VIRAL ETIOLOGY AND An Exploration into HerpesAUTOIMMUNITY Virus Association with

Christopher Bump DC MS IFMCP DCBCN Integrative Health Symposium 2020 [email protected] www.drbump.com LEARNING OBJECTIVES

• Describe herpes viral life-cycle in humans

• Review current research on Herpes virus relative to Autoimmunity

• Explore the Virome from a systems biology perspective

• Review testing and diagnostics and therapeutics Patients with RA have impaired control of EBV infection. Indeed, they have high titers of antibodies against EBV antigens. Their peripheral blood T lymphocytes are less efficient at controlling the outgrowth of EBV-infected B cells. RA patients have more EBV-infected B cells than normal controls, leading to a 10-fold systemic EBV overload…EBV, a widespread virus, highly recognized by antibodies but never eliminated, is an ideal candidate to trigger chronic immune complex disease Autoimmunity Simplified AUTOIMMUNITY DEFINED

When we loose the ability to distinguish self from non-self, and react with blind vigilance. AUTOIMMUNITY DEFINED

• Loss of Self-Tolerance

• Immune responses of an organism against its own healthy cells and tissues.

• Any disease that results from such an aberrant immune response is termed an autoimmune disease. AUTOIMMUNE DISEASES

Alopecia Areata Dego’s Disease Polychondritis Ankylosing Spondylitis Dermatomyositis - Juvenile Polyglandular Syndromes Antiphospholipid syndrome Discoid Autoimmune Addison’s Disease Essential Mixed Cryoglobulinemia and Dermatomyositis Autoimmune Hemolytic Anemia Fibromyalgia – Fibromyositis Primary Agammaglobulinemia Autoimmune Hepatitis Grave’s Disease Primary Biliary Cirrhosis Autoimmune Inner Ear Disease Guillain-Barre Psoriasis Autoimmune Lympho- Hashimoto’s Thyroiditis Raynaud’s Phenomenon proliferative Syndrome (ALPS) Idiopathic Pulmonary Fibrosis Reiter’s Syndrome Autoimmune Thrombocytopenic Idiopathic Thrombocytopenia Purpura (ITP) Rheumatic Fever Purpura (ATP) IgA Nephropathy Rheumatoid Arthritis Bechet’s Disease Insulin Dependent Diabetes (Type I) Sarcoidosis Bullous Pemphigoid Juvenile Arthritis Cardiomyopathy Lupus Sjogren’s Syndrome Celiac Sprue-Dermatitis Meniere’s Disease Stiff-Man Syndrome Chronic Fatigue Syndrome Mixed connective Tissue Disease Takayasu Immune Deficiency Syndrome Multiple Sclerosis Temporal Arteritis/Giant Cell (CFIDS) Myasthenia Gravis Arteritis Chronic Inflammatory Pemphigus Vulgaris Ulcerative Colitis Demyelinating Polyneuropathy Pernicious Anemia Uveitis Cicatricial Pemphigoid Polyarteritis Nodosa Cold Agglutinin Disease Vitiligo CREST Syndrome Wegener’s Granulomatosis Crohn’s Disease

Alessio Fasano Leaky Gut and Autoimmune Diseases Clinic Rev Allerg Immun DOI 10.1007/s12016-011-8291-x Shoenfeld Y and Molina V Infection, vaccines and other environmental triggers of autoimmunity. Autoimmunity, May 2005; 38(3): 235-245 Stejskal J and Stejskal VD. The role of metals in autoimmunity…Neuroendocrinology Letters ISSN 0172-780X Lerner A and Matthias T. Changes in intestinal tight junction permeability associate with industrial food additives explain the rising incidence of autoimmune disease. Autoimmunity Reviews 14(2015) 479 Manze A et al. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Curr Allergy Asthma Rep (2014) 14:404 Vytakek R et al. Increased concentration of two different advanced glycation end-products detected by enzyme immunoassays with new monoclonal antibodies in sera of patients with rheumatoid arthritis BMC Musculoskeletal Disorders 2010, 11:83 Prummel MF et al. The environment and autoimmune thyroid diseases European Journal of Endocrinology (2004) 150 605-618 Marshall TG and Heil R. Electrosmog and autoimmune disease Immune Res DOI 10.1007/s12026-016-8825-7 Stojanovich L. Stress and autoimmunity. Autoimmunity Review 9(2010)A271-A276

