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There are millions of possible antigens. To respond to each antigen, the immune system must quickly produce an antibody by modifying the DNA of a B cell.
I have no idea how this process works, but surely it can't be by trial and error.
So I thought how I would do it:
The part of the pathogens DNA that codes for receptors is copied
then an algorithm is applied that transforms this code into an antibody code.
This code is then pasted into the DNA of the B cell. So the B cell has antibody receptors that fit on the antigen.
But how does it work in reality?
Persistent immunity: Researchers find signals that preserve anti-viral antibodies
Our immune system is capable of a remarkable feat: the ability to remember infections for years, even decades, after they have first been encountered and defeated. While the antibodies we make last only about a month, we retain the means of making them for a lifetime. Until now, the exact mechanism behind this was poorly understood, but researchers at The Wistar Institute have discovered some of the protein signals responsible for keeping the memory of distant viral infections alive within our bodies.
Their study, presented in the Journal of Clinical Investigation, may aid scientists in creating better, more effective vaccines.
"We are particularly interested in how our bodies generate antibodies against viruses and how we maintain anti-viral antibody secreting cells as a hedge against future infection from the same virus," said Jan Erikson, Ph.D., senior author of the study, professor in Wistar's Immunology Program and a member of The Wistar Institute Vaccine Center. "Our study highlights how protein signals sustain the cells that make antibodies against viruses in perpetuity, which we believe is crucial knowledge for the development of vaccines for lasting protection against the flu, for example."
Despite an annual vaccine against the disease, seasonal influenza remains a potent killer, one associated with nearly half a million deaths each year around the globe. The persistence of antibody memory is why older people, who typically suffer more from influenza, fared much better than expected during the 2009 avian influenza pandemic. Previous exposure to -- or vaccination against -- a similar strain provided many older Americans a resistance to the 2009 avian flu. Wistar Vaccine Center researchers are among a number of teams of scientists working toward a universal flu vaccine, one that would forgo the need for an annual flu shot.
The main role of vaccines is to stimulate the production of antibodies that bind to portions of the infectious agent. Once bound, the antibodies provide a target for the immune system, allowing immune cells to attack it or any infected cells in order to clear away disease. Antibodies are highly variable proteins that are produced in huge quantities by a subset of white blood cells, called B cells, that have transformed into antibody factories, termed antibody secreting cells (ASCs). Our immune system produces a broad array of antibodies, but during an infection with a virus, for example, the immune system allows the predominant production of antibodies that are directed against the virus. The cells making these particular antibodies are then selected for preservation.
According to Erikson and her colleagues, this act of preservation requires signals, provided by proteins called BLyS and APRIL. Mice that have been exposed to influenza require these proteins in order to sustain anti-influenza ASCs in their lungs. The researchers found that neutralizing BLyS and APRIL reduced the numbers of anti-viral ASCs found in the lungs and bone marrow, yet interestingly, did not affect the ASCs found in spleen or in lymph nodes nearby the lungs.
BLyS and APRIL bind to another protein called TACI, a receptor found on the surface of ASCs, which the researchers see as an important translator for marking the ASCs that will become long-lived.
"We know from humans that the absence or mutation of the TACI gene leads to common variable immunodeficiency disease (CVID) and these patients suffer from recurrent respiratory illnesses because of low amounts of certain antibodies in their bronchial secretions," said Amaya I. Wolf, Ph.D., the study's lead author and a postdoctoral fellow in the Erikson laboratory. "Our studies show that mice that lack TACI can mount an initial B cell response to viral infection -- and are able to produce antibodies to flu -- but these mice fail to maintain anti-viral ASCs over a long period of time. Importantly, we show that this results in lower anti-viral antibody titers, and mice are less protected against a secondary viral attack at a later time."
"After resolution of a viral infection we want to have ASCs in our lungs to guard our mucosal surfaces, the port of microbial entry, in case of a reinfection with the same virus," Wolf said. "The lung microenvironment after a viral infection allows the ASCs to persist as a sort of local base, a place for the local release of protective antibodies."
"To avoid damage of the lung tissue, the immune system wisely evolved means of keeping the secretion of antibodies under tight control," Wolf explained. "The anti-viral ASCs in the lungs are short-lived and require BLyS and APRIL for their more immediate survival, but also the generation of longer-lived ASCs that take up residence in the bone marrow depends on these signals."
