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Evgeni Dimitrov Department of Surgical Diseases, University Hospital “Prof. Dr. Stoyan Kirkovich”, Stara Zagora, Bulgaria
Department of Surgical Diseases and Anesthesiology, Faculty of Medicine, Trakia University, Stara Zagora, Bulgaria

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Krasimira Halacheva Laboratory of Clinical Immunology, University Hospital “Prof. Dr. Stoyan Kirkovich”, Stara Zagora, Bulgaria

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Georgi Minkov Department of Surgical Diseases, University Hospital “Prof. Dr. Stoyan Kirkovich”, Stara Zagora, Bulgaria
Department of Surgical Diseases and Anesthesiology, Faculty of Medicine, Trakia University, Stara Zagora, Bulgaria

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Emil Enchev Department of Surgical Diseases, University Hospital “Prof. Dr. Stoyan Kirkovich”, Stara Zagora, Bulgaria
Department of Surgical Diseases and Anesthesiology, Faculty of Medicine, Trakia University, Stara Zagora, Bulgaria

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Yovcho Yovtchev Department of Surgical Diseases, University Hospital “Prof. Dr. Stoyan Kirkovich”, Stara Zagora, Bulgaria
Department of Surgical Diseases and Anesthesiology, Faculty of Medicine, Trakia University, Stara Zagora, Bulgaria

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Abstract

Aim

The ability of neutrophil CD16 (nCD16) expression to predict outcome in complicated intra-abdominal infections (cIAIs) has not yet been studied; therefore we aimed to evaluate its potential prognostic value in such patients.

Methods

Between November 2018 and August 2021 a single-center prospective study was performed in the Department of Surgical Diseases at a University Hospital Stara Zagora. A flow cytometry was used to measure the levels of nCD16 before surgery and on the 3rd postoperative day (POD) in 62 patients with cIAIs.

Results

We observed a mortality rate of 14.5% during hospitalization. Survivors had significantly higher perioperative expression of nCD16 than non-survivors (P = 0.02 preoperatively and P = 0.006 postoperatively). As predictor of favorable outcome we found a good predictive performance of preoperative nCD16 (AUROC = 0.745) and a very good predictive performance of postoperative levels (AUROC = 0.846). An optimal preoperative threshold nCD16 = 34.75 MFI permitted prediction of survival with sensitivity and specificity of 66.7% and 77.8%, respectively. A better sensitivity of 72.5% and specificity of 85.7% were observed for threshold = 54.8 MFI on the 3rd POD.

Conclusion

Perioperative neutrophil CD16 expression shows a great potential as a predictor of favorable outcome in patients with cIAIs.

Abstract

Aim

The ability of neutrophil CD16 (nCD16) expression to predict outcome in complicated intra-abdominal infections (cIAIs) has not yet been studied; therefore we aimed to evaluate its potential prognostic value in such patients.

Methods

Between November 2018 and August 2021 a single-center prospective study was performed in the Department of Surgical Diseases at a University Hospital Stara Zagora. A flow cytometry was used to measure the levels of nCD16 before surgery and on the 3rd postoperative day (POD) in 62 patients with cIAIs.

Results

We observed a mortality rate of 14.5% during hospitalization. Survivors had significantly higher perioperative expression of nCD16 than non-survivors (P = 0.02 preoperatively and P = 0.006 postoperatively). As predictor of favorable outcome we found a good predictive performance of preoperative nCD16 (AUROC = 0.745) and a very good predictive performance of postoperative levels (AUROC = 0.846). An optimal preoperative threshold nCD16 = 34.75 MFI permitted prediction of survival with sensitivity and specificity of 66.7% and 77.8%, respectively. A better sensitivity of 72.5% and specificity of 85.7% were observed for threshold = 54.8 MFI on the 3rd POD.

Conclusion

Perioperative neutrophil CD16 expression shows a great potential as a predictor of favorable outcome in patients with cIAIs.

Introduction

On a global scale, the complicated intra-abdominal infections (cIAIs) are associated with high levels of morbidity, prolonged hospital stay in Intensive Care Units and poor prognosis [1]. They constitute a serious potential threat for human health, regardless of their age group, race or socio-economic status. Although over the years, various factors impacting the mortality have been studied, at present, satisfactory methods for prognosis of cIAIs adopted in the clinical practice are not existent. Prediction of disease severity using biomarkers is a simple and rapid way to provide information about the outcome and possible options for modifying the treatment plan.

