Low levels of the key B cell activation marker, HLA-DR, in COVID-19 hospitalized cases are associated with disease severity, dexamethasone treatment, and circulating IL-6 levels

Dobi, Anthony; Dubernet, Arthur; Rakoto, Mahary Lalarizo; Seteyen, Anne-Laure Sandenon; Vagner, Damien; Lebeau, Grégorie; Raffray, L.; Gasque, Philippe

doi:10.1007/s12026-022-09269-w

Cited by 4 publications

(8 citation statements)

References 27 publications

(19 reference statements)

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“…As such, HLADR+ B cells showed positive association with two cholesteryl ester species – ChoE‐18:3 and ChoE‐22:6 (Figure S13), each arising from fatty acids (FA 18:3–LA and FA 22:6–DHA) that bear precursor‐product relationships. HLADR+ B cells are reduced in patients with severe COVID‐19 56 compared with healthy controls and patients with mild COVID independent of dexamethasone treatment. ChoE‐18:3 is a potential source of the elevated ALA (alpha‐linolenic acid) and its downstream products, EPA and DHA that we observed in COVID patients and was also negatively correlated with PLA 2 G2D (Figure S14; Spearman's ρ = −.55, p < .05), a source of inflammatory eicosanoids as described above.…”

Section: Resultsmentioning

confidence: 92%

Deep phenotyping of the lipidomic response in COVID‐19 and non‐COVID‐19 sepsis

Meng,

Sengupta,

Ricciotti

et al. 2023

Clinical & Translational Med

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BackgroundLipids may influence cellular penetrance by viral pathogens and the immune response that they evoke. We deeply phenotyped the lipidomic response to SARs‐CoV‐2 and compared that with infection with other pathogens in patients admitted with acute respiratory distress syndrome to an intensive care unit (ICU).MethodsMass spectrometry was used to characterise lipids and relate them to proteins, peripheral cell immunotypes and disease severity.ResultsCirculating phospholipases (sPLA2, cPLA2 (PLA2G4A) and PLA2G2D) were elevated on admission in all ICU groups. Cyclooxygenase, lipoxygenase and epoxygenase products of arachidonic acid (AA) were elevated in all ICU groups compared with controls. sPLA2 predicted severity in COVID‐19 and correlated with TxA2, LTE4 and the isoprostane, iPF2α‐III, while PLA2G2D correlated with LTE4. The elevation in PGD2, like PGI2 and 12‐HETE, exhibited relative specificity for COVID‐19 and correlated with sPLA2 and the interleukin‐13 receptor to drive lymphopenia, a marker of disease severity. Pro‐inflammatory eicosanoids remained correlated with severity in COVID‐19 28 days after admission. Amongst non‐COVID ICU patients, elevations in 5‐ and 15‐HETE and 9‐ and 13‐HODE reflected viral rather than bacterial disease. Linoleic acid (LA) binds directly to SARS‐CoV‐2 and both LA and its di‐HOME products reflected disease severity in COVID‐19. In healthy marines, these lipids rose with seroconversion. Eicosanoids linked variably to the peripheral cellular immune response. PGE2, TxA2 and LTE4 correlated with T cell activation, as did PGD2 with non‐B non‐T cell activation. In COVID‐19, LPS stimulated peripheral blood mononuclear cell PGF2α correlated with memory T cells, dendritic and NK cells while LA and DiHOMEs correlated with exhausted T cells. Three high abundance lipids – ChoE 18:3, LPC‐O‐16:0 and PC‐O‐30:0 – were altered specifically in COVID. LPC‐O‐16:0 was strongly correlated with T helper follicular cell activation and all three negatively correlated with multi‐omic inflammatory pathways and disease severity.ConclusionsA broad based lipidomic storm is a predictor of poor prognosis in ARDS. Alterations in sPLA2, PGD2 and 12‐HETE and the high abundance lipids, ChoE 18:3, LPC‐O‐16:0 and PC‐O‐30:0 exhibit relative specificity for COVID‐19 amongst such patients and correlate with the inflammatory response to link to disease severity.

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Section: Resultsmentioning

confidence: 92%

Deep phenotyping of the lipidomic response in COVID‐19 and non‐COVID‐19 sepsis

Meng,

Sengupta,

Ricciotti

et al. 2023

Clinical & Translational Med

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“…Furthermore, here we report the emergence of HLA‐DR Low B cells in severe RSV disease. HLA‐DR Low B cells and monocytes have been associated with immunodepression or immunoparalysis, and have been previously reported in sepsis 68 and COVID‐19 67 . In the latter case, the downregulation of HLA‐DR has been associated with STAT3 mediated effect of IL‐6 67 .…”

