Significance of the differences in the prevalence of anti-HLA antibodies in matched pairs of mother’s and cord blood

Ravindranath, Mepur H.; Jucaud, Vadim; Maehara, Curtis; Terasaki, Paul I.

doi:10.1016/j.imlet.2015.11.016

Cited by 2 publications

(3 citation statements)

References 47 publications

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“…Additionally, 27% of healthy highly exposed persistently seronegative individuals expressed potential HLA autoantibodies in at least one locus, tested to two-digit resolution, without apparent consequences. It may be these antibodies are non-reactive against the individual’s HLA type tested at higher resolution, although others have also reported HLA autoantibodies in healthy individuals ( 67 , 68 ), including when using high resolution HLA typing ( 67 ).…”

Section: Discussionmentioning

confidence: 99%

“…HLA antibodies, including HLA autoantibodies, thus occur naturally without deleterious consequences. HLA antibodies are present in pharmaceutical preparations of intravenous immune globulins prepared from pooled blood donors [discussed in ( 67 )] with no documented harm; while active immunization of pregnant women with partner white blood cells has previously been used as infertility treatment ( 72 , 73 ). Fear of induction of autoantibodies remains the primary concern of an alloimmunization strategy and whether such antibodies are indeed harmful in the non-transplant setting warrants directed investigation.…”

Section: Discussionmentioning

confidence: 99%

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Alloimmunity to Class 2 Human Leucocyte Antigens May Reduce HIV-1 Acquisition – A Nested Case-Control Study in HIV-1 Serodiscordant Couples

et al. 2022

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Enveloped viruses, including the Human Immunodeficiency Virus-1 (HIV), incorporate host proteins such as human leucocyte antigens (HLA) into their envelope. Pre-existing antibodies against HLA, termed HLA antibodies, may bind to these surface proteins and reduce viral infectivity. Related evidence includes macaque studies which suggest that xenoimmunization with HLA antigens may protect against simian immunodeficiency virus infection. Since HIV gp120 shows homology with class 2 HLA, including shared affinity for binding to CD4, class 2 HLA antibodies may influence HIV acquisition via binding to gp120 on the viral envelope. We conducted a nested case-control study on HIV serodiscordant couples, comparing the frequency of HLA antibodies among highly exposed persistently seronegative controls with those who went on to acquire HIV (HIV-seroconverters). We first performed low resolution HLA typing on 143 individuals who were HIV-infected at enrollment (index partners) and their corresponding sexual partners (115 highly exposed persistently seronegative individuals and 28 HIV-seroconverters). We then measured HLA class 1 and 2 antibodies in the highly exposed persistently seronegative individuals and HIV-seroconverters at early and late timepoints. We analyzed whether such antibodies were directed at HLA specificities of their HIV-infected index partners, and whether autoantibodies or complement-fixing class 2 HLA antibodies were present. Seventy-nine percent of highly exposed persistently seronegative individuals had HLA antibodies; 56% against class 1 and 50% against class 2 alleles. Half of the group of highly exposed persistently seronegative individuals, prior to seroconversion, expressed class 2 HLA antibodies, compared with only 29% of controls (p=0.05). HIV infection was a sensitizing event leading to de novo development of antibodies against HLA-A and HLA-B loci, but not against class 2 loci. HLA autoantibodies were present in 27% of highly exposed persistently seronegative individuals. Complement-fixing class 2 HLA antibodies did not differ significantly between highly exposed persistently seronegative individuals and seroconverters. In multivariable regression, presence of class 2 HLA antibodies at early timepoints was associated with reduced odds of HIV acquisition (odds ratio 0.330, confidence interval 0.112-0.976, p=0.045). These epidemiological data suggest that pre-existing class 2 HLA antibodies were associated with reduced odds of HIV acquisition.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Alloimmunity to Class 2 Human Leucocyte Antigens May Reduce HIV-1 Acquisition – A Nested Case-Control Study in HIV-1 Serodiscordant Couples

et al. 2022

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“…Fetomaternal transfer of HLA Abs and B cells is known to occur [50, 51]. Recent analysis of the maternal sera indicated that the high MFI of the anti-DRB1 ∗ 01 : 01 persisted in the blood 26 years after alloimmunization, suggesting that the maternal B cells producing the Abs may be long-lived B mem cells.…”

Section: Experimental Approach and Observationsmentioning

confidence: 99%

HLA Class Ia and Ib Polyreactive Anti-HLA-E IgG2a Monoclonal Antibodies (TFL-006 and TFL-007) Suppress Anti-HLA IgG Production by CD19+ B Cells and Proliferation of CD4+ T Cells While Upregulating Tregs

Ravindranath

2017

Journal of Immunology Research

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The anti-HLA-E IgG2a mAbs, TFL-006 and TFL-007, reacted with all HLA-I antigens, similar to the therapeutic preparations of IVIg. Indeed, IVIg lost its HLA reactivity, when its HLA-E reactivity was adsorbed out. US-FDA approved IVIg to reduce antibodies in autoimmune diseases. But the mechanism underlying IVIg-mediated antibody reduction could not be ascertained due to the presence of other polyclonal antibodies. In spite of it, the cost prohibitive high or low IVIg is administered to patients waiting for donor organ and for allograft recipients for lowering antiallograft antibodies. A mAb that could mimic IVIg in lowering Abs, with defined mechanism of action, would be highly beneficial for patients. Demonstrably, the anti-HLA-E mAbs mimicked several functions of IVIg relevant to suppressing the antiallograft Abs. The mAbs suppressed activated T cells and anti-HLA antibody production by activated B cells, which were dose-wise superior to IVIg. The anti-HLA-E mAb expanded CD4+, CD25+, and Foxp3+ Tregs, which are known to suppress T and B cells involved in antibody production. These defined functions of the anti-HLA-E IgG2a mAbs at a level superior to IVIg encourage developing their humanized version to lower antibodies in allograft recipients, to promote graft survival, and to control autoimmune diseases.

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Significance of the differences in the prevalence of anti-HLA antibodies in matched pairs of mother’s and cord blood

Cited by 2 publications

References 47 publications

Alloimmunity to Class 2 Human Leucocyte Antigens May Reduce HIV-1 Acquisition – A Nested Case-Control Study in HIV-1 Serodiscordant Couples

Alloimmunity to Class 2 Human Leucocyte Antigens May Reduce HIV-1 Acquisition – A Nested Case-Control Study in HIV-1 Serodiscordant Couples

HLA Class Ia and Ib Polyreactive Anti-HLA-E IgG2a Monoclonal Antibodies (TFL-006 and TFL-007) Suppress Anti-HLA IgG Production by CD19+ B Cells and Proliferation of CD4+ T Cells While Upregulating Tregs

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