Cluster of differentiation (CD) 16, is a Fragment crystallizable receptor (FcγRIII) which is found on the surface of neutrophils, natural killer (NK) cells, monocytes, macrophages and certain T cells [2, 3]. CD16 has been identified as Fc receptors FcγRIIIa (CD16a) and FcγRIIIb (CD16b), which are involved in signal transduction [4, 5]. FcγRIIIa is expressed on mast cells, macrophages and NK cells as a transmembrane receptor, while FcγRIIIb (nCD16) is only expressed on neutrophils [6, 7]. In the absence of infection, resting neutrophils constitutively express CD16 in contrast to CD64, whose expression on neutrophils is maintained at low levels and rapidly increases in the presence of pathogen-associated molecular patterns (PAMPs), components of the complement system, and proinflammatory cytokines [8]. It has been proven that nCD16 plays a significant role in neutrophil degranulation. FcγRIIIa and FcγRIIIb together are able to activate degranulation, phagocytosis, and oxidative burst, allowing neutrophils to eliminate already opsonized pathogens [4–6]. Decreased expression of CD16 is associated with an increased risk of death and may reflect an increased release of immature neutrophils from the bone marrow following inflammatory stimuli in a systemic immune response [9]. The immature neutrophil progenitors, metamyelocytes are associated with intermediate expression of CD16, whereas myelocytes do not express CD16 [10, 11]. Patients with a systemic inflammatory response or sepsis who die within a week of blood sampling have higher levels of myelocytes and metamyelocytes [12]. In sepsis, the concentration of serum nCD16 increases with the severity of the condition [13], and in patients with severe trauma, nCD16 expression is reduced [14]. Decreased expression of CD16 on neutrophils has been reported in severe systemic inflammatory response [15] and is associated with an increased risk of mortality in the critically ill [9].

The data in the available literature regarding the prognostic qualities of nCD16 is rather scarce, and is lacking in cIAIs. Therefore, we aimed to study the prognostic potential of this biomarker in such patients.

Material and methods

Study population and data collection

This prospective study was performed in the Department of Surgical Diseases (DSD) at a University Hospital “Prof. Dr. Stoyan Kirkovich” Stara Zagora on sixty-two patients with complicated intra-abdominal infections over a 34-month period (November 2018 to August 2021). All patients with cIAIs over 18 years who underwent emergency abdominal surgery were included. The registration number of ethical approval from the hospital ethical committee is № РД-10-275/05.04.2018. The preoperative diagnosis was determined stepwise by clinical evaluation, imaging methods, and laboratory tests, and the final diagnosis was made based on the intraoperative finding.

Expression of cell surface CD16 on neutrophils (nCD16) was measured preoperatively (day 0) and on the 3rd postoperative day (POD). For comparison, we have studied 31 healthy controls with a similar distribution of sex and age to the patients and lack of comorbidity. Before surgery, neutrophil CD16 expression was assessed in 60 (96.8%) patients, as in 2 (3.2%) the peripheral blood sample was clotted, and on the 3rd POD in 58 (93.5%) patients – in 2 (3.2%) the blood sample was clotted and 2 (3.2%) didn't survive before the day of sampling.

Flow cytometry

All peripheral whole blood samples were taken in EDTA anticoagulated tube and stored at room temperature until flow cytometric testing. Flow cytometric analyses were performed 1–3 h after blood sampling. After mixing well, 100-μL aliquots of blood were incubated for 15 min in the dark at room temperature with ready-to-use monoclonal antibodies (anti-CD16PC7, anti-CD14PE, corresponding mouse isotype control) all purchased from Beckman Coulter (USA). Lyse/no wash procedure was performed using the automated TQ-Prep Workstation and Immunoprep Reagent system (Beckman Coulter). A minimum of 100,000 events for each sample were collected on a Cytomics FC500 flow cytometer and analyzed using CXP software (Beckman Coulter). Relative measurement of CD16 expression was obtained by determining the mean fluorescence intensity (MFI) of neutrophils.

Initially neutrophils were labeled as a distinct population based on side scatter/CD14 dot-plot analysis (Fig. 1A and C), after which CD16 expression (mono-parametric histogram Fig. 1B and D) was also measured as MFI relative to the entire neutrophil population [16].

Fig. 1.
Fig. 1.

Gating strategy of measurement of CD16 expression on neutrophils in peripheral blood in patients (A, B) and in healthy controls (C, D), determined by flow cytometry. (A) CD14 vs side scatter (SS) dot-plot histogram allowing discrimination between neutrophils (58.5% in BD gate) and monocytes (3.7% in Y gate). (B) Monoparametric histogram showing the expression of CD16 on gated neutrophils as mean fluorescence intensity (MFI) relative to the entire neutrophil population – MFI = 8.46. (C) CD14 vs side scatter (SS) dot-plot histogram allowing discrimination between neutrophils (36.6% in BD gate) and monocytes (6.0% in Y gate). (D) Monoparametric histogram showing the expression of CD16 on gated neutrophils as mean fluorescence intensity MFI) relative to the entire neutrophil population – MFI = 133.0

Citation: European Journal of Microbiology and Immunology 14, 1; 10.1556/1886.2023.00046

Statistical analysis

For statistical analysis, we used statistical software SPSS version 19 for Windows (IBM, Chicago, Illinois, USA). Pre- and postoperative cutoff values of nCD16 were obtained from receiver operating characteristic (ROC) curves drawn for each group according to 28‐day survival. Continuous variables were compared using Mann-Whitney U test (IQR) or Student's t-test (SD), and categorical variables were compared Fisher's exact test or χ2 test. P-values <0.05 were considered statistically significant.

Ethics statement

The study was approved by the Ethics Committee of the University Hospital “Prof. Dr Stoyan Kirkovich” Stara Zagora (№ РД-10-275/05.04.2018). All procedures performed in the study involving human participants were in accordance with the ethical standards of the 1964 WMA Helsinki Declaration and its later amendments or comparable ethical standards.

