Isotypic and IgG Subclass Restriction of the Humoral Immune Responses to Human T-Lymphotropic Virus Type-I

Lal, Renu B.; Buckner, Cindy M.; Khabbaz, Rima F.; Kaplan, Jonathan E.; Reyes, Gregory; Hadlock, Kenneth G.; Lipka, Jim; Foung, Steven K. H.; Chan, Lily; Coligan, John E.

doi:10.1006/clin.1993.1043

Cited by 21 publications

(16 citation statements)

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“…IgG1 was expected, as the subclass is commonly induced after viral infections such as measles, hepatitis B, human T-lymphotropic virus, rubella, and B19V, which like AAV is a member of the Parvoviridae (Morgan-Capner and Thomas, 1988;Lal et al, 1993;Franssila et al, 1996;Rey et al, 2000;Toptygina et al, 2005). IgG2 was also shown to be a constituent of the AAV-specific antibody response (Madsen et al, 2009;Murphy et al, 2009), but it is low as for B19V (Lal et al, 1993;Franssila et al, 1996;Toptygina et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Serum IgG and Neutralizing Factors Against Adeno-Associated Virus (AAV) Types 1, 2, 5, 6, 8, and 9 in the Healthy Population: Implications for Gene Therapy Using AAV Vectors

Boutin

Monteilhet²,

Véron³

et al. 2010

Human Gene Therapy

804

782

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Adeno-associated viruses (AAVs) are small, nonenveloped single-stranded DNA viruses that require helper viruses to facilitate efficient replication. Despite the presence of humoral responses to the wild-type AAV in humans, AAV remains one of the most promising candidates for therapeutic gene transfer to treat many genetic and acquired diseases. Characterization of the IgG subclass responses to AAV and study of the prevalence of both IgG and neutralizing factors to AAV types 1, 2, 5, 6, 8, and 9 in the human population are of importance for the development of new strategies to overcome these immune responses. Natural exposure to AAV types 1, 2, 5, 6, 8, and 9 can result in the production of antibodies from all four IgG subclasses, with a predominant IgG1 response and low IgG2, IgG3, and IgG4 responses. Prevalences of anti-AAV1 and -AAV2 total IgG determined by enzyme-linked immunosorbent assay were higher (67 and 72%) than those of anti-AAV5 (40%), anti-AAV6 (46%), anti-AAV8 (38%), and anti-AAV9 (47%). Furthermore, data showed that cross-reactions are important. The two highest neutralizing factor seroprevalences were observed for AAV2 (59%) and AAV1 (50.5%) and the lowest were observed for AAV8 (19%) and AAV5 (3.2%). Vectors based on AAV5, AAV8, and AAV9 may have an advantage for gene therapy in humans. Furthermore, among individuals seropositive for AAV5, AAV8, and AAV9, about 70-100% present low titers. Better characterization of the preexisting humoral responses to the AAV capsid and cross-reactivity will allow development of new strategies to circumvent AAV acquired immune responses.

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Section: Discussionmentioning

confidence: 99%

Prevalence of Serum IgG and Neutralizing Factors Against Adeno-Associated Virus (AAV) Types 1, 2, 5, 6, 8, and 9 in the Healthy Population: Implications for Gene Therapy Using AAV Vectors

Boutin

Monteilhet²,

Véron³

et al. 2010

Human Gene Therapy

804

782

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“…GM and KM allotypes are associated with the susceptibility to and outcome of infection by several infectious agents (1-3, 6-13, 21, 23-26, 28-30, 33, 35). GM allotypes are strongly associated with IgG subclass concentrations (19,22,27,34), making them relevant to viral immunity, as the antibody responses to most viral epitopes appear to be IgG subclass (IgG1 and IgG3) restricted (15,37,39).These observations led us to hypothesize that GM and KM allotypes might contribute to the outcome of HCV infection through their possible influence on allotype-restricted antibody responses to the viral antigens. In addition, since particular GM and KM phenotypes have been shown to interact in influencing humoral immunity to certain viral epitopes (1), we wished to determine whether such epistatic interactions were associated with the outcome of HCV infection.…”

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confidence: 97%

mentioning

confidence: 99%

Epistatic Effects of Immunoglobulin GM and KM Allotypes on Outcome of Infection with Hepatitis C Virus

