Salivary Ferritin Changes in Patients with COVID-19

High ferritin serum levels can be found in patients with macrophage activation syndrome, and increased serum ferritin due to cytokine storm have been reported in severe COVID-19 patients. Saliva is being increasingly used in COVID-19 tests as a diagnostic sample for virus detection and quantification. This study aimed to evaluate the possible changes in ferritin in saliva in COVID-19 patients. In addition, the effects of different inactivation SARS-CoV-2 treatments in ferritin measurements in saliva, the correlation between ferritin in saliva and serum, and the possible effects of correction of ferritin values by total protein were assessed. Ferritin was measured in saliva from healthy (n = 30) and COVID-19 (n = 65) patients with severe, (n = 18) or mild (n = 47) disease, depending on the need for nasal flow oxygen or assisted respiration. Ferritin was also measured in paired serum and saliva samples (n = 32) from healthy and COVID-19 patients. The evaluated inactivation protocols did not affect the assay’s results except the addition of 0.5% SDS. Significantly higher ferritin was found in the saliva of COVID-19 patients (median; 25–75th percentile) (27.75; 9.77–52.2 µg/L), compared with healthy controls (4.21; 2.6–8.08 µg/L). Individuals with severe COVID-19 showed higher ferritin values in saliva (48.7; 18.7–53.9) than mild ones (15.5; 5.28–41.3 µg/L). Significant correlation (r = 0.425; p < 0.001) was found between serum and saliva in ferritin. Ferritin levels were higher in COVID-19 patients in serum and saliva, and the highest values were found in those patients presenting severe symptomatology. In conclusion, ferritin in saliva has the potential to be a biomarker to evaluate severity in patients with COVID-19.

Download Full-text

Cytokine Profiles of Macrophage Activation Syndrome Associated with Rheumatic Diseases

The Journal of Rheumatology ◽

10.3899/jrheum.090662 ◽

2010 ◽

Vol 37 (5) ◽

pp. 967-973 ◽

Cited By ~ 56

Author(s):

JUNKO MARUYAMA ◽

SHIGEKO INOKUMA

Keyword(s):

Rheumatic Diseases ◽

Lupus Erythematosus ◽

Macrophage Activation Syndrome ◽

Macrophage Activation ◽

Laboratory Data ◽

Serum Levels ◽

Interferon Γ ◽

Cytokine Profiles ◽

Factor Α ◽

Activation Syndrome

Objective.To elucidate the cytokine profiles of macrophage activation syndrome (MAS) in relation to underlying rheumatic diseases and prognosis.Methods.The clinical features and laboratory data of 18 patients with MAS and rheumatic diseases were retrospectively analyzed. Serum levels of macrophage colony-stimulating factor (M-CSF), interleukin 18 (IL-18), tumor necrosis factor-α, interleukin 6, interferon-γ, ferritin, and ß2-microglobulin (ß2m) were measured. These data were compared between underlying diseases and between those who died and those who recovered.Results.Of the 18 patients with MAS, 9 had underlying systemic lupus erythematosus (SLE), 7 had adult-onset Still’s disease (AOSD), 1 had rheumatoid arthritis (RA), and 1 had antiphospholipid syndrome. Three patients with SLE and 1 patient with RA died. The serum M-CSF and IL-18 levels were substantially elevated in all the patients. In the patients with SLE, the M-CSF level was higher than the IL-18 level (median: 4879 vs 1341 pg/ml, p = 0.0054), and it was the reverse in the patients with AOSD (5883 vs 228,350 pg/ml, p = 0.0017). The serum M-CSF and ß2m levels were significantly higher in the patients who died than in those who recovered (M-CSF: 18,245 vs 3404 pg/ml, p = 0.019; ß2m: 18.8 vs 5.4 mg/dl, p = 0.0058).Conclusion.The cytokine profiles associated with MAS differed between patients with SLE and patients with AOSD. The patients with SLE showed a prominent increase in serum M-CSF levels, as did the patients with AOSD in serum IL-18 level. Patients who died had higher serum M-CSF and ß2m levels, and this suggests that aggressive treatment for patients with MAS and these profiles should be promptly started.