KNOWN ANTECEDENTS OR TRIGGERS FOR AI

• Genes • Nutrient deficiency

• Viruses • Food proteins: Gluten, Casein

• Bacteria • Nutrient excess

• Parasites • Chronic immune weakness • Dysbiosis • E-smog • Intestinal permeability • Heavy metals • Food additives • Hormones • Glyphosate • Personal care products • Ultraviolet light

• Chimerism • Nanoparticles

• Troposheric pollutants • Drugs

• Stress • Silica References for AI Antecedents

1. Jo¨rg S. et. al.Environmental factors in autoimmune diseases and their role in multiple sclerosis. Cell. Mol. Life Sci. (2016) 73:4611–4622 DOI 10.1007/s00018-016-2311-1 2. Duntas LH. Environmental factors and autoimmune thyroiditisNature Clinical Practice Endocrinology & Metabolism August 2008 4:8, 454-460 3. Butnaru D., Shoenfeld Y. Adjuvants and lymphoma risk as part of the ASIA spectrum. Immunol Res (2015) 61:79–89 DOI 10.1007/s12026-014-8622-0 4. Fournie´ GJ. et.al.Induction of Autoimmunity Through Bystander Effects. Lessons from Immunological Disorders Induced by Heavy Metals Journal of Autoimmunity (2001) 16, 319–326) doi:10.1006/jaut.2000.0482 5. Molina V. Shoenfeld Y. Infection, vaccines and other environmental triggers of autoimmunity Autoimmunity, May 2005; 38(3): 235–245 6. Zandman-Goddard G. Shoenfeld Y. Parasitic infection and autoimmunity. Lupus (2009) 18, 1144–1148 7. Marshall TG, Rumann Heil TJ. Electrosmog and autoimmune disease Immunol Res DOI 10.1007/s12026-016-8825-7 8. Fasano, A. Leaky Gut and Autoimmunity. Clinic Rev Allerg Immunol (2012) 42:71–78 DOI 10.1007/s12016-011-8291x 9. Due SR. et. al. Cumulative Childhood Stress and Autoimmune Diseases in Adults PsychosomMed. 2009 February ; 71(2): 243– 250. doi:10.1097/PSY.0b013e3181907888. 10. Floreani A, Leung PSC, Gershwin ME. Environmental Basis of Autoimmunity Clinic Rev Allerg Immunol DOI 10.1007/s12016-015-8493-8 11. Alexander Marson A, William J. Housley WJ, and David A. Hafler DA.J Clin Invest. 2015;125(6):2234–2241. doi:10.1172/JCI78086. • Co-evolutionaryVIRUSES development AND of nearly HUMANS? estimated 100 to WHY 400 million years.

• EBV infects ONLY humans

• 95% adults test positive

• Better classified as human ‘virobionts’ as expressed by latency expression of 9 genes vs >100 and mRNAs in lytic cycle

• In Latency ‘immortalize’ infected cells

• Latent expression is enriched with viral genes with the capacity to subvert important cellular processes, such as differentiation, survival and proliferation

• Lytic expression includes genes with transcriptional and polymerase

activitiesCruz -andMuñoz ME.structural et. al. Beta and Gammaproteins, Human Herpesviruses: aiming Agonistic to produce and Antagonistic new Interactions infectious with the Host Immune System Frontiers in Microbiology January 2018 | Volume 8 | Article 2521 viruses. • 42% of the human genome is comprised of viral sequences

• Herpesviruses assist in protection against secondary infection by pathogenic bacteria

• NK Cell arming: NK cells are an arm of innate immunity, exhibit a memory-like response, and release IFNy with re- stimulation of CMV and EBV Cruz-Muñoz ME. et. al. Beta and Gamma Human Herpesviruses: Agonistic and Antagonistic Interactions with the Host Immune System Frontiers in Microbiology January 2018 | Volume 8 | Article 2521 • 10% of children infected by EBV develop Mono

• Predisposition of Chronic Active Epstein Barr Virus (CAEBV) is attributed to one single gene mutation.

