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Author: Stephen J. Klemawesch, MD

Fc Receptor Therapy

Fc Receptor Therapy

There are five types of immune proteins called immunoglobulins (Ig):  IgG, IgD, IgA, IgM and IgE.  In general, these immune proteins are an integral part of our host defense system.  However, just as Benedict Arnold turned traitor to the American cause, so too our immune proteins can sometimes go awry.  This is the definition of auto-immune disease, i.e. our own immune proteins attack us. 

There are two ends of all five immune proteins and they are called the F ab end and the Fc end.  F ab stands for “fraction that binds antigen”.  It is the end of the protein that has specific target recognition capabilities.  For instance, our Ig proteins we make from having been vaccinated for Tetanus have a very specific F ab end that only recognizes Tetanus, and thereby protects us from the disease by binding to it.

Fc stands for “fraction that is crystallizable” referring to how it was first discovered chemically – by crystallization techniques.  But the Fc end of the molecule controls the immune function of the protein.  The Ig exerts its effect when the Fc end of the protein fits into an Fc-receptor (much like an electric plug fitting into an outlet). 

In the case of auto-immune diseases this has provided a mechanism to treat these diseases.  To date, one of the most effective therapies for some auto-immune diseases is using intravenous immunoglobulin infusions (IVIG).  This treatment has been a God-send in a number of auto-immune diseases such as Kawasaki disease, dermatomyositis, toxic epidermal necrolysis, immune thrombocytopenic purpura (ITP) and Guillain Barre syndrome to name a few.  Basically, it works in part by flooding the body with Ig molecules containing Fc ends making it difficult for the abnormal Ig proteins to find an available Fc receptor.  Think of the plastic devices used to “childproof” electrical outlets.

New on the horizon is the development of monoclonal antibodies to block Fc receptors.  Currently there are seven

different monoclonal antibodies being developed for this purpose.  So far, they seem to be both safe and effective, but

none have been developed long enough to be FDA approved.  In addition to providing help for a whole variety of auto-immune diseases they may also find a very special niche in treating some fetal diseases during pregnancy.  Of special research interest in this regard are hemolytic disease of the fetus, fetal alloimmune thrombocytopenia and anti-Ro disease which causes fetal heart block. 

Air Pollution and Health

Air Pollution and Health

It may seem hard to believe but every day we breathe in more than 10,000 liters of air.  Depending on the degree of pollutants in that air, the human lungs can either cope with it or not. As I write these words, I can’t help but think of one of the “I Love Lucy” episodes where she and Ethel get a job in a candy factory hand wrapping expensive chocolates as they come down a conveyor belt.  Early on, the belt moves slowly and the girls do fine.  But as it speeds up, they can no longer keep up with the wrappings and resort to what many of you will remember as hilarious alternatives.  Unfortunately, our lungs don’t have a sense of humor and when overtaxed they become ill. 

Luckily our lungs have a number of good coping mechanisms, both mechanical and immunologic.  The airway epithelium cells have very tight junctions which create an excellent barrier.  In addition, the micro-cilia in the lungs are constantly beating to “fan” pollutants out of the lungs.  Finally, mucus production can trap particulates and dilute gases and vapors thereby reducing their toxicity.  Surfactant, a second cousin to mucus, also is very effective in diluting and detoxifying gaseous pollutants including ozone. 

There are a variety of immunologic defense mechanisms, most of which work by removing free radicals and reducing oxidative stress on the delicate lung tissues.  However, when exposure is too great or prolonged over time these systems fail with two negative consequences.  One is inflammation which leads to lung damage and scarring and the development of COPD.  The other is greater propensity for infection.  If the tight junction barrier is faulty it allows microbes easier penetration into lung tissue.  And, if the protective immune responses are over-taxed, they can’t adequately shift from pollution protection to microbial defense. 

T3SS and T4SS

T3SS and T4SS

Even though bacteria far predate human existence, we have co-evolved once humans hit the scene.  It may be hard to believe in terms of cell count but our total number of human cells (10 trillion cells) is exceeded by a logarithm by the number of bacteria in our microbiota (100 trillion cells).  We humans carry roughly 35,000 different species of bacteria on us and in us.  Despite the very large variety of bacteria on planet earth only about 100 species cause human illness.  But, these 100 have endured in large part because of adaptations to evade human defense mechanisms. 