Download Full-text

SOLUBLE ST2 AND CD163 AS POTENTIALBIOMARKERS TO DIFFERENTIATE PRIMARY HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS FROM MACROPHAGE ACTIVATION SYNDROME

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2019.008 ◽

2019 ◽

Vol 11 (1) ◽

Cited By ~ 2

Author(s):

Zhuo Gao ◽

Yini Wang ◽

Jingshi Wang ◽

Jia Zhang ◽

Zhao Wang

Keyword(s):

Healthy Subjects ◽

Macrophage Activation Syndrome ◽

Macrophage Activation ◽

Serum Levels ◽

Haemophagocytic Lymphohistiocytosis ◽

Soluble St2 ◽

Tnf Α ◽

Significant Difference ◽

Ifn Γ ◽

Activation Syndrome

Abstract Background and Objective: The differentiation of primary haemophagocytic lymphohistiocytosis (pHLH) and macrophage activation syndrome (MAS) poses a challenge to hematologists. The aim of this study was (1) to compare the levels of soluble ST2 (sST2), sCD163, IL-10, IFN-γ, TNF-α and IL-18 in patients with pHLH and MAS and (2) to investigate whether they can help differentiate the two diseases. Methods: A total of 54 participants were recruited in this study, including 12 pHLH patients, 22 MAS patients and 20 healthy subjects. We measured the levels of sST2 and sCD163 in serum by ELISA. The serum levels of IL-10, IFN-γ, TNF-α and IL-18 were detected using a Luminex 200 instrument. Results: The serum levels of sST2 and sCD163 in MAS patients were markedly higher than that in pHLH patients (363.13 ± 307.24 ng/ml vs 80.75 ± 87.04 ng/ml, P = 0.004; 3532.72 ± 2479.68 ng/ml vs 1731.96 ± 1262.07 ng/ml, P = 0.046). There was no significant difference in the expression of IFN-γ (306.89 ± 281.60 pg/ml vs 562.43 ± 399.86 pg/ml), IL-10 (20.40 ± 30.49 pg/ml vs 8.3 ± 13.14 pg/ml), IL-18 (463.33 ± 597.04 pg/ml vs 1247.82 ± 1318.58 pg/ml) and TNF-α (61.48 ± 84.69 pg/ml vs 106.10 ±77.21 pg/ml) between pHLH and MAS. Conclusion: Patients with pHLH and MAS show some differences in cytokine profiles. The elevated levels of IFN-γ, IL-10, IL-18 and TNF-α can contribute to the diagnosis of HLH, but may not discriminate pHLH from MAS. Levels of sST2 and sCD163 may serve as markers to distinguish pHLH from MAS.

Download Full-text

Elevated circulating levels of interferon-γ and interferon-γ-induced chemokines characterise patients with macrophage activation syndrome complicating systemic juvenile idiopathic arthritis

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2015-209020 ◽

2016 ◽

Vol 76 (1) ◽

pp. 166-172 ◽

Cited By ~ 98

Author(s):

Claudia Bracaglia ◽

Kathy de Graaf ◽

Denise Pires Marafon ◽

Florence Guilhot ◽

Walter Ferlin ◽

...

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Macrophage Activation Syndrome ◽

Macrophage Activation ◽

Systemic Juvenile Idiopathic Arthritis ◽

Serum Levels ◽

Interferon Γ ◽

Mrna Levels ◽

Circulating Levels ◽

Activation Syndrome

ObjectivesInterferon-γ (IFNγ) is the pivotal mediator in murine models of primary haemophagocytic lymphohistiocytosis (pHLH). Given the similarities between primary and secondary HLH (sec-HLH), including macrophage activation syndrome (MAS), we investigate the involvement of the IFNγ pathway in MAS by evaluating levels of IFNγ and of the induced chemokines, and their relation with laboratory parameters of MAS in systemic juvenile idiopathic arthritis (sJIA) patients with MAS and in a murine MAS model.MethodsThe Luminex multiplexing assay was used to assess serum levels of interleukin (IL)-1β, IL-6, IFNγ and of the IFNγ-induced chemokines CXCL9, CXCL10 and CXCL11 in patients with sec-HLH (n=11) and in patients with sJIA (n=54), of whom 20 had active MAS at sampling. Expression of IFNγ-induced chemokines was assessed in IL-6 transgenic mice in which MAS is induced by TLR4 stimulation with lipopolysaccharide.ResultsLevels of IFNγ and of IFNγ-induced chemokines were markedly elevated during active MAS and sec-HLH and were significantly higher in patients with MAS compared with active sJIA without MAS. Levels in patients with active sJIA without MAS were comparable to those of patients with clinically inactive sJIA. During MAS, ferritin and alanine transferase levels and neutrophil and platelet counts were significantly correlated with serum levels of IFNγ and CXCL9. In murine MAS, serum levels of ferritin were significantly correlated with mRNA levels of Cxcl9 in liver and spleen.ConclusionsThe high levels of IFNγ and of IFNγ-induced chemokines and their correlation with the severity of laboratory abnormalities of MAS suggest a pivotal role of IFNγ in MAS.

Download Full-text

Follistatin-like Protein 1 and the Ferritin/Erythrocyte Sedimentation Rate Ratio Are Potential Biomarkers for Dysregulated Gene Expression and Macrophage Activation Syndrome in Systemic Juvenile Idiopathic Arthritis

The Journal of Rheumatology ◽

10.3899/jrheum.121131 ◽

2013 ◽

Vol 40 (7) ◽

pp. 1191-1199 ◽

Cited By ~ 40

Author(s):

Mark Gorelik ◽

Ndate Fall ◽

Mekibib Altaye ◽

Michael G. Barnes ◽

Susan D. Thompson ◽

...