• Up to 15 different genes are related to CAEBV immune disregulation

• In CAEBV B-cells, T-cells and NK are infected

• NKCruz cells-Muñoz ME. et.responding al. Beta and Gamma Human Herpesviruses: to Herpes Agonistic and Antagonistic viral Interactions with the Host Immune System Frontiers in Microbiology January 2018 | Volume 8 | Article 2521 simulation are CD57 cells. University of Utah Genetic Science Learning Center https://learn.genetics.utah.edu/content/cells/scale/ University of Utah Genetic Science Learning Center https://learn.genetics.utah.edu/content/cells/scale/ DISEASES ASSOCIATED WITH HERPES VIRUS INFECTIONS • B, T and NK cell lymphomas • Kaposi sarcoma

• Carcinoma of stomach • Primary effusion and nasopharnyx lymphoma

• Infectious mononucleosis • KSV-inflammatory cytokine syndrome • Chronic Active EBV (CAEBV) • HCMV organ specific diseases • Hemophagocytic Lymphohistocytosis • Roseola infantumin (HLH) (HHV6&7) DEFINING THE HERPES

• Alpha: HHS1,CLASS HHS2, HHS3(Zoster)VIRUSES are neurotropic in nerve cells of the sensory ganglia

• Beta: HHV5 (CMV), HHV6A, HHV6B and HHV7

• Gamma: HHV4(EBV) and KSHV (Karposi sarcoma)

• Beta and Gamma create ‘latent’ infection in immune cells

Paludan SR. et al. Recognition of herpesviruses by the innate immune system. Nature Review/Immunology:Volume 11 Feb. 2011;143 Cruz-Muñoz ME. et. al. Beta and Gamma Human Herpesviruses: Agonistic and Antagonistic Interactions with the Host Immune System Frontiers in Microbiology January 2018 | Volume 8 | Article 2521 From epidemiological studies and in vitro work, a number of factors have been identified which may drive the change from a latent to a lytic gene expression profile in EBV infected cells. In latently infected individuals it has been shown that stress (e.g. sleep deprivation) leads to increased EBV genome production, and EBV lytic transcription factor BZLF1 may be induced by glucocorticoids, demonstrating a link between the host environment and permissivity of viral reactivation.

Routes of Immunologic Control

Cruz-Muñoz ME. et. al. Beta and Gamma Human Herpesviruses: Agonistic and Antagonistic Interactions with the Host Immune System Frontiers in Microbiology January 2018 | Volume 8 | Article 2521 1 in particular, differs among lupus patients and healthy controls with controls maintaining a limited humoral response and failing to produce long Delogu LG et.al. Infectious diseases and autoimmunity J Infect Dev Ctries 2011; 5(10) 679-687. Microbe/Antigen Antibodies

Self Protein

Molecular Mimicry CHALLENGES FOR RESEARCH

• Universality or ubiquity of infection in population ~ 95% worldwide

• Residence of Herpesvirus is the immune system

• Therefore difficult to determine causality or consequence with exacerbation of infection

• Clinical intervention suggests a stronger causal association; a patient with progressive MS was infused with CD8 T cells directed against EBV-latency antigens showing reduction of

the clinicalCruz-Muñoz ME.symptoms et. al. Beta and Gamma Human Herpesviruses: Agonistic and Antagonistic Interactions with the Host Immune System Frontiers in Microbiology January 2018 | Volume 8 | Article 2521 SEROLOGIC TESTING EBV

• EBV VCA (Viral Capsid Antigen)IgM: Appears in acute infection and disappears in ~6 weeks.

• EBV VCA IgG: appears early, peaks in 2-4 weeks then decreases slightly; maintains chronic elevation.

• EBV EA (Early Antigen) IgG: indicates acute infection. Disappears in 3 to 6 months, but may remain elevated. (20%)

• EBNA (Nuclear Antigen) IgG: appears ~ 4 to 6 months indicating past infection. Remains elevated. TESTING CMV, HHV-6 & MYCOPLASMA

• CMV (HHV-5) IgG: postive indicates prior exposure

• HHV-6 IgG: positive indicates prior exposure

• Mycoplasma Pneumoae IgG: positive indicates prior exposure

• DNA/PCR testing is available tudies have suggested that EBV is associated with autoimmune disease, such as SLE, RA, MA, autoimmune thyroiditis, inflammato

