Identification of novel biomarkers of acute phase response in chickens challenged with Escherichia coli lipopolysaccharide endotoxin.

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.

Expression and significance of procalcitonin, leukotriene B4, serum amyloid A, and C-reactive protein in children with different types of pneumonia: An observational study.

This study aimed to investigate the expression and significance of serum procalcitonin (PCT), leukotriene B4 (LTB4), Serum amyloid A (SAA), and C-reactive protein (CRP) in children with different types of pneumonia caused by different pathogenic infections. One hundred and one children with pneumonia admitted to The Fifth People Hospital of Zhuhai from July 2019 to June 2020 were enrolled and divided into 38 cases in the bacterial group, 30 cases in the mycoplasma group, and 33 cases in the virus group according to the different types of pathogens. The patients were divided into 42 cases in the noncritical group, 33 cases in the critical group, and 26 cases in the very critical group according to the pediatric clinical illness score (PCIS), and 30 healthy children were selected as the control group during the same period. Comparison of serum PCT, SAA: bacterial group > mycoplasma group > viral group > control group with significant differences (P < .05). Receiver operator characteristic (ROC) analysis showed that the area under the curves (AUCs) of serum PCT, LTB4, SAA, and CRP for the diagnosis of bacterial pneumonia were 1.000, 0.531, 0.969, and 0.833, respectively, and the AUCs for the diagnosis of mycoplasma pneumonia were 0.653, 0.609, 0.547, and 0.652, respectively, and the AUCs for the diagnosis of viral pneumonia were 0.888, 0.570, 0.955, and 1.000, respectively. Comparison of serum PCT, LTB4, SAA: very critical group > critical group > noncritical group > control group, with significant differences (P < .05). Serum PCT, LTB4, and SAA were negatively correlated with PCIS score by Pearson analysis (P < .05). Serum PCT and SAA showed diagnostic value for bacterial pneumonia, and serum SAA and CRP showed diagnostic value for viral pneumonia; serum PCT, LTB4, and SAA correlate with severity of disease and show higher expression with worsening of the condition.

Detection of haptoglobin and serum amyloid A as biomarkers in naturally infected Mycoplasma bovis calves.

The livestock sector of Pakistan is increasing rapidly and it plays important role both for rural community and national economy. It is estimated that almost 8 million rural people are involved in livestock rearing and earning about 35-40 % of their income from the livestock sector. Mycoplasma bovis (M. bovis) infection causes significant economic losses in dairy animals especially young calf in the form of clinical illnesses such as pneumonia, poly-arthritis, respiratory distress and mortality. M. bovis is hard to diagnose and control because of uneven disease appearance and it is usually noticed in asymptomatic animals. For the identification of M. bovis in sub-clinical and clinical samples, determination of acute phase proteins i.e., haptoglobin (Hp) and serum amyloid A (SAA) are important tools for the timely diagnosis of disease. Therefore, early diagnosis of disease and hemato-biochemical changes are considered beneficial tools to control the infectious agent to uplift the economy of the dairy farmers. For this purpose, blood samples were collected from 200 calves of Bovidae family. Serum was separated from blood samples to determine the concentration of Hp and SAA, while blood samples were processed to determine hematological changes in blood from calves by using hematological analyzer. The blood plasma obtained from the blood samples was processed to measure oxidative stress factors. Lungs tissues from slaughterhouses/ morbid calves were collected to observe histopathological changes. The results of present study indicated that level of SAA and Hp remarkably increased (P < 0.05) in M. bovis infected calves in comparison to healthy calves. The oxidative stress markers indicated that nitric oxide and MDA levels in the infected calves increased significantly (P < 0.05), while infected claves had considerably lower levels of superoxide dismutase, catalase and glutathione. These findings indicate that oxidative stress play role to increase the level of APPs, while monitoring of APPs levels may serve as a valuable addition to the clinical evaluation of naturally infected calves with M. bovis. The hematological parameters were decreased significantly (P < 0.05). Altogether, this study suggests that Hp and SAA are proposed as promising biomarkers for detecting naturally occurring M. bovis infection in calves.

Prognostic potential of copper, zinc, copper/zinc ratio, cobalamin, and serum amyloid A in cats with panleukopenia.