Results

Patients characteristics

The observed in-hospital mortality was 14.5%. The patients who died had higher median age than survivors: 79 (61–86) years vs. 65 (47.5–75) years, P = 0.032. Fatal outcome was associated with diffuse peritonitis (P = 0.024), unlike gender (P = 1.000), comorbidity (P = 0.423) and source of infection (P = 0.466) (Table 1).

Table 1.

Patients characteristics

VariableTotal populationSurvivors (n = 53)Non-Survivors (n = 9)P value
Sex, n (%)1.000
 male/female35 (56.5)/27 (43.5)30 (85.7)/23 (85.2)5 (14.3)/4 (14.8)
Age, years (IQR)65 (49.5–76.25)65 (47.5–75)79 (61–86)0.032
Peritonitis, n (%)0.024
 Local37 (59.7)35 (66)2 (22.2)
 Diffuse25 (40.3)18 (34)7 (77.8)
Source, n (%)0.466
 Appendicular15 (24.2)14 (26.4)1 (11.1)
 Hepatobiliary22 (35.4)19 (35.8)3 (33.3)
 Gastroduodenal12 (19.3)9 (17)3 (33.3)
 Colorectal7 (11.3)6 (11.3)1 (11.1)
 Jejunoileal2 (3.2)1 (1.9)1 (11.1)
 Gynecological4 (6.4)4 (7.5)0 (0)
Comorbidity, n (%)45 (72.6)37 (69.8%)8 (88.9%)0.423
 Cardiovascular38 (61.3)31 (58.5)7 (77.8)0.462
 Endocrine8 (12.9)8 (15.1)0 (0)0.59
 Neurologic7 (11.3)5 (9.4)2 (22.2)0.266
 Excretory5 (8.1)3 (5.7)2 (22.2)0.149
 Oncologic3 (4.8)3 (5.7)0 (0)1.000

Inflammatory biomarkers

Perioperative concentrations of leucocytes (P = 0.141 before surgery and P = 0.194 after surgery) and C-reactive protein (P = 0.085 before surgery and P = 0.083 after surgery), as well as preoperative percentages of neutrophils (P = 0.99) showed no association with final outcome. In contrast, higher neutrophil levels on postoperative day 3 discriminated successfully deceased patients from those who survived (73.3 ± 9.7 vs 84.3 ± 9.7%, P = 0.007) (Table 2).

Table 2.

Perioperative levels of inflammatory biomarkers

VariableTotal populationSurvivorsNon-survivorsP value
WBC0, ×109/L ±SD12.3 ± 6.112.8 ± 6.19.5 ± 5.50.141
WBC3, ×109/L (IQR)8.7 (6.8–12.8)8.3 (6.7–12.4)13.6 (7.9–14.9)0.194
Neu0, % ±SD79.7 ± 8.779.7 ± 8.479.8 ± 11.10.99
Neu3, % ±SD74.9 ± 10.273.3 ± 9.784.3 ± 9.70.007
CRP0, mg L−1 ±SD177.7 ± 103.9168.3 ± 106.4232.8 ± 68.50.085
CRP3, mg L−1 ±SD143.9 ± 70.6138.1 ± 69.9187.3 ± 64.40.083
nCD160, MFI (IQR)44.25 (29.58–73.33)48.8 (31.5–75.6)25.5 (10.7–49.2)0.02
nCD163, MFI ±SD70.72 ± 30.8274.78 ± 30.241.16 ± 16.230.006

Neutrophil CD16

On the 3rd POD (nCD163) we established significantly higher levels of neutrophil CD16 expression compared to the preoperatively measured (nCD160): 71.05 (48.48–89.95) MFI vs. 44.25 (29.58–73.33) MFI, P = 0.001 (Fig. 2A). The healthy controls had more than 2 times higher levels of nCD16 than patients with cIAIs before surgery: 98.8 (87.5–116) MFI vs. 44.25 (29.58–73.33) MFI, P < 0.0001 (Fig. 2B).

Fig. 2.
Fig. 2.

Box-plot and dot-plot of nCD16: (A) Comparing CD16 expression on neutrophils in patients with cIAIs before surgery (n = 60) and postoperatively (n = 58) using box-plot and dot-plot (B) Comparing CD16 expression on neutrophils in patients with cIAIs (n = 60) and healthy controls (n = 31) using box-plot and dot-plot nCD16 – neutrophil CD16 expression; 3rd POD – third postoperative day; cIAIs – complicated intra-abdominal infections

Citation: European Journal of Microbiology and Immunology 14, 1; 10.1556/1886.2023.00046

Preoperative nCD16 expression successfully discriminated patients with a favorable outcome, whereas higher values were associated with lower mortality. The median nCD160 in survivors was almost twice as high compared to non-survivors - 48.8 (31.5–75.6) MFI vs. 25.5 (10.7–49.2), P = 0.02, and this regularity was preserved on the 3rd POD - 74.78 ± 30.2 MFI vs. 41.16 ± 16.23 MFI, P = 0.006 (Table 2).

Preoperatively, we found a good prognostic ability of nCD16 (AUROC = 0.745) and a very good on the 3rd POD (AUROC = 0.846) (Fig. 3). The favorable outcome was successfully predicted at a preoperative threshold >34.75 MFI with a sensitivity of 66.7% and specificity of 77.8%, as well as postoperatively at a threshold nCD163 value >54.8 MFI with a sensitivity of 72.5% and a specificity of 85.7% (Table 3).