One such system is the “secretion system”.  The two most common of which are: type 3 secretion system (T3SS) and type 4 secretion system (T4SS).   One such system made the news the year one of this newsletters authors was born, 1976.  Legionella has used T4SS for a very long time to avoid destruction by one of its natural predators: amoeba.  At an American Legion meeting in Philadelphia in 1976 amoebas (containing Legionella) contaminating the air conditioning ducts in the hotel were inhaled by conventioneers.  Thirty-four people died from the bacteria leaving its safe haven of the amoeba and entering the lungs of the humans.  Hence, the bacteria using this T4SS survival tactic was christened “Legionella”. 

Enterohemorrhagic E. coli (O157) uses a T3SS protein to cause the severe bloody diarrhea that can occur from ingesting contaminated/undercooked meat.  In this case the E. coli uses the T3SS protein to lock itself to the human intestinal cells so it can’t be displaced, meanwhile releasing a toxin that causes the bloody stools. 

H. pylori (another GI pathogen) uses T3SS to lock itself on to stomach cells.  Once firmly attached it then releases another protein called urease, which neutralizes stomach acid so the acid can’t destroy the bacteria.  H. pylori causes stomach ulcers and if it remains untreated over time can cause stomach cancer.  To date, it’s the only bacteria known to cause cancer.

One final example is Yersinia pestis the bacteria that causes plague.  Once Yersinia enters the human blood stream via a rat bite, it is immediately swallowed by our white blood cells.  But before the white blood cells can destroy the bacteria, the Yersinia releases T3SS which inactivates the immune proteins.  The Yersinia then uses its inactivated white blood cell as a taxi cab to carry it throughout the human body.  Perhaps the early Greeks had already known about Yersinia’s trickery leading to their application of treachery via the Trojan horse. 

As bad as this all sounds, the good news is that humans have evolved a multi-dimensional brain.  This in turn has led to many new strategies to fight the pathogenic bacteria.  Two therapies currently being developed are glycodendrimers and pilicides, both of which inactivate the T3SS/T4SS molecules.  Also, in the works is a genetic vaccine that also inactivates the T3SS/T4SS molecules.  Finally, a chemical called salidylidene acylhydrazide is being researched for its ability to prevent bacteria from secreting the T3SS/T4SS proteins. 

Dear Dr. K,

Dear Dr. K,

Recently I got a severe leg abrasion when I had an accident on my motorcycle.  I needed surgery to clean the leg and stop all the bleeding.  Three days later my leg got red and swollen and itched.  My surgeon gave me an antibiotic thinking it was infected.  But the culture was negative, and the leg kept getting worse.  Then, he gave me prednisone and the leg got better quickly.  Any ideas?

Well, I’m no Dr. House, but since I know your food allergies include gelatin, I suspect you reacted to a hemostatic agent containing gelatin.  “Hemostatic” means to stop bleeding and hemostatic agents are vital to surgeons.  Gelatin is used in many of them because its’ protein structure provides a scaffold that promotes clot formation.  It is available in two forms:   a matrix (sponge, film or powder) or as a foam.   Examples in common use today include:  Surgifoam, Surgiflo, Gelfoam, Floseal, MeroPack, Thrombi-Gel, Gelfoam, and Optisphere.  There are non-gelatin products available that are made from cellulose. 

Unfortunately, the story doesn’t end there as you need to be aware of gelatin exposure in other medical settings.  Some medical devices contain gelatin.  Some vascular grafts contain gelatin as do some heart valve replacements.  Some bone replacement implants contain gelatin and are used in both skeletal and dental products.  IV fluids are generally safe but some of what are called colloid fluids (often used for patients in shock) contain gelatin.  As it turns out, no colloid fluids in the USA contain gelatin, but gelatin containing fluids are frequently used in Europe. 

