New evidence that incompetent T regs are a root cause of asthma perhaps allergy and autoimmune as well

We know from previous research that the T reg or"good guy" cells in folks with autoimmune disease seemed to be 'incompetent'. They appeared to not be able to turn off the inappropriate autoimmune reaction started by the auto reactive antibodies ( think tiny chemical guided missiles) produced by 'rogue" B cells and continued and increased by the 'bad guy' T effector cells. The autoantibodies label our cells as needing to be attacked and the T effectors enthusiastically follow their directions.

We think we know that T regs in folks with normally functioning immune systems seem able to tamp down the autoimmune reactions before they start.

Apparently those of us suffering from one of the 80 or so named autoimmune disease could use properly functioning T regs. Perhaps the T regs working as they should would be enough to stop disease progression. No one is quite sure, but it is beginning to appear more and more like that may be true.

Now we have evidence that malfunctioning T regs may be at the heart of asthma as well. It seems that folks with asthma have lots of extra T regs in their lungs. Far more than in the lungs of folks without asthma. This is what we would expect if the job of T regs was to settle down over active immune responses like inflammation in the lungs.

You see the T regs of those of us with asthma still answer the call to stop the autoimmune inflammatory damage but when they get to the correct site in the body, they are incompetent. They cannot do their job. Hence more and more T regs are called in by the out of control inflammatory signals being given off by the damaged tissue. Sadly no matter how many T regs arrive, they cannot do anything to help.

If a way could be found to fix our T regs with some form of the multiple ways we know to change gene expression than we might get competent correctly functioning T regs. Please God from my hand to your ear. Then at least some if not all asthma, allergy, eczema, and autoimmune disease might be able to be stopped.

That day is still a long way off. But heroic lab scientist keep chipping away at what we do not know so that one day we will know enough so no one has to suffer from these horrors again.

Below is an abstract of a study done by fine folks at the University of Manchester which found the extra T regs in the lungs of asthma patients thus linking a possible cause of asthma with a probable cause of other autoimmune disease. Note when they mention 'effector lymphocyte activity' they are talking about our old nemesis, the 'bad guy' cells, T effectors. T effs attack our tissues in autoimmune disease.

One might infer that some kind of plasmapheresis or shifting/sorting of our blood cells to eliminate T effectors would stop disease, but sadly the T effs may be just a different side of the same coin that is T regs. Eliminate T effectors and then our incompetent T regs would convert into competent T effectors. Some studies appear to show that T effs change into T regs and vice versa.

The likely problem that we, the afflicted, have with our immune system, then, is that our T regs somehow do not function correctly to stop inflammation in the T reg configuration, but when they are in the T effector configuration they can function to cause inflammation, tissue damage and the killing of pathogens.

Probably if the T effectors configuration did not function correctly we would have died of infection long ago. So instead of hating them for the pain they cause, we should be glad that they can function to stop disease. They just are like unruly guard dogs that attack everything friend and foe alike. Hopefully someday we will have a method to train them to behave.

Here is the abstract:

Chest. 2010 May 7. [Epub ahead of print]
Increased airway T regulatory cells in asthmatic subjects.
Smyth LJ, Eustace A, Kolsum U, Blaikely J, Singh D.
University of Manchester, NIHR Translational Research Facility, Manchester Academic Health Science Centre, University Hospital Of South Manchester Foundation Trust, Southmoor Road, Manchester, UK. M23 9LT.

Abstract
BACKGROUND: Tregulatory cells (Tregs) may play a role in suppression of effector lymphocyte activity in asthma. We hypothesized that Treg numbers would be increased in patients with more severe asthma. We also investigated the regulatory function of CD4 cells by expression of CTLA4, and the number of these cells that are intra-epithelial lymphocytes expressing CD103.

OBJECTIVES: The primary aim was to investigate Treg numbers in the BAL of patients with moderate to severe asthma compared to mild asthma and healthy controls. The secondary aim was to investigate BAL CD4+CTLA4 and CD4+CD103 expression in these groups.