According to Wolf, it might be possible to manipulate ASC behavior to prolong or strengthen the effectiveness of vaccines. Drugs that induce targeted production of ASC survival factors, such as BLyS and APRIL or manipulation of their signals through TACI, their receptor, could theoretically help to maintain specific antibodies. While the seasonal flu is constantly mutating -- necessitating an annual vaccine -- even weakly reactive antibodies could be protective if there are enough of them and if their production is sustained.
One interesting observation from this study, the researchers say, is that the persistence of ASCs in different tissues appears to be regulated differently. This has spurred plans for the Erikson laboratory to conduct a genome-wide molecular survey in collaboration with Wistar Professor Louise Showe, Ph.D., director of Wistar's genomics facility.
Funding for this study was provided through grants from the National Institutes of Health and the Commonwealth of Pennsylvania.
Building a family tree of B-cells
To assemble their map, the researchers extracted the B-cells from blood samples from 22 young, healthy adults. Using a high-throughput genetic sequencing machine, which reads out the individual nucleotides that make up a cell’s genetic code, they created a large library of antibody-producing genes from all the B-cells in the sample.
They traced the lineage of B-cells by counting the number of acquired mutations in the cells’ genes, finding that cells in later generations had more genetic mutations. The researchers also looked for evidence that the B-cells had switched the types of antibody they produced. This switching process allows the immune system to customize its response to incoming threats.
“Each B-cell starts out as a single cell that makes a certain type of antibody,” Horns said. “If it protects you, it expands and creates descendants.”
Using a variety of analytical techniques, the researchers were able to identify the various classes of antibodies and approximate their prevalence.
About three-quarters of the cells the team analyzed were programmed to create the IgM antibody class. IgM is “the default class in which all antibodies are born,” Horns said. “When activated by immune challenge, they undergo class switching.”
A large proportion of IgM cells switch to producing the IgG antibody class, the body’s most important virus fighters. These cells can give rise to four different IgG sub-classes that have specific anti-viral properties.
A lesser fraction of IgM-producing cells go on to create IgA antibodies, which fend off invading bacteria and also help “good” bacteria in the digestive tract stay in a healthy balance.
The smallest number of IgM cells switch to producing the IgE antibody class, which triggers inflammation in the body and can create an allergic response if it becomes too active.
What Happens After You Get the COVID-19 Vaccine?
An immunologist explains how the vaccine trains your immune system to fight the coronavirus.
This article was updated on May 10, 2021.
The Pfizer and Moderna mRNA vaccines currently being rolled out to the public are considered an incredible scientific achievement. But, many might wonder, what exactly do they do?
Here to clear up that mystery, Beth Moore, Ph.D. , the Interim Chair and Professor of Microbiology & Immunology at Michigan Medicine, breaks down what happens after the shot goes into your arm.
1 minute after COVID vaccination
Pick an arm and roll up your sleeve. After answering a few screening questions, the shot goes in.
Along with salt, sugar and a fat coating, the most important ingredient in the vaccine is the mRNA, a tiny instruction manual for your cells to use to make the infamous SARS-CoV-2 spike protein. Scientists figured out that the coronavirus uses its spike protein to attach to molecules called ACE2 receptors on the outside of your cells to get inside.
“Once inside the cell, the mRNA from the vaccine is taken up by your ribosomes and translated into many copies of the spike protein,” says Moore. Then, the mRNA is broken down and the newly-formed spike protein is released from the cell.
15 minutes after
After their jab, most people will be asked to sit and wait a 15-minute observation period, to watch for rare allergic reactions. Those with a history of serious allergic reactions should prepare to wait up to 30 minutes. Reactions have ranged from hives to anaphylactic shock and are quickly treated with Benadryl for a mild reaction or epinephrine for anaphylaxis.
12 hours to 10 days later
Your arm might be a little sore or maybe you’ll feel some fatigue after the first shot. What’s happening?
Your immune system is gearing up, Moore explains. After your cells use the mRNA to develop the spike protein, immune messenger cells called dendritic cells come into play.
“Dendritic cells are patrolling and will come in contact with the antigen that they haven’t seen before and raise the alarm, travel to a lymph node, find the right T and B cells and activate them,” Moore says.
Fatigue and soreness, she explains, are the result of substances called cytokines and chemokines that help direct more immune cells to the infected site, causing inflammation. Some people report temporary swelling of the lymph nodes in their armpit after receiving the vaccine, as well.
