Understanding Transport Pathways of the Immune System Substances


Today, we are going to learn about granzyme A, interferon-gamma, and an appropriately named receptor called Sortilin. People with healthy and functional immune systems use the Sortilin receptors, granzyme A and, interferon-gamma together to patrol their body for infected cells and fight viruses and bacteria. However, if you aren’t so lucky, and say you were low on serum and the Sortilin couldn’t sort, then what’s your granzyme A to do?

Well, it finds another receptor, because it’s savvy. It jumps in with some Vampires. Sorry, I meant with the VAMP7 molecules and makes its way to fight infected cells. However, without the Sortilin, less interferon-gamma is available, so it’s significantly weaker at fighting viruses and bacteria.

So, what does this all mean in the big picture? Well I can’t say for sure, but it’s always good that they are figuring out what our immune system is doing. Maybe I should say what our immune system isn’t doing and why. This is just a simple snapshot, I recommend you actually read the press release, you may gleam more from it than I did.
Plus, they used another cool metaphor. This time the immune system is… wait for it… The Post Office. It wraps and delivers packages. I LOVE IT! (If this seems weird, you can go back in the archives to understand my fascination with metaphors for the immune system, Here and Here.)

Researchers Elucidate Transport Pathway of Immune System Substances

To transport substances from the site of their production to their destination, the body needs a sophisticated transport and sorting system. Various receptors in and on the cells recognize certain molecules, pack them and ensure that they are transported to the right place. One of these receptors is Sortilin. It is present in the cells of the nervous system, the liver, and the immune system. Studies by Stefanie Herda and Dr. Armin Rehm (Max Delbrück Center for Molecular Medicine, MDC, Berlin-Buch and Charité–Universitätsmedizin Berlin) and the immunologist Dr. Uta Höpken (MDC) have now shown that the receptor Sortilin plays an important role in the function of the immune system.
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Examining the Quality of Life in CVID


Health Related Quality of Life in Common Variable Immunodeficiency

Here’s an interesting Italian study published in the Yonsei Medical Journal exploring the quality of life in patients with CVID.

They  “used generic health status and general psychological health questionnaires to determine the range of issues that needed to be considered in examining the burden of common variable immunodeficiency CVID.”

When I read the words “generic health status and general psychological health questionnaires” , I pictured them holding up a happy face and a frowning face and asking, “which better describes your mood after your infusion?” It’s not like that at all though. They rate it on a few different methods, that have fun and misleading acronyms. I’ll break it down here first, to hopefully help familiarize you with them before reading through the actual study.

I’m really not trying to insult anybody’s intelligence, I just know that when I read through the article I had to go back to this part and start over. I need these things broken down a few times before it sticks. I figure if I’m like that, others are probably having the same issues.


made up of 8 dimensions (so lets call it SF-36? Yes, yes, brilliant idea! )

  1. Physical Function (PF)
  2. Role Physical (RF)
  3. Bodily Pain (PB)
  4. General Health (GH)
  5. Vitality (VT)
  6. Social Functioning (SF)
  7. Role Emotional (RE)
  8. Mental Health (MH)


The General Health Questionnaire is a self-administered 12-item questionnaire designed to measure psychological distress and to detect current non-psychotic psychiatric disorders, such as depression and anxiety.


The 20-item Toronto Alexithymia Scale (TAS-20) questionnaire was used to evaluate alexithymia, i.e., the difficulty in identifying and describing feelings. It gives three subscale scores, measuring, respectively, the difficulty in identifying feelings, the difficulty in describing and communicating feelings, and the tendency to focus on the concrete details of external events rather than on feelings, fantasies, and other aspects of one’s own inner experience (“externally oriented thinking”).  Did you get that? Because there will be a test later.

And last but not least, the;


For each patient, an overall clinical severity evaluation of the disease was given by the physician and by the patient him/herself. The Physician Global Assessment (PhGA) and the Patient Global Assessment (PtGA) comprised the questions, “In your opinion, compared to other patients with the same condition, how severe is the disease of patient X?” and “In your experience, how severe is your disease?”, respectively.

