Gene Signature Fingerprints Stratify SLE Patients in Groups with Similar Biological Disease Profiles: A Multicenter Longitudinal Study

Wahadat, M. Javad; Schonenberg-Meinema, Dieneke; Helden-Meeuwsen, Cornelia G van; Tilburg, Sander J van; Groot, Natasja M. De; Schatorjé, Ellen; Hoppenreijs, Esther P A H; Müller, P; Brinkman, D. M. C.; Dvorak, Denis; Verkaaik, Marleen; Berg, J.M. van den; Bouchalová, Kateřina; Kamphuis, Sylvia; Versnel, Marjan A.

doi:10.2139/ssrn.3877467

Cited by 2 publications

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“…These two sets of three modules each, A28/S1 and A28/S2, displayed distinct kinetics and amplitude of response after the first and second doses. In an earlier report, we have shown that module repertoire analyses permitted the delineation of distinct interferon signatures and that those signatures could stratify patients with SLE (30), an observation that has since been confirmed in independent studies (41)(42)(43). We report here that distinct interferon signatures are elicited following vaccination.…”

Section: Discussionsupporting

confidence: 77%

High–temporal resolution profiling reveals distinct immune trajectories following the first and second doses of COVID-19 mRNA vaccines

et al. 2022

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Knowledge of the mechanisms underpinning the development of protective immunity conferred by mRNA vaccines is fragmentary. Here, we investigated responses to coronavirus disease 2019 (COVID-19) mRNA vaccination via high–temporal resolution blood transcriptome profiling. The first vaccine dose elicited modest interferon and adaptive immune responses, which peaked on days 2 and 5, respectively. The second vaccine dose, in contrast, elicited sharp day 1 interferon, inflammation, and erythroid cell responses, followed by a day 5 plasmablast response. Both post-first and post-second dose interferon signatures were associated with the subsequent development of antibody responses. Yet, we observed distinct interferon response patterns after each of the doses that may reflect quantitative or qualitative differences in interferon induction. Distinct interferon response phenotypes were also observed in patients with COVID-19 and were associated with severity and differences in duration of intensive care. Together, this study also highlights the benefits of adopting high-frequency sampling protocols in profiling vaccine-elicited immune responses.

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Section: Discussionsupporting

confidence: 77%

High–temporal resolution profiling reveals distinct immune trajectories following the first and second doses of COVID-19 mRNA vaccines

et al. 2022

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“…Cluster B consisted of type 1 IFN driven inflammation-related genes (a cluster we found upregulated in systemic autoimmune conditions). 44, 45 Cluster C consisted of genes involved in mitochondrial anti-inflammatory action and cholesterol pump genes (a hall mark cluster of monocytes in patients with major depressive disorder [MDD]). 30 The found clusters are similar to the upregulated gene clusters found in previous studies in MDD, bipolar disorder (BD), and various autoimmune disorders (thyroid autoimmune disease, type 1 diabetes, Sjögren disease and SLE).…”

Section: Resultsmentioning

confidence: 99%

Severe fatigue as symptom of long COVID is characterized by increased expression of inflammatory genes in monocytes, increased serum pro-inflammatory cytokines, and increased CD8+ T-lymphocytes: A putative dysregulation of the immune-brain axis, the coagulation process, and auto-inflammation to explain the diversity of long COVID symptoms

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Mersha

et al. 2022

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BackgroundA significant proportion of patients with SARS-CoV-2 infection develops long COVID with fatigue as one of the most disabling symptoms. We performed clinical and immunologic profiling of fatigued and non-fatigued long COVID patients and age and gender matched healthy controls (HCs).MethodsWe included 37 long COVID patients with and 36 without severe fatigue and assessed inflammation-related monocyte gene expression, serum levels of inflammatory cytokines, and leukocyte and lymphocyte subsets 3-6 months after hospital discharge, and followed clinical symptoms up to one year.ResultsLong COVID with fatigue represented a severe variant with many symptoms (median 9 [IQR 5.0-10.0] symptoms) and signs of cognitive failure (41%) and depression (>24%). Symptoms persisted up to one year follow-up. Fatigued patients showed increased expression of inflammatory genes in monocytes, increased serum IL-6, TNF-α, galectin-9, and CXCL10, and increased CD8+ T-lymphocytes compared to HCs.Non-fatigued long COVID patients were arbitrarily divided in those with moderately severe disease (4 [2.5-5.0] symptoms, primarily impaired fitness, n=25) and those with mild disease (1 [1.0-2.0] symptom, n=11). Symptoms in non-fatigued long COVID patients persisted up to one year follow-up. Moderately severe patients showed reduced CD45RO- naïve CD4+ T-lymphocytes and CD25+FOXP3+ regulatory CD4+ T-lymphocytes and limited monocyte and serum (galectin-9) inflammation. Mild patients showed monocyte and serum (IL-6, galectin-9) inflammation and decreased CD4+ T-lymphocyte subsets (T-helper 1 cells).ConclusionLong COVID with fatigue is associated with many concurrent and persistent symptoms up to one year after hospitalization and with clear signs of low grade inflammation and increased CD8+ T-lymphocytes. We showed that long COVID is a clinical and immunologic heterogeneous disorder. Diagnostic tools and personalized therapies combatting the diverse immune abnormalities might be required to alleviate the persisting disabling complaints of the patients.

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Gene Signature Fingerprints Stratify SLE Patients in Groups with Similar Biological Disease Profiles: A Multicenter Longitudinal Study

Cited by 2 publications

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High–temporal resolution profiling reveals distinct immune trajectories following the first and second doses of COVID-19 mRNA vaccines

High–temporal resolution profiling reveals distinct immune trajectories following the first and second doses of COVID-19 mRNA vaccines

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