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Published in: Medical Microbiology and Immunology 3-4/2018

01-08-2018 | Original Investigation

Deficit of IgG2 in HIV-positive pregnant women is responsible of inadequate IgG2 levels in their HIV-uninfected children in Malawi

Authors: Silvia Baroncelli, Clementina Maria Galluzzo, Giuseppe Liotta, Mauro Andreotti, Sandro Mancinelli, Robert Mphwere, Enok Bokola, Roberta Amici, Maria Cristina Marazzi, Leonardo Palombi, Francesca Lucaroni, Marina Giuliano

Published in: Medical Microbiology and Immunology | Issue 3-4/2018

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Abstract

Background

Transplacental passage of IgGs is impaired in HIV + pregnant women, possibly determining an inadequate immunological protection in their children. We aimed to determine the impact of maternal immunological IgG profile and immunoactivation status on the efficiency of transplacental passage of IgG subclasses in HIV + mothers.

Methods

16 mother/infants pairs were studied in Malawi. Mothers received antiretroviral therapy (ART) from the third trimester of pregnancy. Determinations of pre-ART levels of maternal sCD14, of IgG subclasses in mothers at delivery and in their 1-month-old infants, were performed using commercial ELISA kits.

Results

At delivery, after a median of 10 weeks of ART, 12/16 mothers were hypergammaglobulinemic, with IgG levels (20.5 mg/ml, 95% CI:18.8–26.8) directly correlated to the plasmatic levels of sCD14 (r = 0.640, p = 0.014). IgG1 levels (17.9 mg/ml) accounted for 82% of IgG, IgG3 and IgG4 levels were in the normal range. A profound deficit of IgG2 was observed both in mothers (0.60 mg/ml) and in infants (0.14 mg/ml). Placental transfer ratio (range 0.16–0.42) did not show a selective impairment between the different IgG subclasses. The transplacental passage of all IgG subclasses was decreased in the presence of maternal IgG over 16 mg/ml (significantly for IgG1, p = 0.031) and of high levels of sCD14 (p = 0.063).