BACKGROUND: Copper (Cu), zinc (Zn), and the copper/zinc ratio (Cu/Zn), which have been studied in gastrointestinal disorders of humans, may facilitate disease prognosis. OBJECTIVE: Evaluate the predictive potential of Cu, Zn, cobalamin, and serum amyloid A (SAA) as prognostic indicators in cats with feline panleukopenia (FPV) on admission. ANIMALS: Client-owned cats diagnosed with FPV and controls. METHODS: Serum Cu and Zn concentrations were assessed using the spectrophotometric method and serum concentrations of SAA and cobalamin were measured by chemiluminescent immunoassay. RESULTS: On admission, survivor cats with FPV had significantly higher serum Cu and SAA concentrations and Cu/Zn ratios and significantly lower serum Zn and cobalamin concentrations than controls. Furthermore, non-survivor cats with FPV had significantly higher serum Cu and SAA concentrations and Cu/Zn ratios and significantly lower cobalamin concentrations than survivors and controls. Prognostic thresholds were calculated, with positive predictive value (PPV) for survival of 90% for Cu (≥120.3 µg/dL), 90% for Cu/Zn (≥1.34), 90% for cobalamin (≤430.4 pg/mL), and 90% for SAA (≥0.85 mg/L). CONCLUSIONS AND CLINICAL IMPORTANCE: Cu (0.93 area under curve [AUC]), Cu/Zn (0.95 AUC), cobalamin (0.98 AUC), and SAA (0.98 AUC) were excellent biomarkers for predicting prognosis in cats with FPV. Their effectiveness, as assessed by sensitivity (100%), specificity (80%), AUC (0.98), and PPV (90%) from receiver operating characteristic analysis, emphasizes the performance of cobalamin and SAA.

Usefulness of serum amyloid A for the diagnosis of pyelonephritis in cats: A prospective evaluation.

BACKGROUND: The diagnosis of pyelonephritis in cats is challenging and development of a noninvasive and accurate biomarker is needed. HYPOTHESES: Serum amyloid A (SAA) is increased in cats with pyelonephritis, but not in cats with other urinary tract diseases. ANIMALS: A cohort of 125 cats (149 observations). METHODS: This was a prospective study. Group 1 included cats with a diagnosis of pyelonephritis either confirmed by bacterial culture of pelvic urine (Group 1a) or presumed (1b). Group 2 included cats for which pyelonephritis was ruled out (with certainty: Group 2a or judged unlikely: Group 2b). SAA concentration was compared between groups, and accuracy of SAA for the diagnosis of pyelonephritis was calculated using a Receiver Operating Characteristic (ROC) curve analysis. RESULTS: Median SAA concentration was significantly higher in Group 1a (86.8 mg/L [73.3; 161.5]; n = 8) than in Group 2a (4 mg/L [1.8; 5.6], n = 19; P < .001) and in Group 2b (5.4 mg/L [3.1; 9.7], n = 113; P < .001). It was also significantly higher in Group 1b (98.8 mg/L [83.1; 147.3]; n = 9) than in Group 2b (P < .001) and Group 2a (P < .001). Optimal diagnostic cut-off for SAA concentration was 51.3 mg/L. yielding a sensitivity of 88% (95% confidence interval: [64%; 99%]) and a specificity of 94% (95% confidence interval: [88%; 97%]). CONCLUSIONS AND CLINICAL IMPORTANCE: Measurement of SAA could be used to rule out pyelonephritis in the case of low suspicion of the disease. Increased SAA concentration is suggestive of pyelonephritis despite a lack of specificity.

Morphological findings in different subtypes of hepatic amyloid.

The classic findings have been well described for light-chain amyloid involving the liver. In addition to light chain, however, many additional proteins are now known to be amyloidogenic and can involve the liver. A total of 58 surgical pathology specimens with amyloid deposits were analyzed for patterns of amyloid deposition, including amyloid from light chain lambda (N = 17), light chain kappa (N = 15), transthyretin (N = 15), serum amyloid A (N = 4), apolipoprotein A1 (N = 4), fibrinogen alpha (N = 2), LECT2 (N = 1). Amyloid deposits predominately targeted the liver vasculature, including the walls of the hepatic arteries, portal veins, and sinusoids. While there was overlap, light chain amyloid predominately involved the sinusoids, while transthyretin amyloid predominately targeted the hepatic arteries, especially the larger ones in the hilum and larger portal tracts. Serum amyloid A formed nodular deposits that started in the portal vasculature but then extended into the portal tract stroma, leading to large, bulbous, portal-based amyloid deposits. Apolipoprotein A amyloid also formed large portal-based nodules. Fibrinogen was mild and subtle on H&E and predominately affected portal veins. Amyloid deposits in hilar nerves were prominent with amyloid light chain, transthyretin, and apolipoprotein A1. In conclusion, the histology of hepatic amyloid is diverse and shows several distinct clusters of findings that can aide in recognition in surgical pathology specimens.