Your immune system can’t tell the difference between just a spike protein and the actual virus. “Feeling a bit run down is just a sign your immune system is working,” Moore says. But if you don’t feel tired or sore, don’t worry. Not everyone feels these effects.
In April 2021, use of the Janssen/J&J COVID-19 vaccine was paused after six women—out of 6.8 million who received the one-shot vaccine--developed a rare clotting disorder. The condition is similar to a reaction some people have to an anti-clotting medication called heparin.
However, the CDC lifted the pause ten days later after meeting to discuss guidance for patients and healthcare providers.
“The bottom line is this is a very rare complication, but not clear yet what causes it. The benefits still outweigh risks, especially for people with no history of clotting disorders,” says Moore. People who are concerned can consider opting for one of the mRNA vaccines, which are not linked to this clotting disorder.
3 to 4 weeks later
Both of the mRNA vaccines require two shots: three weeks later for the Pfizer vaccine and four weeks for Moderna. During that waiting period, “hopefully, your B cells are generating good plasma cells and making neutralizing antibodies,” says Moore. Neutralizing antibodies block the coronavirus from entering your cells and making you sick. But these can be relatively short-lived. Hence the need for the second dose which can help generate longer-lived immune cells that can respond to the spike protein. Many people report a much stronger reaction to the second dose, including fever, fatigue and muscle aches.
“Because you already have antibodies on-board from the first dose, you’re going to get a little bit more robust immune response the second time,” Moore says. “At the same time, you are boosting the immune response to be bigger, better and faster and really locking in the memory of it.”
Don’t be tempted to avoid the second shot to avoid potentially feeling sick. The danger of not getting the second dose is you’d have short term protective antibodies from plasma cells, but no long term memory cells, explains Moore.
Meaning within time (and how time much has yet to be determined), you could have no protection.
In addition, these side effects are temporary—compared to the far more serious, and potentially deadly—effects of COVID-19.
6 weeks later
Remarkably, the current COVID-19 mRNA vaccines were 95% effective at preventing COVID-19 in clinical trials two weeks after the second dose. Moore believes that may be due in part to how targeted the vaccines are.
“With natural infection with the virus, the body may generate an immune response to multiple proteins on the outside and inside of the virus—but ones that aren’t doing any good because they don’t block the spike protein from ACE2.” The mRNA vaccines only code for the correct protein. “That’s one of the reasons why people who have already been infected with COVID-19 should get the vaccine. Even if you’ve survived the infection, you don’t know if you have good neutralizing antibodies or a lot of irrelevant antibodies.”
The future after receiving a COVID-19 vaccine
More vaccines are coming soon, using different technologies. The AstraZeneca and Janssen vaccines, both studied at Michigan Medicine, each use inactivated adenoviruses to deliver the gene for the spike protein to your cells . Says Moore, “Immunologically, they may have an advantage in that the more foreign material you give your body to respond, the bigger more robust response you get.”
As the vaccines are rolled out to more and more people, studies are ongoing to see how long immunity will last, if people who are vaccinated can still spread the virus and whether the virus will mutate to the point where the vaccines are no longer effective.
To the last point, “all viruses mutate,” says Moore. “The good news is the vaccine is still effective because the mutations haven’t changed the basic structure of the spike protein so much that the neutralizing antibodies are not effective,” she adds. But scientists will continue to monitor these variants to see if eventually the vaccines will need to be modified.
As far as when we can take off our masks and gather together again, the verdict is still out.
“We know that if you make a neutralizing antibody against the spike protein, that means the virus can’t attach to the ACE2 receptor on the cells in your body easily,” Moore explains. “With a good neutralizing antibody response, the vaccinated person is unlikely to have a clinically significant (or even noticeable) infection, but it may still be possible for that person to breathe out the infectious live virus.”
Until data come in from studies of vaccinated people, it’s too big a risk to stop taking precautions.
Your Immune System Evolves to Fight Coronavirus Variants
A lot of worry has been triggered by discoveries that variants of the pandemic-causing coronavirus can be more infectious than the original. But now scientists are starting to find some signs of hope on the human side of this microbe-host interaction. By studying the blood of COVID survivors and people who have been vaccinated, immunologists are learning that some of our immune system cells&mdashwhich remember past infections and react to them&mdashmight have their own abilities to change, countering mutations in the virus. What this means, scientists think, is that the immune system might have evolved its own way of dealing with variants.