Armed with these tests and ninety-six patients (50 males and 46 females) they came up with some interesting results.

“We examined the possibility that the quality of life may be influenced by the ages of the patients; the length of CVID disease; the presence or absence of chronic sinusitis, chronic lung disease, or chronic diarrhea; and whether the subject received gammaglobulin therapy at home or in a hospital setting. The duration of disease did not influence health status, while the most seriously affected HRQoL measures were due to the presence of chronic clinical conditions…  patients with chronic lung disease and chronic diarrhea had the lowest health related quality of life values.” 

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Rare Cells Regulate Immune Responses


Happy Monday, I’m back! Unfortunately, I haven’t been feeling good. Migraines and extreme fatigue have kept me confined to the couch and bed. I’ve been what my husband calls a “sleep-a-potamus”, or “sleep-a-lot-a-mus.” I have a doctors appointment coming up November 1st, and I plan to talk to him about this, it’s happening to often. Booo.

Now, back to interesting things. Like regulatory B cells and how they can fight inflammation. Yay, B cells!

Before we get into the new study from Duke University about this rare B cell and how it may stop inflammation due to autoimmune disorders, lets take a look at a quote from Autoimmune Manifestations in Common Variable Immunodeficiency by Cunningham-Rundles C.. This is to remind you how autoimmune complications may affect CVID, and why this study may be important to you.

“About 20% of subjects with common variable immune deficiency (CVID) develop an autoimmune complication…including rheumatoid arthritis, juvenile rheumatoid arthritis, pernicious anemia, thyroiditis, alopecia, primary biliary cirrhosis, vitiligo systemic lupus erythematosus, all series agree that of the autoimmune conditions, the commonest are antibodies to hematologic tissues, especially immune thrombocytopenia purpura and autoimmune hemolytic anemia.”

I think I’m seeing a trend. As I read thought this report I thought, I’ve already read this, because it’s so similar to the article that’s up here about regulatory T cells entitled “New Molecule Puts The Brakes on Inflammation.” I had to come back an re-read that article to make sure I wasn’t reading the same study. Alas, they are not the same, they just have similar findings, and similar sounding cells.

The previous article was studying a regulatory T cell molecule called “IL-27”, by the University of Pennsylvania, and this one is studying a regulatory B cell protein called “IL-10,” by Duke University.

It’s a study, it’s doing study things, that are technical, and may be kind of boring if you aren’t a scientist or doctor. The important thing is, that like the other article, they are making advances in possibly stopping inflammation due to autoimmune diseases. This is exciting! It’s still in the beginning stages and needs more research. I love that they are looking into the “regulatory” cells and finding new and exciting ways to use them to stop inflammation. I hope it continues and shows results in our near future. I heart science.

Rare cells regulate immune responses; may offer novel treatment for autoimmune diseases

Reproducing a rare type of B cell in the laboratory and infusing it back into the body may provide an effective treatment for severe autoimmune diseases such as multiple sclerosis or rheumatoid arthritis, according to researchers at Duke University Medical Center.

The findings, which were demonstrated in mice, highlight the unique properties of a subset of B cells that normally controls immune responses and limits autoimmunity, in which an organism mistakenly attacks its own healthy tissue. The work appears Oct. 14, 2012, in the journal Nature.
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CVID, should you get the flu shot?



“Should I get the flu shot?”
If you take part in any board or forum for CVID or PIDD you have seen this question come up, or perhaps asked it yourself. Like so many of our questions, there’s no cut and dry answer. That “Variable” in CVID can really throw a wrench in understanding things clearly.

So what should you do? You should ask your doctor. Some of us have problems producing B and T cells, getting the vaccine would make your body work hard for nothing, your doctor may not recommend you get immunized. Others’ B and T cells may not be so depleted and may have a chance to create the memory cells needed for immunization. Therefore, your doctor may likely recommend you get the shot.