METHODS: Airway lymphocytes obtained by bronchoscopy from healthy controls (6), patients with mild (15) and moderate to severe asthma (13) were characterised by multi-parameter flow cytometric analysis using 3 methods to determine the numbers of CD4+ Treg cells: CD4+CD25(bright), CD4+CD25+CD127-, CD4+FoxP3+.

RESULTS: %CD4+FoxP3+ Tregs were increased in BAL of patients with moderate to severe asthma (median 4.8%) compared to both mild asthma patients (median 2.5%, p=0.03) and healthy subjects (median 0.95, p=0.003). Similar findings were observed for CD4+CD25+CD127- Treg numbers, but not CD4CD25(bright). CD4+ CTLA4 and CD103 expression were raised in moderate to severe asthma patients compared to mild asthma and healthy controls.

CONCLUSIONS: The number of cells displaying regulatory capacity, either through FoxP3 expression or CTLA4 expression, are increased in moderate to severe asthma. CD4+CD103+ intra-epithelial lymphocytes can be retained at tissue sites of inflammation; our findings indicate a role for these cells in asthma pathophysiology.

PMID: 20453071 [PubMed - as supplied by publisher]

Keep on Cleaning Surfaces and Washing hands, MRSA Rates are up Ten Fold

Dangerous skin and surface transferred bacteria (MRSA being only one) continue to increase in prevalence (and much worse virulence) throughout the United States. With no new antibiotics on the horizon and the ones we now use having little or no effect the only measure to limit these resistant bacteria is ever more cleaning and hand washing.

Ten percent bleach solutions are the best for killing these bacteria on surfaces. Alcohol also is capable of killing many of these bacteria, but is not as comprehensive as bleach solutions. Ultra violet light (as in sunlight) also kills them. Soap and water does very little but spread them around on the contaminated surfaces.

Any surface touched by any human can harbor these bacteria. The bacteria can still be cultured from completely dry surfaces for weeks after being initially contaminated. Bare wood is the safest surface material as they seem to die rather quickly on wood. Plastic is the absolute worse. An eight week test with various materials including plastic, metal, wood and cloth found that there was no diminishment in infectivity on plastic over the eight week period. Dry cloth as in sheets, towels and pillow cases was also surprising capable of causing infections for weeks. It had been thought that bacteria died on linens and towels rather quickly. But in this test using MRSA they did not. Why they survive so long on cloth, is unknown. With plastic there seems to be a good reason for their extremely long survival. Apparently even smooth feeling plastic contains millions of tiny depressions in the surface that are perfect incubators for bacteria.

Door handles, computer key boards, desk tops, text book covers are all key areas that may contain these newly evolved antibiotic resistant bacteria.

Good luck out there. Keep cleaning commonly touched areas in the classroom and keep washing your hands regularly. (Even though soap and water mostly move the bacteria around on surfaces, they are effective on the hands as the soap lifts the bacteria and running water carries them off the hands to the drain.)

A good way to know if you have washed long enough is to repeat the ABC song in your head as you wash. Wash all surfaces on your hands especially the finger tips. Scrub hard you are using friction and lubrication to break the connection of the bacteria to your skin cells. Once the connections are broken and loosen by soap and friction, away go the bacteria. It seems that bacteria have millions of tiny villi on their surfaces that act a lot like Velcro, but soap loosens their hold on human skin cells. When you finish the ABC song you have probably washed sufficiently.



The number of children hospitalized with dangerous drug-resistant staph infections surged tenfold in recent years, a study has found.

Disease incidence increased from two cases to 21 cases per 1,000 hospital admissions from 1999 to 2008. Most infections were caught in the community, not in the hospital.

The study, which was published Monday in the journal Pediatrics, involved methicillin-resistant staph infections, called MRSA. These used to occur mostly in hospitals and nursing homes, but they are increasingly showing up in other settings among children and adults. Recent evidence suggests hospital-acquired MRSA cases may be declining while community-acquired cases are becoming more common.

The results are "a good example of how something that is not unexpected remains alarming," said Dr. Buddy Creech, an infectious disease specialist at Vanderbilt University who was not involved in the study.

