Seasonal and Nonseasonal Longitudinal Variation of Immune Function

Horst, Rob ter; Jaeger, Martin; Wijer, Lisa Van de; Heijden, Wouter A van der; Janssen, Anna M W; Smeekens, Sanne P.; Brouwer, Michelle A. E.; Cranenbroek, Bram van; Aguirre-Gamboa, Raúl; Netea‐Maier, Romana T.; Herwaarden, Antonius E. van; Lemmers, Heidi; Dijkstra, Helga; Joosten, Irma; Koenen, Hans J. P. M.; Netea, Mihai G.

doi:10.4049/jimmunol.2000133

Cited by 24 publications

(20 citation statements)

References 22 publications

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“…Ter Horst et al. (2021) also suggest a seasonality in some responses ( 140 ), and anecdotally this has been observed in BD patients with worsening symptoms during autumn. Age related changes have also been cited by these studies and IL-6 associated quantitative trait loci were identified.…”

Section: Discussionmentioning

confidence: 98%

Saliva and Serum Cytokine Profiles During Oral Ulceration in Behçet’s Disease

et al. 2021

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Behçet’s disease (BD) is a chronic, multi-systemic disorder of unknown aetiology typified by recurrent oral and genital mucocutaneous lesions, uveitis and vasculitis. Innate and adaptive immune system dysregulation has been implicated in pathogenesis with alterations in serum cytokine profiles. Few studies have investigated salivary cytokines in BD, despite more than 90% of BD patients first presenting with oral ulceration. The aim of this pilot study was twofold; firstly to investigate whether cytokine levels in matched serum and saliva samples show a differential profile in BD (with and without oral ulcers), recurrent aphthous stomatitis (RAS) and healthy controls (HCs), and secondly, to explore if any differential profiles in serum and/or saliva could provide a panel of cytokines with diagnostic and therapeutic potential for BD. Concentrations of 12 cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IFN-γ, TNF-α, TNF-β) were measured using the Human Th1/Th2 11-Plex FlowCytomix™ kit with IL-17A, in BD (N=20), RAS (N=6) and HCs (N=10). A differential range of cytokines was detected in serum and saliva with the majority of cytokine levels higher in saliva. The most prevalent salivary cytokines were IL-1β, IL-2, IL-8, IL-10 and TNF-α present in all samples in contrast to serum where the most prevalent cytokine detected was IL-8 (91.9%). The least abundant cytokine was IFN-γ in both saliva (43.2%) and serum (2.7%). After normalizing saliva for protein content, BD patients with oral ulcers (BD-MA) had significantly higher levels of salivary IL-1β (p=0.01), IL-8 (p=0.02), TNF-α (p=0.004) and IL-6 (p=0.01) than HCs. Notably, BD patients without oral ulcers (BD-MQ) also had significantly higher salivary IL-1β, IL-8 and TNF-α (p ≤ 0.05) than HCs. During relapsed (BD-RE) and quiet (BD-Q) systemic episodes, salivary IL-β and TNF-α were also significantly increased with IL-8 significantly higher only in BD-Q (p=0.02). BD oral ulcers signify a potential reactivation of systemic inflammation. Identifying cytokines released during asymptomatic episodes and oral ulceration might lead to targeted drug therapy to prevent recurrent oral ulcers and possible disease relapse. This is the first study to report salivary cytokine levels in BD. The detectable levels suggests cytokine profiling of BD saliva may provide an alternative, less invasive, sensitive procedure for frequent monitoring of disease activity and progression.