Pandey

Astemborski

Thomas

2004

J Virol

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Immunoglobulin GM and KM allotypes-genetic markers of ␥ and chains, respectively-are associated with immune responsiveness to several infectious pathogens and with survival in certain viral epidemics. We hypothesized that GM and KM allotypes affect the outcome of hepatitis C virus (HCV) infection. To test this hypothesis, we serologically allotyped 100 persons with well-documented clearance of HCV infection and 198 matched persistently infected persons. None of the GM or KM phenotypes by itself was associated with the clearance or persistence of HCV infection. Particular combinations of these phenotypes, however, were significantly associated with the outcome of HCV infection. Subjects with GM 1,17 5,13 and KM 1,3 phenotypes were over three times (odds ratio Hepatitis C virus (HCV) is a major health problem, affecting over 170 million people worldwide (47). Of persons acutely infected with HCV, about 15% spontaneously clear the virus. Among the factors influencing the outcome of HCV infection, the host genetic factors are thought to play a predominant role. Reports from several studies documenting consistent associations of particular HLA alleles with viral persistence and clearance support this contention (40,41,43). Allelic variation at the HLA loci, however, accounts for only a small percentage of the total interindividual variation in the outcome of HCV infection (41), suggesting involvement of additional genetic factors that might modify the host immune responsiveness to this pathogen.[Immunoglobulin (Ig) GM and KM allotypes-hereditary antigenic determinants of IgG heavy chains and -type light chains, respectively-are associated with viral immunological properties and thus are ideal candidate genetic systems for investigations to identify risk-conferring factors in HCV pathogenesis. GM and KM allotypes are associated with the susceptibility to and outcome of infection by several infectious agents (1-3, 6-13, 21, 23-26, 28-30, 33, 35). GM allotypes are strongly associated with IgG subclass concentrations (19,22,27,34), making them relevant to viral immunity, as the antibody responses to most viral epitopes appear to be IgG subclass (IgG1 and IgG3) restricted (15,37,39).These observations led us to hypothesize that GM and KM allotypes might contribute to the outcome of HCV infection through their possible influence on allotype-restricted antibody responses to the viral antigens. In addition, since particular GM and KM phenotypes have been shown to interact in influencing humoral immunity to certain viral epitopes (1), we wished to determine whether such epistatic interactions were associated with the outcome of HCV infection. MATERIALS AND METHODSStudy population. Between 1988 and 1989, a cohort was recruited in Baltimore, Md., of persons who had injected illicit drugs in the preceding 10 years, were more than 17 years of age, and were free of manifestations of AIDS (44). Within this cohort, a subset of 1,667 individuals was identified as the HCV subcohort because they had antibodies to HCV and had made at le...

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“…Serum samples were tested for HTLV-I-specific isotypic antibodies based on a method described previously [Lal et al, 1993]. Briefly, r21e-spiked Western blot strips (Cambridge-Biotech, Rockville, MD) were sequentially probed under identical conditions, first with a child's serum, then with a mouse monoclonal antibody (mAb) specific for human IgG (clone HP6017), IgA (clone HP6123), or IgM (clone HP6083) (Hybridoma Reagent Laboratory, Kingsville, MD), and finally by incubation with alkaline phosphatase-conjugated antimouse IgG as the third antibody.…”

Section: Laboratory Methodsmentioning

confidence: 99%

Estimating the time of HTLV-I infection following mother-to-child transmission in a breast-feeding population in Jamaica

et al. 1999

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Mother-to-child transmission of human T-cell lymphotropic virus type I (HTLV-I) is primarily due to prolonged breast-feeding (>6 months) in the postnatal period. Most infant infections are not identifiable until 12 to 18 months of age by available whole virus Western blot serologic tests because of their inability to distinguish passively transferred maternal antibody from infant antibody. We investigated two methods to assess more accurately the time of infant infection. In prospectively collected serial biospecimens, HTLV-I-specific immunoglobulin (Ig) isotypes of IgM and IgA were determined by Western blot and HTLV-I proviral DNA was detected by polymerase chain reaction (PCR). IgA and IgG reactivity was assessed in periodic serum samples from 16 HTLV-I-seropositive children while IgM reactivity was assessed in 9 of the 16 children. Approximately three to five samples were tested for each child. IgG reactivity was observed in 100% of children at 24 months of age and 73% of children at 6-12 months of age; however, this could represent maternal and not infant antibody. Both IgA and IgM reactivity were insensitive indicators of infection, with only 50% of children showing reactivity at 24 months of age. PCR testing was performed in biospecimens obtained from 11 of these children. An estimated median time of infection of 11.9 months was determined by PCR, which was similar to the median time to infection determined by whole virus Western blot (12.4 months; P = 0.72). PCR tests support a median time to infection that is similar to that estimated by whole virus Western blot.

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Isotypic and IgG Subclass Restriction of the Humoral Immune Responses to Human T-Lymphotropic Virus Type-I

Cited by 21 publications

References 0 publications

Prevalence of Serum IgG and Neutralizing Factors Against Adeno-Associated Virus (AAV) Types 1, 2, 5, 6, 8, and 9 in the Healthy Population: Implications for Gene Therapy Using AAV Vectors

Prevalence of Serum IgG and Neutralizing Factors Against Adeno-Associated Virus (AAV) Types 1, 2, 5, 6, 8, and 9 in the Healthy Population: Implications for Gene Therapy Using AAV Vectors

Epistatic Effects of Immunoglobulin GM and KM Allotypes on Outcome of Infection with Hepatitis C Virus

Estimating the time of HTLV-I infection following mother-to-child transmission in a breast-feeding population in Jamaica

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