Still unsure? Yeah, me too. The Immune Deficiency Foundation(IDF) recommends that we all get the vaccine;

Why do we recommend that everyone be immunized? First, some patients with a primary immunodeficiency may benefit from the vaccine. Even if they do not, there is little down side to receiving the inactivated vaccine. Family members who are able to respond to the vaccine will be protected (a good thing in its own right). Even if the patient with primary immunodeficiency does not respond to the immunization, he or she will benefit from having everyone else in the family protected from infection and not susceptible to bringing the virus home with them. We want to create a “protective cocoon” of immunized persons surrounding our patients so that they have less chance of being exposed.

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Is CVID Just Mimicking other GI Conditions?


Is your GI playing pantomime games?

Here is another study, with a lot of statistics and big words. But what’s important to take away from it is the amount of problems CVID can mimic in the GI and bowels. Just like Celiacs in the previous article, this one points out that and a few others.

Referring to the GI tissue patterns in CVID, “Its features can mimic lymphocytic colitis, collagenous enterocolitis, celiac disease, lymphocytic gastritis, granulomatous disease, acute graft-versus-host disease, and inflammatory bowel disease.”

It’s good to aware of this, and be able to show your doctor if you have in the past or do in the future run into these or other similar diagnosis. It may be worth double checking them. It’s also interesting to note that 2/3’s of the patients had no plasma cells in their GI biopsy.

This isn’t to say that you could never have these conditions, you certainly could. You just need to be aware that CVID may be playing some convoluted, hide-and-seek pantomime game with the doctor.

That darn CVID, always trying to play games when you’re trying to be serious, it really needs to work on its timing.

Gastrointestinal tract pathology in patients with common variable immunodeficiency (CVID): a clinicopathologic study and review.

Common variable immunodeficiency (CVID) is characterized by a host of gastrointestinal (GI) lesions that can mimic other conditions.

We reviewed clinical documentation and samples from 132 separate GI biopsy or resection sites on 20 CVID patients obtained over a 26-year period, including biopsies from the colon (34), esophagus (19), small intestine (38), and stomach (35), a partial gastrectomy, small bowel resection, colectomy, 2 cholecystectomies, and 1 appendectomy.
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Gluten-free diet improved only 2 out of 12 patients with CVID


This is interesting. I like it because I don’t want to give up gluten. Therefore, I feel perfectly OK about the pumpkin bread I’m going to bake. Of course I’ll go on to find out I’m one of the two.

I’m going to follow this up with another really interesting GI article. But sadly no, it’s not going to say that bacon is good for you, nor will is say that you should be eating Nutella out of the jar with your fingers. I’ll have it up a little later. After pumpkin bread.

The enteropathy associated with common variable immunodeficiency: the delineated frontiers with celiac disease.


The enteropathy associated with common variable immunodeficiency (CVID) is poorly characterized, and its possible relationships with well-defined causes of enteropathy, such as celiac sprue (CS), remain debated. We aimed to assess the clinical and histopathological features of the enteropathy associated with CVID.


The medical files of 50 CVID patients with gastrointestinal symptoms were analyzed retrospectively. Histological, phenotypic, and molecular analysis of intestinal endoscopic specimens was centrally performed.


Chronic diarrhea was the most frequent gastrointestinal symptom (92%), and biological evidence of malabsorption was observed in 54% of patients. Chronic gastritis associated or not with pernicious anemia and microscopic colitis were the most frequently observed histopathological features in gastric and colonic mucosa, respectively. Small-bowel biopsies available in 41 patients showed moderate increase in intestinal intraepithelial lymphocytes in 31 patients (75.6%) and villous atrophy in 21 patients (51%). Distinctive features from CS were a profound depletion in plasma cells and follicular lymphoid hyperplasia. Presence of peripheral blood CD8+ hyperlymphocytosis was predictive of intestinal intraepithelial hyperlymphocytosis. Intravenous (i.v.) immunoglobulin (Ig) therapy had no effect on enteropathy-related symptoms. Gluten-free diet improved only two out of 12 patients with villous atrophy, whereas all patients (7/7) responded to steroid therapy.