Together with EBV-induced B-cell activation, other mechanisms, such as molecular mimicry, have been implicated in support of a role of EBV in contributing to breach of self tolerance and d gs correlate with what observed in AITD patients, further supporting the association between HHV-6A infection and AITD development. Moreover, these effects are 6A specific, emphasizing the differences between the two HHV Abs against citrullinated peptides derived from EBV nuclear antigen appear years before RA and cross-react with human citrullinated fibrin. Citrullinated proteins are potential ar Filipino patients with SLE have elevated prevalence and concentrations of antibodies against EBV, CMV, HSV-1 and HSV-2 antigens, along with altered anti- EBNA-1 specificities. EBV reactivation is more common among Filipino patients with SLE compared with healthy Filipinos and may contribute to SLE pathogenesis in this population.

The anecdotal presence of human herpesvirus 6 (HHV-6) in HT specimens prompted us to study a possible association between HHV-6 and HT. Our analysis of fine needle thyroid aspirates and blood from HT patients and controls shows that HHV-6 prevalence and load are highly increased in HT patients. lls…by molecular mimicry, with the synthesis of viral proteins that resemble cellular molecules. The virus could also induce aberrant expression of histocompatibility molecules thereby promoting the presentation of auto HHV-6 AUTOIMMUNITY MECHANISMS

• Multiple Sclerosis: molecular mimicry or excessive complement activation

• Connective Tissue Diseases: (RA, SLE, SSc) Molecular mimicry and increased release of self- antigen via increased apoptosis.

• Hashimoto’s Thyroiditis: Up-regulation of MHC II (HLA) on thyrocytes induced by HHV-6 infection

Broccolo F, Fusetti L, Luca Ceccherini-Nelli L. Possible Role of Human Herpesvirus 6 as a Trigger of Autoimmune Disease. The Scientific World JournalVolume 2013, Article ID 867389, 7 pages http://dx.doi.org/10.1155/2013/867389 Based on the present studies, EBV infection can cause autoimmune diseases, such as systemic lupus erythematous (SLE), multiple sclerosis (Ms), rheumatoid arthritis (RA), Sjögren’s syndrome, and autoimmune hepatitis. The EBV has also been reported in patients with autoimmune thyroid disorders. host’s genetic factors contribute significantly to autoimmune disease. Numerous putative mechanisms have been associated with

In the present study, we analyzed a large number of patients, and revealed that the population with EBV DNA in synovial tissues was larger in RA than in OA patients, which is consistent with previous findings. These results indicate that EBV infection c Of the environmental factors, substantial amount of data indicates that EBV is directly or indirectly involved in the pathogenesis of MS. Moreover, cellular, exosomal, plasma and erythrocyte miRNAs profiles indicate that these profiles are disrupted in MS patients, compared to healthy controls. onse develops through the modification of the patient’s own antigens, molecular mimicry, induction of T Figure 1. Pathogenesis of Graves’ disease (GD). * viral and bacterial infections, iodine, stress, medications, external radiation, radioactive iodine, toxins, selenium and vitamin D3 deficiency, lymphopenia, smoking, CD8+ T lymphocyte deficiency.

Int. J. Mol. Sci. 2019, 20, 3145

SUSAN WITH SCLERODERMA

• Susan, 51yrs, very ‘high energy’, presented in January 2015 with a Dx of Diffuse , which was interfering with her life. She felt stiffness, ache and pain systemically, and had unbearable fatigue. She could barely use her hands nor open her mouth due to TMJD. Rest did not help, though she was having PT 3x/week. She reported being fit, strong, healthy and active her entire life, with no prior illnesses up until the prior year. She had hysterectomy due to fibroids and left carpal tunnel surgery due to immobility within the year.

• After much doctoring it was concluded that she was suffering from Scleroderma and that she should take myfortic as immune suppression therapy for the rest of her life. She did not tolerate the drug and had to stop.

• She takes an ACE inhibitor for blood pressure, xanax for sleep along with bourbon and THC. • Susan’s back story: She admits to wanting to help every one, for as long as she can remember. She recalls at age 10 taking care of her mother after a stroke and for the past 8 years she continued to care her aging mother, and for the previous 2, both her mother and father. She went 24/7 for 2 years while both parents were failing, having not slept for nearly 4 months. Her parents died within a week of each other in April of 2014. She recalls using her right hand and her teeth to help her mother get dressed. And despite her fatigue, had to continue to push through her day to day responsibilities.