Many medicines contain gelatin either to form the capsule (for example Advil Liqui-gels) or as a binder.   Since the number of OTC and prescription drugs is so large, it is advisable to read labeling on any medication you plan to take.  A few intraocular lens implants (used in cataract surgery) contain gelatin, but most do not. 

Finally, some vaccines contain gelatin.  Most notable is the MMR vaccine.  There is an interesting side story to the MMR vaccine that is worth mentioning.   Although allergic reactions to MMR are rare, when they do occur doctors initially thought it was due to egg allergy as the vaccine is prepared in an egg medium.  But when these cases were more closely studied, it turned out that the gelatin, not egg, was the provocateur.  Actually, children with egg allergy an receive MMR without any concern for allergic reaction.  A few other vaccines may contain gelatin depending on the manufacturer:  rabies vaccine, typhoid vaccine, yellow fever vaccine, and one type of flu vaccine. 

Jellyfish Allergy

Jellyfish Allergy

Floridians need to be aware that jellyfish can not only be a source of an unpleasant sting, but also of allergic reactions.   In fact, life threatening allergy (anaphylaxis) was first described in 1901 by two scientists; Charles Richet and Paul Portier who were studying jellyfish.  They began their studies at the behest of Prince Albert of Monaco who was an avid oceanographer.  He asked them to study the sting of the Portuguese man-of-war.   They used the venom from both the man-of-war and the sea anemone in dog studies. 

Because the concept of vaccination was new to science, they wondered if they could “vaccinate” dogs with the venom to build up protection.  Unexpectedly (because they used too large of doses) and to their dismay, the second injection caused some of the dogs to die suddenly, because they failed to provide “phylaxis” (now called prophylaxis).  They called the events aphylaxis (eventually termed anaphylaxis) meaning “against” “protection”.  As a dog lover I’m sorry for the dogs, but I guess it would have been worse if they had experimented on the prince. 

Jellyfish belong to the phylum Cnidaria which refers to the cnida, a specialized explosive organelle that causes stings.  The cnida produce a variety of proteins which can lead to allergic sensitization: congestin, hyaluronidase, collagenase, proteinase, hypnotoxin, thalassin, nuclease, and phosphatase. 

There are 10,000 species of jellyfish and their numbers are increasing due to global warming.  The most common jellyfish allergy is skin allergy either immediate or delayed.  The immediate reaction is hives that occur in addition to the “stings”.  The hives respond to antihistamine therapy but the stings do not.  The delayed reaction is akin to poison ivy allergy in that an itchy blistering develops several days after the immediate stings.  This type of allergy responds best to steroids, either topical or oral. 

The next most common reaction is food allergy reaction with itchy rash and GI symptoms after ingesting jellyfish.  In some cultures, the umbrella (outer portion) of the jellyfish is a common food. 

Anaphylaxis is the rarest form of allergy but can be life threatening.  Most cases occur in people with frequent and repeated contact with jellyfish especially surfers and open water swimmers. 

Dear Dr. K; When I recently started taking Coreg for newly diagnosed hypertension my previously well controlled asthma got worse. Are they related?

Dear Dr. K; When I recently started taking Coreg for newly diagnosed hypertension my previously well controlled asthma got worse. Are they related?

The short answer is yes, the long answer requires explanation.  First of all, asthma and hypertension are both very common conditions with 9% of American adults having asthma and up to 25% having hypertension.  Certain factors can contribute to both conditions:  stress, obesity, sedentary life style, excess salt intake, and sleep-disturbed sleep.  Correcting these factors can help both conditions.

In terms of medications, many of the medicines used to treat asthma and hypertension can act on opposing sides of the autonomic nervous system.  The autonomic nervous system controls the smooth muscles found in both our bronchial tubes and our blood vessels and heart.  Unfortunately, medicines that can relax heart and blood vessel smooth muscle (thereby lowering BP) can sometimes constrict bronchial smooth muscle (narrowing airways and causing asthma). 

Coreg contains a beta-blocker meaning it blocks the beta input into blood vessels and the heart and thereby relaxes them and lowers BP.  Unfortunately, it also blocks beta input into bronchial tubes which causes them to tighten, thereby causing asthma.  Many of the medications used to treat asthma work through the beta system as stimulants (agonists).  Many inhalers contain short acting or long acting beta agonists: albuterol, Advair, Symbicort, Breo, Dulera.  Blocking the beta system reduces their benefit. 

