Management Autoimmune Health Extravaganza Reactivity...

Case Management of Autoimmune Reactivity

Health Extravaganza2013

Aristo Vojdani, PhD 1

Aristo Vojdani, PhD

Health Extravaganza 2013

Anaheim, CA

• Develop dietary protocols that promote healthy gut microbiota.

• Assess intestinal permeability to large molecules that activate immune responses.

• Use testing methods for predictive antibodies to identify target tissues of autoimmune reactivity.

• Implement strategies to manage/prevent autoimmune reactivity.

Patient with Multiple Sclerosis, Gluten Ataxia, Gut and Blood‐Brain

Barrier Permeability

Patient with Multiple Sclerosis, Gluten Ataxia, Gut and Blood‐Brain

Barrier Permeability

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A 42 year‐old man5’8” in height weighing 182 lbs. following

a 3‐week history of progressive neck,

back and muscle pain with weakness of

the limbs was referred to a neurologist.

On the day prior to referral, he

developed difficulty in passing urine with

tingling and sensory disturbance in his

trunk and legs to a degree where he was

unable to climb stairs.

A series of immunological profilesand neurological examinations wasinitiated.

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TESTS RESULTS TESTS RESULTS

Chemistry Normal Mycobacteria Negative

Hemoglobin 10.8 g/dl Borrelia Negative

ANA Normal CMV Negative

Rheumatoid factor Normal EBV Negative

Immune complexes Normal Herpes Type 6

Negative

Total Ig Normal HTLV‐1 and ‐2 Negative

Cardiolipidantibodies

Normal Syphilis Negative

Thyroid function Normal CSF protein 0.7 g/L

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Neurological examination revealed reduced

corrected visual acuity of 6/48 in the right eye and

6/36 in the left eye with normal eye movements.

The patient had pyramidal weakness in both legs

with mildly‐based gait. Pinprick examination

demonstrated hemisensory level below D10 on both

sides. An MRI scan of the brain showed mild white

matter abnormalities with mild generalized atrophy,

which has been observed in patients with MS.

However, to exclude the possibility of gluten

sensitivity, anti‐gliadin, transglutaminase, and GAD‐

65 antibody tests were performed.




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2

3

4

5

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Gliadin tTg‐2 tTg‐6 GAD‐65

IgG, IgM and IgA antibody levels tested against different antigens in patients with multiple sclerosis (MS) expressed as index.

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Additionally, the following tests were also

performed: IgG, IgM and IgA antibody against LPS,

zonulin/occludin, intestinal ZOT receptor, cell junction

protein, MMP‐3, brain ZOT binding protein, brain ZOT

receptor, calprotectin, GFAP, α‐B crystallin, BBB protein,

and MBP. Results are summarized in the following figure.

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IgG, IgM and IgA antibody levels tested against different antigens in patients with multiple sclerosis (MS) expressed as index. They show a significant elevation in antibody levels against MBP and GFAP, confirming the abnormal MRI findings and a diagnosis of MS. Furthermore, a significant elevation of antibodies against zonulin/occludin, calprotectin and BBB protein indicated involvement of the GI tract with enhanced gut and BBB permeability in this patient.

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Taken all together, the results of the neurological examination, highly abnormal zonulin/occludin and calprotectin results, the significant elevations in antibody levels against gliadin, tTg‐6, GAD‐65, MBP, GFAP, and BBB protein support the diagnosis of gluten ataxia.

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Based on these test results, the

patient was put on a gluten‐free diet and

given 1 g intravenous methylprednisolone

for five days with some resultant clinical

improvement. At this point the patient

was put on β‐seron, showing significant

improvement fifteen days later.

Furthermore, 200 mg of minocycline

IV glutathione, plus probiotics glutamine,

N‐acetylcysteine, EPA/DHA, vitamin D,

lactoferrin, xylitol, and boswellic acid

were given for repairing the damaged

BBB and gut barriers. Three months after

this regimen the patient’s overall health

had improved significantly.

