Archive for the ‘Autoimmune’ Category

How important is Vitamin D for autoimmune disease?

Tuesday, March 9th, 2010

Nature Reviews RheumatologyIt’s hard to overemphasize the importance. Consider this paper published in Nature Reviews Rheumatology in which the authors assert that the…

…immunoregulatory and anti-inflammatory properties” of vitamin D can be used for the “control of autoimmune diseases.”

They note that…

“…Epidemiological evidence indicates a significant association between vitamin D deficiency and an increased incidence of several autoimmune diseases,”

Which include…

“a variety…from rheumatoid arthritis to systemic lupus erythematosus, and possibly also multiple sclerosis, type 1 diabetes, inflammatory bowel diseases, and autoimmune prostatitis.”

(Extra highlight for autoimmune prostatitis because very few are aware how common this is.) Of great practical importance is their observation that…

“The net effect of the vitamin D system on the immune response is an enhancement of innate immunity coupled with multifaceted regulation of adaptive immunity.”

PsychoneuroendocrinologyWe are awash in studies on vitamin D, here’s one more for good measure. This paper, recently published in the journal Psychoneuroendocrinology, focuses on its use in the treatment of autoimmune disease that attacks the brain and nervous system. The authors begin by noting that…

“It has been known for more than 20 years that vitamin D exerts marked effects on immune and neural cells…it has been shown that diminished levels of vitamin D…is a risk factor for various brain diseases.”

They further state that…

“…vitamin D has been found to be a strong candidate risk-modifying factor for Multiple Sclerosis (MS)…”

And proceed to..

“…assess how vitamin D imbalance may lay the foundation for a range of adult disorders, including brain pathologies (Parkinson’s disease, epilepsy, depression) and immune-mediated disorders (rheumatoid arthritis, type I diabetes mellitus, systemic lupus erythematosus or inflammatory bowel diseases).”

These are some of the reasons why I always screen for vitamin D sufficiency.

Gluten sensitivity and brain disease: neuronal transglutaminase

Monday, March 8th, 2010

Annals of NeurologyThe authors of this paper published in Annals of Neurology make an important statement:

“Gluten sensitivity typically presents as celiac disease, a chronic, autoimmune-mediated, small-intestinal disorder. Neurological disorders occur with a frequency of up to 10% in these patients. However, neurological dysfunction can also be the sole presenting feature of gluten sensitivity.”

Antibodies directed toward transglutaminase in the gut are a well-known diagnostic feature of celiac disease. These investigators have identified another member of the transglutaminase family:

“…a novel neuronal transglutaminase isozyme and investigated whether this enzyme is the target of the immune response in patients with neurological dysfunction.” They found that “Whereas the development of anti-transglutaminase 2 IgA is linked with gastrointestinal disease, an anti-transglutaminase 6 IgG and IgA response is prevalent in gluten ataxia, independent of intestinal involvement.”

(Ataxia is loss of the ability to coordinate muscle movement, especially as it appears with difficulty walking.) Their conclusion:

“Antibodies against transglutaminase 6 can serve as a marker…to identify a subgroup of patients with gluten sensitivity who may be at risk for development of neurological disease.

If you are gluten sensitive, you can have neurological disease without celiac involvement.

RDW is an inexpensive but powerful indicator often overlooked on your routine blood test

Sunday, March 7th, 2010

Archives of Internal Medicine 0210RDW stands for Red (Blood Cell) Distribution Width, an index for the degree of variability in the size and shape of your red blood cells. Recent studies are showing it to be a powerful indicator of overall health and the risk of death from multiple causes. RDW is always included in the standard Complete Blood Count (CBC), one of the most routine lab tests in modern medicine, but there’s evidence that the usual lab reference range is too broad and it’s value is not widely appreciated. It has been established for some time that RDW predicts mortality form cardiovascular disease, but this study recently published in the Archives of Internal Medicine is particularly interesting because it shows that RDW predicts mortality in the general population independent of cardiovascular disease. The authors state:

“Higher RDW values were strongly associated with an increased risk of death…Even when analyses were restricted to nonanemic participants or to those in the reference range of RDW (11%-15%) without iron, folate, or vitamin B12 deficiency, RDW remained strongly associated with mortality. The prognostic effect of RDW was observed in both middle-aged and older adults for multiple causes of death.”

Two weeks later the another paper was published in the same journal on the same topic that begins with this observation:

“Red blood cell distribution width (RDW), an automated measure of red blood cell size heterogeneity (eg, anisocytosis) that is largely overlooked, is a newly recognized risk marker in patients with established cardiovascular disease (CVD).”

They set out to investigate

“the association of RDW with all-cause mortality and with CVD, cancer, and chronic lower respiratory tract disease mortality in 15,852 adult participants.”

Their conclusion:

“Higher RDW is associated with increased mortality risk in this large, community-based sample, an association not specific to CVD.”

