Cervicovaginal Overproduction of Specific IgG to Human Immunodeficiency Virus (HIV) Contrasts with Normal or Impaired IgA Local Response in HIV Infection

Bélec, Laurent; Dupré, Thierry; Prazuck, Thiérry; Tévi-Bénissan, Carol; Kanga, J. M.; Pathey, Olivier; Lü, X.S.; Pillot, J.

doi:10.1093/infdis/172.3.691

Cited by 111 publications

(70 citation statements)

References 28 publications

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“…Nevertheless, consistent with previous reports (31,61,62), we identified lower proportions of intestinal IgA Abs in HIV-1-infected patients compared with control subjects. This decreased proportion of IgA in intestinal lavage samples of HIV-1-infected patients may arise in part due to transudation of serum IgG across a compromised mucosal barrier (31,62).…”

Section: Discussionsupporting

confidence: 93%

Mucosal Plasma Cell Repertoire During HIV-1 Infection

Scamurra

Nelson

Lin

et al. 2002

The Journal of Immunology

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Impaired development of local Ab responses may predispose HIV-1-infected patients to an increased rate, severity, and duration of mucosal infections. We characterized the repertoire of Ig-producing cells in the intestinal effector compartment (the lamina propria) of HIV-1-infected (n = 29) and seronegative control (n = 27) subjects. The density of Ig-producing cells per area was similar in both groups. However, the proportions of IgA-producing cells were lower in both the duodenum and colon from HIV-1-infected patients compared with those of control subjects (p < 0.05), with compensatory increases in IgG-producing cells in the colon and IgM-producing cells in the duodenum. Similarly, among Abs in the lumen the proportions of IgA were also decreased and the proportions of IgG were increased among HIV-1-infected patients. On a molecular level, VH gene repertoire analyses by RT-PCR revealed comparable proportions of the VH3 family among duodenal IgA transcripts (50–53%) from both groups. VH3 expression was decreased only for IgM among patients with advanced HIV-1 disease (n = 6) compared with that of control subjects (n = 8) (48 ± 8 vs 62 ± 13%; p < 0.01). Moreover, the frequencies of individual IgM and IgA VH3 genes were comparable in each group, including rates of putative HIV-1 gp120-binding VH3 genes (V3-23, V3-30, V3-30/3-30.5). We conclude that, despite a decrement in local IgA producing cells, the density and molecular VH repertoire of mucosal plasma cells are relatively intact among patients with HIV-1 infection. These data suggest that HIV-1-infected patients use functional regulatory mechanisms to provide sufficient VH diversity and effective induction and differentiation of mucosal B cells.

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Section: Discussionsupporting

confidence: 93%

Mucosal Plasma Cell Repertoire During HIV-1 Infection

Scamurra

Nelson

Lin

et al. 2002

The Journal of Immunology

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“…This observation supports the finding of others [57,58], and suggests the presence of a responsive immune system at this site. Increased levels of IgG have also been identified in blood [59] of HIV1 women compared to low-risk subjects.…”

Section: Discussionsupporting

confidence: 92%

“…Increased levels of IgG have also been identified in blood [59] of HIV1 women compared to low-risk subjects. Similar patterns of Ig appear in the lung [59] and the female LGT [58], with increased IgG compared to static or reduced sIgA levels. Studies on intestinal mucosa have suggested that this unexpected predominance of IgG over IgA may result from abnormal Ig production in the mucosa rather than from serum leakage [60].…”

Section: Discussionmentioning

confidence: 59%

Immunity in the Female Lower Genital Tract and the Impact of HIV Infection

Ahmed¹,

Al-Doujaily²,

Johnson

et al. 2001

Scand J Immunol

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This study investigates the distribution of immunocompetent cells in the ectocervix, and cytokine and immunoglobulin (Ig) levels in cervicovaginal secretions to determine whether they are altered in asymptomatic human immunodeficiency virus (HIV) infection. Ectocervical biopsies from 10 HIV1 and 10 presumed HIV-ve women were studied by immunocytochemistry. Levels of Igs in cervicovaginal secretions were quantified by radial immunodiffusion (RID) and cytokine levels by ELISA. HIV1 women had significantly increased numbers of CD8 1 lymphocytes resulting in reversal of the CD4:CD8 ratio. There was a significant increase in the proportion of activated CD81 HLA-DR1 and CD4 1 HLA-DR 1 lymphocytes, but not in CD81 TIA-11 cells. The epithelium of the cervix from HIV1 subjects showed a significant increase in both numbers of macrophages (CD681) and proportions of activated macrophages (CD681 HLA-DR1) compared to normal. The stroma contained increased proportions of inductive (D11) and suppressive (D11 D71) macrophages but a decrease in effector phagocyte (D71) proportions and Langerhans' cells. Significantly lower tumour necrosis factor (TNF)-a levels were observed in cervicovaginal secretions from HIV1 subjects. IgG levels were 4 times higher and IgM levels twice higher in cervicovaginal secretions from HIV1 women, compared to results from normal subjects. These results suggest a response within the CD8 1 cells in HIV1 women, yet these cells may have a low cytolytic capacity. The raised proportions of HLA-DR1 and D11 CD4 1 macrophages could act as antigen-presenting cells (APC) for CD4 1 CD45RO1 lymphocytes, and represent a local acquired response. However, the close juxtaposition of these cells offers the potential for them to act as a local reservoir of virus and promote its proliferation. The increase of IgG over sIgA in secretions of HIV1 subjects provides evidence suggesting a dysregulation of local humoral immunity.