&ldquoEssentially, the immune system is trying to get ahead of the virus,&rdquo says Michel Nussenzweig, an immunologist at the Rockefeller University, who conducted some recent studies that tracked this phenomenon. The emerging idea is that the body maintains reserve armies of antibody-producing cells in addition to the original cells that responded to the initial invasion by SARS-CoV-2, the virus that causes COVID. Over time some reserve cells mutate and produce antibodies that are better able to recognize new viral versions. &ldquoIt&rsquos really elegant mechanism that that we&rsquove evolved, basically, to be able to handle things like variants,&rdquo says Marion Pepper, an immunologist at the University of Washington, who was not involved in Nussenzweig&rsquos research. Whether there are enough of these cells, and their antibodies, to confer protection against a shape-shifting SARS-CoV-2 is still being figured out.
Last April, when the pandemic was reaching its first peak in New York City, Nussenzweig and his colleagues sprang into action and began collecting the blood of COVID survivors. There were disturbing early reports of reinfection and waning antibodies, and the scientists wanted to understand how long the immune system could sustain its ability to respond to the novel threat. They took blood samples from people who had been hit by SARS-CoV-2 one month after the infection and then again six months later. What the scientists found was somewhat encouraging. Blood collected at the later date did have lower levels of circulating antibodies, but that made sense because the infection had cleared. And levels of the cells that make antibodies, called memory B cells, remained constant or even increased in some people over time. After an infection, these cells hang around in the body&rsquos lymph nodes and maintain the ability to recognize the virus. If a person gets infected a second time, memory B cells activate, quickly produce antibodies and block the virus from creating a second serious infection.
In a follow-up test, the Rockefeller scientists cloned these reserve B cells and tested their antibodies against a version of SARS-CoV-2 designed to look like one of the new variants. (The experimental virus lacked the ability to replicate, which made it safer to use in the lab.) This virus had been genetically engineered to have specific mutations in its spike protein, the part of the coronavirus that attaches to human cells. The mutations mimicked a few of the ones currently found in the variants of concern. When researchers tested the reserve cells against this mutated virus, they saw some cells produced antibodies that glommed on to the mutated spike proteins&mdasheven though these spikes were different than those on the original virus. What this means is that the antibodies had changed over time to recognize different viral features. The research was published in Nature in January. &ldquoWhat the paper shows us is that, in fact, the immune response is evolving&mdashthat there&rsquos some dynamic changes over this period of time,&rdquo Nussenzweig says.
Recently he and his team tested the six-month-old B cell clones against other engineered viruses that more closely mimic variants of concern, such as B.1.351. This variant contains a set of mutations called K417N, E484K and N501Y. In a preliminary study that has not yet undergone peer review and was posted online on March 8, the researchers found a subset of antibodies produced by these cells showed increased abilities to recognize and block these highly mutated variants.
This phenomenon can be explained by a process called &ldquosomatic hypermutation.&rdquo It is one of the reasons that your immune system can make up to one quintillion distinct antibodies despite the human genome only having 20,000 or so genes. For months and years after an infection, memory B cells hang out in the lymph nodes, and their genes that code for antibodies acquire mutations. The mutations result in a more diverse array of antibodies with slightly different configurations. Cells that make antibodies that are very good at neutralizing the original virus become the immune system&rsquos main line of defense. But cells that make antibodies with slightly different shapes, ones that do not grip the invading pathogen so firmly, are kept around, too.
That kind of hoarding has long mystified immunologists. Why would your body hold on to second-rate B cells? Perhaps, Pepper says, it does so because the cells might be good at responding to closely related viral versions that could pop up. Viruses have been infecting hosts for millions of years, and variants are not a new phenomenon. To keep hosts alive, the immune system must have evolved a mechanism to keep up, and these corps of reserves&mdashsome producing antibodies that could be a better match for new viral versions&mdashcame in handy. Basically, in a struggle for life and death with a virus, it is good to have backups. Pepper has published results showing that people who recovered from COVID had evidence of increased mutation in their memory B cells after only three months.