Gut Inflammatory Diseases

Food Allergies, Celiac Diseaseand Autoimmunities

Enhanced Gut Permeability

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THE ROOT CAUSE OF AUTOIMMUNITYTHE ROOT CAUSE OF AUTOIMMUNITY




MUCOSAL IMMUNE ABNORMALITIES

IMBALANCED GUT FLORA

INTESTINAL BARRIER DYSFUNCTION

SYSTEMIC INFLAMMATION

NEUROINFLAMMATION

NEUROINVASION

NEURODEGENERATION

From mucosal immune abnormalities to neuroinflammation and neurodegeneration.13

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THE PROPER ENVIRONMENT FOR PROPER GROWTH

Like all living things, bacteria need the appropriate nurturing environment in order to achieve maximum growth potential. Different kinds of bacteria thrive or fail according to the kinds of nutrients in the media that constitute their environment. 16

A culture medium is a special medium used in microbiological laboratories to grow different kinds of microorganisms. A growth or a culture medium is composed of agar plus different nutrients, such as blood, heart, brain, chocolate, soy, egg, rice, sugar, salt, yeast, etc. that are essential for a microbial growth.

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Examples of differential media

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S. aureus onTryptic Soy Agar

C. albicans onRice Agar

S. enteritidis onMacConkey Agar

K. pneumoniae onEosin‐methylene Blue Agar

Legionella onBuffered Charcoal Yeast Extract Agar

Salmonella onTriple Sugar Iron Agar

Xanthomonas onAcidified Potato Dextrose Agar

Examples of culture media

S. typhimurium onHektoen Enteric Agar

Gamma Hemolysis onBlood Agar

H. influenzae onChocolate Agar

S. epidermis onMannitol Salt Agar

Chaetomium onCorn Meal Agar

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• Tight Junction Proteins

• Actomyosin Network

• Gut Bacteria

• Large Molecules

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ALTERNATIVE THERAPIES, 2013, 19(1):12-24)

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The permeability of the epithelium to very small sugar molecules such as lactulose/mannitol—used for the past 50 years to gauge intestinal permeability—does not necessarily correlate with epithelial permeability to macromolecules…the article presents evidence indicating that increased intestinal, antigenic permeability plays a key role in the development of various inflammatory and autoimmune disorders.

The permeability of the epithelium to very small sugar molecules such as lactulose/mannitol—used for the past 50 years to gauge intestinal permeability—does not necessarily correlate with epithelial permeability to macromolecules…the article presents evidence indicating that increased intestinal, antigenic permeability plays a key role in the development of various inflammatory and autoimmune disorders.

Bacterial Endotoxin(LPS)

IgG, IgM, IgA

ActomyosinNetwork

IgA

Occludin / ZonulinIgG, IgM, IgA

The triggers and mechanisms involved in enhanced (exacerbated) intestinal permeability and how to use the next generation of testing for Intestinal Permeability Identification (IPI).

Permeability/Dysbiosis Epithelial Cell Damage Tight Junction Damage

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LPS

Occludin/

Zonulin

Acto‐

myosin

Clinical Indication Clinical Approach

+ ‐ ‐ Gut flora dysbiosis; low‐grade inflammation; metabolic

disorder

Pre‐ and probiotics

+ + ‐Breakdown in intestinal barrier integrity by bacterial

antigens through paracellular pathway; low‐grade

inflammation; metabolic disorder


Heal the gut

‐ + ‐Breakdown in intestinal barrier integrity by factors other

than bacterial antigens, through paracellular pathway

Reduce stress

Heal the gut

+ ‐ +Breakdown in intestinal barrier integrity by bacterial

antigens through transcellular pathway; low‐grade

inflammation; metabolic disorder


Heal the gut

‐ ‐ +Autoimmunity (such as Celiac Disease) against mucosal

epithelium and other tissue cell cytoskeleton

Anti‐inflammatories.

‐ + +

Breakdown in tight junction integrity by factors other

than bacterial antigens and autoimmunity against

mucosal epithelium.

