Frequency of Effector Memory Cells Expressing Integrin α4β7 Is Associated With TGF-β1 Levels in Therapy Naïve HIV Infected Women With Low CD4+ T Cell Count

Kasarpalkar, Nandini; Bhowmick, Shilpa; Patel, Vainav; Savardekar, Lalita; Agrawal, Sachee; Shastri, Jayanthi; Bhor, Vikrant M.

doi:10.3389/fimmu.2021.651122

Cited by 7 publications

(7 citation statements)

References 57 publications

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“…We thus undertook the evaluation of circulating IL‐6 and sMAdCAMlevels in our cohort. Indeed, with respect to the latter, we have recently highlighted a role for the modulation of sMAdCAM and expression of its receptor integrin α4β7 present on monocytes, lymphocytes in the context of HIV pathogenesis 34 . As expected, we observed elevated IL‐6 levels, with the highest being observed in hypoxemic individuals, in plasma of all groups compared to seronegative controls (Figure 3A).…”

Section: Resultssupporting

confidence: 76%

“…Indeed, with respect to the latter, we have recently highlighted a role for the modulation of sMAdCAM and expression of its receptor integrin α4β7 present on monocytes, lymphocytes in the context of HIV pathogenesis. 34 As expected, we observed elevated IL-6 levels, with the highest being observed in hypoxemic individuals, in plasma of all groups compared to seronegative controls (Figure 3A). Additionally, extending our previously reported results 23 obtained with sMAdCAM in mild infection, we observed a progressive decline in these levels across mild as well as hypoxemic patients that seemed converse to the pattern observed for IL-6 (Figure 3B).…”

Section: Contribution Of Smadcam and Il-6 To Covid-19 Associated Lymp...supporting

confidence: 85%

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Opposing roles for sMAdCAM and IL-15 in COVID-19 associated cellular immune pathology

Singh

Kasarpalkar

Bhowmick

et al. 2022

Journal of Leukocyte Biology

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Immune cell dysregulation and lymphopenia characterize COVID‐19 pathology in moderate to severe disease. While underlying inflammatory factors have been extensively studied, homeostatic and mucosal migratory signatures remain largely unexplored as causative factors. In this study, we evaluated the association of circulating IL‐6, soluble mucosal addressin cell adhesion molecule (sMAdCAM), and IL‐15 with cellular dysfunction characterizing mild and hypoxemic stages of COVID‐19. A cohort of SARS‐CoV‐2 infected individuals (n = 130) at various stages of disease progression together with healthy controls (n = 16) were recruited from COVID Care Centres (CCCs) across Mumbai, India. Multiparametric flow cytometry was used to perform in‐depth immune subset characterization and to measure plasma IL‐6 levels. sMAdCAM, IL‐15 levels were quantified using ELISA. Distinct depletion profiles, with relative sparing of CD8 effector memory and CD4+ regulatory T cells, were observed in hypoxemic disease within the lymphocyte compartment. An apparent increase in the frequency of intermediate monocytes characterized both mild as well as hypoxemic disease. IL‐6 levels inversely correlated with those of sMAdCAM and both markers showed converse associations with observed lympho‐depletion suggesting opposing roles in pathogenesis. Interestingly, IL‐15, a key cytokine involved in lymphocyte activation and homeostasis, was detected in symptomatic individuals but not in healthy controls or asymptomatic cases. Further, plasma IL‐15 levels negatively correlated with T, B, and NK count suggesting a compensatory production of this cytokine in response to the profound lymphopenia. Finally, higher levels of plasma IL‐15 and IL‐6, but not sMAdCAM, were associated with a longer duration of hospitalization.