Screening of novel biomarkers for acute kidney transplant rejection using DIA-MS based proteomics.

BACKGROUND: Kidney transplantation is the preferred treatment for patients with end-stage renal disease. However, acute rejection poses a threat to the graft long-term survival. The aim of this study was to identify novel biomarkers to detect acute kidney transplant rejection. METHODS: The serum proteomic profiling of kidney transplant patients with T cell-mediated acute rejection (TCMR) and stable allograft function (STA) was analyzed using data-independent acquisition mass spectrometry (DIA-MS). The differentially expressed proteins (DEPs) of interest were further verified by enzyme-linked immunosorbent assay (ELISA). RESULTS: A total of 131 DEPs were identified between STA and TCMR patients, 114 DEPs were identified between mild and severe TCMR patients. The verification results showed that remarkable higher concentrations of serum amyloid A protein 1 (SAA1) and insulin like growth factor binding protein 2 (IGFBP2), and lower fetuin-A (AHSG) concentration were found in TCMR patients when compared with STA patients. We also found higher SAA1 concentration in severe TCMR group when compared with mild TCMR group. The receiver operating characteristics (ROC) analysis further confirmed that combination of SAA1, AHSG, and IGFBP2 had excellent performance in the acute rejection diagnosis. CONCLUSIONS: Our data demonstrated that serum SAA1, AHSG, and IGFBP2 could be effective biomarkers for diagnosing acute rejection after kidney transplantation. DIA-MS has great potential in biomarker screening of kidney transplantation.

Asthmatic patients with high serum amyloid A have proinflammatory HDL: Implications for augmented systemic and airway inflammation.

RATIONALE: Serum amyloid A (SAA) is bound to high-density lipoproteins (HDL) in blood. Although SAA is increased in the blood of patients with asthma, it is not known whether this modifies asthma severity. OBJECTIVE: We sought to define the clinical characteristics of patients with asthma who have high SAA levels and assess whether HDL from SAA-high patients with asthma is proinflammatory. METHODS: SAA levels in serum from subjects with and without asthma were quantified by ELISA. HDLs isolated from subjects with asthma and high SAA levels were used to stimulate human monocytes and were intravenously administered to BALB/c mice. RESULTS: An SAA level greater than or equal to 108.8 µg/mL was defined as the threshold to identify 11% of an asthmatic cohort (n = 146) as being SAA-high. SAA-high patients with asthma were characterized by increased serum C-reactive protein, IL-6, and TNF-α; older age; and an increased prevalence of obesity and severe asthma. HDL isolated from SAA-high patients with asthma (SAA-high HDL) had an increased content of SAA as compared with HDL from SAA-low patients with asthma and induced the secretion of IL-6, IL-1ß, and TNF-α from human monocytes via a formyl peptide receptor 2/ATP/P2X purinoceptor 7 axis. Intravenous administration to mice of SAA-high HDL, but not normal HDL, induced systemic inflammation and amplified allergen-induced neutrophilic airway inflammation and goblet cell metaplasia. CONCLUSIONS: SAA-high patients with asthma are characterized by systemic inflammation, older age, and an increased prevalence of obesity and severe asthma. HDL from SAA-high patients with asthma is proinflammatory and, when intravenously administered to mice, induces systemic inflammation, and amplifies allergen-induced neutrophilic airway inflammation. This suggests that systemic inflammation induced by SAA-high HDL may augment disease severity in asthma.

Serum alpha 1-acid glycoprotein and interleukin-8 elevations in felines with localized and metastatic tumors.

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.

Association of serum amyloid A and prognosis in people with diabetes and COVID-19: A retrospective cohort study.

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.

Clinical diagnostic value of IL-14, 1L-16 and SAA in periodontitis.