Conclusions

Transplacental passage was reduced for all IgG subclasses and inversely correlated to high levels of maternal IgGs and to the degree of immunoactivation. The profound depression of IgG2 in mothers suggests that IgG2 neonatal levels mostly reflect the maternal deficit rather than a selective impairment of IgG2 transfer.
Literature
2.
go back to reference de Moraes-Pinto MI, Verhoeff F, Chimsuku L, Milligan PJ, Wesumperuma L, Broadhead RL, Brabin BJ, Johnson PM, Hart CA (1998) Placental antibody transfer: influence of maternal HIV infection and placental malaria. Arch Dis Child Fetal Neonatal 79:F202CrossRef de Moraes-Pinto MI, Verhoeff F, Chimsuku L, Milligan PJ, Wesumperuma L, Broadhead RL, Brabin BJ, Johnson PM, Hart CA (1998) Placental antibody transfer: influence of maternal HIV infection and placental malaria. Arch Dis Child Fetal Neonatal 79:F202CrossRef
3.
go back to reference Wilkinson AL, Pedersen SH, Urassa M, Michael D, Andreasen A, Todd J, Kinung’hi SM, Changalucha J, McDermid JM (2017) Maternal systemic or cord blood inflammation is associated with birth anthropometry in a Tanzanian prospective cohort. Trop Med Int Health 22:52–62. https://doi.org/10.1111/tmi.12799 CrossRefPubMed Wilkinson AL, Pedersen SH, Urassa M, Michael D, Andreasen A, Todd J, Kinung’hi SM, Changalucha J, McDermid JM (2017) Maternal systemic or cord blood inflammation is associated with birth anthropometry in a Tanzanian prospective cohort. Trop Med Int Health 22:52–62. https://​doi.​org/​10.​1111/​tmi.​12799 CrossRefPubMed
5.
go back to reference Ljunggren K, Broliden PA, Morfeldt-Manson L, Jondal M, Wahren B (1988) IgG subclass response to HIV in relation to antibody-dependent cellular cytotoxicity at different clinical stages. Clin Exp Immunol 73:343–347PubMedPubMedCentral Ljunggren K, Broliden PA, Morfeldt-Manson L, Jondal M, Wahren B (1988) IgG subclass response to HIV in relation to antibody-dependent cellular cytotoxicity at different clinical stages. Clin Exp Immunol 73:343–347PubMedPubMedCentral
9.
go back to reference de Moraes-Pinto MI, Almeida AC, Kenj G, Filgueiras TE, Tobias W, Santos AM, Carneiro-Sampaio MM, Farhat CK, Milligan PJ, Johnson PM, Hart CA (1996) Placental transfer and maternally acquired neonatal IgG immunity in HIV infection. J Infect Dis 173:1077–1084CrossRefPubMed de Moraes-Pinto MI, Almeida AC, Kenj G, Filgueiras TE, Tobias W, Santos AM, Carneiro-Sampaio MM, Farhat CK, Milligan PJ, Johnson PM, Hart CA (1996) Placental transfer and maternally acquired neonatal IgG immunity in HIV infection. J Infect Dis 173:1077–1084CrossRefPubMed
11.
go back to reference Babakhanyan A, Ekali GL, Dent A, Kazura J, Nguasong JT, Fodjo BAY, Yuosembom EK, Esemu LF, Taylor DW, Leke RGF (2016) Maternal human immunodeficiency virus-associated hypergammaglobulinemia reduces transplacental transfer of immunoglobulin G to plasmodium falciparum antigens in Cameroonian neonates. Open Forum Infect Dis 3:ofw092. https://doi.org/10.1093/ofid/ofw092 CrossRefPubMedPubMedCentral Babakhanyan A, Ekali GL, Dent A, Kazura J, Nguasong JT, Fodjo BAY, Yuosembom EK, Esemu LF, Taylor DW, Leke RGF (2016) Maternal human immunodeficiency virus-associated hypergammaglobulinemia reduces transplacental transfer of immunoglobulin G to plasmodium falciparum antigens in Cameroonian neonates. Open Forum Infect Dis 3:ofw092. https://​doi.​org/​10.​1093/​ofid/​ofw092 CrossRefPubMedPubMedCentral
12.
go back to reference Moro L, Bardají A, Nhampossa T, Mandomando I, Serra-Casas E, Sigaúque B, Cisteró P, Chauhan VS, Chitnis CE, Ordi J, Dobaño C, Alonso PL, Menéndez C, Mayor A (2015) Malaria and HIV infection in Mozambican pregnant women are associated with reduced transfer of antimalarial antibodies to their newborns. J Infect Dis 211:1004–101. https://doi.org/10.1093/infdis/jiu547 CrossRefPubMed Moro L, Bardají A, Nhampossa T, Mandomando I, Serra-Casas E, Sigaúque B, Cisteró P, Chauhan VS, Chitnis CE, Ordi J, Dobaño C, Alonso PL, Menéndez C, Mayor A (2015) Malaria and HIV infection in Mozambican pregnant women are associated with reduced transfer of antimalarial antibodies to their newborns. J Infect Dis 211:1004–101. https://​doi.​org/​10.​1093/​infdis/​jiu547 CrossRefPubMed