Several distinctive features differentiate CVID enteropathy from other causes of enteropathy including CS. Replacement i.v. Ig therapy is insufficient to improve gastrointestinal symptoms. Steroids are effective in reducing inflammation and restoring mucosal architecture.

Malamut G, Verkarre V, Suarez F, Viallard JF, Lascaux AS, Cosnes J, Bouhnik Y, Lambotte O, Béchade D, Ziol M, Lavergne A, Hermine O, Cerf-Bensussan N, Cellier C.


Université Paris Descartes, France. georgia.malamut@egp.aphp.fr

via The enteropathy associated with common va… [Am J Gastroenterol. 2010] – PubMed – NCBI.

New Ig Treatment called HyQ… Well, maybe


New GAMMAGARD product in the works… Well, Maybe

Baxter has been developing a new Ig treatment called HyQ. They are working in conjunction with San Diego based Halozyme to make a product that combines Gammagard, with Halozyme’s recombinant human hyaluronidase (rHuPH20). Most sites describe this new treatment as “a drug that allows patients to self-administer treatments instead of visiting a hospital or clinic to receive IVs.”

How is that different from Subcutaneous Ig infusions and what the heck is recombinant human hyaluronidase you ask? Well I wondered the same thing, and here’s what I’ve learned.

Recombinant human hyaluronidase (rHuPH20) is an enzyme that promotes diffusion and absorption of drugs or fluids by temporarily breaking down hyaluronic acid. Hyaluronic acid is a gel like substance in our subcutaneous fat that protects it from foreign substances. The rHuPH20 breaks down the cell matrix, and the GAMMAGARD gets absorbed right in. If you’re like me after reading this the first time and find your head is cocked to the side like a dog listening to wolves play on the discovery channel, this video breaks it down with pictures. Please explain this with a video and pictures.

It’s already being used in a couple different areas, like insulin, rehydration, and pediatrics. It’s easier, faster and less painful to do a subcutaneous saline drip for little kids and babies who have small or hard to access veins. The video leads you to believe that it doesn’t affect the skin and collagen because it’s under the skin and is absorbed quickly. I’m really curious about this one. I wonder when in conjunction with the immune globulin if it would cut down on local reactions or take them away? It also says on the website to not take any antihistamines while using it because it slows down the absorption. I find that intriguing also.
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This is a few months old, but still a timely news brief for all of us Americans. I see from the stats, that we are being viewed all over the world, so I’ll get back to worldly pertinent information shortly.

Supreme Court

Supreme Court (Photo credit: afagen)

I don’t know where our healthcare will come from or look like in the next few years, but it seems like we have a good group representing our interests.

I don’t want to get political, but I think no matter your views, if you have any form of PIDD and have had to deal with insurance companies, you can appreciate what The IDF and these other groups have worked for, and it seems are continuing to work towards.

Immune Deficiency Foundation Response to the Supreme Court Decision on the Affordable Care Act
Posted on: 07-2-2012

TOWSON, MD, June 28, 2012—The Immune Deficiency Foundation (IDF) has been working with other patient organizations representing plasma users and other rare diseases throughout the two-year debate on healthcare reform that led to the Affordable Care Act and since its passage to ensure that insurance reforms benefit patients with primary immunodeficiency diseases. Essential reforms contained in the Affordable Care Act that IDF successfully advocated for include the elimination of discrimination based on pre-existing medical conditions, elimination of annual and lifetime insurance coverage caps, limits to annual out-of-pocket costs and the elimination of the ability of insurers to discontinue coverage for people because of a new medical diagnoses.