OBJECTIVES: Periodontitis is a chronic infectious disease, which leads to inflammatory destruction of periodontal supporting tissues. Interleukin 14 (IL-14), Interleukin 16 (IL-16) and serum amyloid A (SAA) have been demonstrated to be abnormally expressed in inflammatory diseases. Therefore, this study was performed to analyzed the expression and potential clinical values of IL-14, 1L-16 and SAA in periodontitis. MATERIALS AND METHODS: A total of 100 periodontitis patients and 100 healthy volunteers were recruited and the saliva and serum samples were collected. Then the C-reactive protein (CRP), procalcitonin (PCT), IL-14, 1L-16 and SAA levels in the saliva and serum of periodontitis patients were measured by Elisa kits. Besides, the significance of CRP, PCT, IL-14, 1L-16 and SAA in periodontitis patients were analyzed by receiver operating characteristic (ROC) analysis. RESULTS: The results showed that CRP, PCT, IL-14, 1L-16 and SAA levels were significantly increased in the the saliva and serum of the periodontitis patients. Additionally, the area under the curve (AUC) of saliva CRP, PCT, IL-14, 1L-16 and SAA for the diagnosis of periodontitis were 0.9035, 0.9435, 0.9508, 0.9500 and 0.9467, respectively. The AUC of serum CRP, PCT, IL-14, 1L-16 and SAA for the diagnosis of periodontitis were 0.9035, 0.9435, 0.9508, 0.9500 and 0.9467, respectively. What's more, the diagnostic value of IL-14, 1L-16 and SAA were enhanced when combining with CRP and PCT. CONCLUSION AND CLINICAL RELEVANCE: This study demonstrated that IL-14, IL-16 and SAA expressions were upregulated in periodontitis patients and exhibited a significant significance for periodontitis diagnosis.

Effect of Bariatric Surgery on Serum Amyloid A Protein: a Systematic Review and Meta-analysis.

BACKGROUND: Obesity is a chronic inflammatory condition and this meta-analysis evaluated the impact of bariatric surgery on SAA. METHODS: Studies included all types of bariatric surgery where SAA was measured before and after the surgical procedure. RESULTS: 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. CONCLUSION: 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.

Association between Serum Amyloid A Levels and Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

BACKGRUOUND: To date, consistent data have not been reported on the association between serum amyloid A (SAA) levels and type 2 diabetes mellitus (T2DM). The purpose of this study was to systematically summarize their relationship. METHODS: Databases including PubMed, Cochrane Library, Embase, Web of Science, and MEDLINE were searched until August 2021. Cross-sectional and case-control studies were included. RESULTS: Twenty-one studies with 1,780 cases and 2,070 controls were identified. SAA levels were significantly higher in T2DM patients than in healthy groups (standardized mean difference [SMD], 0.68; 95% confidence interval [CI], 0.39 to 0.98). A subgroup analysis showed that the mean age of participants and the continent that participants were from were related to differences in SAA levels between cases and controls. Furthermore, in T2DM patients, SAA levels were positively associated with body mass index (r=0.34; 95% CI, 0.03 to 0.66), triglycerides (r=0.12; 95% CI, 0.01 to 0.24), fasting plasma glucose (r=0.26; 95% CI, 0.07 to 0.45), hemoglobin A1c (r=0.24; 95% CI, 0.16 to 0.33), homeostasis model assessment for insulin resistance (r=0.22; 95% CI, 0.10 to 0.34), C-reactive protein (r=0.77; 95% CI, 0.62 to 0.91), and interleukin-6 (r=0.42; 95% CI, 0.31 to 0.54), but negatively linked with highdensity lipoprotein cholesterol (r=-0.23; 95% CI, -0.44 to -0.03). CONCLUSION: The meta-analysis suggests that high SAA levels may be associated with the presence of T2DM, as well as lipid metabolism homeostasis and the inflammatory response.

Acute Phase Protein Response in Native and Imported Horses After Routine Combination Vaccination Protocol.

Fibrinogen and serum amyloid A (SAA) are commonly measured equine acute phase proteins. Limited data exist on SAA and fibrinogen responses to combination vaccination protocols in horses. A prospective cohort study evaluating SAA, fibrinogen, and rectal temperature following a standard combination vaccination. Blood for measurement of SAA and serum fibrinogen and rectal temperatures were obtained before (0 hour) and after vaccination (24, 48, 72, 96, 168 hours). After vaccination, SAA and fibrinogen increased in all horses. Imports had elevated SAA from 24-168 hours, whereas native horses returned to baseline by 168 hours. Compared to native horses, SAA was significantly higher in imports (coefficient 24-168 hours 358, 95%CI: 46-671 mg/L; P = .03). Fibrinogen increased significantly from 24 to 168 hours postvaccination, but groups did not differ (coefficient -16; 95%CI: -69 to 37 mg/dL; P = .5). Absolute rectal temperatures were significantly higher in imports throughout, including 0 hour (median 37.8; IQR 37.7-38.0 vs. 37.3; 37.1-37.3; P = .002). At 24 hours postvaccination when temperatures significantly increased above baseline in both groups, there was a small but significant difference in the percent change relative to baseline (coefficient 1.9; 95%CI 0.8%-2.9%; P = .002). A standard combination vaccination protocol elicited an acute phase response in all horses. Compared to native previously vaccinated horses, imports had a stronger SAA response. The observed response is worthy of consideration when examining recently vaccinated imported horses.