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Section: Discussionmentioning

confidence: 98%

Saliva and Serum Cytokine Profiles During Oral Ulceration in Behçet’s Disease

et al. 2021

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“…In fact, including the patients' age did not improve the RF model performance. Age has been evaluated extensively in the past also using the same flow cytometry panels used in the current study [16,17]. Although aging influences the immune cell composition (e.g., young vs old), within the age-interval (mean age 44-56) of our study cohort, as expected and as analyzed, the outcome of the RF model was hardly influenced.…”

Section: Discussionmentioning

confidence: 61%

“…All antibodies were titrated and tested before use. Percentages of immune cell subsets were manually analyzed using Kaluza software version 2.1 (Beckman-Coulter, Brea, CA, USA) as described previously [16,17,19].…”

Section: Methodsmentioning

confidence: 99%

Blood-Based Immune Profiling Combined with Machine Learning Discriminates Psoriatic Arthritis from Psoriasis Patients

Mulder

Reek

et al. 2021

IJMS

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Psoriasis (Pso) is a chronic inflammatory skin disease, and up to 30% of Pso patients develop psoriatic arthritis (PsA), which can lead to irreversible joint damage. Early detection of PsA in Pso patients is crucial for timely treatment but difficult for dermatologists to implement. We, therefore, aimed to find disease-specific immune profiles, discriminating Pso from PsA patients, possibly facilitating the correct identification of Pso patients in need of referral to a rheumatology clinic. The phenotypes of peripheral blood immune cells of consecutive Pso and PsA patients were analyzed, and disease-specific immune profiles were identified via a machine learning approach. This approach resulted in a random forest classification model capable of distinguishing PsA from Pso (mean AUC = 0.95). Key PsA-classifying cell subsets selected included increased proportions of differentiated CD4+CD196+CD183-CD194+ and CD4+CD196-CD183-CD194+ T-cells and reduced proportions of CD196+ and CD197+ monocytes, memory CD4+ and CD8+ T-cell subsets and CD4+ regulatory T-cells. Within PsA, joint scores showed an association with memory CD8+CD45RA-CD197- effector T-cells and CD197+ monocytes. To conclude, through the integration of in-depth flow cytometry and machine learning, we identified an immune cell profile discriminating PsA from Pso. This immune profile may aid in timely diagnosing PsA in Pso.

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“…Seasonality is an important environmental factor that influences immune responses ( 46 , 47 ). Samples from 100 melanoma patients (Stage II, III and IV) which were stained using the MoT test were collected from December 2020 until June 2021.…”

Section: Resultsmentioning

confidence: 99%

Development of a Flow Cytometry Assay to Predict Immune Checkpoint Blockade-Related Complications

Schilling

Glehr

Kapinsky³

et al. 2021

Front. Immunol.

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Treatment of advanced melanoma with combined immune checkpoint inhibitor (ICI) therapy is complicated in up to 50% of cases by immune-related adverse events (irAE) that commonly include hepatitis, colitis and skin reactions. We previously reported that pre-therapy expansion of cytomegalovirus (CMV)-reactive CD4+ effector memory T cells (TEM) predicts ICI-related hepatitis in a subset of patients with Stage IV melanoma given αPD-1 and αCTLA-4. Here, we develop and validate a 10-color flow cytometry panel for reliably quantifying CD4+ TEM cells and other biomarkers of irAE risk in peripheral blood samples. Compared to previous methods, our new panel performs equally well in measuring CD4+ TEM cells (agreement = 98%) and is superior in resolving CD4+ CD197+ CD45RA- central memory T cells (TCM) from CD4+ CD197+ CD45RA+ naive T cells (Tnaive). It also enables us to precisely quantify CD14+ monocytes (CV = 6.6%). Our new “monocyte and T cell” (MoT) assay predicts immune-related hepatitis with a positive predictive value (PPV) of 83% and negative predictive value (NPV) of 80%. Our essential improvements open the possibility of sharing our predictive methods with other clinical centers. Furthermore, condensing measurements of monocyte and memory T cell subsets into a single assay simplifies our workflows and facilitates computational analyses.

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Seasonal and Nonseasonal Longitudinal Variation of Immune Function

Cited by 24 publications

References 22 publications

Saliva and Serum Cytokine Profiles During Oral Ulceration in Behçet’s Disease

Saliva and Serum Cytokine Profiles During Oral Ulceration in Behçet’s Disease

Blood-Based Immune Profiling Combined with Machine Learning Discriminates Psoriatic Arthritis from Psoriasis Patients

Development of a Flow Cytometry Assay to Predict Immune Checkpoint Blockade-Related Complications

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