• Susan used to exercise all the time with classes and resistance machines. Since taking care of her parents, this stopped, and her only relaxation and play was to float on her air mattress in her pool during the summer and dance “like a crazy woman” on Fridays and Saturday nights. The later she had to stop due to illness.

• Happily married for 25 years, has a 21 year old son, feels she eats well, and keeps her weight in a good place. Feels she still looks really good for being 51.

• Has active social life, mostly at clubs, and enjoys being the ‘life of the party’. • Susan’s Exam, tests and questionnaires. 1/10/2015

• Ht 5’4”, 126, BP supine:143/88 standing:125/83

• Breathing: up-side down, abdomen; distended, and full. Systemic palpable tenderness, , slight swelling in hands and wrist, with painful and limited mobility.TMJ limited and painful mobility.

• MSQ: 65, Bowel transit: long, Stress assessment: elevated adaptive and exhaustion phase. (Burn-out) INTERVENTION FOR SUSAN

• At initial presentation: 1/10/2015

• Magnesium CitraMalate: 250 mg bid

• B-Complex: 1 bid

• Immune support: 2 capsules bid

• Antioxidant formula with emphasis on GSH

• Added HCL support due to GERD, bloat and indigestion Elevated SED: 42

Elevated C-RP: 17.7

Elevated ANA: 1:160

Susan K 3/26/2014 Susan K 1/29/2015

Elevated EBV ab VCA IgG >600.0

DHEA Functionally low

Elevated hsC-RP: 6.10 Susan K 1/29/2015

Salivary 4pt Cortisol • At report of findings: 2/21/2015

• Strict elimination diet with limited gluten free grains. This meant no bourbon or coffee.

• Hepatic Detoxification to support both Phase I and Phase II pathways

• Quiet and distressing time: yin yoga

• Compliant…to a point • Follow up OV 3/21/2105

• Did well with 28-day detox program; less pain, more mobility. Facial skin feels softer, less swelling.

• Initiate 3 weeks of anti-inflammation protocol, with curcumin based medicinal food powder.

• Begin adrenal support: adaptogen: 1 bid

• L-Theanine: 400 mg at bed time and as needed

• Yoga is too slow • Follow up 6/9/2015

• RoS: Energy much better, lower legs still sore, and hard to touch; hands and face less swollen, smoother, improved mobility, less pain.

• Bowels still not moving well and feels bloated.

• Compliant with diet and life-style; to a point.

• Back to dancing and beginning to exercise lightly at gym • Follow up 9/5/2017 (not a misprint)

• MSQ 26

• Concerned about cysts in liver

• Energy is good, skin and joints all smooth and flexible

• Adheres about 75% of original elimination diet, but really likes to drink on weekends. Alcohol energizes and she doesn’t inebriate.

• Minimal doctoring, but still de-stressing

• Bowels still a problem Susan K 10/26/2017

ANA ab:Negative Susan K 10/26/2017

DHEA normal, healthy

Vit D ratio: perfect

C-RP, cardiac, better

HHV-6 - elevated

References for Interventions.

1. Kohli, K; Ali, J; Ansari, M; Raheman, Z. Curcumin: A natural anti-inflammatory agent. Indian Journal of Pharmacology; Ponicherry 37.3 (May/June2005): 141-147. 2. Long S, Romani AMP. Role of Cellular Magnesium in Human Diseases. Austin J Nutr Food Sci. ; 2(10):2015 3. Murphy EA, Davis JM and Carmichael MD. Immune modulating effects of b-glucan. Current Opinion in Clinical Nutrition and Metabolic Care 2010, 13:656–661 4. Hayes JD and Mclellan LI. Glutathione and Glutathione-dependent Enzymes Represents Co-ordinately Regulated Defence Against Oxidative Stress. Free Rad Res.31:1999 273-300. 5. Wright J and LenardL. Why Stomach Acid Is Good for You: Natural Relief from Heartburn, Indigestion. M Evans 2001 6. Yong-Song Gaun and Qing He. Plants Consumption and Liver Health. Evidence-Based Complementary and Alternative Medicine Volume 2015, Article ID 824185, 10 pages http://dx.doi.org/10.1155/2015/824185 7. Liang Y-R, Chang Liu, Xiang L-P and Zheng X-Q.Health Benefits of Theanine in Green Tea: A Review. Tropical Journal of Pharmaceutical Research October 2015; 14(10): 1943-1949 8. Winston D. Adaptogens: Herbs for Strength, Stamina, and Stress Relief. Simon and Schuster, Sep 17, 2019