Journals of GerontologyAnother paper just published in The Journals of Gerontology confirms these findings with an analysis of seven community-based studies of older adults. Their conclusion:

“RDW is a routinely reported test that is a powerful predictor of mortality in community-dwelling older adults with and without age-associated diseases.”

Diabetes Care 0210.2This paper just published in the journal Diabetes Care reports on the link between RDW, metabolic syndrome and cardiovascular disease: “A possible explanation for the observed association between RDW and MetS is that high RDW reflects an underlying inflammatory state that leads to impaired erythrocyte (red blood cell) maturation and anisocytosis (size variation), as suggested previously (1–3). In fact, MetS exacerbates oxidative and inflammatory stress in obese adults, which is a potential mechanism for the increased cardiovascular risk in this condition.”

European Journal of Heart FailureAnd as you would expect, the European Journal of Heart Failure recently published a study on heart failure that compares RDW with N-terminal brain natriuretic peptide (NT-proBNP) in which the authors conclude:

“Red cell distribution width is a readily available test in the HF-population with similar independent prognostic power to NT-proBNP across the first to third quartiles. Prognostic models in HF (heart failure) should include RDW.”

Digestive Diseases and SciencesAnd the ‘plot thickens’. In this paper published in the journal Digestive Diseases and Sciences the investigators observe:

“Impaired iron absorption or increased loss of iron was found to correlate with disease activity and markers of inflammation in inflammatory bowel disease (IBD). Red cell distribution width (RDW) could be a reliable index of anisocytosis with the highest sensitivity to iron deficiency.”

Their compelling conclusion:

“Among the laboratory tests investigated, including fibrinogen, CRP, ESR, and platelet counts…analysis indicated RDW to be the most significant indicator of active UC [ulcerative colitis]. For CD [Crohn's disease], CRP was an important marker of active disease.”

Archives of Pathology & Laboratory MedicineLastly, you’ll appreciate the broadest statement yet about the value of this inexpensive and readily available marker. In a recent paper published in the Archives of Pathology & Laboratory Medicine. The authors begin by chiming in with the neighborhood chorus:

“A strong independent association has been recently observed between elevated red blood cell distribution width (RDW) and increased incidence of cardiovascular events;”

but they aim to

“assess whether RDW is associated with plasma markers of inflammation.”

Their conclusion:

“To our knowledge, our study demonstrates for the first time a strong, graded association of RDW with hsCRP and ESR independent of numerous confounding factors.”

In other words, RDW is inexpensive, easily obtained, and a powerful marker for inflammation in general, the common denominator of most chronic disease.

Here’s the ‘take home’ message (if you’ve gotten this far): If you have almost any blood work done at all it’s likely to include RDW automatically. Make good use of it, keeping in mind that laboratory reference ranges do not reflect the latest research and your doctor may not be aware of this. Functional medicine doctors want RDW to be no more than 13%.

A possible explanation for the observed association between RDW and MetS is that high RDW reflects an underlying inflammatory state that leads to impaired erythrocyte maturation and anisocytosis, as suggested previously (13). In fact, MetS exacerbates oxidative and inflammatory stress in obese adults, which is a potential mechanism for the increased cardiovascular risk in this condition

Resveratrol relieves inflammation in the colon

Wednesday, March 3rd, 2010

Current Drug MetabolismWe need evidence-based medicines for chronic inflammation that are free of side-effects and wholesome for the body. Numerous studies have reported on the diverse therapeutic and anti-inflammatory properties of resveratrol. Inflammation in the digestive tract is a ubiquitous component of many chronic disorders; it’s reassuring to see these studies that confirm its biological activity against inflammation in the intestines.

European Journal of PharmacologyHere we have a study just published in the European Journal of Pharmacology showing the effect of resveratrol in a model of ulcerative colitis, “a nonspecific inflammatory disorder characterized by oxidative and nitrosative stress, leucocyte infiltration and upregulation of inflammatory mediators.” The authors note that “Resveratrol is a polyphenolic compound found in grapes and wine, with multiple pharmacological actions, mainly anti-inflammatory, antioxidant, antitumour and immunomodulatory activities.” They documented the positive effect of resveratrol on a number inflammatory signalling pathways, and observed that the “resveratrol group significantly attenuated the clinical signs such as loss of body weight, diarrhea and rectal bleeding improving results from disease activity index and inflammatory score.” Their conclusion: The “resveratrol diet represents a novel approach to the treatment of chronic intestinal inflammation.”