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Section: Resultssupporting

confidence: 76%

Section: Contribution Of Smadcam and Il-6 To Covid-19 Associated Lymp...supporting

confidence: 85%

Opposing roles for sMAdCAM and IL-15 in COVID-19 associated cellular immune pathology

Singh

Kasarpalkar

Bhowmick

et al. 2022

Journal of Leukocyte Biology

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“…Considering the already demonstrated role of inflammatory cytokines in the development of pathology of COVID-19 (12) we undertook to evaluate how inflammatory profiles (Th1/Th2/Th17) correlated both cross-sectionally as well as longitudinally with varying disease states. Further, the role of an important emerging mediator of gut inflammation and mucosal homing, sMAdCAM, was examined in light of its significant role in the pathology of chronic inflammatory conditions including those with viral aetiology (13–17). This aspect of our study is especially noteworthy in the context of accumulating evidence for the gut as a potential sanctuary site for SARS-CoV-2 and persistent immunological sequelae observed in apparently virus free individuals (18–20).…”

Section: Discussionmentioning

confidence: 99%

sMAdCAM:IL-6 ratio influences disease progression and anti-viral responses in SARS-CoV-2 infection

Jagtap

Bhor

Bhowmick³

et al. 2020

Preprint

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IMPORTANCE: Recent studies positing the gut as a sanctuary site for viral persistence in SARS-CoV-2 infection highlight the importance of assimilating profiles of systemic as well as gut inflammatory mediators to understand the pathology of COVID-19. Also, the role of these markers in governing virus specific immunity following infection remains largely unexplored. OBJECTIVE: To evaluate the role of systemic and gut inflammatory markers in disease progression and development of anti-viral humoral immunity following SARS-CoV-2 infection. DESIGN, SETTING AND PARTICIPANTS: This cohort study (n=58) of SARS-CoV-2 infected individuals included a group of in-patients (n=36) at various stages of disease progression together with convalescent individuals (n=22) recruited between April and June 2020 (peak of the epidemic) from a tertiary care hospital in Mumbai, India. Follow-up of 11 in-patients at day 7 post diagnosis was carried out, resulting in a total of 47 in-patient samples. EXPOSURES: Diagnosis of SARS-CoV-2 infections was confirmed by reverse transcriptase-polymerase chain reaction-based testing of nasopharyngeal/oropharyngeal samples. MAIN OUTCOMES AND MEASURES: Primary outcomes were the measurement of inflammatory markers including Th1/Th2/Th17 cytokines and levels of soluble mucosal addressin cell adhesion molecule (sMAdCAM) in plasma. Anti-viral humoral response was measured by rapid antibody test (IgG, IgM) and chemiluminescent immunoassay (CLIA) (IgG). Also antibodies binding to SARS-CoV-2 proteins were measured by surface plasmon resonance (SPR). Secondary outcomes were correlation of the inflammatory signature with clinical information, including age, sex, disease duration and co-morbidities. RESULTS: Twenty eight of 36 (78%) in-patients and 19 of 22 (86%) convalescents were males. Out of 47 in-patient samples, 22 (46%), 11 (23%) and 14 (30%) were IgG-/IgM-, IgG+/IgM+ and IgG+/IgM- respectively. Of 22 convalescent samples, 3 (14%), 1 (4%) and 17 (77%) were respectively IgG-/IgM-, IgG+/IgM+ and IgG+/IgM-. Two out of 22 (9%) convalescents showed high IL-6 levels (>100pg/ml) and 4 (18%) had high TNF levels (>30pg/ml). However, the convalescents (n =22) had significantly lower levels of IL-6 [Median=27.48 (IQR=23.54-39.92)] compared to followed up in-patients (n = 11) at day 0 [Median=111(IQR=68-129.7), p =0.0002] and higher levels of sMAdCAM [Median=1940 (1711-2174) pg/ml] compared to these individuals at day 0 [Median=1701 (IQR=1532-1836) pg/ml; p=0.032] and day 7 [Median=1534 (IQR=1236-1654) pg/ml; p=0.0007]. Further, IL-6 and sMAdCAM levels among in-patients inversely correlated with one another (r =-0.374, p = 0.009, CI = 95%). When expressed as a novel integrated marker, sMIL (sMAdCAM/IL-6 ratio) index, these levels were incrementally and significantly higher across various disease states with convalescents exhibiting the highest values [Median= 64.74 (IQR=47.33-85.58)]. Also, the sMIL index was significantly higher in convalescents (with class-switched responses) compared to IgG+/IgM+ individuals at early stages of infection [Median=28.65 (IQR=13.63-96.26), p = 0.034]. Real-time measurement by SPR of plasma antibody binding to viral nucleocapsid (NC), receptor binding domain (RBD) and spike (S) revealed waxing and waning of plasma antibody responses to all 3 targets. Importantly, sMAdCAM levels as well as sMIL index (fold change) correlated with peak association rates of RBD-binding (r = 0.462, p = 0.03, CI = 95%) and fold change in binding to S (r = 0.68, p = 0.050, CI = 95%) respectively. CONCLUSION AND RELEVANCE: Our results highlight key systemic and gut-associated immune parameters that need to be monitored and investigated further to optimally guide therapeutic and prophylactic interventions for COVID-19.

