Inherent to some immunobullous disorders is potential for intraepidermal or dermal–epidermal junction fragility, a phenomenon that may compromise biopsy specimen integrity and direct immunofluorescence (DIF) interpretation. In these situations, cutaneous adnexal structures (e.g. hair follicles, sweat apparatus) usually remain intact. Whether periadnexal DIF findings are reliable in diagnosing immunobullous conditions is unknown.
We evaluated 56 cutaneous specimens with diagnostic immunoglobulin (Ig) deposition patterns that contained adnexal structures. In a corollary study, we examined 145 hematoxylin-eosin-stained frozen specimens to determine biopsy factors associated with the presence of adnexal structures.
Periadnexal DIF findings offered diagnostic sensitivity in conditions with linear or cell-surface Ig deposition or lupus band. Periadnexal DIF findings were unreliable in dermatitis herpetiformis. Biopsy specimens from scalp and genitalia were most likely to contain folliculosebaceous units and sweat duct apparatus, respectively. Relative depth of biopsy correlated directly with the likelihood of identifying sweat duct apparatus but not folliculosebaceous units.
Periadnexal DIF findings may add diagnostic sensitivity in DIF evaluation of pemphigoid, pemphigus and lupus erythematosus. Pathologists can guide clinicians to biopsy certain anatomic sites and to obtain sufficient biopsy depth to increase the probability of capturing adnexal structures and, therefore, diagnostic yield from DIF specimens.
Aim. To characterize the clinical and immunological profile of patients with PF or PV with umbilical involvement.
Methods. In total, 10 patients (7 women, 3 men; age range 24–70 years, disease duration 3–16 years) diagnosed with either PV (n = 5) or mucocutaneous PF (n = 5) were assessed according to their clinical features, histopathology and immunological findings .
Results. Erythema, erosions, crusts and vegetating skin lesions were the main clinical features of the umbilical region. DIF of the umbilical region gave positive results for intercellular epidermal IgG and C3 deposits in eight patients and for IgG alone in the other two. Indirect immunofluorescence with IgG conjugate showing the typical pemphigus pattern was positive in all 10 patients, with titres varying from 1 : 160 to 1 : 2560. ELISA with recombinant Dsg1 gave scores of 24–266 in PF and 0–270 in PV. Reactivity to recombinant Dsg3 was positive in all five patients with PV (ELISA 22–98) and was negative in all PF sera.
Conclusions. All 10 patients with pemphigus with umbilical presentation had the clinical and immunopathological features of either PF or PV. This peculiar presentation, not yet completely elucidated, has rarely been reported in the literature. A possible explanation for this unique presentation may be the presence of either novel epitopes or an association with embryonic or scar tissue located in the umbilical-cord region.
Full article available at: http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2230.2012.04468.x/abstract
Full article available at: http://www.ncbi.nlm.nih.gov/pubmed/23073990?dopt=Abstract
Case reports 6 patients, aged from 33 to 77 years old, presented with a variable 4 to 40 year history of severe treatment-resistant HHD. All 6 patients were then treated successfully with doxycycline 100 mg per day for at least 3 months.
Discussion An improvement was observed in all 6 patients from 1 week to 3 months after the beginning of treatment. Relapses were observed after various periods. Maintenance half-dose therapy seemed to be beneficial in patients experiencing recurrence. Only one patient developed gastro-intestinal intolerance. No other side effects were reported. Currently, 2 patients have improved and present a decreased number of exacerbations, 2 others are in complete remission after more than 5 years of follow-up. Treatment efficiency is difficult to evaluate in HHD as it is a rare condition. No controlled studies have been published. Local treatments may improve inflammation but do not treat the underlying cause, targeted systemic therapies exist but there is little evidence supporting their use, physical treatments are cumbersome. Besides their antibiotic potential, tetracycline antibiotics also have anti-inflammatory properties and anticollagenase activity via inhibition of matrix metalloproteinases.