THERAPEUTICS: ANTI-EBV NUTRIENTS

• Vitamin C: inhibits EBV activation in human lymphoblastiod cells

• Vitamin D: inhibits and disrupts viral envelope. Anti-microbial

• Vitamin A: inhibits lytic cycle

• Resveratrol: inhibits lytic cycle at numerous sites

• Artemisia: inhibits lytic cycle

• Luteolin: inhibits early promoter proteins

• Apigenin: inhibits early proteins

Kerr JR. J Clin Pathol 2019;72:651–658. doi:10.1136/jclinpath-2019-205822 • Astragalus: extract: inhibits early proteins

• Epigallochatechin-3-gallate: inhibits B-lymphocyte transformation

• THC: inhibits replication of g-herpes virus

• L-arginine: suppresses replication via nitric oxide

• Sulphoraphane: inhibits transactivation of immediate early proteins

• Curcumin: enhances apoptosis

• Baicalein: inhibits replication

• Rutamarin: cellular topoisomerase II catalytic inhibitor

Kerr JR. J Clin Pathol 2019;72:651–658. doi:10.1136/jclinpath-2019-205822 Kerr JR. J Clin Pathol 2019;72:651–658. doi:10.1136/jclinpath-2019-205822 Interestingly, the bioactivity of artemisinin and its semisynthetic derivative artesunate is even broader and includes the in of certain viruses, such as human cytomegalovirus and other members of the Herpesviridae family (e.g., herpes simplex virus type 1 and Epstein

Clinical Infectious Diseases 2008; 47:804–11 The Antiviral Activities of Artemisinin and Artesunate Clinical Infectious Diseases 2008; 47:804– 11 The Antiviral Activities of Artemisinin and Artesunate Clinical Infectious Diseases 2008; 47:804– 11 The clinical study of ascorbic acid and EBV infection showed the reduction in EBV EA IgG and EBV VCA IgM antibody levels over time during IVC therapy that is consistent with observations from the literature that millimolar levels of acrobat hinder viral infection and replication in vitro. ons are now widely recognized as sexually transmitted diseases. Among treatment options, low INTERVENTION: RESTORE BALANCE

• Control what you can control

• Reduce Inflammation

• Reduce Stress, including Oxidative Stress

• Support Immunity

• Nourish the Cells

• Support Detoxification and Cellular Respiration Kindness in the blood: A randomized controlled trial of the gene regulatory impact of prosocial behaviorS. Katherine Nelson-Coffey et. al. Psychoneuroendocrinology 81 (2017) 8–13

• Examined changes in leukocyte gene expression: Conserved Transcriptional Response to Adversity (CTRA)

• 159 adults who were randomly assigned for 4 weeks to engage in prosocial behavior directed 1) towards specific others, 2) prosocial behavior directed towards the world in general, 3) self-focused kindness, or 4) a neutral control task.

• This research has identified a conserved transcriptional response to adversity (CTRA) in circulating leukocytes that is characterized by up-regulation of pro-inflammatory genes and down-regulation of genes involved in innate antiviral responses and antibody production.

A SYSTEMS BIOLOGY APPROACH Source Barabasi A. Network Medicine — From Obesity to the “Diseasome”. New England Journal of Medicine 2007; 357:404- 407. A schematic representation of the senses that are hardwired in the brain.

Jonathan Kipnis J Exp Med doi:10.1084/jem.20172295 The Effect of Psychological Stress and Social Isolation on Neuroimmunoendocrine Communication Julia Cruces Current Pharmaceutical Design, 2014, Vol. 20, No. 00

• Sympathetic nerves terminals found in bone marrow, thymus, spleen and lymphoid tissue.

• Sympathetic stimulation to adrenal medulla cells trigger release of epinephrine and norepinephrine, which bind to 2-adrenergic receptors on leukocytes.