Reduce stress

Anti‐inflammatories

Heal the gut

+ + +

Breakdown of intestinal barrier integrity through

transcellular and paracellular pathways and gut flora

dysbiosis; low‐grade inflammation; metabolic disorder


Anti‐inflammatories

Heal the gut




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CASE REPORTS

• 60 y.o. Male• problems with stiffness started in the neck 15 years ago and gradually progressed to the whole body. Accompanied by muscle weakness. Stiff‐person syndrome.

• Severe swelling of hands and knees. Knee swelling is so bad he is unable to exercise. Was an gymnast and active most of his life and this bothers him. Drinking Coors Light causes a rhinorrhea (nasal discharge and congestion).

• X Rays reveal no radiological evidence of arthritis. ESR mildly elevated at 27.

• Current Medical History: Psoriasis (7‐8 Years), Sleep Apnea (using CPAP of 7)

• Environmental History: Used a product called ‘Roundup’ about 15 years ago

• Been evaluated by numerous physicians. Also has had numerous cleanses through the years

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

Wheat IgG

Wheat IgA

WGA IgG

WGA IgA

Gli‐33 IgG

Gli‐33 IgA

Gli‐17 IgG

Gli‐17 IgA

Gli‐15 IgG

Gli‐15 IgA

Gli‐17 IgG

Gli‐17 IgA

Glutenin‐21 IgG

Glutenin‐21 IgA

Glute+P

ro IgG

Glute+P

ro IgA

Gliadin‐tTG

IgG

Gliadin‐tTG

IgA

tTG‐2 IgG

tTG‐2 IgA

tTG‐3 IgG

tTG‐3 IgA

tTG 6 IgG

tTG‐6 IgA




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0.5

1

1.5

2

2.5

Gluten Grains

Cow's M

ilk

Casein

Casomorphin

Milk Butyrophilin

Whey Protein

Chocolate (milk)

Oats

Yeast

Coffee

Sesame

Buckwheat

Sorghum

Millet

Hemp

Amaranth

Quinoa

Tapioca

Teff

Soy

Egg

Corn

Rice

Potato

• Lab Tests:

– IgG antibodies to gluten, gliadin strongly positive

– Also positive for IgG, IgA to dairy

– Initiated GFD and abstinence from all other food sensitivities including dairy

– Also ordered testing for heavy metal toxicity

• 3 Month Follow Up:

– Joint swelling of knees and ankles completely disappeared and now is significantly more active

– Sleep Apnea significantly better because less swelling in throat

– 20% improvement in stiffness

– Minimal improvement in fatigue

• 34 y.o. male

• Clinical Complaints– Changes in health in last 2 years

– Brain fog

– Fatigue

– Daily low‐grade headaches

– Irritability

– Digestive issues

– Inconsistent and occasional bloody stools

– Acne




• Family History

– Father and Aunt with lupus

– Brother with Celiac

• Gluten‐free diet was implemented

– Symptoms continued

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2

4

6

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10

12

14

16

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ActomyosinIgA

0

0.5

1

1.5

2

2.5

Range

Result

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0.5

1

1.5

2

2.5

3

3.5

4

4.5

Wheat IgG

Wheat IgA

WGA IgG

WGA IgA

Gli‐33 IgG

Gli‐33 IgA

Gli‐17 IgG

Gli‐17 IgA

Gli‐15 IgG

Gli‐15 IgA

Gli‐17 IgG

Gli‐17 IgA

Glutenin‐21 IgG

Glutenin‐21 IgA

Gluteom+P

rodyn…

Gluteom+P

rodyn…

Gliadin‐tTG

…

Gliadin‐tTG

…

Transglutaminase…

Transglutaminase…

Transglutaminase…

Transglutaminase…

Transglutaminase…

Transglutaminase…




0

0.5

1

1.5

2

2.5

Gluten Grains

Cow's M

ilk

Casein

Casomorphin

Milk But

Whey Protein

Chocolate (milk)

