The Role of Immune Reconstitution Inflammatory Syndrome in AIDS‐Related<i>Cryptococcus neoformans</i>Disease in the Era of Highly Active Antiretroviral Therapy

Shelburne, Samuel A.; Darcourt, Jorge; White, A. Clinton; Greenberg, Stephen B.; Hamill, Richard J.; Atmar, Robert L.; Visnegarwala, Fehmida

doi:10.1086/428618

Cited by 281 publications

(232 citation statements)

References 16 publications

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“…63,64 Other risk factors include the duration and extent of immunodeficiency, polymorphisms in cytokine genes, 65 high initial viral load, and the velocity of immune reconstitution. 66 No difference in the risk of developing IRIS has been observed when comparing different drug regimens.…”

Section: Iris and Nirismentioning

confidence: 99%

JC Virus Infection of the Brain

Bag¹,

Curé²,

Chapman³

et al. 2010

AJNR Am J Neuroradiol

118

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SUMMARY:Since its initial description, there have been significant changes in the epidemiology, pathogenesis, and clinical and imaging manifestations of JCV infection of brain. The most common clinical manifestation is PML. Other recently described CNS manifestations are JCE, JCVGCN, and JCM. Although AIDS is the most common predisposing factor for JCV reactivation, there is increasing incidence of brain manifestations of JCV reactivation in non-HIV settings, including different rheumatologic, hematologic, and oncologic conditions; monoclonal antibody therapy; transplant recipients; primary immunodeficiency syndromes; and even in patients without any recognizable immune deficiency. IRIS may develop secondary to restoration of immunity in HIV-positive patients with PML receiving antiretroviral therapy. This is of profound clinical significance and needs to be diagnosed promptly. Imaging plays a crucial role in the diagnosis of the disease, monitoring of treatment response, identifying disease progression, and predicting prognosis. In this article, current understanding of the epidemiology, pathogenesis, clinical presentations, and all aspects of imaging of JCV infection of the brain have been comprehensively reviewed.ABBREVIATIONS: ADC ϭ apparent diffusion coefficient; CNS ϭ central nervous system; cPML ϭ classic PML; Cr ϭ creatine; CTL ϭ cytotoxic T-lymphocytes; DWI ϭ diffusion-weighted imaging; FLAIR ϭ fluid-attenuated inversion recovery; HAART ϭ highly active antiretroviral therapy; HIV ϭ human immunodeficiency virus; ICL ϭ idiopathic CD4 lymphocytopenia; iPML ϭ inflammatory PML; IRIS ϭ immune reconstitution inflammatory syndrome; JCE ϭ JCV encephalopathy; JCM ϭ JCV meningitis; JCV ϭ JC virus; JCVGCN ϭ JCV granular cell neuronopathy; mAb ϭ monoclonal antibody; mIns ϭ myo-inositol; MS ϭ multiple sclerosis; MTR ϭ magnetization transfer ratio; NAA ϭ N-acetylaspartate; NIRIS ϭ neuro-IRIS; PCR ϭ polymerase chain reaction; PML ϭ progressive multifocal leukoencephalopathy; PML-IRIS ϭ PML associated with IRIS; RR ϭregulatory region; SLE ϭ systemic lupus erythematosus

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Section: Iris and Nirismentioning

confidence: 99%

JC Virus Infection of the Brain

Bag¹,

Curé²,

Chapman³

et al. 2010

AJNR Am J Neuroradiol

118

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“…Overzealous inflammatory responses may contribute to immune reconstitution syndrome (IRS) and poor outcomes in patients with opportunistic mycosis [1,4]. IRS associated with invasive fungal infections as been documented in diverse patient populations including, organ transplant recipients however, its pathophysiologic basis has not been fully defined [5][6][7][8].…”

Section: Discussionmentioning

confidence: 99%

Novel immune regulatory pathways and their role in immune reconstitution syndrome in organ transplant recipients with invasive mycoses

Singh¹

2008

Eur J Clin Microbiol Infect Dis

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Immune regulatory pathways involving the newly discovered T regulatory (Treg) and Th17 cells are the principal targets of immunosuppressive agents employed in transplant recipients and key mediators of host inflammatory responses in fungal infections. These novel signaling pathways, in concert with or independent of Th1/Th2 responses have potentially important implications for yielding valuable insights into the pathogenesis of immune reconstitution syndrome (IRS) in transplant recipients, for aiding the diagnosis of this entity, and for achieving a balance of immune responses that enhance host immunity while curbing unfettered inflammation in IRS.

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“…In patients with disseminated cryptococcal fungemia, rates of IRIS were 6-fold higher compared to those with cryptococcal infection but without cryptococcemia. Higher CSF cryptococcal antigen titers at initial meningitis diagnosis and persistence of positive cultures after treatment were both risk factors for later development of IRIS upon commencing ART [3,18].…”

Section: Antigenic Burdenmentioning

confidence: 98%

“…There have been three retrospective and one prospective cohort studies of cryptococcal meningitis IRIS conducted among patients in France, Uganda, Houston, and Thailand [3,9,18,49]. Among the 255 patients cumulatively described, the incidence of IRIS is near 30%.…”

Section: Biomarkers For Cryptococcal Meningitis (Cm)mentioning

confidence: 99%

“…In IRIS, a culturenegative meningitis occurs which appears to be triggered by the presence of residual antigen in the CSF. The spectrum of cryptococcal disease in IRIS is not always restricted to the meninges and can also manifest as atypical disseminated disease, such as cutaneous lesions, lymphadenopathy, mediastinitis, pneumonitis with ARDS, and CNS cryptococcomas [9,18,50,51,52]. In these cases, a paucity of organisms is usually recovered but copious granulomatous inflammation exists.…”

Section: Biomarkers For Cryptococcal Meningitis (Cm)mentioning

confidence: 99%

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Biomarkers of HIV Immune Reconstitution Inflammatory Syndrome

et al. 2008

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Dysregulation of the immune system drives HIV pathogenesis. As we develop new ways to treat HIV and AIDS, we encounter new clinical ramifications of our treatment on regulatory components of the immune system. HIV-associated Immune Reconstitution Inflammatory Syndrome (IRIS) occurs after initiation of anti-retroviral therapy (ART) with inappropriate and dysbalanced restoration of the immune system resulting in pathologic inflammatory reactions with significant morbidity. IRIS is most commonly associated with latent, occult, or past infections, including tuberculosis, Cryptococcus neoformans, and Mycobacterium avium-complex. We discuss common clinical presentations, new diagnostic modalities, current hypotheses of IRIS pathogenesis, and future directions of IRIS-related research, focusing on the identification of biomarkers that can be used to predict and diagnose IRIS.

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The Role of Immune Reconstitution Inflammatory Syndrome in AIDS‐RelatedCryptococcus neoformansDisease in the Era of Highly Active Antiretroviral Therapy

Cited by 281 publications

References 16 publications

JC Virus Infection of the Brain

JC Virus Infection of the Brain

Novel immune regulatory pathways and their role in immune reconstitution syndrome in organ transplant recipients with invasive mycoses

Biomarkers of HIV Immune Reconstitution Inflammatory Syndrome

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