Suboptimal Immune Reconstitution in Vertically HIV Infected Children: A View on How HIV Replication and Timing of HAART Initiation Can Impact on T and B-cell Compartment

Cotugno, Nicola; Douagi, Iyadh; Rossi, Paolo; Palma, Paolo

doi:10.1155/2012/805151

Cited by 28 publications

(26 citation statements)

References 125 publications

(138 reference statements)

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“…This further points out the impaired recall/maintenance of antigen-specific memory B cells in patients with CGD, which, in the case of measles, should confer serologic memory for the entire lifespan in healthy subjects. 20 A similar scenario occurs in other diseases characterized by chronic immune activation, 16,30,31 in which the capacity to confer durable protection after vaccination is reduced and related to low memory B-cell frequencies. 32,33 Thus a possible explanation for the loss of long-term memory in patients with CGD can be an ineffective polyclonal activation of memory B cells, which usually maintain serologic memory.…”

Section: Discussionmentioning

confidence: 76%

Defective B-cell proliferation and maintenance of long-term memory in patients with chronic granulomatous disease

Cotugno

Finocchi

Cagigi

et al. 2015

Journal of Allergy and Clinical Immunology

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Background: Chronic granulomatous disease (CGD) is a primary immune deficiency characterized by a defect in reactive oxygen species production. Although the effect of CGD mainly reflects on the phagocytic compartment, B-cell responses are also impaired in patients with CGD. Objective: We sought to investigate how defective gp91 phox expression in patients with CGD and CGD carriers might affect the B-cell compartment and maintenance of long-term memory. Methods: We studied the B-cell compartment of patients with CGD in terms of phenotype and ability to produce reactive oxygen species and proliferate on stimuli differently directed to the B-cell receptor and Toll-like receptor 9. We further studied their capacity to maintain long-term memory by measuring cellular and serologic responses to measles. Results: We show that the memory B-cell compartment is impaired among patients with CGD, as indicated by reduced total (CD19 1 CD27 1 ) and resting (CD19 1 CD27 1 CD21 1 ) memory B cells in parallel to increased naive (CD19 1 CD27 2 IgD 1 ) B-cell frequencies. Data on CGD carriers reveal that such alterations are related to gp91 phox expression. Moreover, proliferative capabilities of B cells on selective in vitro stimulation of B-cell receptor or Toll-like receptor 9 pathways were reduced in patients with CGD compared with those seen in age-matched healthy control subjects. Significantly lower measles-specific antibody levels and antibody-secreting

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Section: Discussionmentioning

confidence: 76%

Defective B-cell proliferation and maintenance of long-term memory in patients with chronic granulomatous disease

Cotugno

Finocchi

Cagigi

et al. 2015

Journal of Allergy and Clinical Immunology

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“…As described in adult infection, ART-treated children demonstrate reduced levels of immune activation that, however, do not reach those of uninfected controls (1, 20, 55, 92). It is clear that early ART reduces the size of the latent HIV reservoir both in paediatric and adult infection (93, 94).…”

Section: Introductionmentioning

confidence: 77%

Immune activation and paediatric HIV-1 disease outcome

Roider

Muenchhoff

Goulder

2016

Current Opinion in HIV and AIDS

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Purpose of review The paediatric HIV epidemic is changing. Over the past decade, new infections have substantially reduced whilst access to antiretroviral therapy (ART) has increased. Overall this success means that numbers of children living with HIV are climbing. In addition, the problems in adults of chronic inflammation resulting from persistent immune activation even following ART-mediated suppression of viral replication are magnified in children infected from birth. Recent findings Features of immune ontogeny favor low immune activation in early life, whilst specific aspects of paediatric HIV infection tend to increase it. A subset of ART-naïve non-progressing children exists in whom normal CD4 counts are maintained in the setting of persistent high viremia and yet in the context of low immune activation. This sooty mangabey-like phenotype contrasts with non-progressing adult infection characterized by the expression of protective HLA class I molecules and low viral load. The particular factors contributing to raised or lowered immune activation in paediatric infection, and that ultimately influence disease outcome, are discussed. Summary Novel strategies to circumvent the unwanted long-term consequences of HIV infection may be possible in children in whom natural immune ontogeny in early life militates against immune activation. Defining the mechanisms underlying low immune activation in natural HIV infection would have applications beyond paediatric HIV.

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“…The reasons for this are likely to be multifactorial and include: a depleted/inadequate immunological memory for childhood infections and vaccinations; destruction/skewing of B‐ and T‐cell repertoires; and persistently low CD4 counts in relation to healthy age‐matched children (reviewed in 55). Mathematical modelling of data from large European and African cohorts indicates that CD4 cell recovery depends strongly on both the age and CD4 count at ART initiation 56, 57.…”

Section: When To Start Artmentioning

confidence: 99%

Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV‐1 infection 2015: optimizing health in preparation for adult life

et al. 2015

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The 2015 Paediatric European Network for Treatment of AIDS (PENTA) guidelines provide practical recommendations on the management of HIV‐1 infection in children in Europe and are an update to those published in 2009. Aims of treatment have progressed significantly over the last decade, moving far beyond limitation of short‐term morbidity and mortality to optimizing health status for adult life and minimizing the impact of chronic HIV infection on immune system development and health in general. Additionally, there is a greater need for increased awareness and minimization of long‐term drug toxicity. The main updates to the previous guidelines include: an increase in the number of indications for antiretroviral therapy (ART) at all ages (higher CD4 thresholds for consideration of ART initiation and additional clinical indications), revised guidance on first‐ and second‐line ART recommendations, including more recently available drug classes, expanded guidance on management of coinfections (including tuberculosis, hepatitis B and hepatitis C) and additional emphasis on the needs of adolescents as they approach transition to adult services. There is a new section on the current ART ‘pipeline’ of drug development, a comprehensive summary table of currently recommended ART with dosing recommendations. Differences between PENTA and current US and World Health Organization guidelines are highlighted and explained.

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Suboptimal Immune Reconstitution in Vertically HIV Infected Children: A View on How HIV Replication and Timing of HAART Initiation Can Impact on T and B-cell Compartment

Cited by 28 publications

References 125 publications

Defective B-cell proliferation and maintenance of long-term memory in patients with chronic granulomatous disease

Defective B-cell proliferation and maintenance of long-term memory in patients with chronic granulomatous disease

Immune activation and paediatric HIV-1 disease outcome

Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV‐1 infection 2015: optimizing health in preparation for adult life

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