Section: Discussionmentioning

confidence: 72%

“…Interestingly, IL-6 signalling has also been associated with downregulation of HLA-DR expression in monocytes and B cells in COVID-19. 60,67 Various neutrophil subsets have been associated with severe RSV disease, including mature, immature, progenitor and suppressive subsets, which highlight different roles of neutrophils depending on disease severity level. 50 The progenitor neutrophil subset was characterized by high Ki67 expression, as well as by low expression of granulocyte lineage markers such as CD24, CD11b, CD66b and CD11c.…”

Section: Discussionmentioning

confidence: 99%

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Single‐cell immune profiling reveals markers of emergency myelopoiesis that distinguish severe from mild respiratory syncytial virus disease in infants

Zivanovic,

Öner,

Abraham

et al. 2023

Clinical & Translational Med

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Whereas most infants infected with respiratory syncytial virus (RSV) show no or only mild symptoms, an estimated 3 million children under five are hospitalized annually due to RSV disease. This study aimed to investigate biological mechanisms and associated biomarkers underlying RSV disease heterogeneity in young infants, enabling the potential to objectively categorize RSV‐infected infants according to their medical needs. Immunophenotypic and functional profiling demonstrated the emergence of immature and progenitor‐like neutrophils, proliferative monocytes (HLA‐DRLow, Ki67+), impaired antigen‐presenting function, downregulation of T cell response and low abundance of HLA‐DRLow B cells in severe RSV disease. HLA‐DRLow monocytes were found as a hallmark of RSV‐infected infants requiring hospitalization. Complementary transcriptomics identified genes associated with disease severity and pointed to the emergency myelopoiesis response. These results shed new light on mechanisms underlying the pathogenesis and development of severe RSV disease and identified potential new candidate biomarkers for patient stratification.

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“…Previous studies showed a decrease of the activation marker HLA-DR on B cells following dexamethasone treatment in severe COVID-19 infections and its association with disease severity. Furthermore, patients with sepsis show decreased levels of HLA-DR + B cells, signifying their role during active inflammation ( 62 , 63 ).…”

Section: Discussionmentioning

confidence: 99%

Mononuclear cell composition and activation in blood and mucosal tissue of eosinophilic esophagitis

Gruden,

Kienzl,

Ristic

et al. 2024

Front. Immunol.

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IntroductionEosinophilic esophagitis (EoE) is a chronic, inflammatory, antigen-driven disease of the esophagus. Tissue EoE pathology has previously been extensively characterized by novel transcriptomics and proteomic platforms, however the majority of surface marker determination and screening has been performed in blood due to mucosal tissue size limitations. While eosinophils, CD4+ T cells, mast cells and natural killer (NK) T cells were previously investigated in the context of EoE, an accurate picture of the composition of peripheral blood mononuclear cells (PBMC) and their activation is missing.MethodsIn this study, we aimed to comprehensively analyze the composition of peripheral blood mononuclear cells and their activation using surface marker measurements with multicolor flow cytometry simultaneously in both blood and mucosal tissue of patients with active EoE, inactive EoE, patients with gastroesophageal reflux disease (GERD) and controls. Moreover, we set out to validate our data in co-cultures of PBMC with human primary esophageal epithelial cells and in a novel inducible mouse model of eosinophilic esophagitis, characterized by extensive IL-33 secretion in the esophagus.ResultsOur results indicate that specific PBMC populations are enriched, and that they alter their surface expression of activation markers in mucosal tissue of active EoE. In particular, we observed upregulation of the immunomodulatory molecule CD38 on CD4+ T cells and on myeloid cells in biopsies of active EoE. Moreover, we observed significant upregulation of PD-1 on CD4+ and myeloid cells, which was even more prominent after corticosteroid treatment. With co-culture experiments we could demonstrate that direct cell contact is needed for PD-1 upregulation on CD4+ T cells. Finally, we validated our findings of PD-1 and CD38 upregulation in an inducible mouse model of EoE.DiscussionHerein we show significant alterations in the PBMC activation profile of patients with active EoE in comparison to inactive EoE, GERD and controls, which could have potential implications for treatment. To our knowledge, this study is the first of its kind expanding the multi-color flow cytometry approach in different patient groups using in vitro and in vivo translational models.

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Low levels of the key B cell activation marker, HLA-DR, in COVID-19 hospitalized cases are associated with disease severity, dexamethasone treatment, and circulating IL-6 levels

Cited by 4 publications

References 27 publications

Deep phenotyping of the lipidomic response in COVID‐19 and non‐COVID‐19 sepsis

Deep phenotyping of the lipidomic response in COVID‐19 and non‐COVID‐19 sepsis

Single‐cell immune profiling reveals markers of emergency myelopoiesis that distinguish severe from mild respiratory syncytial virus disease in infants

Mononuclear cell composition and activation in blood and mucosal tissue of eosinophilic esophagitis

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