Immunologist Shane Crotty of the La Jolla Institute for Immunology says the backup idea is a good one. &ldquoMemory B cells are your immune system&rsquos attempt to make variants of its own as a countermeasure for potential viral variants in the future,&rdquo he says. In a study published in Science in February, Crotty and his colleagues showed that patients retained various degrees of immune reactions to the virus five to eight months after infection&mdashand concluded that most people could have a durable response. &ldquoYour immune system is creating a library of memory B cells that aren&rsquot all the same so that they can potentially recognize things that aren&rsquot identical,&rdquo Crotty says.
But are there enough of these reserve antibodies, and are they good enough at neutralizing new viral versions to protect us? The answer to this question is still unknown, but it may be a matter of timing. Laura Walker, an immunologist at Adagio Therapeutics in Waltham, Mass., recently published a study in Science Immunology showing about a 10-fold reduction in the neutralizing ability of circulating antibodies against the virus after five months. But like Nussenzweig&rsquos team, she and her colleagues found there was a sustained memory B cell population. Walker&rsquos group cloned a variety of memory B cells and tested their antibodies against the variants. She says the variants were able to evade many antibodies, but about 30 percent stuck to the new virus particles. This means that a new infection may still be able to get started before the B cell reserves ramp up their production of antibodies. But even though the virus will have a head start, and infection could occur, the B cell response could still limit it and provide protection against severe disease. &ldquoThe question is whether there will be enough, and we don&rsquot know that yet,&rdquo Walker says. But &ldquoI would expect that your antibody titers, even if low, should still prevent the worst of it, like hospitalization or death.&rdquo
Escape from serious COVID could also be aided by another line of immune system defenses: T cells. These cells do not go after pathogens directly, but a subclass of them seek out infected cells and destroy them. Immunologists say that T cells have a somewhat broad-brush approach to recognizing pathogens&mdashthey respond to fragments from various parts of the virus, unlike the highly spike-specific nature of B cells&mdashand this makes them less likely to be fooled by variant shape-shifting. In a study released on March 1, which has not yet gone through peer review, Crotty and Alessandro Sette, also at the La Jolla Institute for Immunology, tested T cells from people who had been exposed to SARS-CoV-2, either naturally or through vaccination. Their T cell response was not dampened by the variants. Sette says that while a weakened B cell response could let the virus get a foothold, it is plausible that T cell activity will keep it from running rampant through the body. &ldquoIn a scenario where infection is not prevented, you could have a T cell response that could modulate the severity of the infection,&rdquo he says.
In the coming months researchers will continue to track these cells, using newly developed gene sequencing tools and cloning techniques to follow our responses to variants and new vaccines. These methods are providing immunologists with new abilities to monitor the spectrum of a population&rsquos reactions to a widespread infection in real time. &ldquoWe have the ability to study and describe the immune system in a way we have never been able to do before. It&rsquos an amazing window into the human immune response,&rdquo Nussenzweig says.
Read more about the coronavirus outbreak from Scientific American here. And read coverage from our international network of magazines here.
Some COVID-19 Vaccines Require More Than One Shot
To be fully vaccinated, you will need two shots of some COVID-19 vaccines.
- Two shots: If you get a COVID-19 vaccine that requires two shots, you are considered fully vaccinated two weeks after your second shot. Pfizer-BioNTech and Moderna COVID-19 vaccines require two shots.
- One Shot: If you get a COVID-19 vaccine that requires one shot, you are considered fully vaccinated two weeks after your shot. Johnson & Johnson&rsquos Janssen COVID-19 vaccine only requires one shot.
If it has been less than two weeks since your shot, or if you still need to get your second shot, you are NOT fully protected. Keep taking steps to protect yourself and others until you are fully vaccinated (two weeks after your final shot).
Learn how to find a COVID-19 vaccine so you can get it as soon as you can.
DOSAGE AND DISTRIBUTION
Biologics can cost thousands of dollars monthly and require special handling, as they are often less stable than chemically derived drugs and require controlled temperature and light, as well as protection from jostling when in liquid form. For example, many large proteins cannot be shaken to reconstitute, as shaking can destroy the protein structure.
Biologics are medications targeted to specific genotypes or protein receptors. They are most commonly stored, handled, and delivered by specialty pharmacies, distributors that specialize in administering complex-molecule products for small populations and have specialized handling and processing and mailing processes in place to accommodate these complex medications. In many ways, biologics are considered designer drugs that are targeted for patients with uncommon diseases or for genetic subclasses of patients who have widely prevalent diseases.
