Autoimmune Diseases

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When the immune system continuously produces auto-antibodies against antigens of own body, or activates T-cells that attack self-antigens, it causes a damage of tissues and organs, i.e. autoimmune disease. Finding of antibody against self-antigens is by itself not a proof of autoimmune disease, as auto-antibodies are frequently found as a temporary after-effect of tissue destruction.


Organism defends itself against the effect of auto-antibodies by - clonal deletion, - clonal inactivation, or anergy, - immunological ignorance: AAG-specific cells are sometimes, despite their ability to recognize antigens, not activated.

Apoptosis participates in the peripheral clonal deletion of adult autoreactive T-cells in the peripheral lymphatic system, and elimination of activated T-lymphocytes. In autoimmune diseases there is a resistance of autoreactive T-lymphocytes toward apoptosis, with the level of resistance being higher in females than males.


In many autoimmune diseases mutations of somatic cells, active on various levels of immune system, are considered an important pathogenetic factor.


Possible, or partial, causes of development of auto-antibodies are:

1/ Genetic predisposition caused by a certain allele, i.e. carriers of alleles HLA-DR-3 and HLA-DR-4 get IIDM 500x more often than carriers of alleles DR2+DR2;

2/ Hormonal influences, indicated by sex incidence, particularly during puberty: ratio male/female in systemic lupus erythematosus 10:1, while for ankylosing spondylitis 1:3;

3/ Autoantigens from immunoprivileged areas, i.e. brain, eye, testis, uterus, that leave those locations, via blood, but not via lymphatic passages, and react with T-cells with release of no auto-antibodies, because auto-antibodies are accompanied by TGF-Beta (transforming growth factor beta), that causes an activation of TH2 cells instead of destructive TH1 cells. Despite that auto-antigens from such areas trigger autoimmune diseases, i.e. myelin basic protein (MBP) of brain triggers multiple sclerosis, one of the most frequent autoimmune disases. Similarly eye injury releases proteins with immune response to them which threaten un-injured normal eye, i.e. sympathetic ophthalmia, and infertility is sometimes caused by spermatozoid antibodies. Contrary to that, embryo, or fetus, with its multiple from father inherited foreign antigens, is immunologically fully tolerated, because placenta makes maternal T-cells anergic.

4/ Infections, as antibodies against certain microbial antigens, or T-cells, can cross-react with auto-antigens, as it is with antibodies against streptococcus A with autoantigens in heart, causing endocarditis, in joints, causing polyarthritis, and in kidneys, a cause of glomerulonephritis.


Immune mechanisms of autoimmune disease correspond with the allergic reactions of type II through V.


Examples for allergic reactions type II, i.e. cytotoxic, are autoimmune hemolytic anemia and Goodpasture’s syndrome, where autoantibodies against basal membrane cause destruction of tissues in kidneys and lungs, and IgG is deposited in kidneys along glomerular capillaries that triggers severe inflammatory reaction.


Allergic reactions type III, triggered by production and deposition of immune complexes, or antigen-antibody complexes, take place in systemic lupus erythematosus, serum sickness, exogenous allergic alveolitis, i.e. ‘pigeon-breeder’s lung’ due to antigens in pigeons excreta, or ‘farmer’s lungs’ due to yeast antigens in hay.


Allergic reactions of type IV, or delayed type hypersensitivity, occur in rheumatoid arthritis, multiple sclerosis, IDDM where CD8 T-cells destroy self-Beta-cells, coeliakia, poison ivy and poison sumac, primary rejection of organ transplant.


Examples for type V are auto-antibodies that activate hormonal receptors, as is the case in Graves’ disease, or block them, as takes place in myasthenia gravis.


Autoimmune diseases are divided into two groups:

1/ diseases where antigen is organ-specific, i.e. Hashimoto’s thyroiditis, Addison’s disease, pernicious anemia, IDDM, etc.,

2/ diseases where antigen is not organ-specific, i.e. scleroderma, rheumatoid arthritis, systemic lupus erythematosus, etc.

But there are autoimmune diseases where antigen is organ-specific but antibodies react also with other antigens, i.e. idiopathic thrombocytopenic purpura, Sjogren syndrome, idiopathic leukopenias.


For autoimmune diseases fetal precursor cell transplantation of thymus, intestine, adrenal cortex, placenta, is advised, while specifically for scleroderma, fetal precursor cell transplantation of skin, mesenchyme, placenta, liver, as well as thymus, adrenal cortex, hypothalamus.


A 72 years’ old female had rheumatic pains in muscles and joints since puberty. She suffered an acute hepatitis at the age of 35. Nine years ago diagnosis of scleroderma was made: stiffness and swelling of fingers, hand and foot joints, swelling of face, dysphagia, increasing pains in hand joints, Raynaud-like attacks with change of weather. She received cortison injections for 9 years. On 4/26/84 fetal cell transplantation of liver, mesenchyme, hypothalamus, anterior pituitary, adrenal cortex, skin, was carried out. Three months later she stopped taking cortisone, her muscle strength increased, sleep improved and such improvement continued for 18 months, with no further negative reports. VI.BIBLIOGRAPHY [299]


Our experience with treatment of autoimmune diseases by cell transplantation was reported at the 1st Symposium on Human fetal Tissue Transplantation in Moscow, December 4 – 7, 1995, under the title: “Experience of clinical use of transplantation of human embryonic tissues in treatment of rheumatic diseases of children.” A heterologous group of patients from the Pediatric Department of the Moscow Medical Academy with different diagnoses, such as scleroderma (2 patients), rheumatoid arthritis (3 patients), dermatomyositis (2 patients), mixed connective tissue disease (1 patient), was treated by fetal cell transplantation of adrenal cortex, liver, thymus, placenta, hypothalamus, mesenchyme, that had one thing in common, i.e. there was no therapy left for them and they were going to be sent back to regional hospitals for palliative care. The patients were from 8 – 14 years of age, 2 males, 6 females. None of the patients were cured, but all improved so that their label ‘incurable’ was removed. The formerly called ‘collagen diseases’, which by definition are still classified as incurable, are succesfully treated by fetal precursor cell transplantation but the treatment must begin early and not when the patient becomes totally unresponsive to any known treatment.