13.
go back to reference Farquhar C, Nduati R, Haigwood N, Sutton W, Mbori-Ngacha D, Richardson B, John-Stewart G (2005) High maternal HIV-1 viral load during pregnancy is associated with reduced placental transfer of measles IgG antibody. J Acquir Immune Defic Syndr 40:494–497CrossRefPubMedPubMedCentral Farquhar C, Nduati R, Haigwood N, Sutton W, Mbori-Ngacha D, Richardson B, John-Stewart G (2005) High maternal HIV-1 viral load during pregnancy is associated with reduced placental transfer of measles IgG antibody. J Acquir Immune Defic Syndr 40:494–497CrossRefPubMedPubMedCentral
14.
go back to reference Gaensbauer JT, Rakhola JT, Onyango-Makumbi C, Mubiru M, Westcott JE, Krebs NF, Asturias EJ, Fowler MG, McFarland E, Janoff EN (2014) Impaired Haemophilus influenza type-b transplacental antibody transmission and declining antibody avidity through the first year of life represent potential vulnerabilities for HIV-exposed but uninfected infants. Clin Vaccine Immunol 21:1661–1667. https://doi.org/10.1128/CVI.00356-14 CrossRefPubMedPubMedCentral Gaensbauer JT, Rakhola JT, Onyango-Makumbi C, Mubiru M, Westcott JE, Krebs NF, Asturias EJ, Fowler MG, McFarland E, Janoff EN (2014) Impaired Haemophilus influenza type-b transplacental antibody transmission and declining antibody avidity through the first year of life represent potential vulnerabilities for HIV-exposed but uninfected infants. Clin Vaccine Immunol 21:1661–1667. https://​doi.​org/​10.​1128/​CVI.​00356-14 CrossRefPubMedPubMedCentral
16.
go back to reference Abu-Raya B, Smolen KK, Willems F, Kollmann TR, Marchant A (2016) Transfer of maternal antimicrobial immunity to HIV-exposed uninfected newborns. Front Immunol 31:338 Abu-Raya B, Smolen KK, Willems F, Kollmann TR, Marchant A (2016) Transfer of maternal antimicrobial immunity to HIV-exposed uninfected newborns. Front Immunol 31:338
17.
go back to reference Ben-Hur H, Gurevich P, Elhayany A, Avinoach I, Schneider DF, Zusman I (2005) Transport of maternal immunoglobulins through the human placental barrier in normal pregnancy and during inflammation. Int J Mol Med 16:401–407PubMed Ben-Hur H, Gurevich P, Elhayany A, Avinoach I, Schneider DF, Zusman I (2005) Transport of maternal immunoglobulins through the human placental barrier in normal pregnancy and during inflammation. Int J Mol Med 16:401–407PubMed
18.
go back to reference Cumberland P, Shulman CE, Maple PA, Bulmer JN, Dorman EK, Kawuondo K, Marsh K, Cutts FTM (2007) Maternal HIV infection and placental malaria reduce transplacental antibody transfer and tetanus antibody levels in newborns in Kenya. J Infect Dis 196:550–557. https://doi.org/10.1086/519845 CrossRefPubMed Cumberland P, Shulman CE, Maple PA, Bulmer JN, Dorman EK, Kawuondo K, Marsh K, Cutts FTM (2007) Maternal HIV infection and placental malaria reduce transplacental antibody transfer and tetanus antibody levels in newborns in Kenya. J Infect Dis 196:550–557. https://​doi.​org/​10.​1086/​519845 CrossRefPubMed
23.
go back to reference Bosire R, Farquhar C, Nduati R, Broliden K, Luchters S, Van de Perre P, De Vincenzi I, Merkel M, Wachuka V, Mbori-Ngacha D, John-Stewart G, Lohman-Payne B, Reilly M (2017) Higher transplacental pathogen-specific antibody transfer among pregnant women randomized to triple antiretroviral treatment versus short course zidovudine. Pediatr Infect Dis J. https://doi.org/10.1097/INF.0000000000001749. (Epub ahead of print)CrossRef Bosire R, Farquhar C, Nduati R, Broliden K, Luchters S, Van de Perre P, De Vincenzi I, Merkel M, Wachuka V, Mbori-Ngacha D, John-Stewart G, Lohman-Payne B, Reilly M (2017) Higher transplacental pathogen-specific antibody transfer among pregnant women randomized to triple antiretroviral treatment versus short course zidovudine. Pediatr Infect Dis J. https://​doi.​org/​10.​1097/​INF.​0000000000001749​. (Epub ahead of print)CrossRef
