Distinct systemic microbiome and microbial translocation are associated with plasma level of anti-CD4 autoantibody in HIV infection

Xu, Wanli; Luo, Zhenwu; Alekseyenko, Alexander V.; Martin, Lisa; Wan, Zhuang; Ling, Binhua; Qin, Zhiqiang; Heath, Sonya L.; Maas, Kendra; Cong, Xiaomei; Jiang, Wei

doi:10.1038/s41598-018-31116-y

Cited by 22 publications

(20 citation statements)

References 90 publications

(70 reference statements)

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“…Due to their role in regulating immune function and metabolism, gut microbes are key contributors in the maintenance of host health [51][52][53][54] . The fecal microbiota and its translocation from the gastrointestinal tract into systemic circulation has been considered as a key driver of immune response and systemic inflammation [55][56][57][58] . Abnormal presence of gut microbes in the plasma can initiate and intensify inflammatory cascades 59 .…”

Section: Discussionmentioning

confidence: 99%

Plasma microbiome in COVID-19 subjects: an indicator of gut barrier defects and dysbiosis

Prasad

Floyd

et al. 2021

Preprint

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The gut is a well-established route of infection and target for viral damage by SARS-CoV-2. This is supported by the clinical observation that about half of COVID-19 patients exhibit gastrointestinal (GI) symptoms. We asked whether the analysis of plasma could provide insight into gut barrier dysfunction in patients with COVID-19 infection. Plasma samples of COVID-19 patients (n=30) and healthy control (n=16) were collected during hospitalization. Plasma microbiome was analyzed using 16S rRNA sequencing, metatranscriptomic analysis, and gut permeability markers including FABP-2, PGN and LPS in both patient cohorts. Almost 65% (9 out 14) COVID-19 patients showed abnormal presence of gut microbes in their bloodstream. Plasma samples contained predominately Proteobacteria, Firmicutes, and Actinobacteria. The abundance of gram-negative bacteria (Acinetobacter, Nitrospirillum, Cupriavidus, Pseudomonas, Aquabacterium, Burkholderia, Caballeronia, Parabhurkholderia, Bravibacterium, and Sphingomonas) was higher than the gram-positive bacteria (Staphylococcus and Lactobacillus) in COVID-19 subjects. The levels of plasma gut permeability markers FABP2 (1282 [plusmn]199.6 vs 838.1[plusmn]91.33; p=0.0757), PGN (34.64[plusmn]3.178 vs 17.53[plusmn]2.12; p<0.0001), and LPS (405.5[plusmn]48.37 vs 249.6[plusmn]17.06; p=0.0049) were higher in COVID-19 patients compared to healthy subjects. These findings support that the intestine may represent a source for bacteremia and may contribute to worsening COVID-19 outcomes. Therapies targeting the gut and prevention of gut barrier defects may represent a strategy to improve outcomes in COVID-19 patients.

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Section: Discussionmentioning

confidence: 99%

Plasma microbiome in COVID-19 subjects: an indicator of gut barrier defects and dysbiosis

Prasad

Floyd

et al. 2021

Preprint

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“…The increase of anti-CD4 IgG in acute HIV infection may attribute to the increase of autoantigens, such as debris arise from massive CD4 + T-cell apoptosis, sCD4, or HIV protein binding CD4 complex (Lederman et al, 2011;Koppensteiner et al, 2012;Luo et al, 2017b). Moreover, AHI induced epithelial apoptosis and mucosal barrier dysfunction, which results in microbial translocation, immune activation, inflammation, and autoantibodies production (Shirai et al, 1992;Petta et al, 2018;Xu et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, autoimmune diseases mainly occur in the immunologic reconstitution phase after ART in chronically infected patients (Zandman-Goddard and Shoenfeld, 2002;Iordache et al, 2014). The mechanisms of pathogenic anti-CD4 IgG production remain unknown, and persistent immune activation and inflammation after ART may contribute to the breakdown of tolerance (Xu et al, 2018). Furthermore, autoantigens from apoptotic CD4 + T cells, sCD4, or released HIV protein-bound CD4, may provide the antigen stimulation for generation of pathologic autoantibodies in post-ART HIV-infected individuals (Luo et al, 2017a).…”

Section: Discussionmentioning

confidence: 99%

Effects of Early and Delayed Antiretroviral Therapy on Plasma Anti-CD4 Autoreactive IgG and Its Association With CD4+ T-Cell Recovery in Acute HIV-Infected Individuals

Song

Luo

et al. 2020

Front. Pharmacol.

