A One-Minute Blood Test Detects Decreased Immune Function and Increased Clinical Risk in COVID-19 Patients

Abstract Upon infection with SARS-CoV-2, the virus that causes COVID-19, most people will develop no or mild symptoms. However, a small percentage of the population will become severely ill, and some will succumb to death. The clinical severity of COVID-19 has a close connection to the dysregulation of the patient’s immune functions. We previously developed a simple, nanoparticle-enabled blood test that can determine the humoral immune status in animals. In this study, we applied this new test to analyze the immune function in relation to disease severity in COVID-19 patients. From the testing of 153 COVID-19 patient samples and 142 negative controls, we detected a drastic decrease of humoral immunity in COVID-19 patients who developed moderate to severe symptoms, but not in patients with no or mild symptoms. The new test may be potentially used to monitor the immunity change and predict the clinical risk of patients with COVID-19.

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A 1-minute blood test detects decreased immune function and increased clinical risk in COVID-19 patients

Scientific Reports ◽

10.1038/s41598-021-02863-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Chirajyoti Deb ◽

Allan N. Salinas ◽

Tianyu Zheng ◽

Aurea Middleton ◽

Katelyn Kern ◽

...

Keyword(s):

Immune Function ◽

Disease Severity ◽

Humoral Immunity ◽

Blood Test ◽

Immune Status ◽

Clinical Severity ◽

Immune Functions ◽

Humoral Immune ◽

Clinical Risk ◽

Negative Controls

AbstractUpon infection with SARS-CoV-2, the virus that causes COVID-19, most people will develop no or mild symptoms. However, a small percentage of the population will become severely ill, and some will succumb to death. The clinical severity of COVID-19 has a close connection to the dysregulation of the patient’s immune functions. We previously developed a simple, nanoparticle-enabled blood test that can determine the humoral immune status in animals. In this study, we applied this new test to analyze the immune function in relation to disease severity in COVID-19 patients. From the testing of 153 COVID-19 patient samples and 142 negative controls, we detected a drastic decrease of humoral immunity in COVID-19 patients who developed moderate to severe symptoms, but not in patients with no or mild symptoms. The new test may be potentially used to monitor the immunity change and predict the clinical risk of patients with COVID-19.

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Elotuzumab Enhances the Th2-Mediated Immune Response of Dendritic Cell Induced By Immunomodulatory Drugs (IMiDs)

Blood ◽

10.1182/blood-2019-129680 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4342-4342

Author(s):

Yoshiko Azuma ◽

Tomoki Ito ◽

Muneo Inaba ◽

Kai Imai ◽

Masaaki Hotta ◽

...

Keyword(s):

Immune Response ◽

Immune System ◽

Dendritic Cell ◽

Humoral Immunity ◽

Immune Status ◽

Fold Increase ◽

Immune Dysfunction ◽

Th2 Response ◽

Humoral Immune ◽

Before And After

Background: Elotuzumab, a humanized IgG1 monoclonal antibody targeting SLAMF7, is useful for the treatment of Relapsed or Refractory multiple myeloma (RRMM) in combination with Lenalidomide (LEN). However, cellular and molecular mechanisms underlying the immunomodulatory effects of elotuzumab still remain largely unclear. We have previously reported that LEN displays immunopotentiating activity that enhances Th2-mediated response at dendritic cell (DC) phase as upstream immune cascade associated with humoral immunity. DCs are pivotal cells in the sense of orchestrating both cell-mediated (linking with Th1) and humoral (linking with Th2) immunity as masters of the immune system. Series of analyses have clarified myeloid DCs (mDCs) play an important role in allergic immune response by the induction of Th2 response. Here, we focused on the effects of elotuzumab in combination with LEN on the function of human mDCs. Methods: Purified blood human CD11+ mDCs from healthy adult volunteers using cell sorting were cultured and analyzed by flow cytometry and ELISA. Serum were obtained from 16 MM patients with before and after elotuzumab therapy. This study was approved by the Institutional Review Board of Kansai Medical University. Results: We found that surface expression of SLAMF7 on mDCs was upregulated in response to Th2-inducing cytokine, thymic stromal lymphopoietin (TSLP) and the expression level was higher in response to TSLP than in response to toll-like receptor ligand R848. Elotuzumab at clinical in vivo plasma concentration of 30 to 300 µg/ml did not affect mDC survival and their CD86 and OX40-ligand expression when stimulated with 0.3 µM LEN and/or TSLP for 24 h. LEN enhanced TSLP-mediated Th2-recruiting chemokine CCL17/TARC from mDCs which functions as chemoattractant for memory Th2 cells and contribute to allergy and humoral immune responses, and elotuzumab significantly enhanced the LEN-mediated production of CCL17/TARC (TSLP+LEN as control vs. TSLP+LEN+100 µg/ml elotuzumab; 1.23 fold increase: p=0.003, and control vs. TSLP+LEN+300 µg/ml elotuzumab; 1.38 fold increase: p=0.038). This finding suggest elotuzumab enhances Th2-mediated immune profile at upstream phase of humoral immunity. In addition, serum CCL17 levels were analyzed in RRMM patients before and after 3 cycle elotuzumab administration (n=16). We found, serum CCL17 levels after elotuzumab administration were significantly higher compared with those before elotuzumab treatment (after; 1512 ± 459 pg/ml vs. before; 402.2 ± 87.4 pg/ml: p = 0.013). Conclusion: MM involves an element of humoral immune dysfunction. Immune status is important for the prognosis of MM, and clinical outcome can be improved by the recovery of immune status. In this context, our data showing the enhancement of Th2-mediated response by elotuzumab provide a plausible explanation for the observed clinical benefit of this antibody-drug in MM. This function of elotuzumab seems to be relevant to the treatment of MM patients under humoral immune dysfunction. Based on our data in focusing on DCs in the immune system, elotuzumab and IMiDs could function as immunostimulators of humoral immunity via mDCs, and this finding elucidated an additional cellular target of elotuzumab. Disclosures Ito: Celgene: Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding.