Fig. 3.
Fig. 3.

ROC Curves of nCD16: (A) ROC Curve of nCD16 before surgery (n = 60) for prediction of survival (AUROC = 0.745) (B) ROC Curve of nCD16 on postoperative day 3 (n = 58) for prediction of survival (AUROC = 0.846) ROC Curve – receiver operating characteristic curve nCD16 – neutrophil CD16 expression

Citation: European Journal of Microbiology and Immunology 14, 1; 10.1556/1886.2023.00046

Table 3.

Sensitivity, Specificity and AUROCs A. preoperatively B. on the 3rd POD

Cut-offSensitivity, %Specificity, %AUROCStd. Error95% CIP-value
Lower boundUpper bound
nCD16034.7566.777.80.7450.0960.5580.9320.02
nCD16354.872.585.70.8460.0560.7360.9550.003

Discussion

Despite advances in diagnostics, surgical management, and antimicrobial therapy in recent years, complicated intra-abdominal infections are still associated with high morbidity and mortality [1, 17]. They affect large and heterogeneous groups of patients, which makes it difficult to create a general treatment algorithm and emphasizes the need for an individual approach for each patient. The main pre-condition for the effective treatment of the cIAIs includes early diagnosis and prognosis, a suitable antimicrobial therapy and timely and appropriate source control. The early prognostic assessment could significantly reduce the disease severity and improve the outcome by introducing changes with regard to the aggressiveness of the therapeutic approach.

In case of intra-abdominal infection, the local inflammatory response in the peritoneal cavity attracts neutrophils, which arrive at the site within 2–4 h [18]. They are first-line defense cells with function to recognize and respond to infection depending on normal surface receptor expression [9]. On neutrophils, surface expression of the high- and low-affinity receptors for the IgG heavy chain, CD64 and CD16, mediate effector functions [9, 19]. Neutrophils have a short lifespan in circulation (<24 h), but in the presence of infection, their life is prolonged by action of the inflammatory mediators [20]. A delay in neutrophil apoptosis is observed, and that allows their continued function, whereat specific regulatory mechanisms are required to limit the extent of neutrophil activity and restore homeostasis [21]. This is achieved by inducing neutrophil apoptosis. Apoptotic cells undergo several characteristic changes, including changes in the cell membrane that allow their engulfment by macrophages [21, 22]. The level of surface expression of CD16 is proven to be an indicator of the apoptotic status of neutrophils, which was assessed by a very strong positive correlation between lower surface levels of CD16, chromatin condensation, DNA fragmentation, and loss of cellular functions [23].

CD16 expression on neutrophils was found to be a biomarker associated with sepsis [15], which has never been investigated in patients with cIAIs. According to Hsu et al. [15], nCD16 decreases in parallel with an increase in the severity of sepsis. In vivo et in vitro nCD16 expression is significantly decreased by bacterial membrane components, IgG opsonized particles and cytokines [9, 24]. Resting neutrophils constitutively express CD16, which we confirmed by the significantly higher expression in healthy controls compared to cIAIs (98.8 MFI vs. 44.25 MFI, P < 0.0001). In contrast, neutrophil expression of CD64 in the absence of infection is maintained at low levels, but the appearance of PAMPs, components of the complement system and pro-inflammatory cytokines leads to higher expression [8]. In the same cohort, but in another paper published earlier this year [25] we confirmed these findings by the observation of higher nCD64 expression before surgery in patients with cIAIs than in healthy controls (74.4% vs. 45.5%, respectively, P < 0.0001).

Neutrophil CD16 plays a significant role in activating degranulation, phagocytosis, and the oxidative burst, allowing neutrophils to eliminate already opsonized pathogens [4]. Decreased CD16 expression is associated with an increased risk of mortality and reflects increased release following inflammatory stimuli in systemic immune response to immature bone marrow neutrophils that have low or absent CD16 expression [9]. In our study postoperative levels of nCD16 were significantly higher than preoperative (71.05 MFI vs. 44.25 MFI, respectively, P = 0.001), possibly due to decreased release of immature neutrophils from the bone marrow and successful control of the systemic inflammatory response. We found almost two-fold lower expression of nCD16 in non-survivors both preoperatively (25.5MFI vs. 48.8 MFI. P = 0.02) and on the 3rd POD (41.16 MFI vs. 74.78 MFI, P = 0.006). Our previously published paper investigating prognostic value of nCD64 in the same cohort [25] described significantly higher preoperative expression in non-survivors compared to survivors (96.8% vs. 71.85%, P = 0.02). The same observation was also found after surgery (P = 0.024), as in the patients with a favorable outcome the levels were reduced to 56.3%, while non-survivors had evidence of a persistent pro-inflammatory reaction, as they kept the expression of nCD64 high: 90.7%. Both these finding suggested that the systemic pro-inflammatory response is a leading factor in determining the risk of fatal outcome. We observed good prognostic ability of nCD16 preoperatively (AUROC = 0.745) and very good of 3rd POD (AUROC = 0.846). Favorable outcome was successfully predicted at a preoperative cut-off >34.75 MFI with a sensitivity of 66.7% and a specificity of 77.8%, as well as postoperatively at a cut-off value > 54.8 MFI with a sensitivity of 72.5% and a specificity of 85.7%. So far, nCD16 has not been investigated as a prognostic biomarker in patients with cIAIs. In sepsis, Hanna et al. [9], like us, reported that decreased nCD16 expression was associated with an increased risk of death.