• Gluco-coriticoids also bind to receptors on various immune cells.

• Both stress hormones exert a wide range of effects on immune cell functioning including cellular trafficking, proliferation, cytokine secretion, antibody production and cytolytic activity.

TAKE AWAYS

• Herpes class viruses are ubiquitous, unavoidable, and can establish a mutual relation with humans.

• EBV, HHV-6 and CMV are directly associated with numerous diseases including cancers and autoimmunity.

• There are numerous environmental triggers for AI with herpes virus being a major one.

• Life-style management and plant based medicines are effective in controlling herpes virus and AI. It’s all about perspective! ADDENDUM GEORGE: A CASE STUDY OF RHEUMATOID ARTHRITIS

• George is 59 year old male who was referred by a local MD for concerns regarding a worsening of symptoms related to rheumatoid arthritis. He did not tolerate prednisone and was seeking an alternative to pharmaca. He began with symptoms of systemic ache, pain, fatigue and swelling about 2 years prior, and despite trials of various medications, his RA-factor continued to elevate. He reported no remarkable health history, and prior to this RA diagnosis, rarely needed to see a doctor.

• He did have some history with IBS which seemed to be stress related but he did not need medication at all for this. He did have his tonsils removed at age 5, and assumes he was prescribed penicillin prior to this. He recalls having a short bout of mono in college but did not loose time due to this. He has remained active and athletic through the years, enjoying running, and misses this. He is biking now, which he feels he tolerates, though his RA can flair if he pushes too hard. He has two grown children, both emancipated. • He has not given any consideration to his life-style, as he is a healthy weight and can eat anything, with only mild reactions of gut symptoms of gas and bloat, which he attributes to age. George works as computer engineer and sits for extended periods at his computer. He made it VERY clear he did not want to change his diet. He felt as though he ate well, did not abuse anything, but had no restrictions. He was NOT going to go on a gluten free diet. GEORGE’S EXAM AND LAB FINDINGS

• Height: 70” Weight 174 BMI = 25

• BP: 122/78 p 64 lying 124/ 82 p 72 standing

• Multiple areas of palpable pain, especially in knees, hands, hips and c-spine, over all mild reaction.

• ROM of cervical and lumbar spine was limited and sore, and trigger points noted systemically. • MSQ: 68

• RA-Factor: 211 H (<14 IU/m)

• CCP IgG Ab: >60 H (<20 units)

• C-reactive protein: 0.5 ( <0.8)

• t-Transglutaminase IgG: 12 H (>9 pos)

• EBV Ab VCA IgG: 2986 (>120 pos)

• Insulin: 13.9 (0-29.1uUI/mL) GEORGE’S INTERVENTION

• Elimination diet, especially gluten and a strict Paleo orientation: Proteins, fats and veggies.

• Medicinal food shake formulated to support anti-inflammation and immunity. 3 weeks 3 shakes/day.

• Undenatured Type II collagen: 1 tablet BID

• Weekly Chiropractic treatment. GEORGE 4-WEEK FOLLOW UP

• George reports less ache, pain and stiffness, down to about 3 to 4 from 7-8 originally. Enjoying the treatment sessions.

• Gut is more stable, didn’t realize he had so many issues now that it feels better.

• Sleeping better

• Doesn’t like the diet, but will continue because he is feeling better. GEORGE’S NEXT PHASE OF TX

• Continue with strict gluten free diet with elimination of other antigenic foods.

• Continue Paleo orientation.

• Begin Medicinal Food shakes formulated to support biotransformation and cellular respiration. 8 weeks at 2 shakes per day in second 4-weeks.

• Continue with weekly treatments for 4 weeks then reduce to every other week. GEORGE’S 90 DAY FOLLOW UP LABS

• MSQ: 36 (previous 68)

• RA-factor: 117 H (previous 211)

• CCP AB IgG: 22 H (previous >60)

• t-Transglutaminase IgG: 3 (previous 12)

• Insulin: 5.1 (previous 13.9) GEORGE’S 6 MONTH FOLLOW UP LABS

• MSQ: 27

• RA factor: 10 wnl

• CCP Ab: <20 wnl

• Insulin: 5.5

• hsC-RP: 3.6 mg/L (<1.0 normal >3.0 high)