The study involved 25 children's hospitals; the tenfold increase in hospitalizations probably occurred nationwide, said Dr. Jason Newland, the lead author and an infectious disease physician at Children's Mercy Hospitals and Clinics in Kansas City, Mo., and the University of Missouri-Kansas City.

Almost 30,000 children were hospitalized with MRSA infections at the hospitals studied during the 10-year period. Most had skin or muscle infections, and 374 of them died. Although NewlandMRSA caused those deaths, it can be deadly and is blamed for more than 18,000 deaths in children and adults nationwide each year.

The study didn't examine whether deaths or the severity of infections increased.

http://www.latimes.com/news/nationworld/nation/la-na-staph-20100517,0,5579892.story

Genentech offers real hope for ending allergy and asthma

I believe we have real hope for an effective long term way to turn off inappropriate allergy and asthma symptoms. Genentech which is among the largest biotech companies in the world if not the largest has announced they have discovered a way to not only differentiate the bad guy B cells that cause our allergic reactions but to selectively block the function of only these B cells leaving the rest of the B cell population intact. Since B cells make the antibodies that protect us from virus and bacterial attack (and possible death without them), it is HUGE news to have found a way to have selectively turned off just the "bad guy" B cells responsible for the "evil" IgE that makes so many of our lives so miserable.

Genentech is also a deep pocket company so it should be able to finance the extremely expensive, tortuously long and Byzantinely complex Food and Drug Administration required clinical trial ordeal. (FDA rhymes with delay.) Many potential cures for autoimmune and allergic diseases have been lost to patients by the "valley of death" caused by these immoral barricades the FDA puts between laboratory discovered potential cures and patients. Some of these delays seem to have to do with politics of Big Pharma and their real goal of profits, profits, profits. Delays that increase profits for Big Pharma are good delays. Since FDA derives significant funding from Big Pharma whatever Big Pharma wants, Big Pharma gets. But Genentech is a member of Big Pharma. As such their treatment might actually get through. Let's hope so.

Of course we have all been disappointed by past promises for good allergy treatments, Xolair comes to mind. I hope that Genentech is being truthful with their announcement in the prestigious Journal of Clinical Investigations. Some companies seem to over hype announcements like this--say for instance Osiris' Prochymal. So who knows? But I do believe there is real hope that our children may have truly effective treatments for allergies and asthma. Base on the article below, this Genentech breakthrough appears to be one likely candidate.

If this works for allergy and asthma, similar selective monoclonals might work for autoimmune disease as well. If we could only turn off the "bad" B cells that are making the auto antibodies which keep the autoimmune disease pot boiling, then the symptoms of the autoimmune disease would end. Go new science discoveries!

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Eliminating the Source of Asthma Causing Immune Molecules

ScienceDaily (May 11, 2010) — Asthma and other allergic diseases are caused by inappropriate immune responses. Soluble IgE molecules, produced by immune cells known as B cells, are key immune mediators of these diseases. Therapeutic targeting of IgE in the blood can neutralize its effects and is an effective treatment for moderate-to-severe allergic asthma. However, this approach does not halt IgE production and patients need to be treated repeatedly.

But now, a team of researchers, at Genentech Inc., South San Francisco, has developed a way to specifically eliminate IgE-producing B cells, providing a potential new long-lasting therapeutic approach to treating asthma and other allergic diseases.

IgE-producing B cells express on their surface an IgE molecule that is slightly different to the IgE molecules that they secrete. The team, led by Lawren Wu, generated a therapeutic molecule known as a monoclonal antibody that targets the portion of human IgE that is contained in IgE molecules on the surface of B cells but not in IgE molecules in the blood. When mice expressing human IgE were treated with this monoclonal antibody, their levels of IgE in the blood decreased substantially as did their numbers of IgE-producing B cells.

As the monoclonal antibody provided mice with protection in a model of allergic asthma, the authors suggest that targeting IgE-producing B cells using monoclonal antibodies similar to those described in this study might be of benefit to individuals with asthma and other allergic diseases.

The research appears in the Journal of Clinical Investigation.

http://www.sciencedaily.com/releases/2010/05/100510174620.htm