Luckily scientists have come to understand this dichotomy. This has led to the development of “cardio-selective” beta blockers.  These drugs are much less likely to have negative effect on asthma as they are formatted to work mostly on the heart and blood vessels.  Perhaps your doctor could switch you from Coreg (a non-cardio selective) to a cardio-selective beta blocker. 

High Fat Diet and Food Allergy

High Fat Diet and Food Allergy

Over the past thirty years there has been a dramatic increase in both obesity and food allergy.  In fact, the rate of increase for both conditions has followed the same identical track.  For this reason, and others, scientists at Washington University School of Medicine have done exhaustive research to see if there might be a common cause.  As it turns out a high fat diet is the answer.  The rise in obesity is directly linked to the high fat content of “The Western Diet”.  As it turns out, a high fat diet also can lead to food allergy for three main reasons:  mast cells, gut permeability, and change in microbiota. 

Mast cells are the “worker bees” for allergic conditions.  They are the cells that contain and release histamine and other allergic mediators.  A high fat diet leads to an accumulation of excess Mast cells inside the intestine walls.  A high fat diet also makes the walls of the intestine more porous (or “leaky”) thus allowing greater penetration of food allergens.

Finally, a high fat diet alters the normal healthy microbiome towards one that is pro-inflammatory.  This increase in total body inflammation promotes both allergic and auto-immune conditions. 

PFAS

PFAS

PFAS stands for pollen food allergy syndrome.  It used to be called OAS (oral allergy syndrome) but the new name better characterizes the pathogenesis.  Using highly technical immunologic terms, it is called Class II food allergy.  Class I food allergy refers to the common/classic form of food allergy where sensitivity occurs due to ingesting the food.  In Class II food allergy, the sensitivity occurs from exposure to pollen and leads to cross reactivity with a food. 

The symptoms involve immediate itching and sometimes mild swelling of the lips, tongue, mouth and throat.  Sometimes the itching can even extend from the oral cavity to the back of the nose or ears.  Occasionally these oral symptoms are accompanied by difficulty swallowing and/or nausea.  Almost always the symptoms are both self-limiting and mild.  But the immediate nature of the onset makes people fearful of possible anaphylaxis.  That is why its important to distinguish PAS from traditional food allergy issues. 

The most common pollen-food cross reactivities are:  mugwort pollen and peach and chestnut; ragweed pollen and banana, melons, kiwi and peaches; grass pollen and tomato, peach, and apple; and birch pollen and apple, apricot, carrot, celery, cherry, chestnut, hazelnut, kiwi, peanut, pear, raspberry, soybean, strawberry, tomato and walnut. 

Of interest, cooking a food can sometimes degrade the cross-reactivity protein so that PAS doesn’t occur.  Otherwise, avoidance is the best therapy.

Q – Tips: COVID-19

Q – Tips: COVID-19

The two main tests being used during this pandemic are nasal swabs to detect active infection, and antibody tests to detect prior infection.    

The nasal swab uses a polymerase chain reaction (PCR) which is a chemical tool that amplifies tiny amounts of nucleic acid to allow detection of viral RNA.

Antibody tests fall into two main categories:  detection and protective value. The two main detection assays are for either spike glycoprotein (allows the virus to enter human cells) or nucleocapsid phosphoprotein (the most abundant protein).  Both can confirm a prior corona virus infection.  

Neutralizing antibody assay is used to determine if the presence of antibodies can “kill” (neutralize) the corona virus in a test tube.  This type of testing will be used to determine how effective corona virus vaccines will be. 

New Mobile Check In App!

New Mobile Check In App!

We have launched our new Mobile Check In app. You may download it by clicking the download on the right side of this page, or by scanning the QR Code in the office. You can check in from the parking lot. If you are going to be waiting for your shot in the car just click the box that says “yes, in car” and in the comment section please add the color and make of your car.

Of course, you can still check in from the IPad in the lobby.