24.
go back to reference Okoko BJ, Wesumperuma LH, Ota MO, Pinder M, Banya W, Gomez SF, McAdam KP, Hart AC (2001) The influence of placental malaria infection and maternal hypergammaglobulinemia on transplacental transfer of antibodies and IgG subclasses in a rural West African population. J Infect Dis 184:627–632. https://doi.org/10.1086/322808 CrossRefPubMed Okoko BJ, Wesumperuma LH, Ota MO, Pinder M, Banya W, Gomez SF, McAdam KP, Hart AC (2001) The influence of placental malaria infection and maternal hypergammaglobulinemia on transplacental transfer of antibodies and IgG subclasses in a rural West African population. J Infect Dis 184:627–632. https://​doi.​org/​10.​1086/​322808 CrossRefPubMed
25.
go back to reference Pirillo MF, Liotta G, Andreotti M, Jere H, Sagno JB, Scarcella P, Mancinelli S, Buonomo E, Amici R, Marazzi MC, Vella S, Palombi L, Giuliano M (2017) CMV infection in a cohort of HIV-exposed infants born to mothers receiving antiretroviral therapy during pregnancy and breastfeeding. Med Microbiol Immunol 206:23–29. https://doi.org/10.1007/s00430-016-0478-6 CrossRefPubMed Pirillo MF, Liotta G, Andreotti M, Jere H, Sagno JB, Scarcella P, Mancinelli S, Buonomo E, Amici R, Marazzi MC, Vella S, Palombi L, Giuliano M (2017) CMV infection in a cohort of HIV-exposed infants born to mothers receiving antiretroviral therapy during pregnancy and breastfeeding. Med Microbiol Immunol 206:23–29. https://​doi.​org/​10.​1007/​s00430-016-0478-6 CrossRefPubMed
29.
go back to reference Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G, Rao S, Kazzaz Z, Bornstein E, Lambotte O, Altmann D, Blazar BR, Rodriguez B, Teixeira-Johnson L, Landay A, Martin JN, Hecht FM, Picker LJ, Lederman MM, Deeks SG, Douek DC (2006) Microbial translocation is a cause of systemic immune activation in chronic HIV. infection Nat Med 12:1365–1371. https://doi.org/10.1038/nm1511 CrossRefPubMed Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G, Rao S, Kazzaz Z, Bornstein E, Lambotte O, Altmann D, Blazar BR, Rodriguez B, Teixeira-Johnson L, Landay A, Martin JN, Hecht FM, Picker LJ, Lederman MM, Deeks SG, Douek DC (2006) Microbial translocation is a cause of systemic immune activation in chronic HIV. infection Nat Med 12:1365–1371. https://​doi.​org/​10.​1038/​nm1511 CrossRefPubMed
30.
go back to reference Hashira S, Okitsu-Negishi S, Yoshino K (2000) Placental transfer of IgG subclasses in a Japanese population. Pediatr Int 42:337–342CrossRefPubMed Hashira S, Okitsu-Negishi S, Yoshino K (2000) Placental transfer of IgG subclasses in a Japanese population. Pediatr Int 42:337–342CrossRefPubMed
31.
go back to reference Schauer U, Stemberg F, Rieger CH, Borte M, Schubert S, Riedel F, Herz U, Renz H, Wick M, Carr-Smith HD, Bradwell AR, Herzog W (2003) IgG subclass concentrations in certified reference material 470 and reference values for children and adults determined with the binding site reagents. Clin Chem 49:1924–1929CrossRefPubMed Schauer U, Stemberg F, Rieger CH, Borte M, Schubert S, Riedel F, Herz U, Renz H, Wick M, Carr-Smith HD, Bradwell AR, Herzog W (2003) IgG subclass concentrations in certified reference material 470 and reference values for children and adults determined with the binding site reagents. Clin Chem 49:1924–1929CrossRefPubMed
35.
