Autoimmune Diseases

Prepared by: John Robert D. Fundal, RMT

Introduction

• Autoimmune diseases are traditionally classified into two based on its

target/s:

1. Organ-specific Autoimmune disease

• Targets a single tissue or a single organ

2. Non-organ-specific Autoimmune disease (Systemic

autoimmune disease)
• Targets more than one tissue or organ
ORGAN-SPECIFIC AUTOIMMUNITY
Organ-Specific Autoimmunity
Disease Target Autoantibodies Associated
ENDOCRINE SYSTEM
Addison’s Disease Adrenal Glands • Antibody to Adrenal Cells
Grave’s Disease Thyroid Glands • Thyroid-stimulating hormone receptor
antibodies (TRAbs)
• Antithyroglobulin Antithyroid peroxidase
(TPO)
Hashimoto’s Thyroiditis Thyroid Glands • Antithyroglobulin
• Antithyroid peroxidase (TPO)
Type 1 Diabetes Mellitus Pancreas • Anti-insulin
• Islet cell antibodies
• Anti–IA-2 and anti–IA-2βA
• Antibody to glutamic acid phosphatase (GAD)
GASTROINTESTINAL SYSTEM
Autoimmune hepatitis (AIH) Liver • AIH-1—smooth muscle antibodies; ANAs
• AIH-2—anti-liver kidney microsomal antibody
(anti-LKM-1); anti-liver cytosol type 1
antibody (anti-LC-1)
Celiac Disease Small intestine and other organs • Antitransglutaminase (tTG)
• Antibodies to deamidated gliadin peptides
(DGPs)
• Endomysial antibodies
Pernicious Anemia Stomach • Parietal cell antibody
• Intrinsic factor antibody
Primary biliary cirrhosis Intrahepatic bile ducts • Intrahepatic bile ducts
Organ-Specific Autoimmunity
Disease Target Autoantibodies Associated
NERVOUS SYSTEM
Multiple Sclerosis Myelin sheath of nerves • Antibodies to myelin basic protein
Myasthenia gravis Nerve-muscle synapses • Antibodies to acetylcholine receptors (AChR)
• Anti-muscle-specific kinase (MuSK)
• Antibody to the lipoprotein LRP4

CIRCULATORY SYSTEM
Autoimmune Hemolytic Anemia Red Blood Cells • Antibody to RBCs
Autoimmune thrombocytopenic purpura Platelets • Antiplatelet antibody
Rheumatic fever Heart • Streptococcal antibodies that cross-react
with cardiac tissue
URINARY SYSTEM
Poststreptococcal glomerulonephritis Kidneys • Streptococcal antibodies that cross-react
with kidney tissue
Goodpasture’s syndrome Kidneys, lungs • Antibody to an antigen in the renal and
pulmonary basement membranes
OTHER SYSTEMS
Scleroderma Connective tissue • Antinuclear antibodies: anti-Scl-70,
anticentromere antibody
Sjögren’s syndrome Sjögren’s syndrome • Antinuclear antibodies
• Rheumatoid factor
• Antisalivary duct antibodies
• Antilacrimal gland antibodies
ENDOCRINE SYSTEM
1. Addison’s Disease
• Caused by exogenous agent such as Mycobacterium tuberculosis or have an
idiopathic cause, believed to have an immunologic mechanism.

• Autoantibodies directed against adrenal cells are believed to play main role in
the pathogenesis of Addison’s disease.

• The destruction of Adrenal glands decreases the production of Cortisol and

Aldosterone.

• The diagnosis is confirmed by demonstration of anti-adrenal antibodies by

indirect immunofluorescence test.
2. Grave’s Disease
2. Grave’s Disease
3. Hashimoto’s Disease

• Hashimoto’s thyroiditis is an autoimmune disease of the thyroid gland named

after the Japanese physician Hakaru Hashimoto.

• Characterized by the production of antibodies to two major thyroid proteins,

thyroid peroxidase and the hormone thyroglobulin.