This is the first study (to the best of our knowledge) that analyzes the prognostic performance of nCD16 in patients with cIAIs. As limitation we can highlight the single-center experience and the small sample size.

Conclusion

The perioperative expression of CD16 on neutrophils shows prognostic qualities as a significant predictor of survival in patients with complicated intra-abdominal infections.

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Conflict of interest/Competing interests

The authors declare no conflicts of interest or competing interests.

Consent for publication

All authors approved the final draft of the manuscript and gave their consent for publication.

References

  • 1.

    Sartelli M, Chichom-Mefire A, Labricciosa FM, Hardcastle T, Abu-Zidan FM, Adesunkanmi AK, et al. The management of intra-abdominal infections from a global perspective: 2017 WSES guidelines for management of intra-abdominal infections. World J Emerg Surg 2017;12:29. https://doi.org/10.1186/s13017-017-0141-6.

    • Search Google Scholar
    • Export Citation
  • 2.

    Janeway C. Appendix II. CD antigens. In: Immunobiology, 5th ed. New York: Garland; 2001. ISBN 978-0-8153-3642-6.

  • 3.

    Georg P, Astaburuaga-García R, Bonaguro L, Brumhard S, Michalick L, Lippert LJ, et al. Complement activation induces excessive T cell cytotoxicity in severe COVID-19. Cell 2021;185(3):493512.e25. https://doi.org/10.1016/j.cell.2021.12.040.

    • Search Google Scholar
    • Export Citation
  • 4.

    Wang Y, Jönsson F. Expression, role, and regulation of neutrophil Fcγ receptors. Front Immunol. 2019;10(1958). https://doi.org/10.3389/fimmu.2019.01958.

    • Search Google Scholar
    • Export Citation
  • 5.

    Nagelkerke SQ, Schmidt DE, de Haas M, Kuijpers TW. Genetic variation in low-to-medium-affinity Fcγ receptors: functional consequences, disease associations, and opportunities for personalized medicine. Front Immunol. 2019;10:2237. https://doi.org/10.3389/fimmu.2019.02237.

    • Search Google Scholar
    • Export Citation
  • 6.

    Zhang Y, Boesen CC, Radaev S, Brooks A, Fridman WH, Sautes-Fridman C, et al. Crystal structure of the extracellular domain of a human FcγRIII. Immunity September 2000;13(3):38795. https://doi.org/10.1016/S1074-7613(00)00038-8.

    • Search Google Scholar
    • Export Citation
  • 7.

    Lippold S, Knaupp A, de Ru AH, Tjokrodirijo RTN, van Veelen PA, van Puijenbroek E, et al. Fc gamma receptor IIIb binding of individual antibody proteoforms resolved by affinity chromatography-mass spectrometry. MAbs 2021;13(1):1982847. https://doi.org/10.1080/19420862.2021.1982847.

    • Search Google Scholar
    • Export Citation
  • 8.

    Li S, Huang X, Chen Z, Zhong H, Peng Q, Deng Y, et al. Neutrophil CD64 expression as a biomarker in the early diagnosis of bacterial infection: a meta-analysis. Int J Infect Dis 2013 Jan;17(1):e12-23. https://doi.org/10.1016/j.ijid.2012.07.017.

    • Search Google Scholar
    • Export Citation
  • 9.

    Hanna MOF, Abdelhameed AM, Abou-Elalla AA, Hassan RM, Kostandi I. Neutrophil and monocyte receptor expression in patients with sepsis: implications for diagnosis and prognosis of sepsis. Pathog Dis 2019;77(6):ftz055. https://doi.org/10.1093/femspd/ftz055.

    • Search Google Scholar
    • Export Citation
  • 10.

    Elghetany MT, Ge Y, Patel J, Martinez J, Uhrova H. Flow cytometric study of neutrophilic granulopoiesis in normal bone marrow using an expanded panel of antibodies: correlation with morphologic assessments. J Clin Lab Anal 2004;18:3641. https://doi.org/10.1002/jcla.20001.

    • Search Google Scholar
    • Export Citation
  • 11.

    Paudel S, Ghimire L, Jin L, Jeansonne D, Jeyaseelan S. Regulation of emergency granulopoiesis during infection. Front Immunol 2022;13:961601. https://doi.org/10.3389/fimmu.2022.961601.

    • Search Google Scholar
    • Export Citation
  • 12.

    Mare TA, Treacher DF, Shankar-Hari M, Beale R, Lewis SM, Chambers DJ, et al. The diagnostic and prognostic significance of monitoring blood levels of immature neutrophils in patients with systemic inflammation. Crit Care 2015;19:57. https://doi.org/10.1186/s13054-015-0778-z.

    • Search Google Scholar
    • Export Citation
  • 13.

    Muller Kobold AC, Zijlstra JG, Koene HR, de Haas M, Kallenberg CG, Tervaert JW. Levels of soluble Fc gammaRIII correlate with disease severity in sepsis. Clin Exp Immunol 1998;114:2207. https://doi.org/10.1046/j.1365-2249.1998.00727.x.

    • Search Google Scholar
    • Export Citation
  • 14.