Conclusions Doxycycline appears to be an interesting therapeutic option in Hailey-Hailey disease.
Full article available at: http://www.ncbi.nlm.nih.gov/pubmed/22779708
An autoimmune disease develops when the body’s immune system fails to recognize normal body tissues and attacks and destroys them as if they were foreign, rather than attacking an outside organism. The cause is not fully understood, but in some cases it is thought that autoimmune diseases are triggered by exposure to microorganisms or other environmental causes, especially in people with a genetic predisposition to the disorder. A single organ or multiple organs and tissues may be affected.
There are many autoimmune diseases with symptoms that range from mild rashes to life-threatening conditions that attack major organ systems. Though each disease is different, immune-system malfunction is present in all of them. Disease symptoms vary depending on which tissue is targeted for destruction. Symptoms common to all autoimmune disorders include fatigue, dizziness, malaise, and low-grade fever.
Autoimmune disorders are frequently classified into organ-specific disorders and non-organ-specific types. Organs and tissues frequently affected include the endocrine gland, such as thyroid, pancreas, and adrenal glands; components of the blood, such as red blood
cells; and the connective tissues, skin, muscles, and joints.
In organ-specific disorders, the autoimmune process is directed mostly against one organ. But patients may experience several organ-specific diseases at the same time. In non-organ-specific disorders, autoimmune activity is widely spread throughout the body. This includes Rheumatoid Arthritis (joints), Systemic Lupus Erythematosus, and Dermatomyositis (connective tissue).
According to the American Autoimmune Related Diseases Association, about 75 percent of autoimmune disease cases occur in women, particularly those who have had children. The cause is not fully understood, but in some cases it is thought to be triggered by exposure to microorganisms especially in people with a genetic predisposition to the disorder.
Common types of localized autoimmune disorders:
- Addison’s disease (adrenal)
- Autoimmune hepatitis (liver)
- Celiac disease (GI tract)
- Crohn’s disease (GI tract)
- Graves’ disease (overactive thyroid)
- Guillain-Barre syndrome (central nervous system)
- Hashimoto’s thyroiditis (lowered thyroid function)
- Multiple sclerosis
- Raynaud’s phenomenon (fingers, toes, nose, ears)
- Type 1 Diabetes Mellitus (pancreas islets)
- Ulcerative colitis (GI tract)Common types of systemic autoimmune diseases:
- Lupus [Systemic Lupus Erythematosus] (skin, joints, kidneys, heart, brain, red blood cells, other)
- Polymyalgia Rheumatica (large muscle groups)
- Rheumatoid arthritis (joints; less commonly lung, skin, and Juvenile rheumatoid arthritis)
- Scleroderma (skin, intestine, less commonly lung)
- Sjogren’s syndrome (salivary glands, tear glands, joints)
- Systemic Sclerosis
- Temporal Arteritis / Giant Cell Arteritis (arteries of the head and neck)
The types of autoimmune disease treated at SCCA with stem cell transplants include:
- Multiple Sclerosis
- Systemic Sclerosis
- Systemic Lupus Erythermatosus
- Rare neurologic diseases
Other autoimmune diseases treated at SCCA include:
- Autoimmune Cerebellar Degeneration
- Autoimmune Peripheral Neuropathies
- Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
- Gait Ataxia with Late Age Onset Polyneuropathy (GALOP)
- Lambert Eaton Myasthenic Syndrome
- Myasthenia Gravis
- Opsoclonus/Myoclonus (Anti-Ri)
- Rasmussen’s Encephalitis
- Stiff Person Syndrome
- Tropical Spastic Paraperesis HTLV-1 Associated Myelopathy (TSP/HAM)
Autoimmune diseases that affect blood cells are discussed under Blood Disorders.