For some very rare disorders, such as Gaucher’s disease, the number of patients in the United States might not exceed 1,000. The high cost of developing and marketing a product, combined with a small target population translates into a considerable per-patient cost. Often, specialized clinics treat patients and/or administer these drugs.
Dosage forms of chemical drugs are highly variable, and concentrations usually are easy to determine. Yet, because biologic molecules are too large to be taken orally without being destroyed before passing through the intestine into the blood stream, they usually are injected or infused. Also, potency is more difficult to quantify for biologic agents, and monitoring is a key component of early therapy.
New modes of administration, such as via food that is directly or indirectly transgenic, are being studied. An example of the latter is goat’s milk that produces an anti-malarial compound. Transdermally administered vaccines also are under investigation.
Epigenetics is the study of gene expression, particularly factors unrelated to changes in gene sequence that may turn it "on" or "off." Genes are DNA blueprints that code for RNA, which is translated into protein, like a cytokine. When an immune cell activates and needs to produce cytokines to signal other cells, the cytokine gene needs to be in an "on" state for this to occur. If the gene is in an "off" state, it cannot be stimulated, no matter what cues are present around the cell.
Scientists study how gene status is regulated through epigenetic processes that alter the on/off state, generally by regulating how tightly DNA is packed around proteins in the nucleus. Tightly wound DNA is inaccessible and "off," while loosely wound DNA is accessible and "on." Understanding epigenetic mechanisms may lead to new therapy, and drugs that target epigenetic processes are currently being studied in clinical trials. Instead of blocking a harmful protein with antibodies, a drug that targets epigenetic mechanisms may potentially prevent that harmful protein from being made in the first place.
Serimmune launches new immune response mapping service for COVID-19
Immune intelligence startup Serimmune hopes to better understand the relationship between antibody epitopes (the parts of antigen molecules that bind to antibodies) and the SARS-CoV-2 virus.
The company’s proprietary technology, originally developed at UC Santa Barbara, provides a new and specific way of mapping the entire array of an individual’s antibodies through a small blood sample. They do this through the use of a bacterial peptide display — a sort of screening mechanism that can isolate plasmid DNA from antibody-bound bacteria in the sample. This DNA can then be sequenced to identify epitopes, which provide information about which antigens someone may have been exposed to, as well as how their immune system responded to them.
“It’s a very highly multiplexed and exquisitely specific way of looking at the epitopes found by antibodies in a specimen,” said Serimmune CEO Noah Nasser, who has a degree in molecular biology from UC San Diego and has previously worked for several diagnostics companies.
This week, Serimmune announced the launch of a new application of their core technology to help understand the disease states of and immune responses to SARS-CoV-2, the virus that causes COVID-19.
“So what we do is we take these antibody profiles we build, and we’re able to then map those back with about a 12 amino acid specificity to the SARS-CoV-2 proteome,” said Nasser. “And what we find is that antibody expression is highly correlated to disease state, so we can distinguish mild, moderate, severe and asymptomatic disease on the basis of antibodies that are present in the specimen.”
The more patient data Serimmune can collect, the better its core technology becomes at finding patterns across different antigen exposure and disease severity. Noticing those patterns sooner won’t only help physicians and researchers to better understand how the SARS-CoV-2 virus operates, but can also inform new approaches to diagnostics, treatments and vaccines for any antigen.
Serimmune’s launch of its new COVID antibody epitope mapping service is a way of making this data more accessible to customers like vaccine companies, government agencies and academic labs that have shown interest in better understanding the immune response to SARS-CoV-2.
“The key was to zero in on the information that researchers wanted to know and standardize that,” said Nasser. “We can actually now provide these results back in as few as two days from sample receipt.”
Beyond this new service, Serimmune also has plans to launch a longitudinal clinical study on immunity to SARS-CoV-2. Using a painless at-home collection kit, study participants send in small blood samples to Serimmune, which then uses its core technology to outline an individual immunity map.
“We provide their results back to them in the form of a personal immune landscape to COVID,” said Nasser. “And what we’re trying to do is to understand over time how that immune response changes, and what happens to that immune response on repeated exposure to COVID.”
The mapping technology is now so specific that it can tell whether a patient has antibodies from natural exposure to the SARS-CoV-2 virus or from a vaccine, he added.
While the primary focus for Serimmune remains these applications to the COVID-19 pandemic for now, Nasser also mentioned that the company has plans to move into personalized medicine, potentially offering their mapping service directly to interested patients.