    White-Owen C, Alexander JW, Babcock GF. Reduced expression of neutrophil CD11b and CD16 after severe traumatic injury. J Surg Res. 1992;52:226.

    • Search Google Scholar
    • Export Citation
  • 15.

    Hsu KH, Chan MC, Wang JM, Lin LY, Wu CL. Comparison of Fcγ receptor expression on neutrophils with procalcitonin for the diagnosis of sepsis in critically ill patients. Respirology 2011 Jan;16(1):15260. https://doi.org/10.1111/j.1440-1843.2010.01876.x.

    • Search Google Scholar
    • Export Citation
  • 16.

    Lakschevitz FS, Hassanpour S, Rubin A, Fine N, Sun C, Glogauer M. Identification of neutrophil surface marker changes in health and inflammation using high-throughput screening flow cytometry. Exp Cell Res 2016;342(2):200209. https://doi.org/10.1016/j.yexcr.2016.03.007.

    • Search Google Scholar
    • Export Citation
  • 17.

    Blot S, Antonelli M, Arvaniti K, Blot K, Creagh-Brown B, de Lange D, et al. Epidemiology of intra-abdominal infection and sepsis in critically ill patients: “AbSeS”, a multinational observational cohort study and ESICM Trials Group Project. Intensive Care Med 2019;45(12):17031717. https://doi.org/10.1007/s00134-019-05819-3.

    • Search Google Scholar
    • Export Citation
  • 18.

    Gotts JE, Matthay MA. Sepsis: pathophysiology and clinical management. BMJ. 2016;23;353:i1585.

  • 19.

    Barb AW. Fc γ receptor compositional heterogeneity: considerations for immunotherapy development. The J Biol Chem. 2021;296:100057. https://doi.org/10.1074/jbc.REV120.013168.

    • Search Google Scholar
    • Export Citation
  • 20.

    Beghini J, Giraldo PC, Riboldi R, Amaral RL, Eleutério J Jr, Witkin SS, et al. Altered CD16 expression on vaginal neutrophils from women with vaginitis. Eur J Obstet Gynecol Reprod Biol 2013;167(1):9699. https://doi.org/10.1016/j.ejogrb.2012.11.008.

    • Search Google Scholar
    • Export Citation
  • 21.

    Fox S, Leitch AE, Duffin R, Haslett C, Rossi AG. Neutrophil apoptosis: relevance to the innate immune response and inflammatory disease. J Innate Immun 2010;2:21627. https://doi.org/10.1159/000284367.

    • Search Google Scholar
    • Export Citation
  • 22.

    Rungelrath V, Kobayashi SD, DeLeo FR. Neutrophils in innate immunity and systems biology-level approaches. Wiley Interdiscip Rev Syst Biol Med. 2020;12(1):e1458. https://doi.org/10.1002/wsbm.1458.

    • Search Google Scholar
    • Export Citation
  • 23.

    Nusbaum P, Laine C, Seveau S, Lesavre P, Halbwachs‐Mecarelli L. Early membrane events in polymorphonuclear cell (PMN) apoptosis: membrane blebbing and vesicle release, CD43 and CD16 down-regulation and phosphatidylserine externalization. Biochem Soc Trans 2004;32:4779.

    • Search Google Scholar
    • Export Citation
  • 24.

    Wagner C, Deppisch R, Denefleh B, Hug F, Andrassy K, Hänsch GM. Expression patterns of the lipopolysaccharide receptor CD14, and the FCgamma receptors CD16 and CD64 on polymorphonuclear neutrophils: data from patients with severe bacterial infections and lipopolysaccharide-exposed cells. Shock 2003;19:512. https://doi.org/10.1097/00024382-200301000-00002.

    • Search Google Scholar
    • Export Citation
  • 25.

    Dimitrov E, Halacheva K, Minkov G, Enchev E, Yovtchev Y. Prognostic performance of neutrophil CD64 expression in patients with complicated intra-abdominal infections - a prospective study. Scand J Clin Lab Invest 2023;83(5):323329. https://doi.org/10.1080/00365513.2023.2225221.

    • Search Google Scholar
    • Export Citation
  • 1.

    Sartelli M, Chichom-Mefire A, Labricciosa FM, Hardcastle T, Abu-Zidan FM, Adesunkanmi AK, et al. The management of intra-abdominal infections from a global perspective: 2017 WSES guidelines for management of intra-abdominal infections. World J Emerg Surg 2017;12:29. https://doi.org/10.1186/s13017-017-0141-6.

    • Search Google Scholar
    • Export Citation
  • 2.

    Janeway C. Appendix II. CD antigens. In: Immunobiology, 5th ed. New York: Garland; 2001. ISBN 978-0-8153-3642-6.

  • 3.

    Georg P, Astaburuaga-García R, Bonaguro L, Brumhard S, Michalick L, Lippert LJ, et al. Complement activation induces excessive T cell cytotoxicity in severe COVID-19. Cell 2021;185(3):493512.e25. https://doi.org/10.1016/j.cell.2021.12.040.

    • Search Google Scholar
    • Export Citation
  • 4.

    Wang Y, Jönsson F. Expression, role, and regulation of neutrophil Fcγ receptors. Front Immunol. 2019;10(1958). https://doi.org/10.3389/fimmu.2019.01958.

