Warren symposium follows legacy of geneticist giant

If we want to understand how the brain creates memories, and how genetic disorders distort the brain’s machinery, then the fragile X gene is an ideal place to start. That’s why the Stephen T. Warren Memorial Symposium, taking place November 28-29 at Emory, will be a significant event for those interested in neuroscience and genetics. Stephen T. Warren, 1953-2021 Warren, the founding chair of Emory’s Department of Human Genetics, led an international team that discovered Read more

Mutations in V-ATPase proton pump implicated in epilepsy syndrome

Why and how disrupting V-ATPase function leads to epilepsy, researchers are just starting to figure Read more

Tracing the start of COVID-19 in GA

At a time when COVID-19 appears to be receding in much of Georgia, it’s worth revisiting the start of the pandemic in early 2020. Emory virologist Anne Piantadosi and colleagues have a paper in Viral Evolution on the earliest SARS-CoV-2 genetic sequences detected in Georgia. Analyzing relationships between those virus sequences and samples from other states and countries can give us an idea about where the first COVID-19 infections in Georgia came from. We can draw Read more
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autoantibodies

More evidence for autoantibodies in severe COVID-19

A recent paper from Emory pathologist Cheryl Maier and colleagues provides more evidence for autoantibodies in critically ill COVID-19 patients. Autoantibodies are signs that the immune system attacking the body itself, and are features of diseases such as lupus and rheumatoid arthritis. They have been proposed as an explanation for the severity of some acute COVID-19 cases, as well as continued symptoms in long COVID.

Generally, antibodies are a good thing, and a major goal of COVID-19 vaccination is to drive the immune system to generate protective antibodies against the coronavirus. With autoantibodies and COVID, the idea is that intense inflammation coming from viral infection is causing immune cells to become confused. Not every COVID-19 patient’s immune system goes off the rails, but the train wreck seems to happen more often in COVID-19.

Last year, immunologist Ignacio Sanz’s lab at Emory demonstrated that patients with severe COVID-19 display signs of immune dysregulation similar to those seen in lupus. A follow-up preprint found the suspected autoantibodies, and several other labs have observed autoantibodies in COVID-19 that may be sabotaging antiviral responses or perturbing blood clotting. Now, an active topic of investigation is whether the autoantibodies last longer or don’t diminish as quickly in long COVID. Stay tuned.

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Cheryl Maier, MD, PhD

However, in the current paper in Cell Reports Medicine, autoantibodies were also found in most control samples from intensive care unit patients with pneumonia or sepsis, who are experiencing a state of systemic inflammation comparable to severe COVID-19.

“It’s a reminder that autoantibodies are not necessarily unique to COVID,” Maier says. “They may be more dramatic in COVID, but we see autoantibodies associated with other severe diseases too.”

Maier is medical director for Emory’s Special Coagulation Laboratory, and her team came to the autoimmunity question from a side angle. They were investigating blood clots and hyperviscosity in COVID-19 patients, and wanted to check whether high concentrations of antibodies might be an explanation. Antibodies are proteins, after all, and if someone’s blood is full of them, they thicken it.

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Posted on June 3, 2021 by Quinn Eastman in Immunology Leave a comment

What are rods and rings?

This image of mouse embryonic fibroblasts comes from Cara Schiavon, a graduate student in Rick Kahn’s lab in the Department of Biochemistry. It was impressive enough to capture interest from Emory Medicine‘s graphics designer Peta Westmaas. The light green shapes are “Rods and Rings,” structures that were identified just a few years ago by scientists studying how cells respond to antiviral drugs, such as those used against hepatitis C.

The rod and ring structures appear to contain enzymes that cells use for synthesizing DNA building blocks. Patients treated with some antiviral drugs develop antibodies against these enzymes.

The turquoise color represents microtubules, components of cells’ internal skeletons. The orange color shows DNA within nuclei. The spots in the nuclei are areas where DNA is more compact. The overall image is a “z-stack projection” acquired using the Olympus FV1000 confocal microscope in Emory’s Integrated Cellular Imaging Core.

Posted on April 2, 2018 by Quinn Eastman in Uncategorized Leave a comment

Following lupus troublemaker cells, via DNA barcodes

People with systemic lupus erythematosus can experience a variety of symptoms, such as fatigue, joint pain, skin rashes and kidney problems. Often the symptoms come and go in episodes called flares. In lupus, the immune system goes haywire and produces antibodies that are directed against the body itself.

The immune system can produce many types of antibodies, directed against infectious viruses (good) or against human proteins as in lupus (harmful). Each antibody-secreting cell carries a DNA rearrangement that reflects the makeup of its antibody product. Scientists can use the DNA to identify and track that cell, like reading a bar code on an item in a supermarket.

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Iñaki Sanz, MD is a Georgia Research Alliance Eminent Scholar, director of the Lowance Center for Human Immunology and head of the Rheumatology division in the Department of Medicine.

Postdoc Chris Tipton, GRA Eminent Scholar Iñaki Sanz and colleagues at Emory have been using these DNA bar codes to investigate some fundamental questions about lupus: where do the autoantibody-producing cells come from? Are they all the same?

Their findings were published in Nature Immunology in May, and a News and Views commentary on the paper calls it “a quantum advance in the understanding of the origin of the autoreactive B cells.” It’s an example of how next-generation sequencing technology is deepening our understanding of autoimmune diseases.

The Emory team obtained blood samples from eight patients experiencing lupus flares and compared them to eight healthy people who had recently been vaccinated against influenza or tetanus.

When the immune system is responding to something it’s seen before, like when someone receives a booster vaccine, the bar codes of the antibody-producing cells look quite similar to each other. A set of just a few antibody-producing cells multiply and expand, making what looks like clones. In contrast, the researchers found that in lupus, many different cells are producing antibodies. Some of the expanded sets of cells are producing antibodies against infectious agents.

“We expected to see an expansion of the cells that produce autoantibodies, but instead we saw a very broad expansion of cells with all types of specificities,” Tipton says.

To use a Star Wars analogy: a booster vaccine response looks like the Clone Wars (oligoclonal — only a few kinds of monsters), but a lupus flare looks like a visit to Mos Eisley cantina (polyclonal — many monsters). Read more

Posted on July 23, 2015 by Quinn Eastman in Immunology Leave a comment