go back to reference Weiss PJ, Wallace MR, Oldfield EC 3rd, O’Brien J, Janoff EN (1995) Response of recent human immunodeficiency virus seroconverters to the pneumococcal polysaccharide vaccine and Haemophilus influenzae type b conjugate vaccine. J Infect Dis 171:1217–1222CrossRefPubMed Weiss PJ, Wallace MR, Oldfield EC 3rd, O’Brien J, Janoff EN (1995) Response of recent human immunodeficiency virus seroconverters to the pneumococcal polysaccharide vaccine and Haemophilus influenzae type b conjugate vaccine. J Infect Dis 171:1217–1222CrossRefPubMed
36.
go back to reference Reimer CB, Black CM, Holman RC, Wells TW, Ramirez RM, Sa-Ferreira JA, Nicholson JK, McDougal JS (1988) Hypergammaglobulinemia associated with human immunodeficiency virus infection. Monogr Allergy 23:83–96PubMed Reimer CB, Black CM, Holman RC, Wells TW, Ramirez RM, Sa-Ferreira JA, Nicholson JK, McDougal JS (1988) Hypergammaglobulinemia associated with human immunodeficiency virus infection. Monogr Allergy 23:83–96PubMed
37.
go back to reference De Milito A, Nilsson A, Titanji K, Thorstensson R, Reizenstein E, Narita M, Grutzmeier S, Sönnerborg A, Chiodi F (2004) Mechanisms of hypergammaglobulinemia and impaired antigen-specific humoral immunity in HIV-1 infection. Blood 103:2180–2186CrossRefPubMed De Milito A, Nilsson A, Titanji K, Thorstensson R, Reizenstein E, Narita M, Grutzmeier S, Sönnerborg A, Chiodi F (2004) Mechanisms of hypergammaglobulinemia and impaired antigen-specific humoral immunity in HIV-1 infection. Blood 103:2180–2186CrossRefPubMed
38.
go back to reference Macchia D, Almerigogna F, Parronchi P, Ravina A, Maggi E, Romagnani S (1993) Membrane tumour necrosis factor-alpha is involved in the polyclonal B-cell activation induced by HIV-infected human T cells. Nature 363:464–466CrossRefPubMed Macchia D, Almerigogna F, Parronchi P, Ravina A, Maggi E, Romagnani S (1993) Membrane tumour necrosis factor-alpha is involved in the polyclonal B-cell activation induced by HIV-infected human T cells. Nature 363:464–466CrossRefPubMed
40.
go back to reference Hosmalin A, Lebon P (2006) Type I interferon production in HIV-infected patients. J Leukoc Biol 80:984–993CrossRefPubMed Hosmalin A, Lebon P (2006) Type I interferon production in HIV-infected patients. J Leukoc Biol 80:984–993CrossRefPubMed
41.
go back to reference Ferreira MU, Kimura EAS, Katzin AM, Santos-Neto LL, Ferrari JO, Villalobos JM, de Carvalho ME (1998) The IgG-subclass distribution of naturally acquired antibodies to Plasmodium falciparum, in relation to malaria exposure and severity. Ann Trop Med Parasitol 92:245–256CrossRefPubMed Ferreira MU, Kimura EAS, Katzin AM, Santos-Neto LL, Ferrari JO, Villalobos JM, de Carvalho ME (1998) The IgG-subclass distribution of naturally acquired antibodies to Plasmodium falciparum, in relation to malaria exposure and severity. Ann Trop Med Parasitol 92:245–256CrossRefPubMed
42.
go back to reference Tongren JE, Drakeley CJ, McDonald SL, Reyburn HG, Manjurano A, Nkya WM, Lemnge MM, Gowda CD, Todd JE, Corran PH, Riley EM (2006) Target antigen, age, and duration of antigen exposure independently regulate immunoglobulin G subclass switching in malaria. Infect Immun 74:257–264CrossRefPubMedPubMedCentral Tongren JE, Drakeley CJ, McDonald SL, Reyburn HG, Manjurano A, Nkya WM, Lemnge MM, Gowda CD, Todd JE, Corran PH, Riley EM (2006) Target antigen, age, and duration of antigen exposure independently regulate immunoglobulin G subclass switching in malaria. Infect Immun 74:257–264CrossRefPubMedPubMedCentral
43.
go back to reference Rouhani M, Zakeri S, Mehrizi AA, Djadid ND (2015) Comparative analysis of the profiles of IgG subclass-specific responses to Plasmodium falciparum apical membrane antigen-1 and merozoite surface protein-1 in naturally exposed individuals living in malaria hypoendemic settings. Iran Malar J 14:58. https://doi.org/10.1186/s12936-015-0547-0 CrossRefPubMed Rouhani M, Zakeri S, Mehrizi AA, Djadid ND (2015) Comparative analysis of the profiles of IgG subclass-specific responses to Plasmodium falciparum apical membrane antigen-1 and merozoite surface protein-1 in naturally exposed individuals living in malaria hypoendemic settings. Iran Malar J 14:58. https://​doi.​org/​10.​1186/​s12936-015-0547-0 CrossRefPubMed