“We believe that this has value to individual patients in understanding their immune status and what antigens they’ve been exposed to,” he said. Until then, Serimmune plans to continue growing its database with more patient samples.
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Lupus Blood Tests
Antibodies form in the body as a response to infection. When an invader (antigen) enters the body, white blood cells known as B lymphocytes react by making special types of proteins called antibodies. Antibodies are your body’s way of remembering an antigen if it enters the body again, the antibodies will recognize it, combine with it, and neutralize it to prevent you from becoming infected. However, with autoimmune diseases such as lupus, the immune system can produce antibodies (auto-antibodies) that attack your body’s cells as though they were invaders, causing inflammation, damage, and even destruction. Several blood tests can be performed to detect specific auto-antibodies and help make the diagnosis of lupus. These blood tests are not conclusive by themselves, but combining the tests with certain physical findings can help to corroborate a diagnosis.
Anti-Nuclear Antibody (ANA) Test
Anti-nuclear antibodies (ANA) are autoantibodies to the nuclei of your cells. 98% of all people with systemic lupus have a positive ANA test, making it the most sensitive diagnostic test for confirming diagnosis of the disease. The test for anti-nuclear antibodies is called the immunofluorescent antinuclear antibody test. In this test, a blood sample is drawn and sent to a laboratory. Serum from the blood sample is then added to a microscopic slide prepared with specific cells (usually sections of rodent liver/kidney or human tissue culture cell lines) on the slide surface. If the patient has antinuclear antibodies, their serum will bind to the cells on the slide. Then, a second antibody tagged with a fluorescent dye is added so that it attaches to the serum antibodies and cells that have bound together. Lastly, the slide is viewed using a fluorescence microscope, and the intensity of staining and pattern of binding are scored at various dilutions. The test is read as positive if fluorescent cells are observed.
Usually, the results of the ANA test are reported in titers and patterns. The titer gives information about how many times the lab technician diluted the blood plasma to get a sample of ANAs. Each titer involves doubling the amount of test fluid, so that the difference between a titer of 1:640 and 1:320 is one dilution. A titer above a certain level then qualifies as a positive test result. ANA titers may increase and decrease over the course of the disease these fluctuations do not necessarily correlate with disease activity. Thus, it is not useful to follow the ANA test in someone already diagnosed with lupus.
The pattern of the ANA test can give information about the type of autoimmune disease present and the appropriate treatment program. A homogenous (diffuse) pattern appears as total nuclear fluorescence and is common in people with systemic lupus. A peripheral pattern indicates that fluorescence occurs at the edges of the nucleus in a shaggy appearance this pattern is almost exclusive to systemic lupus. A speckled pattern is also found in lupus. Another pattern, known as a nucleolar pattern, is common in people with scleroderma.
It is important to realize that even though 98% of people with lupus will have a positive ANA, ANAs are also present in healthy individuals (5-10%) and people with other connective tissue diseases, such as scleroderma and rheumatoid arthritis. Moreover, about 20% of healthy women will have a weakly positive ANA, and the majority of these people will never develop any signs of lupus. One source cites that some ten million Americans have a positive ANA, but fewer than 1 million of them have lupus. Therefore, a positive ANA test alone is never enough to diagnosis systemic lupus. Rather, a physician will order an ANA test if the patient first exhibits other signs of lupus. This is because by itself, the test has low diagnostic specificity for systemic lupus, but its value increases as a patient meets other clinical criteria. It is possible for people with lupus to have a negative ANA, but these instances are rare. In fact, only 2% of people with lupus will have a negative ANA. People with lupus who have a negative ANA test may have anti-Ro/SSA or antiphospholipid antibodies.
Other Diagnostic Tests
In people with a positive ANA, more tests are usually performed to check for other antibodies that can help to confirm the diagnosis. Certain autoantibodies and substances in the blood can give information about which autoimmune disease, if any, is present. To check for these antibodies, doctors usually order what is called an ANA panel, which checks for the following antibodies: anti-double-stranded DNA, anti-Smith, anti-U1RNP, anti-Ro/SSA, and anti-La/SSB. Some laboratories also include other antibodies in their panel, including antinucleoprotein, anticentromere, or antihistone.