Keyword(s):

Gene Expression ◽

Juvenile Idiopathic Arthritis ◽

Sedimentation Rate ◽

Macrophage Activation Syndrome ◽

Macrophage Activation ◽

Systemic Juvenile Idiopathic Arthritis ◽

Serum Levels ◽

Erythrocyte Sedimentation ◽

Activation Syndrome ◽

New Onset

Objective.Follistatin-like protein 1 (FSTL-1) is a secreted glycoprotein overexpressed in certain inflammatory diseases. Our objective was to correlate FSTL-1 levels with gene expression, known biomarkers, and measures of disease activity in systemic juvenile idiopathic arthritis (sJIA), including macrophage activation syndrome (MAS).Methods.FSTL-1 serum levels were measured by ELISA in 28 patients with sJIA, including 7 patients who developed MAS, and 30 healthy controls. Levels were correlated with erythrocyte sedimentation rate (ESR), ferritin, and soluble interleukin-2 receptor-α (sIL-2Rα). Gene expression based on FSTL-1 levels was analyzed in peripheral blood mononuclear cells (PBMC).Results.Serum levels of FSTL-1 were elevated at time of presentation of sJIA (mean 200.7 ng/ml) and decreased to normal (mean 133.7 ng/ml) over 24 months (p < 0.01). FSTL-1 levels were markedly elevated during acute MAS (mean 279.8 ng/ml) and decreased to normal following treatment (p < 0.001). FSTL-1 levels correlated with serum markers of inflammation, including sIL-2Rα and ferritin. Ferritin/ESR ratio was superior to ferritin, sIL-2Rα, and FSTL-1 in discriminating MAS from new-onset sJIA. PBMC from patients with FSTL-1 levels > 200 ng/ml showed altered expression of genes related to innate immunity, erythropoiesis, and natural killer cell dysfunction. Two patients with the highest FSTL-1 levels at disease onset (> 300 ng/ml) ultimately developed MAS.Conclusion.Elevated pretreatment serum FSTL-1 levels in sJIA are associated with dysregulated gene expression suggestive of occult MAS, and may have utility in predicting progression to overt MAS. Ferritin/ESR ratio may be superior to ferritin alone in discriminating overt MAS from new-onset sJIA.

Download Full-text

Comparison of serum cytokine profiles in macrophage activation syndrome complicating different background rheumatic diseases in children

Rheumatology ◽

10.1093/rheumatology/keaa299 ◽

2020 ◽

Vol 60 (1) ◽

pp. 231-238

Author(s):

Mao Mizuta ◽

Masaki Shimizu ◽

Hitoshi Irabu ◽

Masaaki Usami ◽

Natsumi Inoue ◽

...

Keyword(s):

Rheumatic Diseases ◽

Roc Curve ◽

Macrophage Activation Syndrome ◽

Macrophage Activation ◽

Active Phase ◽

Serum Levels ◽

Type I ◽

Roc Curve Analysis ◽

Serum Neopterin ◽

Activation Syndrome

Abstract Objectives To compare the cytokines involved in the development of macrophage activation syndrome (MAS) in different background rheumatic diseases and to identify serum biomarkers for MAS diagnosis. Methods Serum neopterin, IL-6, IL-18 and soluble TNF receptor (sTNFR) type I (sTNFR-I) and type II (sTNFR-II) levels were determined using ELISA in 12 patients with SLE, including five with MAS; 12 patients with JDM, including four with MAS; 75 patients with Kawasaki disease (KD), including six with MAS; and 179 patients with systemic JIA (s-JIA), including 43 with MAS. These results were compared with the clinical features of MAS. Results Serum neopterin, IL-18 and sTNFR-II levels were significantly higher during the MAS phase than during the active phase in patients with all diseases. Furthermore, serum sTNFR-I levels were significantly higher during the MAS phase than during the active phase in patients with SLE, KD and s-JIA. Receiver operating characteristic (ROC) curve analysis revealed that serum sTNFR-I levels for SLE, serum IL-18 levels for JDM, and serum sTNFR-II levels for KD and s-JIA had the highest areas under the ROC curve. Serum levels of these cytokines were significantly and positively correlated with serum ferritin levels. Conclusions Overproduction of IFN-γ, IL-18 and TNF-α might be closely related to the development of MAS. Serum levels of sTNFR-I for SLE, IL-18 for JDM, and sTNFR-II for KD and s-JIA might be useful diagnostic markers for the transition from active phase to MAS.

Download Full-text