Journal of Agriculture and Food ChemistryHere is a paper published in the Journal of Agriculture and Food Chemistry that describes a beneficial effect not only on inflammation and tissue damage with colitis but also on the gut flora from even very small doses of resveratrol. In addition to that, they observed “Resveratrol significantly protected the colonic mucosa architecture, reduced body weight loss, diminished the induced anemia and reduced systemic inflammation markers, colonic mucosa prostaglandin E2, cycloxygenase-2, prostaglandin E synthase and nitric oxide levels.” Their conclusion: “These results reinforce the concept of resveratrol as a dietary beneficial compound in intestinal inflammation at doses possibly attainable with resveratrol-enriched nutraceuticals.”

Journal of Investigative SurgeryOne more paper, published in the Journal of Investigative Surgery, documents the beneficial effect of resveratrol on healing after colon surgery. The authors defined their task: “Since anastomotic [connecting two severed tubular parts] healing possesses paramount importance to prevent complications in colorectal surgery, the present study is aimed to evaluate the effect of RSV on the healing of experimental left colonic anastomoses.” Their findings and disclosure: “Histopathological analysis revealed that RSV (resveratrol) administration leads to a better anastomotic healing…Although the precise cellular mechanisms by which RSV enhances anastomotic wound healing is not clear, stimulation of neovascularization (new blood vessels), generation of collagen synthesis, inhibition of overinflammation, and restriction of oxidative injury seems to be of paramount importance.”

How well can you smell: autoimmunity & neuropsychiatric disorders

Sunday, February 28th, 2010

Clinical ImmunologyThere is a connection between how well you can smell, brain damage from autoimmune inflammation, and psychiatric disease. Consider this fascinating paper published in the journal Clinical Immunology in which the authors discuss the inter-relationship between olfactory impairment, autoimmunity and neurological/psychiatric symptoms in several diseases affecting the central nervous system (CNS) such as Parkinson, Alzheimer’s disease, autism, schizophrenia, multiple sclerosis and neuropsychiatric lupus erythematosus. We suggest that common manifestations are not mere coincidences. Current data from animal models show that neuropsychiatric manifestations are intimately associated with smell impairment, and autoimmune dysregulation, via autoantibodies…”

Autoimmunity ReviewsIn another paper published in the journal Autoimmunity Reviews the authors note that “Research in the field of immunology as well as in various brain illnesses is beginning to indicate the increasing relevance of smell in pathophysiology.” They further state “…evidence exists that there may be something unique about the olfactory system that is inextricably related to immunological function. In addition, accumulating evidence confirms the existence of olfactory dysfunction in brain disease, much of which appears at early stages including multiple sclerosis, Alzheimer’s Disease, Parkinson’s Disease, schizophrenia and depression…under certain circumstances, olfactory abnormalities may be associated with autoimmune conditions. Since the organization of the olfactory system is so sensitive, impairment may be noted at an early stage. This may become important in the prediction of certain brain illnesses.”

International Journal of NeuroscienceThis paper recently published in the International Journal of Neuroscience focuses specifically on the link between olfaction, autoimmunity and Parkinson’s Disease. They first describe “the immune alterations observed in PD patients…the increase in the innate immune components including complement and cytokines within their substantia nigra and cerebrospinal fluid (CSF). These alterations extended to the adaptive immune response with the elevation of T cells and autoantibodies…in the peripheral blood and CSF of PD patients.” (Just the kinds of things we test for in the functional medicine approach.) They then describe the link between PD, autoimmunity and olfaction: Smell deficit is one of the earliest signs of PD and a unique observation suggesting olfactory declines to be a consequence of autoimmune mechanisms.”

AutoimmunityAnd the authors of this study published recently in the journal Autoimmunity observe that Psychiatric diseases are often associated with mild alterations in immune functions (e.g., schizophrenia) as well as autoimmune features. Recent evidence suggests that autoimmune diseases (AD) demonstrate a higher prevalence of psychiatric disorders, such as depression and psychosis, than in the normal population. Patients with AD often have an olfactory impairment as well, based on smell studies… ” They report that olfactory gene receptors have brain functions in addition to smell, and go on to describe the genetic polymorphisms (variations) that link autoimmunity, psychiatric disorders and smell impairment.

Israel Medical Association JournalThe paper that concludes this post is tantalizingly entitled Olfaction—A Window to the Mind. Published not long ago in The Israel Medical Association Journal, it is available here in its entirety. The authors comment that “The sense of smell can provide a natural window to the brain. This window provides an opportunity to examine neural mechanisms and brain function in a non-invasive way.” They then undertake a fascinating review of the field of olfactory studies encompassing aspects ranging from autoimmunity and neuropsychiatric disease to sexual function, addiction, social behavior and the discrimination of self from non-self. Their conclusion is worth bearing in mind: “…assessment of the sense of smell and olfactory impairments is usually overlooked by patients and their clinicians. Given the clinical data reviewed here, clinicians should be encouraged to screen for olfactory impairments, which can help in the early diagnosis of CNS diseases such as Parkinson, dementia and schizophrenia, as well as CNS-autoimmune diseases such as neuropsychiatric lupus.”

