Towards standardization of immune functional assays

AbstractRecent advances in the immunotherapy field require evaluation of the immune function to adapt therapeutic decisions. Immune functional assays (IFA) are able to reveal the immune status and would be useful to further adapt/improve patient’s care. However, standardized methods are needed to implement IFA in clinical settings. We carried out an independent validation of a published method used to characterize the underlying host response to infectious conditions using an IFA. We evaluate the reproducibility and robustness of this IFA and associated readout using an independent healthy volunteers (HV) cohort. Expression of a 44 genes-signatures and IFNγ protein secretion and gene-expression was assessed after stimulation. We observed a strong host-response correlation between the two cohorts. We also highlight that standardized methods for immune function evaluation exist and could be implemented in larger-scale studies. This IFA could be a relevant tool to reveal innate/adaptive immune dysfunction in immune-related disorders patients.

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VaccHemInf project: protocol for a prospective cohort study of efficacy, safety and characterisation of immune functional response to vaccinations in haematopoietic stem cell transplant recipients

BMJ Open ◽

10.1136/bmjopen-2018-026093 ◽

2019 ◽

Vol 9 (2) ◽

pp. e026093 ◽

Cited By ~ 5

Author(s):

Anne Conrad ◽

Mathilde Boccard ◽

Florent Valour ◽

Vincent Alcazer ◽

Aydee-Tamara Tovar Sanchez ◽

...

Keyword(s):

Cohort Study ◽

Stem Cell ◽

Immune Function ◽

Immune Status ◽

Haematopoietic Stem Cell ◽

Cell Transplant ◽

Serological Response ◽

Vaccine Response ◽

Functional Assays ◽

Prospective Longitudinal

IntroductionImmune reconstitution after haematopoietic stem cell transplantation (HSCT) is a complex and dynamic process, varying from a state of nearly complete immunosuppression to an expected full immune recovery. Specific vaccination guidelines recommend reimmunisation after HSCT but data regarding vaccine efficacy in this unique population are scarce. New immune functional assays could enable prediction of vaccine response in the setting of HSCT.Methods and analysisA prospective, longitudinal single-centre cohort study of autologous and allogeneic HSCT recipients was designed in order to determine the vaccine response to five vaccine targets (pneumococcus, hepatitis B virus,Haemophilus Influenzaetype b, tetanus and diphtheria) and to correlate it to immune function parameters. A workflow was set up to study serological response to vaccines and to describe the functional immune status of 100 HSCT recipients (50 autologous and 50 allogeneic) before and 3, 12 and 24 months after primary immunisation. At each time point, ‘basic’ immune status recording (serology, immunophenotyping of lymphocyte subsets by flow cytometry) will be assessed. The immune response will furthermore be evaluated before and 3 months after primary vaccination by two ex vivo immune functional assays assessing: (1) tumour necrosis factor alpha, interferon gamma production and host messenger RNA expression on whole-blood stimulation by lipopolysaccharide orStaphylococcus aureusenterotoxin B and (2) T-lymphocyte proliferation in response to a standard mitogen (phytohaemagglutinin) or to selected recall antigens. Reference intervals will be determined from a cohort of 30 healthy volunteers. This translational study will provide data describing vaccine response, immune functionality of HSCT recipients over time and will allow mapping HSCT recipients with regard to their immune function.Ethics and disseminationEthical approval has been obtained from the institutional review board (no 69HCL17_0769). Results will be communicated at scientific meetings and submitted for publication in peer-reviewed journals.Trial registration numberNCT03659773; Pre-results.

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Neuromyelitis optica spectrum: novel concept of pathogenesis, diagnosis and treatment of Devic’s disease

Orvosi Hetilap ◽

10.1556/oh.2009.28724 ◽

2009 ◽

Vol 150 (46) ◽

pp. 2101-2109 ◽

Cited By ~ 1

Author(s):

Péter Csécsei ◽

Anita Trauninger ◽

Sámuel Komoly ◽

Zsolt Illés

Keyword(s):

Neuromyelitis Optica ◽

Water Channel ◽

Diagnostic Procedures ◽

Diagnosis And Treatment ◽

Clinical Settings ◽

Permanent Disability ◽

Therapeutic Decisions ◽

Novel Concept ◽

The Brain

The identification of autoantibodies generated against the brain isoform water channel aquaporin4 in the sera of patients, changed the current diagnostic guidelines and concept of neuromyelitis optica (NMO). In a number of cases, clinical manifestation is spatially limited to myelitis or relapsing optic neuritis creating a diverse. NMO spectrum. Since prevention of relapses provides the only possibility to reduce permanent disability, early diagnosis and treatment is mandatory. In the present study, we discuss the potential role of neuroimaging and laboratory tests in differentiating the NMO spectrum from other diseases, as well as the diagnostic procedures and therapeutic options. We also present clinical cases, to provide examples of different clinical settings, diagnostic procedures and therapeutic decisions.