• These autoantibodies play a major role in the destruction of the thyroid gland,
eventually causing a decline in the output of thyroid hormones resulting in
hypothyroidism.
3. Hashimoto’s Disease - Goiter

• TH1 cells also contribute to the destruction of the thyroid gland in Hashimoto’s
thyroiditis: T cells—as well as B cells and macrophages—infiltrate the thyroid.

• Histologically, the thyroid often more closely resembles a lymphoid follicle

with proliferating germinal centers than a gland with epithelial cells lining the
follicles.

• In some patients the gland, as it attempts to regenerate, may become

enlarged, causing a goiter.
3. Hashimoto’s Disease – Lymphoid Follicle
3. Hashimoto’s Disease - Goiter
4. Type 1 Diabetes Mellitus

• Involves the beta cells of the islets of Langerhans against which there is
formation of autoantibodies.

• The autoimmune attack destroys the beta cells resulting to a decreased

production of insulin and consequently increased level of blood glucose.

• Following the destruction of islet beta cells, there is abnormality in glucose

metabolism resulting in serious metabolic problems that include ketoacidosis
and increased urine productions.
GASTROINTESTINAL SYSTEM
1. Autoimmune Hepatitis
• An immune-mediated liver disease that can lead to end-stage liver failure if
left untreated.
Autoantibodies Target
Autoimmune Hepatitis 1
Antinuclear Autoantibodies (ANA) The target antigens of ANA are heterogenous and
not well defined. ANA have been shown to be
reactive with single- and double-stranded DNA,
centromeres, histones, chromatin, and cyclin A
Anti-Smooth Muscle Autoantibodies Directed against actin and other constituents of the
cytoskeleton, such as tubulin, vimentin, desmin, and
skeletin.
Autoimmune Hepatitis 2
Anti-Liver-Kidney Microsomal Type 1 Cytochrome P450-2D6
Autoantibodies
Anti-Liver Cytosol Type 1 Autoantibodies Folate-metabolizing enzyme formimino transferase
cyclodaminase (FTCD)
2. Celiac Disease
3. Primary Biliary Cirrhosis

• An autoimmune liver disease characterized by immune-mediated destruction

of small intrahepatic bile ducts, leading to chronic cholestasis and fibrosis that
can eventually result in cirrhosis and liver failure.
NERVOUS SYSTEM
1. Multiple Sclerosis
• Demyelination or destruction of the myelin sheaths surrounding central
nervous system.

• Individuals with disease produce autoreactive T cells that take part in the
formation of inflammatory lesions along the myelin sheath of nerve fibers.

• The cerebrospinal fluid (CSF) of patients of MS reveal sensitized T

lymphocytes, which infiltrate the brain tissue and cause characteristic
inflammatory lesions destroying the insular covering (myelin sheath) of the
nerve fibers leading to a number of neurologic dysfunctions.
1. Multiple Sclerosis
2. Myasthenia Gravis

• Myasthenia gravis is formation of antibodies against acetylcholine receptors

present in the motor end-plates of muscle, which blocks the normal binding of
acetylcholine and also induces complement-mediated degradation of the
receptors, resulting in progressive weakness of the muscle
2. Myasthenia Gravis
URINARY SYSTEM
1. Post-streptococcal Glomerulonephritis

• An immune-mediated glomerulonephritis associated with extrarenal bacterial

infections.

• Anti-streptolysin O and Anti-DNAse-B antibody titers are usually elevated.

• The streptococcus bacteria do not attack the kidney directly, but an infection
may stimulate the immune system to overproduce antibodies, which are
circulated in the blood and finally deposited in the glomeruli, causing damage
2. Good Pasteur’s Syndrome

• Characterized by the presence of autoantibody to an antigen in the basement

membranes in the glomeruli of the kidneys and alveoli of the lungs.