The United States Supreme Court voted 5-4 to uphold the constitutionality of the Affordable Care Act. The provision requiring that all Americans have health insurance, known as the individual mandate, which had been contested by some as an overreach of Federal powers, was ruled constitutional under Congress’ power to tax as the Court determined the responsibility payment for not having health insurance in the law should be considered a tax.

With the decision of the Supreme Court to uphold the Affordable Care Act, IDF remains focused on assuring that these critically needed insurance reforms are fully implemented to help Americans with primary immunodeficiency diseases access desperately needed medical care. IDF continues to work tirelessly to ensure that the primary immunodeficiency community is educated about current health care policies and that individuals living with primary immunodeficiency diseases and other rare conditions remain a priority of concern for policymakers as these provisions are implemented.

To read the full opinion of the Supreme Court, please visit http://www.supremecourt.gov/opinions/11pdf/11-393c3a2.pdf

Please continue to check the Advocacy Center and the Policy Matters blog on IDF’s website for updates, clarifications, and webinars at http://primaryimmune.org/idf-advocacy-center

Immune Deficiency Foundation Response to the Supreme Court Decision on the Affordable Care Act

New Molecule Puts the Brakes on Inflamation


I found this curious since a lot CVID patients also battle an array of autoimmune disorders like asthma, arthritis, and GI issues, just name a few. Hopefully, this could be something promising for us in the future.

Oh, and there is another good metaphor in here. If you remember we previously learned about Gun-toting killer T cells? In this immune system explanation, the regulatory T cells are brakes on a car.  I’m learning that not only are T cells uber important, they are descriptively versatile. I get such a kick out of metaphors. I’m easily amused, it’s a gift.

Penn immunologists find a molecule that puts the brakes on inflammation

PHILADELPHIA — We couldn’t live without our immune systems, always tuned to detect and eradicate invading pathogens and particles. But sometimes the immune response goes overboard, triggering autoimmune diseases like lupus, asthma or inflammatory bowel disease.

A new study led by University of Pennsylvania researchers has now identified a crucial signaling molecule involved in counterbalancing the immune system attack.

“The immune response is like driving a car,” said Christopher Hunter, professor and chair in the Department of Pathobiology in Penn’s School of Veterinary Medicine. “You hit the accelerator and develop this response that’s required to protect you from a pathogen, but, unless you have a brake to guide the response, then you’ll just careen off the road and die because you can’t control the speed of the response.”

The research to characterize this immune system “brake” was led by Hunter and Aisling O’Hara Hall, a doctoral candidate in the Immunology Graduate Group. Additional Penn collaborators included scientists from the Penn Genome Frontiers Institute’s Department of Biology and the Perelman School of Medicine’s Department of Medicine. Researchers from Merck Research Laboratories, the National Institute of Allergy and Infectious Disease, Harvard Medical School and Janssen Research and Development also contributed to the work, which was published in the journal Immunity.
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Baxter Discontinues GAMMAGARD S/D



In case you didn’t get the memo, Baxter has made the decision to discontinue manufacturing GAMMAGARD S/D [Immune Globulin Intravenous (Human)] effective December 2012.

They say this is “in response to customer preference and based on a review of the company’s product offerings.”
GAMMAGARD S/D has been in very low demand relative to Baxter’s other immune globulin offerings, GAMMAGARD LIQUID [Immune Globulin Infusion (Human)] 10% and GAMMAGARD S/D lots with IgA <1 μg/mL. Baxter says they can improve customer demands for these products by focusing their manufacturing efforts on GAMMAGARD LIQUID and GAMMAGARD S/D lots with IgA <1μg/mL.
They will continue to offer GAMMAGARD S/D with IgA <1 μg/mL for patients who may need a low IgA immune globulin. GAMMAGARD S/D with IgA <1 μg/mL has the same formulation as GAMMAGARD S/D, with a lower IgA content, and will continue to be offered to customers through their standard ordering and allocation processes.

You can read their formal discontinuation letter at The Immune Deficiency Foundations website.

If this is your Ig of choice be sure to talk to your doctor about a switch if you haven’t already.