Matrix metalloproteinases and tissue damage in <scp>HIV</scp>‐tuberculosis immune reconstitution inflammatory syndrome

Tadokera, Rebecca; Meintjes, Graeme; Wilkinson, Katalin A.; Skolimowska, Keira; Walker, Naomi F.; Friedland, Jon S.; Maartens, Gary; Elkington, Paul; Wilkinson, Robert J.

doi:10.1002/eji.201343593

Cited by 50 publications

(48 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, plasma MMP-7 was elevated in patients with latent TB relative to IGRA negative controls. MMP-7 has previously been implicated in TB-IRIS [ 36 ]. Large-scale population studies would be required to determine whether increased MMP-7 associates with an increased risk of developing active TB and is a marker of low-level disease activity.…”

Section: Discussionmentioning

confidence: 99%

Gender-Dependent Differences in Plasma Matrix Metalloproteinase-8 Elevated in Pulmonary Tuberculosis

et al. 2015

Self Cite

View full text Add to dashboard Cite

Tuberculosis (TB) remains a global health pandemic and greater understanding of underlying pathogenesis is required to develop novel therapeutic and diagnostic approaches. Matrix metalloproteinases (MMPs) are emerging as key effectors of tissue destruction in TB but have not been comprehensively studied in plasma, nor have gender differences been investigated. We measured the plasma concentrations of MMPs in a carefully characterised, prospectively recruited clinical cohort of 380 individuals. The collagenases, MMP-1 and MMP-8, were elevated in plasma of patients with pulmonary TB relative to healthy controls, and MMP-7 (matrilysin) and MMP-9 (gelatinase B) were also increased. MMP-8 was TB-specific (p<0.001), not being elevated in symptomatic controls (symptoms suspicious of TB but active disease excluded). Plasma MMP-8 concentrations inversely correlated with body mass index. Plasma MMP-8 concentration was 1.51-fold higher in males than females with TB (p<0.05) and this difference was not due to greater disease severity in men. Gender-specific analysis of MMPs demonstrated consistent increase in MMP-1 and -8 in TB, but MMP-8 was a better discriminator for TB in men. Plasma collagenases are elevated in pulmonary TB and differ between men and women. Gender must be considered in investigation of TB immunopathology and development of novel diagnostic markers.

show abstract

Section: Discussionmentioning

confidence: 99%

Gender-Dependent Differences in Plasma Matrix Metalloproteinase-8 Elevated in Pulmonary Tuberculosis

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…Several observed responses have been implicated in TB pathogenesis more broadly. These include raised levels of circulating matrix metalloproteinases (MMPs) 55 and tumour necrosis factor alpha (TNFa) levels, 35,56 lending support to the view that they may at least be implicated in PR/IRIS disease manifestations, if not in pathogenesis.…”

Section: Immunopathogenesis and Immune Phenotypesmentioning

confidence: 99%

Paradoxical reactions and immune reconstitution inflammatory syndrome in tuberculosis

Bell

Breen

Miller

et al. 2015

International Journal of Infectious Diseases

View full text Add to dashboard Cite

The coalescence of the HIV-1 and tuberculosis (TB) epidemics in Sub-Saharan Africa has had a significant and negative impact on global health. The availability of effective antimicrobial treatment for both HIV-1 (in the form of highly active antiretroviral therapy (HAART)) and TB (with antimycobacterial agents) has the potential to mitigate the associated morbidity and mortality. However, the use of both HAART and antimycobacterial therapy is associated with the development of inflammatory paradoxical syndromes after commencement of therapy. These include paradoxical reactions (PR) and immune reconstitution inflammatory syndromes (IRIS), conditions that complicate mycobacterial disease in HIV seronegative and seropositive individuals. Here, we discuss case definitions for PR and IRIS, and explore how advances in identifying the risk factors and immunopathogenesis of these conditions informs our understanding of their shared underlying pathogenesis. We propose that both PR and IRIS are characterized by the triggering of exaggerated inflammation in a setting of immunocompromise and antigen loading, via the reversal of immunosuppression by HAART and/or antimycobacterials. Further understanding of the molecular basis of this pathogenesis may pave the way for effective immunotherapies for the treatment of PR and IRIS.

show abstract

“…It has been shown that MMP-mediated collagen degradation is a possible mechanism for TB-associated lung damage [40, 41]. Accordingly, one study has shown increased expression of MMP-1, -3, -7 and -10 in peripheral blood mononuclear cells from TB-IRIS patients [42]. Another study has shown that increases in MMP-8 levels following ART were associated with impaired lung function in TB-IRIS [43].…”

Section: Immunopathology Of Iris Associated With Tbmentioning

confidence: 99%

Immune reconstitution inflammatory syndrome associated with pulmonary pathogens

2017

View full text Add to dashboard Cite

Immune reconstitution inflammatory syndrome (IRIS) is an exaggerated immune response to a variety of pathogens in response to antiretroviral therapy-mediated recovery of the immune system in HIV-infected patients. Although IRIS can occur in many organs, pulmonary IRIS, associated with opportunistic infections such as Mycobacterium tuberculosis and Pneumocystis jirovecii, is particularly associated with high morbidity and mortality. The pathology of IRIS is associated with a variety of innate and adaptive immune factors, including CD4+ T-cells, CD8+ T-cells, γδ T-cells, natural killer cells, macrophages, the complement system and surfactant proteins, Toll-like receptors and pro-inflammatory cytokines and chemokines. Although there are numerous reports about the immune factors involved in IRIS, the mechanisms involved in the development of pulmonary IRIS are poorly understood. Here, we propose that studies using gene-deficient murine and nonhuman primate models will help to identify the specific molecular targets associated with the development of IRIS. An improved understanding of the mechanisms involved in the pathology of pulmonary IRIS will help to identify potential biomarkers and therapeutic targets in this syndrome.

show abstract

Matrix metalloproteinases and tissue damage in HIV‐tuberculosis immune reconstitution inflammatory syndrome

Cited by 50 publications

References 41 publications

Gender-Dependent Differences in Plasma Matrix Metalloproteinase-8 Elevated in Pulmonary Tuberculosis

Gender-Dependent Differences in Plasma Matrix Metalloproteinase-8 Elevated in Pulmonary Tuberculosis

Paradoxical reactions and immune reconstitution inflammatory syndrome in tuberculosis

Immune reconstitution inflammatory syndrome associated with pulmonary pathogens

Contact Info

Product

Resources

About