    • Search Google Scholar
    • Export Citation
  • 5.

    Nagelkerke SQ, Schmidt DE, de Haas M, Kuijpers TW. Genetic variation in low-to-medium-affinity Fcγ receptors: functional consequences, disease associations, and opportunities for personalized medicine. Front Immunol. 2019;10:2237. https://doi.org/10.3389/fimmu.2019.02237.

    • Search Google Scholar
    • Export Citation
  • 6.

    Zhang Y, Boesen CC, Radaev S, Brooks A, Fridman WH, Sautes-Fridman C, et al. Crystal structure of the extracellular domain of a human FcγRIII. Immunity September 2000;13(3):38795. https://doi.org/10.1016/S1074-7613(00)00038-8.

    • Search Google Scholar
    • Export Citation
  • 7.

    Lippold S, Knaupp A, de Ru AH, Tjokrodirijo RTN, van Veelen PA, van Puijenbroek E, et al. Fc gamma receptor IIIb binding of individual antibody proteoforms resolved by affinity chromatography-mass spectrometry. MAbs 2021;13(1):1982847. https://doi.org/10.1080/19420862.2021.1982847.

    • Search Google Scholar
    • Export Citation
  • 8.

    Li S, Huang X, Chen Z, Zhong H, Peng Q, Deng Y, et al. Neutrophil CD64 expression as a biomarker in the early diagnosis of bacterial infection: a meta-analysis. Int J Infect Dis 2013 Jan;17(1):e12-23. https://doi.org/10.1016/j.ijid.2012.07.017.

    • Search Google Scholar
    • Export Citation
  • 9.

    Hanna MOF, Abdelhameed AM, Abou-Elalla AA, Hassan RM, Kostandi I. Neutrophil and monocyte receptor expression in patients with sepsis: implications for diagnosis and prognosis of sepsis. Pathog Dis 2019;77(6):ftz055. https://doi.org/10.1093/femspd/ftz055.

    • Search Google Scholar
    • Export Citation
  • 10.

    Elghetany MT, Ge Y, Patel J, Martinez J, Uhrova H. Flow cytometric study of neutrophilic granulopoiesis in normal bone marrow using an expanded panel of antibodies: correlation with morphologic assessments. J Clin Lab Anal 2004;18:3641. https://doi.org/10.1002/jcla.20001.

    • Search Google Scholar
    • Export Citation
  • 11.

    Paudel S, Ghimire L, Jin L, Jeansonne D, Jeyaseelan S. Regulation of emergency granulopoiesis during infection. Front Immunol 2022;13:961601. https://doi.org/10.3389/fimmu.2022.961601.

    • Search Google Scholar
    • Export Citation
  • 12.

    Mare TA, Treacher DF, Shankar-Hari M, Beale R, Lewis SM, Chambers DJ, et al. The diagnostic and prognostic significance of monitoring blood levels of immature neutrophils in patients with systemic inflammation. Crit Care 2015;19:57. https://doi.org/10.1186/s13054-015-0778-z.

    • Search Google Scholar
    • Export Citation
  • 13.

    Muller Kobold AC, Zijlstra JG, Koene HR, de Haas M, Kallenberg CG, Tervaert JW. Levels of soluble Fc gammaRIII correlate with disease severity in sepsis. Clin Exp Immunol 1998;114:2207. https://doi.org/10.1046/j.1365-2249.1998.00727.x.

    • Search Google Scholar
    • Export Citation
  • 14.

    White-Owen C, Alexander JW, Babcock GF. Reduced expression of neutrophil CD11b and CD16 after severe traumatic injury. J Surg Res. 1992;52:226.

    • Search Google Scholar
    • Export Citation
  • 15.

    Hsu KH, Chan MC, Wang JM, Lin LY, Wu CL. Comparison of Fcγ receptor expression on neutrophils with procalcitonin for the diagnosis of sepsis in critically ill patients. Respirology 2011 Jan;16(1):15260. https://doi.org/10.1111/j.1440-1843.2010.01876.x.

    • Search Google Scholar
    • Export Citation
  • 16.

    Lakschevitz FS, Hassanpour S, Rubin A, Fine N, Sun C, Glogauer M. Identification of neutrophil surface marker changes in health and inflammation using high-throughput screening flow cytometry. Exp Cell Res 2016;342(2):200209. https://doi.org/10.1016/j.yexcr.2016.03.007.

    • Search Google Scholar
    • Export Citation
  • 17.

    Blot S, Antonelli M, Arvaniti K, Blot K, Creagh-Brown B, de Lange D, et al. Epidemiology of intra-abdominal infection and sepsis in critically ill patients: “AbSeS”, a multinational observational cohort study and ESICM Trials Group Project. Intensive Care Med 2019;45(12):17031717. https://doi.org/10.1007/s00134-019-05819-3.

    • Search Google Scholar
    • Export Citation
  • 18.

    Gotts JE, Matthay MA. Sepsis: pathophysiology and clinical management. BMJ. 2016;23;353:i1585.

  • 19.

    Barb AW. Fc γ receptor compositional heterogeneity: considerations for immunotherapy development. The J Biol Chem. 2021;296:100057. https://doi.org/10.1074/jbc.REV120.013168.

    • Search Google Scholar
    • Export Citation
  • 20.

