During HIV infection, antibody can block B cells from fighting pathogens

NIH scientists suspect process aims to curb immune-system hyperactivity.

Colorized scanning electron micrograph of a B cell from a human donor.NIAID

For the first time, scientists have shown that in certain people living with HIV, a type of antibody called immunoglobulin G3 (IgG3) stops the immune system’s B cells(link is external) from doing their normal job of fighting pathogens. This phenomenon appears to be one way the body tries to reduce the potentially damaging effects of immune-system hyperactivity caused by the presence of HIV, according to the investigators, but in so doing, it also impairs normal immune function.

The research was led by scientists in the Laboratory of Immunoregulation and the Laboratory of Immunogenetics at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The investigators made their discovery by analyzing blood samples from 83 HIV-uninfected, anonymous donors and 108 people who were living with HIV at various stages of infection. The people living with HIV came from a variety of racial and ethnic backgrounds. Some of these people were being treated for their infection, while others had not yet begun therapy.

The scientists observed that IgG3 appeared on the surface of B cells only under certain conditions. It appeared in people living with HIV, but not in HIV-uninfected people. Also, IgG3 predominantly appeared on B cells of people of African American or black African decent during the chronic phase of untreated HIV infection when the virus was not adequately controlled.

A site on B cells called the B-cell receptor normally binds to foreign entities such as pathogens. This binding stimulates the B cell to produce many copies of the antibody form of the receptor, which can trap a pathogen and mark it for destruction. The scientists found that IgG3 short-circuits this process in certain people living with HIV by docking on the B-cell receptor, blocking it from adequately responding to the pathogen or other intended target. The researchers also demonstrated how other components of the immune system contribute to IgG3 interference with normal B-cell function during HIV infection. Finally, they showed that IgG3 stops binding to B-cell receptors when a chronically infected person starts treatment that controls the virus, illustrating that the IgG3 activity is directly linked to the presence of HIV during chronic infection.

Three Decades of Responding to Infectious Disease Outbreaks

NIAID Director Anthony S. Fauci, M.D., Highlights Lessons from AIDS to Zika

November 14, 2017

 

Map showing global examples of emerging and re-emerging infectious diseases.

 

Soon after his appointment in 1984 as director of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, Anthony S. Fauci, M.D., testified before Congress showing a world map annotated with a single emerging infectious disease threat, HIV/AIDS. Since then, diseases and pathogens including chikungunya, H1N1 influenza, severe acute respiratory syndrome (SARS), West Nile, Ebola and Zika viruses were added, providing a powerful visual reminder of the enduring need to anticipate, detect and manage new and emerging infectious diseases around the globe. In an essay in Annals of Internal Medicine published online today, Dr. Fauci reflects on the ways efforts have been marshalled to address infectious disease outbreaks of the past three decades.

Initial responses to a newly recognized disease, now known as HIV/AIDS, in the early 1980s were criticized as being too slow, the essay notes. “The insidious emergence of HIV/AIDS and the lack of due attention by policymakers illustrate how some outbreaks that start subtly can grow to global proportions if they are not aggressively addressed early on,” Dr. Fauci writes. Between the early 1980s and the early 1990s, federal funding for HIV/AIDS research increased markedly, reaching $1 billion by the end of 1992. The accelerated government response supported both research and research infrastructure, and yielded advances in countering the HIV/AIDS pandemic domestically and internationally. Ultimately, notes Dr. Fauci, sustained support for scientific research coupled with political and community engagement helped transform HIV/AIDS from a nearly universally fatal disease to a condition that can be managed with appropriate treatment.

In contrast to HIV/AIDS, when outbreaks of respiratory diseases caused by SARS coronavirus and influenza viruses have occurred, they generated immediate widespread public attention and prompted concerted responses by presidential administrations and Congress. For example, the 2009 influenza pandemic began in April and an experimental vaccine entered clinical trials by August. However, despite intense efforts to test and manufacture the new vaccine, adequate supplies to protect the broad U.S. population were not available until early winter, after the outbreak had peaked. “This experience,” writes Dr. Fauci, “served as a striking reminder of the inadequacy of our pandemic preparedness capabilities and underscored the need, now being actively pursued, to develop platform technologies that can be applied rapidly to develop vaccines for evolving outbreaks.”

The essay also considers how presidential administrations have responded to the appearance of pathogens ranging from West Nile virus and Ebola to, most recently, the arrival of Zika virus in the Americas. “Leadership at the NIAID has learned many valuable lessons through experiences during the prior administrations with regard to optimal responses to such outbreaks,” Dr. Fauci concludes. “It is critical to apply these lessons to the infectious disease threats that we will inevitably face in the current administration and beyond.”

ARTICLE:

CI Paules, et al. What recent history has taught us about responding to emerging infectious disease threats. Annals of Internal Medicine DOI: 10.7326/M17-2496 (2017).

WHO:

NIAID Director Anthony S. Fauci, M.D., is available to discuss his paper.

 Content last reviewed on November 14, 2017

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Published courtesy of the National Institute of Allergy and Diseases