Oats

Yeast

Coffee

Sesame

Buckwheat

Sorghum

Millet

Hemp

Amaranth

Quinoa

Tapioca

Teff

Soy

Egg

Corn

Rice

Potato

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1

2

3

4

5

6

Parietal + ATPase

Intrinsic Factor

ASCA+A

NCA

Tropomyosin

Thyroglobulin

TPO

21 Hydroxylase

Myocardial

Myosin ‐ a

Phospholipid

Platelet Glyco

Ovary or Testis

Fibulin

Collagen

Arthritic Peptide

Osteocyte

Cytochrome P450

Insulin+Islet Cell

GAD65

MBP

Ganglioside

Tubulin

Cereb

ellar

Synapsin

• After treatment with elimination diet and gut healing protocols

– Sleep 3 hours less per night

– Headaches are gone

– No brain fog

– No irritability

– Consistent stools

– Acne cleared




• 68 y.o. Female

• Clinical Complaints Jan 2011

– Poorly controlled, labile hypertension

– Multiple food allergies

• Medical History– Age 38 life‐‐threatening episode of Toxic Shock Syndrome Received Prolonged ABX therapy.

– Age 40 Diagnosed with Celiac Disease. Had Been following a strict GFD since. Father was also diagnosed with celiac.

– Early forties. • Exercise & allergy induced adult onset asthma• Hashimoto’s Thyroiditis. Managed with Levothyroxine 75mcg.

– Age 45 Uncomplicated Cholecystectomy.– Age 58 worsening peripheral neuropathy–affects walking.– Age 64 had A dissecting aortic rupture. Surgically repaired. Was given 3% survival chance.

• Medications:

– Carvedilol

– Levothyroxine 75mcg qd

– Acyclovir

• Supplements:

– EPA‐‐DHA, CoQ10, Magnesium, Calcium, TMG, Sylimarin, Red Rice Yeast extract, Zyflamend, B12, DHEA, Vit D3, Venaplex, Glutagenics, Probiotics, Chinese Herbal formulas

February 2011

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10

15

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ActomyosinIgA

0

1

2

3

4

5

6

7

8

9

Range

Result

February 2011 February 2011




ARRAY 2 FEB 2011

OCT 2011

AUG 2012

Actomyosin 23.52 28.56 41.36

O/Z IgG 8.3 1.64 7.2

O/Z IgA 0.96 0.99 2.18

O/Z IgM 0.85 2.33 1.57

LPS IgG 7.49 5 2.63

LPS IgA 1.42 1.77 4.48

LPS IgM 0.4 0.4 0.33

ARRAY 4 FEB 2011

OCT 2011

AUG 2012

Cow's Milk +

Casein +

Casomorphin + +

Milk Butyrophil + + +

American Chz + +

Chocolate (milk) +

Sesame + + +

Hemp + + +

Rye + +

Barley + +

Polish Wheat + +

Buckwheat + + +

ARRAY 4 FEB 2011

OCT 2011

AUG 2012

Sorghum + + +

Millet + +

Spelt +

Amaranth + +

Quinoa + + +

Yeast + +

Tapioca + + +

Oats +

Coffee + + +

Corn + + +

Rice + +

Potato + + +

August 2012 positive to: Teff, Soy, Egg

• Other Significant Lab Results (7/10/12):

– Homocysteine 30.9

– CRP 20.14

– Fibrinogen 520

– MCV 101

August 2012

• Infection exacerbated the subclinical Celiac disease resulting in full‐blown CD.

• Despite CD patient, test results show patient not following GFD.

• By August 2012, no gluten reaction detected, however, intestinal antigenic permeability persistent.

• Healing the barrier upon removal of all triggers will take more time.

• Open intestinal barriers are a contributing factor to the multiple autoimmune reactivity.

CASE STUDY

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• 39 y.o. Female

• CC: Joint Pains and Fatigue

• Symptoms started with a severe flu. She developed pain in her joints starting bilaterally in joints of the hand, wrists and knees.