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Background: Plasma levels of anti-CD4 autoantibodies are increased in chronically HIVinfected patients and inversely correlated with CD4 + T-cell recovery under viralsuppressive antiretroviral therapy (ART). However, it remains unknown the effect of early ART on plasma anti-CD4 autoantibody levels in acute HIV infection (AHI).Methods: In this cohort study, we evaluated the effect of early and delayed initiation of ART on plasma anti-CD4 autoantibody levels in AHI individuals (n = 90). Blood samples were collected from men who had sex with men (MSM) with acute infection, pre-ART, and 4, 24, 48, and 96 weeks after ART. Plasma levels of anti-CD4 immunoglobulin G (IgG) were measured by ELISA.Results: We found that plasma anti-CD4 IgG levels were significantly increased in AHI individuals compared with healthy controls (HCs) prior to ART. Notably, early ART decreased plasma anti-CD4 IgG to the levels similar to HCs starting at 24 weeks (W). However, delayed initiation of ART did not significantly reduce plasma anti-CD4 IgG levels in AHI individuals. Moreover, the peripheral CD4 + T-cell counts were inversely correlated with plasma anti-CD4 IgG levels in AHI individuals at 48 and 96 W after early ART but not after delayed ART.Conclusions: Taken together, our findings demonstrate for the first time that early ART, but not delayed initiation of ART, is effective in influencing anti-CD4 autoantibody production and recovering CD4 + T-cell counts in AHI individuals.

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“…This indicates that elevated levels of IgA and IgM may be due to polyclonal B cell activation. Systemic exposure of microbial products leads to polyclonal B cell hyperactivation and elevated levels of Igs (111)(112)(113). From our study, it appears that monocyte/macrophage activation is the likely cause of B cell activation and subsequent increase of total Igs and EndoCAbs in RA patients.…”

Section: Discussionmentioning

confidence: 63%

Heightened Levels of Antimicrobial Response Factors in Patients With Rheumatoid Arthritis

et al. 2020

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Rheumatoid arthritis (RA) is a chronic progressive autoimmune disease leading to considerable disability over time. The disease can be characterized by the presence of multiple autoantibodies in the serum and synovial fluid. Microbial dysbiosis is proposed to play a role in the pathogenesis of RA. Increased systemic bacterial exposure leads to elevated levels of antimicrobial response factors (ARFs) in the circulation. In the present study, we tested whether RA patients have increased levels of ARFs by analyzing the levels of multiple ARFs in serum from RA patients and healthy age and sex-matched controls. The levels of soluble CD14 (sCD14), lysozyme, and CXCL16 were significantly elevated in RA patients compared to healthy controls. Lipopolysaccharide binding protein (LBP) levels remained unchanged in RA patients compared to healthy controls. A positive correlation of LBP with rheumatoid factor (RF) was also found in RA subjects. Interestingly, the levels of anti-endotoxin core antibodies (EndoCAb) IgM, total IgM, EndoCAb IgA, and total IgA were significantly elevated in RA patients compared to healthy controls. No significant changes in the levels of EndoCAb IgG and total IgG were observed in RA patients compared to healthy controls. Furthermore, lysozyme and CXCL16 levels were positively correlated with disease severity among RA subjects. Increases in the levels of several ARFs and their correlations with clinical indices suggest systemic microbial exposure in the RA cohort. Modulation of microbial exposure may play an important role in disease pathogenesis in individuals with RA.

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Distinct systemic microbiome and microbial translocation are associated with plasma level of anti-CD4 autoantibody in HIV infection

Cited by 22 publications

References 90 publications

Plasma microbiome in COVID-19 subjects: an indicator of gut barrier defects and dysbiosis

Plasma microbiome in COVID-19 subjects: an indicator of gut barrier defects and dysbiosis

Effects of Early and Delayed Antiretroviral Therapy on Plasma Anti-CD4 Autoreactive IgG and Its Association With CD4+ T-Cell Recovery in Acute HIV-Infected Individuals

Heightened Levels of Antimicrobial Response Factors in Patients With Rheumatoid Arthritis

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