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Assessment of perceived immune status: comparison of a 1-item question versus the immune function questionnaire

10.26226/morressier.5785edc8d462b80296c996d2 ◽

2016 ◽

Author(s):

Deborah de Kruijff

Keyword(s):

Immune Function ◽

Immune Status

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Supplementation of Merino ewes with cholecalciferol in late pregnancy improves the vitamin D status of ewes and lambs at birth but is not correlated with an improvement in immune function in lambs

Animal Production Science ◽

10.1071/an15085 ◽

2016 ◽

Vol 56 (4) ◽

pp. 757 ◽

Cited By ~ 4

Author(s):

A. Lockwood ◽

A. Currie ◽

S. Hancock ◽

S. Broomfield ◽

S. Liu ◽

...

Keyword(s):

Vitamin D ◽

Immune Function ◽

Tetanus Toxoid ◽

Late Pregnancy ◽

Control Group ◽

Vitamin D Status ◽

Phagocytic Capacity ◽

Specific Antibody Response ◽

Adaptive Immune ◽

Maternal Supplementation

Functional deficiencies of the immune system are known to predispose human and animal neonates to death. Thus, immune competency may be a significant factor influencing the mortality of lambs. Vitamin D has been recognised to improve immune function and is transferred across the placenta. This study tested the hypotheses that (1) supplementation of Merino ewes with cholecalciferol during late pregnancy will increase the concentrations of vitamin D in the ewe and lamb at birth and (2) supplementation of Merino ewes with cholecalciferol during late pregnancy is correlated with an increase in innate phagocytic and adaptive antibody immune responses in the lamb. Merino ewes (n = 53) were injected intramuscularly with 1 × 106 IU cholecalciferol at Days 113 and 141 of pregnancy. A control group (n = 58) consisted of ewes receiving no additional nutritional treatments. The vitamin D status of ewes and lambs was assessed up until 1 month post-lambing. Lamb immune function was assessed by analysing the functional capacity of phagocytes, and the plasma IgG and anti-tetanus-toxoid antibody concentrations between birth and weaning. Maternal supplementation with cholecalciferol increased the plasma 25(OH)D concentrations of both ewes (137 vs 79 nmol/L; P < 0.001) and lambs (49 vs 24 nmol/L; P < 0.001) at birth compared with the controls. Supplementation with cholecalciferol had no significant effect on the phagocytic capacity of monocytes or polymorphonuclear leukocytes, the concentration of IgG in the colostrum or plasma of lambs, or the vaccine-specific antibody response against tetanus toxoid. Overall, the results support our first hypothesis, but suggest that maternal supplementation with 1 × 106 IU cholecalciferol does not improve innate, passive or adaptive immune function in lambs.

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The neuropeptide receptor NMUR-1 regulates the specificity of C. elegans innate immunity against pathogen infection

10.1101/2021.05.06.442992 ◽

2021 ◽

Author(s):

Phillip Wibisono ◽

Shawndra Wibisono ◽

Jan Watteyne ◽

Chia-Hui Chen ◽

Durai Sellegounder ◽

...

Keyword(s):

Innate Immunity ◽

Immune System ◽

Immune Responses ◽

Adaptive Immune System ◽

Innate Immune ◽

Innate Immune Responses ◽

Immune Genes ◽

C Elegans ◽

Adaptive Immune ◽

Functional Assays

A key question in current immunology is how the innate immune system generates high levels of specificity. Like most invertebrates, Caenorhabditis elegans does not have an adaptive immune system and relies solely on innate immunity to defend itself against pathogen attacks, yet it can still differentiate different pathogens and launch distinct innate immune responses. Here, we have found that functional loss of NMUR-1, a neuronal GPCR homologous to mammalian receptors for the neuropeptide neuromedin U, has diverse effects on C. elegans survival against various bacterial pathogens. Transcriptomic analyses and functional assays revealed that NMUR-1 modulates C. elegans transcription activity by regulating the expression of transcription factors, which, in turn, controls the expression of distinct immune genes in response to different pathogens. Our study has uncovered a molecular basis for the specificity of C. elegans innate immunity that could provide mechanistic insights into understanding the specificity of vertebrate innate immunity.

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