The anti-double-stranded DNA antibody (anti-dsDNA) is a specific type of ANA antibody found in about 30% of people with systemic lupus. Less than 1% of healthy individuals have this antibody, making it helpful in confirming a diagnosis of systemic lupus. [The absence of anti-dsDNA, however, does not exclude a diagnosis of lupus.] The presence of anti-dsDNA antibodies often suggests more serious lupus, such as lupus nephritis (kidney lupus). When the disease is active, especially in the kidneys, high amounts of anti-DNA antibodies are usually present. However, the anti-dsDNA test cannot be used to monitor lupus activity, because anti-dsDNA can be present without any clinical activity. Three tests are currently used to detect anti-dsDNA antibodies, namely enzyme-linked immunosorbent assay (ELISA), the Crithidia luciliae immunofluorescence test, and a test called radioimmunoassay.
An antibody to Sm, a ribonucleoprotein found in the nucleus of a cell, is found almost exclusively in people with lupus. It is present in 20% of people with the disease (although the incidence varies among different ethnic groups), but it is rarely found in people with other rheumatic diseases and its incidence in healthy individuals is less than 1%. Therefore, it can also be helpful in confirming a diagnosis of systemic lupus. Unlike anti-dsDNA, anti-Sm does not correlate with the presence of kidney lupus. Prospective studies have been performed as to whether anti-Sm correlates with lupus flares and disease activity, although evidence seems to suggests that it does not. The anti-Sm antibody is usually measured by one of four methods: ELISA, counterimmunoelectrophoreses (CIE), immunodiffusion, or hemagglutination.
Anti-U1RNP antibodies are commonly found along with anti-Sm antibodies in people with SLE. The incidence of anti-U1RNP antibodies in people with lupus is approximately 25%, while less than 1% of healthy individuals possess this antibody. However, unlike anti-dsDNA and anti-Sm antibodies, anti-U1RNP antibodies are not specific to lupus they can be found in other rheumatic conditions, including rheumatoid arthritis, systemic sclerosis, Sjogren’s syndrome, and polymyositis.
Anti-U1RNP has shown to be associated with features of scleroderma, including Raynaud’s phenomenon it has also been linked to other conditions, such as Jaccoud’s arthropathy, a deformity of the hand caused by arthritis. Levels of anti-U1RNP may fluctuate in individuals over time, but this fluctuation has not proven to be a significant indicator of disease activity.
Anti-Ro/SSA and Anti-La/SSB Antibodies
Anti-Ro/SSA and Anti-La/SSB are antibodies found mostly in people with systemic lupus (30-40%) and primary Sjogren’s syndrome. They are also commonly found in people with lupus who have tested negative for anti-nuclear antibodies. Anti-Ro and anti-La can also be found in other rheumatic diseases, such as systemic sclerosis, rheumatoid arthritis, and polymyositis, and are present in low titers in about 15% of healthy individuals. These antibodies are not highly specific for systemic lupus, but they are associated with certain conditions, including extreme sun sensitivity, a clinical subset of lupus called subacute cutaneous lupus erythematosus (SCLE), and a lupus-like syndrome associated with a genetic deficiency of a substance called complement (a system of proteins that helps mediate your body’s immune response). In addition, babies of mothers with anti-Ro and anti-La antibodies are at an increased risk of neonatal lupus, an uncommon condition that produces a temporary rash and can lead to congenital heart block. Therefore, women with lupus who wish to become pregnant should be tested for these antibodies.
Antibodies to histones, proteins that help to lend structure to DNA, are usually found in people with drug-induced lupus (DIL), but they can also be found in people with systemic lupus. However, they are not specific enough to systemic lupus to be used to make a concrete diagnosis.
Serum (blood) Complement Test
A serum complement test measures the levels of proteins consumed during the inflammatory process. Thus, low complement levels reflect that inflammation is taking place within the body. Variations in complement levels exist in different individuals simply due to genetic factors.
- “ANA.” 8 April 2009. Lab Tests Online. 8 April 2009. American Association for Clinical Chemistry. 6 July 2009. – Link
- “Blood Tests.” The Lupus Site. 6 July 2009. – Link
- “Laboratory Tests.” Lupus Foundation of America. 6 July 2009. – Link
- Wallace, Daniel J. The Lupus Book: A Guide for Patients and Their Families. 1st ed. New York: Oxford University Press, 1995.
- Wallace, Daniel J., and Bevra Hannahs Hahn, eds. Dubois’ Lupus Erythematosus. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2007.
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