• Also had significant fatigue. Worsening as the day went on.

• Three months later diagnosed with Rheumatoid Arthritis and started on Prednisone and Methotrexate.

• PMH: Pollen allergies in spring.

0

0.5

1

1.5

2

2.5

3

3.5

4

Gluten Grains

Cow's M

ilk

Casein

Casomorphin

Milk But

Whey Protein

Chocolate (milk)

Oats

Yeast

Coffee

Sesame

Buckwheat

Sorghum

Millet

Hemp

Amaranth

Quinoa

Tapioca

Teff

Soy

Egg

Corn

Rice

Potato

March 2012 March 2012

65

0

1

2

3

4

5

6

7

Parietal + ATPase

Intrinsic Factor

ASCA+A

NCA

Tropomyosin

Thyroglobulin

TPO

21 Hydroxylase

Myocardial

Myosin

Phospholipid

Platelet Glyco

Ovary/Testis

Fibulin

Collagen

Arthritic Peptide

Osteocyte

Cyto P450

Insulin+Islet Cell

GAD65

MBP

Ganglioside

Tubulin

Cereb

ellar

Synapsin

March 2012 July 2012




0

2

4

6

8

10

12

ActomyosinIgA

0

1

2

3

4

5

6Range

Result

July 2012

• Other Tests: Achlorhydria on stomach acid testing.

• Treatment Protocol: Elimination of food allergens, PABA, gut healing, omega 3 fatty acids, substitute for stomach acid.

Follow Up:

Was able to taper off prednisone within 3 months. Occasional flare ups with reintroduction of foods. Increasing omega ‐3’s help on these occasions.

Fatigue improved.

Eight years later never had recurrences, doing great, energy is good.

Catch them early.

The correlation of serum S100B, auto-antibodies and DTIchanges support a link between repeated BBBD andfuture risk for cognitive changes.

The correlation of serum S100B, auto-antibodies and DTIchanges support a link between repeated BBBD andfuture risk for cognitive changes.

71 Proposed mechanism for excitotoxicity from leaky BBB 72




• 25 y.o. Male

• Clinical Complaints

– Repeated sports injuries

– Concussion symptoms

– Balance problems

– Unable to perform in professional sports

• Passed ImPACT test, but not feeling optimal 00.20.40.60.81

1.21.4

Wheat IgG

Wheat IgA

WGA IgG

WGA IgA

Gli‐33 IgG

Gli‐33 IgA

Gli‐17 IgG

Gli‐17 IgA

Gli‐15 IgG

Gli‐15 IgA

Gli‐17 IgG

Gli‐17 IgA

Glutenin‐21…

Glutenin‐21…

Glute+P

ro…

Glute+P

ro…

Gliadin‐tTG

…

Gliadin‐tTG

…

tTG‐2 IgG

tTG‐2 IgA

tTG‐3 IgG

tTG‐3 IgA

tTG‐6 IgG

tTG‐6 IgA

0

1

2

3

4

5

6

Gluten Grains

Cow's M

ilk

Casein

Casomorphin

Milk But

Whey Protein

Chocolate (milk)

Oats

Yeast

Coffee

Sesame

Buckwheat

Sorghum

Millet

Hemp

Amaranth

Quinoa

Tapioca

Teff

Soy

Egg

Corn

Rice

Potato

Detection of LPS, occludin/zonulin, brain, and BBB protein IgG antibodies in a healthy

individual and patient with TBI .

Detection of LPS, occludin/zonulin, brain, and BBB protein IgA antibodies in a healthy


Detection of LPS, occludin/zonulin, brain, and BBB protein IgM antibodies in a healthy





• Dairy‐free diet

• RepairVite Program to heal the gut barrier

• After 3 months returned to professional sports team

TAKE HOME MESSAGE:

• When you remove the right trigger at an early stage, you can return your patients to optimal health and prevent autoimmune reactivity.

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Management Autoimmune Health Extravaganza Reactivity...

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