• Autoantibodies produced in Goodpasture’s syndrome are known to be

specifically directed against the non-collagenous domain of the alpha-3 chain
of type IV collagen.

• This autoantibody reacts with collagen in the glomerular or alveolar basement

membranes and causes damage by type II hypersensitivity.
NON-ORGAN-SPECIFIC AUTOIMMUNITY
Non-Organ-Specific Autoimmune Disease
Disease Target Autoantibodies Associated
SYSTEMIC AUTOIMMUNE DISEASES
Systemic Lupus Erythematosus Multiple cells and organs throughout the body, • Antibodies to double-stranded DNA and other
including the skin, joints, kidneys, brain, heart, nuclear components, such as Sm (ANAs)
lungs • Phospholipid antibodies
• Antibody to RBCs
• Antibody to platelets
• Antibody to lymphocytes
• Antibody to ribosomal components
• Antibody to endothelium Rheumatoid factor
Rheumatoid Arthritis Joints, bone; other tissues in some cases • Anti-CCP (cyclic citrullinated proteins)
• Rheumatoid factor
• Antinuclear antibodies (ANAs)
Wegener’s granulomatosis Joints, bone; other tissues in some cases • Antineutrophil cytoplasmic antibodies (ANCA);
c-ANCA pattern
• Rheumatoid factor ANAs
Scleroderma Connective tissue • Antinuclear antibodies: anti-Scl-70,
anticentromere antibody
Sjogren Syndrome Eyes, mouth • Antinuclear antibodies
• Rheumatoid factor
• Antisalivary duct antibodies
• Antilacrimal gland antibodies
1. Systemic Lupus Erythematosus
• Autoantibodies (IgG, IgM and IgA) are formed primarily against the
components of deoxyribonucleic acid (DNA), but also can be made against
blood cells [red blood cells (RBCs), platelets and leukocytes], clotting factors,
neurons and histones.

• When immune complexes of autoantibodies with various nuclear antigens are

deposited along the walls of small blood vessels, a type III hypersensitivity
reaction develops.

• Laboratory diagnosis of SLE consists of demonstrations of antinuclear

antibodies
1. Systemic Lupus Erythematosus
2. Rheumatoid Arthritis
• Rheumatoid arthritis affects mainly the joints of the hands and feet although it
can extend to other tissues.

• Characterized by inflammation and destruction of cartilage in the joints

causing deformities.
RHEUMATOID FACTOR ANTI-CYCLIC CITRULLINATED PROTEINS
• IgM antibody and is directed • These antibodies can react with
against the FC portion of IgG. citrulline-containing components of the
matrix, including filaggrin, keratin,
• It has been postulated that RFs fibrinogen, and vimentin, and are
may play a role in the pathogenesis thought to correlate with the
of RA by increasing macrophage pathogenesis of RA.
activity and enhancing antigen
presentation to T cells by APCs.
2. Rheumatoid Arthritis
3. Wegener’s Granulomatosis
4. Scleroderma (Systemic sclerosis)

• A multisystem connective tissue disorder of unknown etiology in which

vascular lesions and tissue fibrosis are prominent features.

• Scl patients spontaneously produce autoantibodies against nuclear, nucleolar,

mitochondrial, and other cytoplasmic antigens.

• Scleroderma can be phenotypically classified into two broad clinical

categories:
1. Diffuse cutaneous Scl (dcScl)
2. Limited cutaneous Scl (lcScl).
4. Scleroderma - CREST
5. Sjogren’s Syndrome
• A chronic inflammatory exocrinopathy, an autoimmune disease marked by
dryness of the yes, mouth, and other mucous membranes.

• The disease may evolve from localized exocrine gland involvement to a

systemic disorder, as well as to B cell lymphoproliferative transformation.

• The affected salivary or lacrimal glands are infiltrated with aggregates of

lymphocytes.

• Antinuclear autoantibodies in SS are normally restricted to SS-A/Ro and SS-

B/La.
5. Sjogren’s Syndrome
END