mechanisms relevant for IRD, as well as usefulness of SAA as a biomarker in various IRD. Therefore, over a hundred original papers were collected through an extensive PubMed and Scopus databases search. These recently arising insights will hopefully lead to a better management of IRD patients and might even inspire the development of new therapeutic strategies with SAA as a target.