CD32 Expression is not Associated to HIV-DNA content in CD4 cell subsets of individuals with Different Levels of HIV Control

Abstract

A recent study has pointed out to CD32a as a potential biomarker of HIV-persistent CD4 cells. We have characterized the level and phenotype of CD32+ cells contained in different subsets of CD4 T-cells and its potential correlation with level of total HIV-DNA in thirty HIV patients (10 typical progressors naïve for cART, 10 cART-suppressed patients, and 10 elite controllers). Total HIV-DNA was quantified in different subsets of CD4 T-cells: Trm and pTfh cells. Level and immunephenotype of CD32+ cells were analyzed in these same subsets by flow cytometry. CD32 expression in Trm and pTfh subsets was similar in the different groups, and there was no significant correlation between the level of total HIV-DNA and the level of CD32 expression in these subsets. However, total HIV-DNA level was correlated with expression of CD127 (rho = −0.46, p = 0.043) and of CCR6 (rho = −0.418, p = 0.027) on CD32+ cells. Our results do not support CD32 as a biomarker of total HIV-DNA content. However, analyzing the expression of certain markers by CD32+ cells could improve the utility of this marker in the clinical setting, prompting the necessity of further studies to both validate our results and to explore the potential utility of certain markers expressed by CD32+ cells.

HIV Controllers Have Low Inflammation Associated with a Strong HIV-Specific Immune Response in Blood

“…Many studies indicate that antibody-induced effectors responses mediated through FCGR signaling contribute to the control and prevention of HIV-1 infection (34)(35)(36). FCGR2A (CD32A) receptor has also been reported as a marker of the CD4 ϩ T cell HIV reservoir in HIV-infected patients (37), but more recently contradictory works have shown that CD32 is not a marker of HIV-1 reservoir but of CD4 ϩ T cell activation in HIV ϩ individuals (38,39). Although the role of the Fc receptors in virus control remains to be thoroughly explored, one can speculate that the downregulation of these receptors could be associated with both lower activation/inflammation and the HIV reservoir observed in HIC compared to cART-treated individuals (40).…”

Strategies to eradicate HIV from infected patients: elimination of latent provirus reservoirs

“…However, CD32a is only expressed in ~ 50% of latently infected T cells but is also expressed in cells of myeloid lineage. Additionally, recent analysis has disputed whether latently infected CD4 + cells specifically express this marker [65]. Altogether, because neither of these markers specifically delineate cells latently infected with HIV, their utility for the elimination of this population is questionable.…”

Bringing Gene Therapies for HIV Disease to Resource-Limited Parts of the World

“…For every such hint of a possible route toward a cure, there have been multiple incorrectly interpreted observations (some recent examples: the use of anti-a4b7 antibodies to cure SIV infection in vivo 21,22 and the definition of CD32 as a specific marker for the rebound-competent reservoir [23][24][25][26][27] ) or instructive failures (e.g., the inability of early ART initiation to cure in the ''Mississippi baby'' 28 and the ''San Francisco patient,'' 29 the rebound of virus from the ''Boston patients'' who were myeloablated as part of care for their malignancies, 30 and X4 HIV escape in the ''Essen patient'' after a CCR5D32 bone marrow transplant 31 ). It has also become increasingly evident that the rebound-competent reservoir is vast 32 and that tissuebased immune responses against it might be crippled, especially in those who are treated at later time points after infection.…”