1. Home
  2. Vol 55, No 1 (2023)
  3. Nabilah

The Comparison of Monocyte Human Leukocyte Antigen-D-Related (mHLA-DR) Expression Levels Between Corona Virus Disease 2019 (COVID-19) Patients and Healthy Subjects

Musholli Himmatun Nabilah, Puspa Wardhani, Aryati Aryati, Yetti Hernaningsih, Bambang Pujo Semedi

Abstract


Background: SARS-CoV-2 can trigger a dysfunctional immune response in COVID-19 patients and lead to immunosuppression. HLA-DR molecule expressed on the surface of monocytes, known as mHLA-DR, has been widely used as a reliable marker of immunosuppression. Downregulation of mHLA-DR reflects an immunosuppressed state. This study aimed to compare the expression level of mHLA-DR between COVID-19 patients and healthy subjects concerning immune system dysregulation that can be triggered by SARS-CoV-2 and lead to immunosuppression. Methods: This was an analytic observational study with a cross-sectional design that measured the mHLA-DR expression in EDTA blood samples from 34 COVID-19 patients and 15 healthy subjects using the BD FACSLyricTM Flow Cytometry System. The mHLA-DR examination results were expressed in AB/C (antibodies bound per cell) that were quantified using a standard curve constructed with Quantibrite phycoerythrin beads (BD Biosciences). Results: Expression of mHLA-DR in COVID-19 patients (n = 34) were 21,201 [2,646-92,384] AB/C, with 40,543.5 [9,797-92,384] AB/C mild cases (n = 22), 21,201 [9,831-31,930] AB/C moderate cases (n = 6), and 7,496 [2,646-13,674] AB/C severe to critical cases (n= 6). Expression of mHLA-DR in healthy subjects (n = 15) was 43,161 [25,147-89,846] AB/C. Based on the Mann-Whitney U test, the mHLA-DR expression in COVID-19 patients significantly differed from the mHLA-DR expression in healthy subjects (p = 0.010). Conclusion: The level of mHLA-DR expression in COVID-19 patients was lower and significantly different from healthy subjects. Moreover, immunosuppression could be indicated by the decrease of mHLA-DR expression, which was below the reference range found in severe to critically ill COVID-19 patients.

Keywords


COVID-19; Monocyte Human Leukocyte Antigen-D-Related (mHLA-DR); Immunosuppression

References


WHO. 2022. COVID-19: symptoms and severity. World Health Organization Western Pacific. The last update was on April 18, 2022.

Qin C, Zhou L, Hu Z, et al. Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clin Infect Dis. 2020;71(15):13-4.

Giamarellos-Bourboulis Evangelos J, Netea MG, Rovina N, et al. Complex immune dysregulation in COVID-19 patients with severe respiratory failure. Cell Host Microbe. 2020;27(6):992-1000.

Cervantes, Leticia Kuri, Pampena M, et al. Comprehensive mapping of immune perturbations associated with severe COVID-19. Science Immunology. 2020;15;5(49):4-5.

Peruzzi, Benedetta, Bencini S, et al. Quantitative and qualitative alterations of circulating myeloid cells and plasmacytoid DC in SARS-CoV-2 infection. British Society for Immunology. 2020;161(4):1-8.

Ohno Y, Kitamura H, Takahashi N, et al. IL-6 down-regulates HLA class II expression and IL-12 production of human dendritic cells to impair activation of antigen- specific CD4(+) T cells. Cancer Immunol. 2016;65(2):193-204.

Lukaszewicz, Anne-Claire, Grienary, et al. Monocytic HLA-DR expression in intensive care patients: Interest for prognosis and secondary infection prediction. Crit Care Med. 2009;37 (10): 2746-2747.

Zmijewski, Jaroslaw W, Pittet, Jean-Francois. Human leukocyte antigen-DR deficiency and immunosuppression-related end-organ failure in severe acute respiratory syndrome Coronavirus 2 infection. International Anesthesia Research. 2020; 131(4):989-92.

Thibaud S, Cedric H, Michaela F, et al. Reduced monocytic human leukocyte antigen-DR expression indicates immunosuppression in critically ill COVID-19 patients. Critical Care and Resuscitation. 2020;131(4):994-8.

Steffen D, Clemens G, Katharina A, et al. Case report: Interferon-γ restores monocytic human leukocyte antigen receptor (mHLA-DR) in severe COVID-19 with acquired immunosuppression syndrome. Frontiers in Immunology. 2021;12:1-2.

Pfortmueller, Andrea C, Christian M, Michaela F, Schefold, Joerg C. Assessment of immune organ dysfunction in critical illness: utility of innate immune response markers. Intensive Care Med Exp. 2017;5(49):1-16.

Benjamin B, Justine C, Claire D, et al. Severe COVID-19 is characterized by the co-occurrence of moderate cytokine inflammation and severe monocyte dysregulation. EbioMedicine. 2021;73(103622):1-13.

BD Biosciences. 2014. BD Quantibrite™ Beads PE Fluorescence Quantitation Kit. San Jose, CA 95131 USA.

BD Biosciences. 2014. BD Quantibrite™ Anti–HLA-DR/Anti-Monocyte Kit. San Jose, CA 95131 USA.

Julie D, Alexandre W, Marie-Christine J, et al. Inter-laboratory assessment of flow cytometric monocyte HLA-DR expression in clinical samples. Clinical Cytometry. 2012;84(1):1-4.

Yang L, Liu S, Liu J, et al. COVID-19: Immuno-pathogenesis and Immunotherapeutics. 2020.

Signal Transduction and Targeted Therapy. 5:128.

Sutadji, Christianto J, Widodo, Wahyu AD, Indiastuti, Danti Nur. Mortality comparison of using anti interleukin-6 therapy and using standard treatment in severe COVID-19. Folia Medica Indonesiana. 2021; 57(2).

Munawaroh F, Agustina TB, Hartono K, et al. Characteristics of natural killer (NK) cell and T lymphocyte in COVID-19 patients in Surabaya, Indonesia. Research J.Pharm and Tech. 2022;15(5).

Ihsane B, Fabienne V, Rémy C, Morgane G, Guillaume M. Monocyte HLA-DR measurement by flow cytometry in COVID-19 patients: An interim review. Journal of Quantitative Cell Science. 2020;97A: 1217–21.


Full Text: PDF

Refbacks

  • There are currently no refbacks.