- Immune thrombocytopenia purpura (ITP)
- Autoimmune hemolytic anemia
- Autoimmune neutropenia
Inflammation is a key component of immune responses to infection, but when uncontrolled can lead to autoimmune diseases like Crohn’s disease, rheumatoid arthritis, type I diabetes, ankylosing spondylitis, lupus, psoriasis and multiple sclerosis. In these diseases inflammation is mediated by molecules of the immune system called cytokines and cells that respond to these cytokines called T cells. Autophagy is an ubiquitous process whereby cells degrade their own internal components, either to release valuable nutrients in times of starvation, or to remove damaged or noxious intracellular components. The work by Dr Harris and colleagues showed that autophagy also control release of the inflammatory cytokines and cells that have been implicated in the pathology of autoimmune diseases. The findings suggest that autophagy represents a potent target for new anti-inflammatory therapies, which could be beneficial in a range of autoimmune disorders. The group, in combination with Professor Kingston Mills, now hopes to apply these findings to specific models of autoimmune disease. The work is funded by Science Foundation Ireland as part of a Strategic Research Cluster (SRC) award based in The Trinity Biomedical Sciences Institute. “Autophagy is a common cellular process that is important for the maintenance of normal cell functions. Our work has shown that this process is
important in the control of inflammation and, as such, could represent a particularly efficacious target for new drugs against inflammatory conditions. There are over 80 different autoimmune diseases, most of which are chronic and debilitating and can be difficult and expensive to treat. Any research which helps us to better understand the underlying mechanisms behind the control of inflammation will ultimately lead to better treatments,” explained Dr James Harris.
An Epidemic of Absence: A New Way of Understanding Allergies and Autoimmune Diseases could be co-marketed with the Thomas Rockwell’s children’s classic How to Eat Fried Worms. It begins with the author, Moises Velasquez-Manoff, recounting his border-crossing to Tijuana to infect himself with Necator americanus—hookworms—in an attempt to cure the asthma, hay fever, food allergies, and alopecia that had plagued him since childhood. In the next three hundred pages, the author very cogently explains the idea that led him to willingly infect himself with a parasite known to cause severe diarrhea, anemia, and mental retardation in children.
Velasquez-Manoff marshals the reams of evidence researchers have accumulated to support said concept: the hygiene hypothesis, but with an updated, parasitic twist. The ideas he presents haven’t been accepted by many in the medical community, and there’s little high-quality evidence, in the form of well controlled trials, that exposure to parasites could have positive effects on human health. So, even if the author is thorough, it’s important to keep in mind that the evidence he’s presenting is primarily in the form of correlations.
The Hygiene Hypothesis
A simplistic view of the hygiene hypothesis is that in the absence of something dangerous to fight against—the cholera toxin, for example—immune cells get confused, or bored, and fight against harmless stimuli like dust mites and peanuts instead. But there is a more nuanced view. Our immune systems co-evolved with an enormous community of microbes, and were in fact shaped by them. Many became established, long-term, and vital residents in our guts; the importance, and in fact the very existence, of these commensals has only recently been realized.
Constant exposure to all of these bugs, as a unit, enhanced the regulatory arm of the immune system, modulating responses so that we could tolerate the filthy environment in which we lived while at the same time (hopefully) fighting off those pathogens that posed a mortal threat and not destroying our own bodies in that process. In the martial analogy that is inevitable in discussing immunology, ancient human immune cells that were always surrounded by microbes were like battle-hardened old soldiers who have learned the ability to watch warily when encountering something new, waiting to see whether or not it is dangerous; modern immune cells raised in our hyper-sanitized environment are like new recruits just given their first gun, testy and jumpy at the first hint of a threat and liable to blow up their surroundings in inappropriately directed and outsized force. Experience has not taught them moderation.
Seeing worms everywhere
Yes, he includes autism in the list of modern diseases caused by our out-of-whack immune systems. Along with other cases where immune dysfunction hasn’t been established, like obesity, cardiovascular disease, type 2 diabetes, and cancer.
There are some serious problems with blaming all of these on immune dysfunction, but we’ll focus on a single example: autism. Just as the absence of worms’ mediating effects on our immune system causes some people to have an allergic response to harmless ingested proteins and others to attack their own tissues, the argument goes, chronic inflammation in the womb generates fetuses with autism.