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Leptin, but not immune function, is linked to reproductive responsiveness to photoperiod

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2000.278.6.r1401 ◽

2000 ◽

Vol 278 (6) ◽

pp. R1401-R1407 ◽

Cited By ~ 41

Author(s):

Deborah L. Drazen ◽

Lance J. Kriegsfeld ◽

Jill E. Schneider ◽

Randy J. Nelson

Keyword(s):

Immune Function ◽

Reproductive Function ◽

Keyhole Limpet Hemocyanin ◽

Dark Phase ◽

Immune Functions ◽

Humoral Immune ◽

Short Day ◽

Siberian Hamsters ◽

Body Fat Content ◽

Energy Conserving

Energetic demands are high while energy availability is minimum during winter. To cope with this energetic bottleneck, animals exhibit numerous energy-conserving adaptations during winter, including changes in immune and reproductive functions. A majority of individual rodents within a population inhibits reproductive function (responders) as winter approaches. A substantial proportion of small rodents within a species, however, fails to inhibit reproduction (nonresponders) during winter in the field or in the laboratory when maintained in winter-simulated day lengths. In contrast, immune function is bolstered by short day lengths in some species. The specific mechanisms that link reproductive and immune functions remain unspecified. Leptin is a hormone produced by adipose tissue, and several studies suggest that leptin modulates reproductive and immune functions. The present study sought to determine if photoperiodic alterations in reproductive function and leptin concentrations are linked to photoperiod-modulated changes in immune function. Siberian hamsters ( Phodopus sungorus) were housed in either long (LD 16:8) or short (LD 8:16) day lengths for 9 wk. After 9 wk, blood samples were collected during the middle of the light and dark phase to assess leptin concentrations. One week later, animals were injected with keyhole limpet hemocyanin to evaluate humoral immunity. Body mass, body fat content, and serum leptin concentrations were correlated with reproductive responsiveness to photoperiod; short-day animals with regressed gonads exhibited a reduction in these measures, whereas short-day nonresponders resembled long-day animals. In contrast, immune function was influenced by photoperiod but not reproductive status. Taken together, these data suggest that humoral immune function in Siberian hamsters is independent of photoperiod-mediated changes in leptin concentrations.

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Author Correction: A 1-minute blood test detects decreased immune function and increased clinical risk in COVID-19 patients

Scientific Reports ◽

10.1038/s41598-021-04067-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Chirajyoti Deb ◽

Allan N. Salinas ◽

Tianyu Zheng ◽

Aurea Middleton ◽

Katelyn Kern ◽

...