Autoimmune diseases of the brain and nervous system have a common basis

Friday, February 26th, 2010

Der NervenarztWhile the manifestations of autoimmune disease vary according to the tissues attacked and whether cell-mediated or antibody excess dominates (and the particular signalling molecules activated), as immunologists know they are all ‘variations on a theme’. This interesting paper published in the German journal Der Nervenarzt (The Neurologist) details how difficult it is to discriminate “systemic diseases such as lupus erythematosus, sarcoidosis, Behçet’s disease, and Sjögren’s syndrome that involve the nervous system. “Neither clinical signs nor additional analyses such as serological findings or cerebrospinal fluid analysis are able to differentiate between the diseases with certainty.” That’s how similar they are. However, it can be done and, most importantly, the functional medicine approach using the latest lab investigations can profile the underlying factors that are specific to each person. This is how we get science-based treatment of the causes rather than suppression with steroids.

Gluten can cause brain lesions like ALS

Saturday, February 13th, 2010

American Journal of NeuroradiologyHere is another alarming paper published in the American Journal of Neuroradiology reporting a case of apparent Amyotrophic Lateral Sclerosis (ALS, also known as Lou-Gehrig’s Disease) that was caused by a reaction to gluten. ALS is a particularly vicious autoimmune disease that attacks the central nervous system, typically following a terminal course. The authors note regarding celiac disease that “Initial symptom presentation is variable and can include neurologic manifestations that may comprise ataxia, neuropathy, dizziness, epilepsy, and cortical calcifications rather than gastrointestinal-hindering diagnosis and management.” I’m sure they were relieved to find that “MR imaging findings suggestive of ALS improved after gluten-free diet institution.” (MR = magnetic resonance)

The importance of testing cytokines: rheumatoid arthritis

Friday, February 5th, 2010

It has come to my attention that many doctors remain unfamiliar with the clinical value and importance of testing (blood) cytokines. Cytokines are ‘messenger molecules’ of the immune system involved in the regulation of inflammation. Knowledge of their levels helps not just with early diagnosis and prognosis, but can profile immune system imbalance allowing functional treatment to be precisely targeted and bad reactions avoided (even Echinacea can push some people’s immune system in the wrong direction). There are thousands of studies on clinical conditions for which this is important. Here ’s one for rheumatoid arthritis:

Arthritis & RheumatismUp-regulation of cytokines and chemokines predates the onset of rheumatoid arthritis

This study recently published in the journal Arthritis & Rheumatism (the journal of the American College of Rheumatology) set out to “identify whether cytokines, cytokine-related factors, and chemokines are up-regulated prior to the development of rheumatoid arthritis (RA).” Their conclusion was in line with findings of other investigators: “Individuals in whom RA later developed had significantly increased levels of several cytokines, cytokine-related factors, and chemokines representing the adaptive immune system (Th1, Th2, and Treg cell-related factors.”

Aging and disease—lifestyle choices drive changes in your genes

Friday, January 22nd, 2010

Allergy & ImmunologyThis paper published in the journal Allergy & Immunology discusses the molecular basis of a factor that is crucial for the decisions we make in daily life. This is because our choices and environment change our gene expression as we age, which plays a key role in how we become more prone to autoimmune, inflammatory and malignant disorders as the years go by. In the background there develops a persistent chronic low-grade inflammation. The authors state, “The decline in immunocompetence with age is accompanied by the increase in the incidence of autoimmune diseases. Aging of the immune system… is characterized by…the presence of low-grade chronic inflammation. There is growing evidence that epigenetics, the study of inherited changes in gene expression that are not encoded by the DNA sequence itself, changes with aging. Interestingly, emerging evidence suggests a key role for epigenetics in human pathologies, including inflammatory and neoplastic disorders.” [neoplastic = abnormal growths] They continue to describe the role of key molecular processes such as DNA methylation that we evaluate and treat in our functional medicine approach to chronic disease and aging.

Most doctors are not comfortable diagnosing food allergies

Tuesday, January 19th, 2010

PediatricsFood allergy and food sensitivity are common aggravating factors for chronic inflammation of many kinds. If you think food allergy or sensitivity may be contributing to your problems, be sure to find a doctor who has the right knowledge and experience. This paper just published in the journal Pediatrics examined 407 primary care physicians for their knowledge and confidence about food allergy. The authors report that “…only 24% knew that oral food challenges may be used in the diagnosis of food allergy, 12% correctly rejected that chronic nasal problems are not symptom of food allergy, and 23% recognized that yogurts/cheeses from milk are unsafe for children with immunoglobulin E–mediated milk allergies.” Their polite conclusion: “Knowledge of food allergy among primary care physicians was fair. Opportunities for improvement exist, as acknowledged by participants’ own perceptions of their clinical abilities in the management of food allergy.”