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“…In contrast to observations among uninfected individuals, there usually is a predominance of IgG with defects in sIgA among individuals with HIV infection in mucosal compartments. 32,33 We might have expected, therefore, that the deficits in sIgA production would increase with advanced disease and increasing systemic immunosuppression. We did not find this association.…”

Section: Discussionmentioning

confidence: 99%

Hiv-specific secretory IgA in breast milk of HIV-positive mothers is not associated with protection against HIV transmission among breast-fed infants

Kuhn

Trabattoni

Kankasa

et al. 2006

The Journal of Pediatrics

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Objectives-To test whether secretory immunoglobulin A (sIgA) to human immunodeficiency virus (HIV) antigens in breast milk of HIV-positive women is associated with protection against HIV transmission among breast-fed infants.Study design-Nested, case-control design in which HIV-specific sIgA was measured in breast milk collected from 90 HIV-positive women enrolled in a study in Lusaka, Zambia. Milk samples were selected to include 26 HIV-positive mothers with infected infants (transmitters) and 64 mothers with uninfected infants (nontransmitters).Results-HIV-specific sIgA was detected more often in breast milk of transmitting mothers (76.9%) than in breast milk of nontransmitting mothers (46.9%, P = .009). There were no significant associations between HIV-specific sIgA in breast milk and other maternal factors, including HIV RNA quantities in breast milk, CD4 count, and plasma RNA quantities.Conclusions-HIV-specific sIgA in breast milk does not appear to be a protective factor against HIV transmission among breast-fed infants.Human immunodeficiency virus (HIV) can be transmitted from an HIV-infected mother to her child through breast-feeding. This poses a serious dilemma for health policy-makers. Although complete avoidance of breast-feeding would eliminate the risk of breast-feeding-associated transmission, breast milk substitutes are unaffordable, unavailable, unacceptable, and unsafe for many HIV-infected women in low resource settings. The quantity of viral RNA and cellassociated viral DNA in breast milk from HIV-positive women strongly predicts mother-tochild transmission among breast-fed infants. [1][2][3] What is puzzling, however, is why the majority of breast-fed infants born to HIV-positive mothers remain uninfected despite prolonged exposure. Although breast milk is clearly a route of transmission, human milk is also a rich source of a multitude of innate and specific immune factors that may play a role in modulating the risk of infection. 4 Better understanding of anti-infective properties of breast milk may assist Secretory immunoglobulin A (sIgA) is the predominant immunoglobulin in breast milk and is associated with passive immunity to other (non-HIV) pathogens among breast-fed infants. 5 HIV-specific IgA antibodies are detected in breast milk of a high proportion of HIV-positive, lactating women. [6][7][8] In an in vitro model, sIgA purified from colostrum was able to block one of the pathways involved in HIV penetration across mucosa, that is, transcytosis through epithelial cells, 9 suggesting that sIgA may be related to decreased infectivity of breast milk. Although persistence of HIV-specific IgA and IgM in breast milk was associated with reduced transmission in one study in Rwanda, 10 no protective association was observed in two other studies. 8,11 HIV-specific sIgA has been detected frequently in cervicovaginal samples from exposed but persistently uninfected cohorts of high-risk women, 12-14 suggesting a role for these mucosal responses in resistance to HIV. Purified sIgA from ex...

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Cervicovaginal Overproduction of Specific IgG to Human Immunodeficiency Virus (HIV) Contrasts with Normal or Impaired IgA Local Response in HIV Infection

Cited by 111 publications

References 28 publications

Mucosal Plasma Cell Repertoire During HIV-1 Infection

Mucosal Plasma Cell Repertoire During HIV-1 Infection

Immunity in the Female Lower Genital Tract and the Impact of HIV Infection

Hiv-specific secretory IgA in breast milk of HIV-positive mothers is not associated with protection against HIV transmission among breast-fed infants

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