48.
go back to reference Parker A, Irure Ventura J, Sims D, Echeverría de Carlos A, Gómez de la Torre R, Tricas Aizpún L, Ocejo-Vinyals JG, López-Hoyos M, Wallis G, Harding S (2017) Measurement of the IgG2 response to Pneumococcal capsular polysaccharides may identify an antibody deficiency in individuals referred for immunological investigation. J Immunoassay Immunochem 38:514–522. https://doi.org/10.1080/15321819.2017.1340897 CrossRefPubMed Parker A, Irure Ventura J, Sims D, Echeverría de Carlos A, Gómez de la Torre R, Tricas Aizpún L, Ocejo-Vinyals JG, López-Hoyos M, Wallis G, Harding S (2017) Measurement of the IgG2 response to Pneumococcal capsular polysaccharides may identify an antibody deficiency in individuals referred for immunological investigation. J Immunoassay Immunochem 38:514–522. https://​doi.​org/​10.​1080/​15321819.​2017.​1340897 CrossRefPubMed
50.
go back to reference Heyderman RS, Madhi SA, French N, Cutland C, Ngwira B, Kayambo D, Mboizi R, Koen A, Jose L, Olugbosi M, Wittke F, Slobod K, Dull PM. Group B streptococcus vaccination in pregnant women with or without HIV in Africa: a non-randomised phase 2, open-label, multicentre trial. Lancet Infect Dis 2016 May;16(5):546–555. https://doi.org/10.1016/S1473-3099(15)00484-3 Heyderman RS, Madhi SA, French N, Cutland C, Ngwira B, Kayambo D, Mboizi R, Koen A, Jose L, Olugbosi M, Wittke F, Slobod K, Dull PM. Group B streptococcus vaccination in pregnant women with or without HIV in Africa: a non-randomised phase 2, open-label, multicentre trial. Lancet Infect Dis 2016 May;16(5):546–555. https://​doi.​org/​10.​1016/​S1473-3099(15)00484-3
53.
go back to reference Pensieroso S, Cagigi A, Palma P, Nilsson A, Capponi C, Freda E, Bernardi S, Thorstensson R, Chiodi F, Rossi P (2009) Timing of HAART defines the integrity of memory B cells and the longevity of humoral responses in HIV-1 vertically-infected children. Proc Natl Acad Sci USA 106:7939–7944. https://doi.org/10.1073/pnas.0901702106 CrossRefPubMed Pensieroso S, Cagigi A, Palma P, Nilsson A, Capponi C, Freda E, Bernardi S, Thorstensson R, Chiodi F, Rossi P (2009) Timing of HAART defines the integrity of memory B cells and the longevity of humoral responses in HIV-1 vertically-infected children. Proc Natl Acad Sci USA 106:7939–7944. https://​doi.​org/​10.​1073/​pnas.​0901702106 CrossRefPubMed
54.
go back to reference Moir S, Malaspina A, Ho J, Wang W, Dipoto AC, O’Shea MA, Roby G, Mican JM, Kottilil S, Chun TW, Proschan MA, Fauci AS (2008) Normalization of B cell counts and subpopulations after antiretroviral therapy in chronic HIV disease. J Infect Dis 197:572–579. https://doi.org/10.1086/526789 CrossRefPubMed Moir S, Malaspina A, Ho J, Wang W, Dipoto AC, O’Shea MA, Roby G, Mican JM, Kottilil S, Chun TW, Proschan MA, Fauci AS (2008) Normalization of B cell counts and subpopulations after antiretroviral therapy in chronic HIV disease. J Infect Dis 197:572–579. https://​doi.​org/​10.​1086/​526789 CrossRefPubMed
Metadata
Title
Deficit of IgG2 in HIV-positive pregnant women is responsible of inadequate IgG2 levels in their HIV-uninfected children in Malawi
Authors
Silvia Baroncelli
Clementina Maria Galluzzo
Giuseppe Liotta
Mauro Andreotti
Sandro Mancinelli
Robert Mphwere
Enok Bokola
Roberta Amici
Maria Cristina Marazzi
Leonardo Palombi
Francesca Lucaroni
Marina Giuliano
Publication date
01-08-2018
Publisher
Springer Berlin Heidelberg
Published in
Medical Microbiology and Immunology / Issue 3-4/2018
Print ISSN: 0300-8584
Electronic ISSN: 1432-1831
DOI
https://doi.org/10.1007/s00430-018-0537-2

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