Keyword(s):

Immune Function ◽

Blood Test ◽

Clinical Risk

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Protective Effect of Bergenin against Cyclophosphamide-Induced Immunosuppression by Immunomodulatory Effect and Antioxidation in Balb/c Mice

Molecules ◽

10.3390/molecules23102668 ◽

2018 ◽

Vol 23 (10) ◽

pp. 2668 ◽

Cited By ~ 8

Author(s):

Qiuchen Qi ◽

Zhonghua Dong ◽

Yueyue Sun ◽

Siying Li ◽

Zhongxi Zhao

Keyword(s):

Immune Function ◽

Adverse Reactions ◽

Histological Analysis ◽

Lymphocyte Subsets ◽

Immune Functions ◽

Humoral Immune ◽

Immune Organs ◽

Total Antioxidant ◽

Cellular Immune ◽

Immunosuppressed Mice

In this study, the aim was to investigate the effect of bergenin on immune function and antioxidation in cyclophosphamide (Cy)-induced immunosuppressed mice. Firstly, we estimated its effect on immune organs. Histological analysis and indexes of immune organs showed that cyclophosphamide exhibited spleen and thymus injury compared with the normal control, which was alleviated by bergenin. Secondly, bergenin also enhanced the humoral immune function through increasing the level of IgM and IgG in serum. Thirdly, bergenin also enhanced the cellular immune function. The results indicate that bergenin increased peritoneal macrophage functions, the proliferation of T and B lymphocytes, NK and CTL cell activities, and T (CD4+ and CD8+) lymphocyte subsets. Besides, bergenin also had the ability to modulate the Th1/Th2 balance. Moreover, bergenin prevented the Cy-induced decrease in numbers of peripheral RBC, WBC and platelets, providing supportive evidence for their anti-leukopenia activities. Finally, bergenin also reversed the Cy-induced decrease in the total antioxidant capacity including activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px). In conclusion, bergenin protected against Cy-induced adverse reactions by enhancing humoral and cellular immune functions and augmenting antioxidative activity and could be considered as a potential immunomodulatory agent.

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Use and Clinical Interpretation of Pneumococcal Antibody Measurements in the Evaluation of Humoral Immune Function

Clinical and Vaccine Immunology ◽

10.1128/cvi.00735-14 ◽

2014 ◽

Vol 22 (2) ◽

pp. 148-152 ◽

Cited By ~ 26

Author(s):

Thomas M. Daly ◽

Harry R. Hill

Keyword(s):

Immune Function ◽

Immune Status ◽

Pneumococcal Vaccination ◽

Published Data ◽

Historical Evolution ◽

Specific Data ◽

Cut Points ◽

Humoral Immune ◽

Multiplex Assays ◽

Adequate Response

ABSTRACTPneumococcal vaccination is a commonly used technique for assessing the humoral immune status of a patient suspected of having immunodeficiency. Interpretation of what constitutes an adequate response, however, can be challenging. This is due to the complexity of the data generated from serotype-specific assays, historical variations in the assays used to measure pneumococcal antibodies, and varying recommendations on the relevant cut points that define response. In this review, we summarize the historical evolution of assays used for this purpose and discuss the analytical considerations that have influenced published data. We also examine current clinical recommendations for defining an adequate response to vaccination, with a particular focus on the interpretation of serotype-specific data generated by multiplex assays.

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Changes in CD4+CD8–/CD4–CD8+ Ratio and Humoral Immune Functions in Vitamin B12-Deficient Rats

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.70.4.167 ◽

2000 ◽

Vol 70 (4) ◽

pp. 167-171 ◽

Cited By ~ 8

Author(s):

Ulala Funada ◽

Masahiro Wada ◽

Tetsunori Kawata ◽

Kazumi Mori ◽

Hiroko Tamai ◽

...

Keyword(s):

Vitamin B12 ◽

Immune Function ◽

Control Group ◽

Vitamin B ◽

Immune Functions ◽

Normal Range ◽

Humoral Immune ◽

Deficient Group

To clarify the role of vitamin B12 in the function of cell-mediated and humoral immune functions, the splenocytes expression of CD4, CD8 and serum C3, IgM, IgG concentrations were examined in vitamin B12-deficient rats, and the effect of the administration of methylcobalamin was also studied. The CD4+CD8–/CD4–CD8+ ratio in splenocytes was significantly higher in vitamin B12-deficient rats than in control rats (p < 0.05). The value in the 48 hours after methylcobalamin administration group, was within the normal range (p < 0.05). From these results, the elevation of the CD4+CD8–/CD4–CD8+ ratio by vitamin B12-deficiency was confirmed in rats. The serum C3, IgM and IgG concentrations were lower in the vitamin B12-deficient group than in the control group. These findings suggest that vitamin B12 plays a role in maintaining the immune function in rats.

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