The impact of antiretroviral therapy on the evolution of Fc region mediated humoral immunity toward HIV infection
Notice bibliographique
Résumé
Secondary analyses of RV144, the only vaccine trial ever shown to provide significant protection against human immunodeficiency virus (HIV) infection, have revealed that immunoglobulin G (IgG) antibody (Ab) dependent cellular cytotoxicity (ADCC) activity correlated with vaccinee protection from HIV (Haynes et al., 2012). ADCC is a humoral immune response that depends on the use of Ab fragment crystallizable (Fc) regions to direct HIV lysis through the engagement of Natural Killer (NK) cells. Therefore, RV144 provides an impetus to further characterize immune responses like ADCC that require Ab Fc regions to attract immune system components capable of lysing extracellular HIV virions and HIV infected cells. Antiretroviral therapy (ART), accessed by approximately half the current HIV+ population and recommended immediately upon HIV infection for the vast majority of people by the International Antiviral Society (IAS), is one such factor that has not been assessed for its ability to impact Ab Fc region mediated (Fcm) immunity, despite its ubiquity (Günthard et al., 2016; WHO, 2016). This study investigated the evolution of IgG Fcm immunity over the course of early HIV infection in ART naive individuals and also in individuals who began receiving ART treatment within six months of HIV infection. The ability of blood plasma donated by HIV+ patients in the Montreal Primary Infection Cohort (MPIC) to mediate ADCC and other HIV antigen specific Fcm immune functions, including Ab dependent phagocytosis (ADCP), Ab dependent complement deposition (ADCD) and Ab dependent trogocytosis (ADCT) was assessed. Total and HIV envelope (Env) gp120 glycoprotein specific IgG titers were quantified in the plasma samples. Comparing equal levels of IgG between the plasma samples, ADCP activity was measured toward an Env gp120 target, while ADCD, ADCC and ADCT activities were measured toward target CCR5+ NK cell resistant CEM (CEM.NKr.CCR5) cells infected with bonafide HIV. These particular HIV infected target cells do not expose cluster of differentiation (CD)4 induced (CD4i) epitopes, which are susceptible to Fcm immunity and are protected by the virus during physiological infection. ADCC, ADCP and ADCT were found to mount significantly over time during untreated HIV infection, yielding Spearman correlation coefficients (rs) of rs=0.3836, rs=0.3532 and rs=0.1975, respectively (corresponding to probability [p] values of p=0.0005, p=0.0013 and p=0.0494, respectively), while ADCD activity did not increase as infection progressed. Analysis of covariance (ANCOVA) was calculated between ART treated and ART naive individuals to determine whether ART administration affected the evolution of Fcm immune responses over time. F-scores of 4.72394 (p=0.0313) and 11.6545 (p=0.0008) portrayed that ART administration did indeed mitigate the evolution of ADCC and ADCD responses, unlike ADCP and ADCT. Generalized linear mixed models (GLMMs) and the variance weighted least squares (VWLS) method were then able to deduce the impact of ART initiation timing on the evolution of ADCC, ADCP, ADCD and ADCT responses, after separating the treated patients into three groups, based on whether their ART administration started within 69 days, between 70 to 124 days, or after 124 days post HIV infection. These statistical analyses revealed that early treatment timing did not affect the evolution of ADCC or ADCP responses in the MPIC plasma donors investigated and actually preserved ADCD and ADCT responses over time, as compared to later ART initiation. Collectively, these results do not reject the current IAS consensus that immediate ART treatment initiation is ideal for the preservation of health in people who become infected with HIV. The results do show however, that ADCC, ADCP, ADCD and ADCT activities can be directed towards HIV epitopes that do not require gp120 binding to CD4.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».