Effect of plasma transfusion on serum amyloid A concentration in healthy neonatal foals and foals with failure of transfer of passive immunity.

BACKGROUND: Anecdotal evidence suggests plasma transfusions increase serum amyloid A (SAA) concentrations in healthy neonatal foals making this marker of inflammation inappropriate for therapeutic decision making in such animals. HYPOTHESIS/OBJECTIVES: Administration of hyperimmune fresh frozen plasma (FFP) increases SAA concentration in healthy foals and in foals with failure of transfer of passive immunity (FTPI). ANIMALS: Eighty-six healthy foals. METHODS: Prospective cohort study. Foals <24 hours of age receiving plasma transfusion for treatment of FTPI (serum immunoglobulin G [IgG] concentrations <8 g/L; n = 17) or as a preventative measure for Rhodococcus equi infection (IgG >8 g/L; n = 33) were enrolled. A healthy nontransfused group of foals (IgG >8 g/L; n = 21) also was included. Serum amyloid A concentration was determined before (t0h) and after (t24h) administration of FFP. Changes in blood SAA concentration were assessed using linear regression models. RESULTS: No statistical differences were found in SAA concentration at t0h or t24h among the 3 groups (P > .05, for all comparisons). The variation in SAA concentration before (t0h) and after (t24h) plasma transfusion showed that administration of FFP was not associated with the changes in SAA concentration (P > .05). An association between SAA concentration at t0h and at 24 hours (P < .05) was identified, where foals with higher SAA concentration at t0h also had higher SAA concentration at t24h. CONCLUSIONS AND CLINICAL IMPORTANCE: Administration of FFP to newborn foals was not associated with changes in SAA concentration.

Serum Amyloid A in Stable Patients with Chronic Obstructive Pulmonary Disease Does Not Reflect the Clinical Course of the Disease.

Serum amyloid A (SAA) is a good systemic marker of the exacerbations of chronic obstructive pulmonary disease (COPD), but the significance of SAA in stable patients with COPD has not been widely investigated. We aimed to evaluate the SAA level in peripheral blood from stable patients with COPD and to search for correlations between SAA and other inflammatory markers and clinical characteristics of the disease. Serum SAA, IL-6, IL-8, TNF-alpha, basic blood investigations, pulmonary function testing and a 6-min walk test were performed. The correlations between SAA and other inflammatory markers, functional performance and the number of disease exacerbations were evaluated. A total of 100 consecutive patients with COPD were analyzed. No correlations between SAA and inflammatory markers as well as pulmonary function were found. Hierarchical clustering identified two clusters incorporating SAA: one comprised SAA, PaO2 and FEV1 and the second was formed of SAA and nine other disease markers. The SAA level was higher in patients with blood eosinophils < 2% when compared to those with blood eosinophils ≥ 2% (41.8 (19.5-69.7) ng/mL vs. 18.9 (1.0-54.5) ng/mL, respectively, p = 0.04). We conclude that, in combination with other important disease features, SAA may be useful for patient evaluation in stable COPD.

Detection and Typing of Renal Amyloidosis by Fluorescence Spectroscopy Using the Environmentally Sensitive Fluorophore K114.

PURPOSE: To demonstrate that spectral analysis using the K114 fluorophore can detect and differentiate AL and AA renal amyloidosis. PROCEDURES: Kidney biopsies from patients with AL amyloidosis, AA amyloidosis, and normal samples with no evident pathology were stained with Congo Red and K114. The specimens were imaged on a spectral confocal microscope. RESULTS: Congo Red displayed homogeneous spectra across the three tissue types while K114 chromatically distinguished between normal tissue, AL amyloid, and AA amyloid. Additionally, Congo Red displayed an increased risk of false positive staining compared to K114. Spectral phasors computed from K114-stained tissue sections quantitatively differentiated the three tissue types. K114-stained amyloid deposits displayed a significantly greater increase in brightness after 50 images acquired in rapid succession compared to normal tissue. Quantitative analysis of intensity changes in the background of diseased tissue also differentiated AL and AA amyloid samples, suggesting widespread amyloid deposition. Both amyloid and the backgrounds of diseased samples red-shifted while normal tissue blue-shifted in response to repeated imaging, supporting this theory. CONCLUSIONS: K114 staining of renal biopsies is a promising technique to detect and differentiate types of renal amyloidosis. Due to the advantages this method has over traditional Congo Red staining, the techniques presented here warrant further development for potential use in clinical settings.