PREDICTIVE AUTOANTIBODIES—YOU MAY HAVE AN AUTOIMMUNE DISEASE AND NOT KNOW IT!

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Any disease condition is a continuum. This means that you do not move from being well to having a disease overnight. Just as in Type 2 Diabetes, where you may have dysregulated blood sugar levels (Dysglycemia) many years before you develop the disease, so it is with many autoimmune conditions. You may have autoantibodies in your blood many years before developing the disease. Despite recent advances in treatment, there is a large percentage of people in whom long-term remission of the autoimmune disease cannot be achieved. This leads to poor quality of life and sometimes an early death. As this oft-quoted Benjamin Franklin axiom says “an ounce of prevention is worth a pound of cure”. Several scientific studies in the last few years have shown that you may have tell-tale evidence in your body 5-14 years before developing an autoimmune disease. An autoimmune condition develops when there is an interaction between your genes, an environmental trigger, your immune system and intestinal permeability. Your genes are present from birth but you do not develop an autoimmune disease until later. So what happens? In any autoimmune disease like it is in any other disease, it is an interaction between your genes and the environment that decides your health. As Dr. Eric Topol, a world-renowned cardiologist, geneticist, digital health pioneer, and medical innovator, says,“healthy aging is 100 percent due to genetics and 100 percent due to your environment”.

Autoimmune conditions develop when your immune system makes antibodies against your own tissue ( Autoimmunity).  This can lead to your healthy tissue losing their ability to function normally. For example, in Type 1 Diabetes, your own body makes antibodies against your own pancreatic cells which produce insulin. Insulin is the hormone that keeps your blood sugar in balance. The other, commoner diabetes is Type 2 Diabetes, in which antibodies to pancreatic tissue is not usually present. (Incidentally, these autoantibodies to pancreatic tissue have been found in about 5% of people otherwise diagnosed as Type 2 Diabetes.Watch for post on LADA , Latent Autoimmune Diabetes of the Adult).

In fact, a new staging approach is being used in Type 1 Diabetes taking into consideration the number of autoantibodies present. The staging starts well before the disease develops. This approach is used to prevent or delay the onset of the disease. Perhaps you can start prevention in your child when you are pregnant! Studies have shown the connection between vitamin D deficiency in mothers and autoimmunity in children.

Rheumatoid Arthritis (RA): RA is an autoimmune disease affecting joints, which is characterized by chronic inflammation, causing pain and stiffness in the joints and a poor quality of life. Half of the patients with RA already have X-ray evidence of joint damage at the time of diagnosis. Like most diseases, RA can be treated better if diagnosed early. Therefore, the ability to predict the disease before joint damage occurs will contribute to a better quality of life.

WHO SHOULD BE TESTED FOR AUTOANTIBODIES?

  • Anyone who has a diagnosed autoimmune condition. Studies have shown that if you have one autoimmune disease, the chances of your developing another one are much higher than in the general population.
  • To test for disease progression in people with autoimmune diseases.
  • Anyone with hypothyroidism who has never been tested for thyroid antibodies.
  • First degree relatives (a person’s parent, sibling or child) of people with an autoimmune condition.
  • Patients with painful and stiff joints who haven’t received a definitive diagnosis of RA yet.
  • Anyone interested in better health.

WHAT TESTS SHOULD YOU DO?

A complete workup is very important. However, the following must be included.

  • C-Reactive Protein: This is a marker of inflammation.
  • Vitamin D3 levels: Vitamin D has a major role in your immune system. Low levels of this vitamin have been associated with increased risk of autoimmune diseases. (Vitamin D)
  • Antibodies: This list increases by the day. There are some specialized tests available in some countries which I have not listed here. (For those of you interested in the detailed medical information, please read the article in Autoimmunity reviews6 (2015) Damoiseaux, Jan, et al.).

This table has a short list:

                      ANTIBODY              AUTOIMMUNE CONDITION
ANA Lupus, Scleroderma, Autoimmune Hepatitis, Sjogren’s Disease, Polymyositis, Dermatomyositis, Mixed Connective Tissue Disease, Juvenile Arthritis, Drug-induced Lupus.
Anti-Cyclic Citrullinated Peptide (Anti CCP) Rheumatoid Arthritis
Anti TPO & Anti Thyroglobulin Hashimoto’s Thyroiditis
Anti TSH Receptor Graves’ Disease
Anti-tissue transglutaminase (tTG) antibodies

Endomysial antibodies (EMA)

Deamidated gliadin peptide (DGP) antibodies

(IgA & IgG tests)

Celiac Disease

 

 

Islet Cell Cytoplasmic Autoantibodies (ICA) & Glutamic Acid Decarboxylase Autoantibodies (GADA) Type 1 Diabetes, Late Autoimmune Diabetes of the Adult(LADA).

WHAT IS THE DIFFERENT ABOUT THE FUNCTIONAL AND METABOLIC MEDICINE APPROACH?

Fig 1: Functional & Metabolic Medicine approach versus Conventional Approach:Fork in the road.

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Fig 1

WHAT SHOULD YOU DO?