    Beghini J, Giraldo PC, Riboldi R, Amaral RL, Eleutério J Jr, Witkin SS, et al. Altered CD16 expression on vaginal neutrophils from women with vaginitis. Eur J Obstet Gynecol Reprod Biol 2013;167(1):9699. https://doi.org/10.1016/j.ejogrb.2012.11.008.

    • Search Google Scholar
    • Export Citation
  • 21.

    Fox S, Leitch AE, Duffin R, Haslett C, Rossi AG. Neutrophil apoptosis: relevance to the innate immune response and inflammatory disease. J Innate Immun 2010;2:21627. https://doi.org/10.1159/000284367.

    • Search Google Scholar
    • Export Citation
  • 22.

    Rungelrath V, Kobayashi SD, DeLeo FR. Neutrophils in innate immunity and systems biology-level approaches. Wiley Interdiscip Rev Syst Biol Med. 2020;12(1):e1458. https://doi.org/10.1002/wsbm.1458.

    • Search Google Scholar
    • Export Citation
  • 23.

    Nusbaum P, Laine C, Seveau S, Lesavre P, Halbwachs‐Mecarelli L. Early membrane events in polymorphonuclear cell (PMN) apoptosis: membrane blebbing and vesicle release, CD43 and CD16 down-regulation and phosphatidylserine externalization. Biochem Soc Trans 2004;32:4779.

    • Search Google Scholar
    • Export Citation
  • 24.

    Wagner C, Deppisch R, Denefleh B, Hug F, Andrassy K, Hänsch GM. Expression patterns of the lipopolysaccharide receptor CD14, and the FCgamma receptors CD16 and CD64 on polymorphonuclear neutrophils: data from patients with severe bacterial infections and lipopolysaccharide-exposed cells. Shock 2003;19:512. https://doi.org/10.1097/00024382-200301000-00002.

    • Search Google Scholar
    • Export Citation
  • 25.

    Dimitrov E, Halacheva K, Minkov G, Enchev E, Yovtchev Y. Prognostic performance of neutrophil CD64 expression in patients with complicated intra-abdominal infections - a prospective study. Scand J Clin Lab Invest 2023;83(5):323329. https://doi.org/10.1080/00365513.2023.2225221.

    • Search Google Scholar
    • Export Citation
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Senior editors

Editor(s)-in-Chief: Dunay, Ildiko Rita, Prof. Dr. Pharm, Dr. rer. nat., University of Magdeburg, Germany

Editor(s)-in-Chief: Heimesaat, Markus M., Prof. Dr. med., Charité - University Medicine Berlin, Germany

Editorial Board

  • Berit Bangoura, Dr. DVM. PhD,  University of Wyoming, USA
  • Stefan Bereswill, Prof. Dr. rer. nat., Charité - University Medicine Berlin, Germany
  • Dunja Bruder, Prof. Dr. rer. nat., University of Magdeburg, Germany
  • Jan Buer, Prof. Dr. med., University of Duisburg, Germany
  • Edit Buzas, Prof. Dr. med., Semmelweis University, Hungary
  • Renato Damatta, Prof. PhD, UENF, Brazil
  • Maria Deli, MD, PhD, DSc, Biological Research Center, HAS, Hungary
  • Olgica Djurković-Djaković, Prof. Phd, University of Belgrade, Serbia
  • Jean-Dennis Docquier, Prof. Dr. med., University of Siena, Italy
  • Zsuzsanna Fabry, Prof. Phd, University of Washington, USA
  • Ralf Ignatius, Prof. Dr. med., Charité - University Medicine Berlin, Germany
  • Achim Kaasch, Prof. Dr. med., Otto von Guericke University Magdeburg, Germany
  • Oliver Liesenfeld, Prof. Dr. med., Inflammatix, USA
  • Matyas Sandor, Prof. PhD, University of Wisconsin, USA
  • Ulrich Steinhoff, Prof. PhD, University of Marburg, Germany
  • Michal Toborek, Prof. PhD, University of Miami, USA
  • Susanne A. Wolf, PhD, MDC-Berlin, Germany

 

Dr. Dunay, Ildiko Rita
Magdeburg, Germany
E-mail: ildiko.dunay@med.ovgu.de

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2023  
Web of Science  
Total Cites
WoS
674
Journal Impact Factor 3.3
Rank by Impact Factor

Q2

Impact Factor
without
Journal Self Cites
3.1
5 Year
Impact Factor
3.2
Scimago  
Scimago
H-index
15
Scimago
Journal Rank
0.601
Scimago Quartile Score Microbiology (medical) (Q2)
Microbiology (Q3)
Immunology and Allergy (Q3)
Immunology (Q3)
Scopus  
Scopus
Cite Score
5.0
Scopus
CIte Score Rank
Microbiology (medical) Q2
Scopus
SNIP
0.832

 

European Journal of Microbiology and Immunology
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European Journal of Microbiology and Immunology
Language English
Size A4
Year of
Foundation
2011
Volumes
per Year
1
Issues
per Year
4
Founder Akadémiai Kiadó
Founder's
Address
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
Publisher Akadémiai Kiadó
Publisher's
Address
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
Responsible
Publisher
Chief Executive Officer, Akadémiai Kiadó
ISSN 2062-509X (Print)
ISSN 2062-8633 (Online)

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