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“…Considering the already demonstrated role of inflammatory cytokines in the development of pathology of COVID-19 ( 12 ), we undertook to evaluate how inflammatory profiles (Th1/Th2/Th17) correlated both cross-sectionally and longitudinally with varying disease states. Further, the role of an important emerging mediator of gut inflammation and mucosal homing, sMAdCAM, was examined in light of its significant role in the pathology of chronic inflammatory conditions including those with viral etiology ( 13 – 17 ). This aspect of our study is especially noteworthy in the context of accumulating evidence for the gut as a potential sanctuary site for SARS-CoV-2 and persistent immunological sequelae observed in apparently virus free individuals ( 18 – 20 ).…”

Section: Discussionmentioning

confidence: 99%

sMAdCAM: IL-6 Ratio Influences Disease Progression and Anti-Viral Responses in SARS-CoV-2 Infection

et al. 2021

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The role of sMAdCAM, an important gut immune migratory marker, remains unexplored in COVID-19 pathogenesis considering recent studies positing the gut as a sanctuary site for SARS-CoV-2 persistence. Thus, assimilating profiles of systemic inflammatory mediators with sMAdCAM levels may provide insights into the progression of COVID-19 disease. Also, the role of these markers in governing virus specific immunity following infection remains largely unexplored. A cohort (n = 84) of SARS-C0V-2 infected individuals included a group of in-patients (n = 60) at various stages of disease progression together with convalescent individuals (n = 24) recruited between April and June 2020 from Mumbai, India. Follow-up of 35 in-patients at day 7 post diagnosis was carried out. Th1/Th2/Th17 cytokines along with soluble MAdCAM (sMAdCAM) levels in plasma were measured. Also, anti-viral humoral response as measured by rapid antibody test (IgG, IgM), Chemiluminescent Immunoassay (IgG), and antibodies binding to SARS-CoV-2 proteins were measured by Surface Plasmon Resonance (SPR) from plasma. IL-6 and sMAdCAM levels among in-patients inversely correlated with one another. When expressed as a novel integrated marker—sMIL index (sMAdCAM/IL-6 ratio)—these levels were incrementally and significantly higher in various disease states with convalescents exhibiting the highest values. Importantly, sMAdCAM levels as well as sMIL index (fold change) correlated with peak association response units of receptor binding domain and fold change in binding to spike respectively as measured by SPR. Our results highlight key systemic and gut homing parameters that need to be monitored and investigated further to optimally guide therapeutic and prophylactic interventions for COVID-19.

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Frequency of Effector Memory Cells Expressing Integrin α4β7 Is Associated With TGF-β1 Levels in Therapy Naïve HIV Infected Women With Low CD4+ T Cell Count

Cited by 7 publications

References 57 publications

Opposing roles for sMAdCAM and IL-15 in COVID-19 associated cellular immune pathology

Opposing roles for sMAdCAM and IL-15 in COVID-19 associated cellular immune pathology

sMAdCAM:IL-6 ratio influences disease progression and anti-viral responses in SARS-CoV-2 infection

sMAdCAM: IL-6 Ratio Influences Disease Progression and Anti-Viral Responses in SARS-CoV-2 Infection

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