  • Meet a practitioner who understands the Functional & Metabolic Medicine approach to autoimmunity. There are no pharmaceutical drugs that can be used to prevent autoimmune diseases before they develop.
  • Stop smoking (Easier said than done!). Exposure to cigarette smoke has been associated with higher risk of Rheumatoid Arthritis in those susceptible to it.
  • Reduce toxic exposure.
  • Reduce inflammation.
  • Manage stress.
  • Maintain adequate Vitamin D3 levels (Vitamin D)

REFERENCES

  • Avouac, Jérôme, Laure Gossec, and Maxime Dougados. “Diagnostic and predictive value of anti-cyclic citrullinated protein antibodies in rheumatoid arthritis: a systematic literature review.” Annals of the rheumatic diseases7 (2006): 845-851.
  • Catrina, Anca I., et al. “Lungs, joints and immunity against citrullinated proteins in rheumatoid arthritis.” Nature Reviews Rheumatology 11 (2014): 645-653.
  • Damoiseaux, Jan, et al. “Autoantibodies 2015: From diagnostic biomarkers toward prediction, prognosis and prevention.” Autoimmunity reviews6 (2015): 555-563.
  • Nielen, Markus MJ, et al. “Increased levels of C‐reactive protein in serum from blood donors before the onset of rheumatoid arthritis.” Arthritis & Rheumatism 8 (2004): 2423-2427.
  • Notkins, Abner Louis. “New predictors of disease.” Scientific American3 (2007): 72-79.

VITAMIN D AND AUTOIMMUNITY

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In recent years vitamin D deficiency has become like an epidemic all over the world. Besides autoimmunity, low vitamin D is associated with many diseases like heart disease, diabetes, cancer, hypothyroidism and many more. In fact, almost every cell in your body has vitamin D receptors.

There are 2 forms of vitamin D3 that you need to keep in mind. The one that is usually tested by most practitioners is Vitamin D3. Your body has to convert Vitamin D3 to the active form 1,25 Dihydroxyvitamin D3[1,25(OH)2 D3]. Most of you are familiar with the action of vitamin D in protecting your bones and maintaining blood calcium levels—the “classical” actions of vitamin However, scientific studies in the last several years have shown that vitamin D has several other actions as well—the “non-classical” actions. These are the actions of vitamin D on bone marrow, immune system, breasts, prostate, heart, muscles and intestine. With respect to autoimmune disease, the immunomodulatory (affecting your immune system) actions of Vitamin D are very important.

Vitamin D has the effect of increasing the activity of the innate immune system while restraining the activity of the adaptive immune system. (Chapter 9). This is the reason why adequate vitamin D3 levels are important for treating and perhaps preventing autoimmune diseases. A substantial number of studies have shown an association between low vitamin D and increased incidence of autoimmune diseases like Rheumatoid Arthritis(RA), Multiple Sclerosis(MS), Psoriasis, Inflammatory Bowel Disease (IBD), Type 1 Diabetes, Sjogrens, Lupus and many more. One example that is often cited is the increasing incidence of MS as one moves away from the equator. This is thought to be related to lesser sun exposure at higher latitudes than at the equator.

1,25 DIHYDROXYVITAMIN D3.

In autoimmune conditions sometimes measuring only vitamin D3 levels may not be enough. A few scientific studies have shown that some people with autoimmune disease have high levels of 1,25 Dihydroxyvitamin D3. This is why sometimes we need to measure both the forms of vitamin D. I remember quite a few occasions when my patients (In India) have called me to say that the lab technician has informed them that “no doctor advises this (1,25 OH)2 D) test” so it is unnecessary!

WHY DO PEOPLE BECOME VITAMIN D DEFICIENT?

Humans obtain vitamin D from either food (fortified), supplements or sunlight exposure. Your blood vitamin D levels depend on several factors.

Air quality: Excessive carbon particles in air from burning of fossil fuels may reduce the amount of vitamin D producing UVB rays from reaching your exposed skin.

Skin color: People with dark skin require about 10 fold more exposure to sunlight to produce the same amount of vitamin D as people with lighter skin color.

How much of your skin is exposed? The more bare skin the bigger the surface area of absorption of sunlight.

Use of sunscreens: Though theoretically use of sun screens can block the UVB rays, rarely do people use adequate quantities of sunscreen to bar all UVB from reaching their skin.

Gut Health: If you have unhealthy gut or you have inflammatory bowel disease (IBD), your absorption of vitamin D from supplements is poor.

Liver and Kidney Health: Some types of liver disease may affect bile production. This can affect vitamin D function. In chronic kidney disease (CKD) the vital step of conversion of vitamin D to its active form is affected and this can lead to severe vitamin D deficiency. This is why patients with CKD have their 1,25 Dihydroxyvitamin D3 measured regularly.

Vitamin D receptor (VDR): If you have a genetic variation in VDR you may need a higher dose of vitamin D supplementation.

How much vitamin D3 you take will decide your blood levels of the vitamin. Very low or very high doses, may both be detrimental unless you monitor regularly.

HOW MUCH VITAMIN D SHOULD YOU TAKE AS A SUPPLEMENT?

How much supplementation of vitamin D you need depends on what your blood reports show. It may not be the same dose for everyone because of individual variations. However, it is a much better idea to take a smaller dose (4000-5000 IU) every day rather than a very high dose once a week or once a month. Sometimes a larger dose may be necessary for a short period of time until your blood levels are in the optimal range.

Ideally you should get your vitamin D from sensible sun exposure AND supplementation.

 WHAT IS MOST IMPORTANT ABOUT VITAMIN D AND AUTOIMMUNE CONDITIONS?

Low vitamin D levels have been associated with many autoimmune conditions like

Rheumatoid Arthritis (RA), Multiple Sclerosis(MS), Psoriasis, Inflammatory Bowel Disease (IBD), Type 1 Diabetes, Sjogrens, Lupus and many more. This is because vitamin D affects your immune system function.

Maintaining adequate vitamin D levels may be a major way to prevent developing autoimmune disease. In fact, studies have shown that maintaining adequate vitamin D levels during childhood can prevent the development of Type 1 Diabetes by 29%! This is true for several other autoimmune conditions as well.

If you already have an autoimmune condition maintaining adequate vitamin D levels will make a major difference to how you heal the disease.

Some of you  may need to measure both vitamin D3 and 1,25 Dihydroxyvitamin D3.