The rest of this article can be read here: http://arstechnica.com/science/2012/10/book-review-an-epidemic-of-absence-takes-on-the-worms-youre-missing/
The researchers, from Duke University Medical Center in the US, write about their work on a type of B cell, in a paper that was published online in Nature at the weekend.
B cells are immune cells that create antibodies to attack unwanted pathogens like bacteria and viruses.
The type that the researchers on this study focused on are known as regulatory B cells or B10, after interleukin-10 (IL-10), a cell-signalling protein that the cells use.
B10 cells help control immune response and limit autoimmunity, which is where the immune system attacks the body’s own healthy tissue as if it were an unwanted pathogen.
Although there aren’t many of them, B10 cells play a key role in controlling inflammation: they limit normal immune response during inflammation, thus averting damage to healthy tissue.
Regulating Immune Response Is a Highly Controlled Process
Study author Thomas F. Tedder is a professor of immunology at Duke. He says in a statement that we are only just beginning to understand these recently discovered B10 cells.
He says these regulatory B cells are important because they “make sure an immune response doesn’t get carried away, resulting in autoimmunity or pathology”.
“This study shows for the first time that there is a highly controlled process that determines when and where these cells produce IL-10,” he adds.
What they Did
For their study, Tedder and colleagues used mice to study how B10 cells produce IL-10. For IL-10 production to start, the B10 cells have to interact with T cells, which are involved in switching on the immune system.
They found B10 cells only react to certain antigens. They found that binding to these antigens makes the B10 cells turn off some of the T cells (when they come across the same antigen). This stops the immune system from harming healthy tissue.
This was a new insight into the function of B10 cells that spurred the researchers to see if they could take this further: what if it were possible to use this cellular control mechanism to regulate immune responses, particularly in respect of autoimmunity?
Replicating Large Numbers Outside the Body
B10 cells however are not common, they are extremely rare. So Tedder and colleagues had to find a way to make a ready supply of them outside the body.
They found a way to isolate the B10 cells without damaging their ability to control the immune responses. And they found a way to replicate them in large numbers, as Tedder explains:
“Normal B cells usually die quickly when cultured, but we have learned how to expand their numbers by about 25,000-fold.”
“However, the rare B10 cells in the cultures expand their numbers by four-million-fold, which is remarkable. Now, we can take the B10 cells from one mouse and increase them in culture over nine days to where we can effectively treat 8,000 mice with autoimmune disease,” he adds.
The next stage was to try out the new B10 cells: could they influence autoimmunity sufficiently to affect disease symptoms?
They found when they introduced a small number of B10 cells into mice bred to have a disease similar to multiple sclerosis, their symptoms lessened significantly.
“B10 cells will only shut off what they are programmed to shut off,” explains Tedder.
If you have rheumatoid arthritis, you would want cells that would only go after your rheumatoid arthritis,” he adds.
He and his colleagues suggest their work shows there is potential to remove regulatory cells, replicate them in their millions, and put them back in the body of a person with an autoimmune disease and it will effectively “shut down the disease”, as Tedder describes it:
“This may also treat transplanted organ rejection,” he adds.
The researchers call for more studies to learn how to replicate human B10 cells, and find out how they behave in humans.
Autoimmune diseases are complex, so making a single therapy that targets several diseases without causing immunosuppression is not easy, Tedder explains.
“Here, we’re hoping to take what Mother Nature has already created, improve on it by expanding the cells outside of the body, and then put them back in to let Mother Nature go back to work,” he says.
Grants from the National Institutes of Health, the Lymphoma Research Foundation, and the Division of Intramural Research, National Heart, Lung, and Blood Institute, NIH, helped pay for the study.
Article from: http://www.medicalnewstoday.com/articles/251507.php
Written by Catharine Paddock PhD
Copyright: Medical News Today