Clinical protocol for fetal precursor cell transplantation treatment of autoimmune diseases

This applies to: Systemic lupus erythematosus (SLE), Rheumatoid arthritis (RA), Scleroderma (PSS), Mixed connective tissue disease (MCTD), Polymyositis (PM), Sjogren syndrome (SS), Polyarteritis nodosa (PN), covered entirely under this protocol;

also to: Hashimoto’s thyroiditis, Graves disease, NIDDM, some cases of IDDM,

idiopathic Addison’s disease, failure of other endocrine glands, sometimes combined, covered also under the protocol for ‘Hypoendocrinopathies’;

as well as to Chronic active hepatitis, Primary biliary cirrhosis, Glomerulonephritis, Goodpasture’s syndrome, covered under the respective protocols as well;

Myasthenia gravis, unresponsive Bronchial asthma;

Pemphigus, Bullous pemphigoid, Vitiligo, Atopic dermatitis;

Autoimmune hemolytic anemia, Autoimmune thrombocytopenic purpura, Pernicious anemia.

A proper preparation of the patient for fetal precursor cell transplantation is mandatory. A patient has to be brought into as good a clinical condition as possible by standard therapeutic means, while at the same time lowering the dosage of corticosteroids and other immunosuppressants to a necesary minimum, or discontinuing them altogether, and eliminating non-essential drugs.

Parameters to be followed in patients before and after fetal precursor cell xenotransplantation, and the frequency:

Basic clinical: once a month:

i/ complete blood count with differential,and platelet count

ii/ urinalysis

iii/ sedimentation rate

iv/ serum IgG, IgM, IgA once a month x3, then every 3 months

v/ x-rays of hands or other joints as necessary

vi/ clinical status of arthritis (RA, SS, SLE, PSS, PM, MCTD)

vii/ status of skin lesions (SLE, PSS, PM. MCTD) and photosensitivity (SLE)

viii/ clinical status of oral ulcers (SLE)

ix/ clinical status of nephritis (SLE, MCTD), tubular acidosis (SS), renal hypertension (PSS, PN)

x/ clinical status of pleurisy, pericarditis (SLE, MCTD)

xi/ clinical status of CREST syndrome (PSS), calcinosis, Raynaud phenomenon (in MCTD too), Esophageal dysfunction, Sclerodactyly, Teleangiectasia

Xii / clinical status of lung fibrosis (PSS, PM, MCTD)

xiii/ clinical status of arrhytmia (PSS, PM, PN), mitral valve prolapse (MCTD):

xiv/ clinical status of gastrointestinal mucosal atrophy, pancreatitis, biliary disorder (SS, PSS, PN)

xv/ clinical status of proximal muscle weakness (PM, MCTD), flexion contractures (PSS), mononeurotis multiplex (PN)

xvi/ clinical status of generalized adenopathy (SLE) and fever (PN)

xvii/ Schirmer test for eye dryness, ocular staining (SS)

xix/ biopsy: skin (PSS), muscle (PM), lesion (PN), labial salivary gland (SS), kidney (SLE) as often as necessary

xx/ test of salivary flow and salivary scintiscan (SS) every 3 months

xxi/ EMG findings typical of PM every 3 months

xxii/ angiography (PN) as often as necessary


and once a month x3, then every 3months the following tests:

xxiii/ total lymphocytes

xxiv/ T-lymphocytes (CD3)

xxv/ T-helpers (CD4), T-suppressors (CD8) and CD4/CD8 ratio

xxvi/ NK (CD16)

xxvii/ B-lymphocytes (CD22 and CD19)

xviii/ serum complement (CH50)


Special laboratory: once a month or as often as necessary:

i/ rheumatoid factors (RA, SS, PSS, MCTD)

ii/ latex and bentonite tube dilution tests (RA)

iii/ synovial fluid testing (RA)

iv/ SS-B antibodies (against nuclear antigens) (SS)

v/ LE cell preparation (SS, SLE, MCTD)

vi/ antinuclear antibody (‘ANA’) (SLE, PSS, MCTD)

vii/ circulating antinuclear antibody to nuclear nucleoprotein antigen (MCTD)

viii/ anti-DNA antibodies (SLE, MCTD)

ix/ partial thromboplastin time (SLE)

x/ anticardiolipin antibodies (SLE)

xi/ antibodies to thymic nuclear antigen PM-1, thymic nuclear extract Jo-1(PM)

xii/ serum creatin kinase (PM)

xiii/ C-reactive protein (SLE)


Frequency of office visits: 4 weeks and 48 hours before fetal precursor cell xenotransplantation, 24 hours and then once a week for the first month after fetal precursor cell xeno-transplantation, and once a month thereafter.


Repeated fetal precursor cell transplantation to be carried as often as clinical course requires to maintain the function of all components of immune system at a normal or near-normal level.