L21- Autoimmune Diseases 2

• Autoimmunity


  Immune system's recognition apparatus break down and begin to produce antibodies & T-cells directed against the body's own components
• Autoimmune diseases


  • An attack on self antigen / self cell
  • May be caused by an abnormal immune response to normal self antigen
  • May be caused by a normal immune response to an abnormal self antigen
  • May be caused by an abnormal immune response to an abnormal self antigen
• Progression of autoimmune diseases

  1. Hereditary susceptibility

  2. Triggering vehicle such as a virus

  3. Immune system malfunction
• Features of autoimmune diseases


  • Occurrence of more than one type of autoimmune disorders in an individual
  • Higher incidence among females
  • Usually non-reversible (chronic)
  • Familiar history
  • Certain HLA haplotypes
• Mechanisms of autoimmunisation


  1. Molecular mimicry - Cross reacting foreign Ags

  2. Polyclonal B cell activation

  3. Breakdown of immunological homeostasis (tolerance)

  4. Sequestered Antigens
• Systemic (or non-organ specific) autoimmune diseases

  • Rheumatoid arthritis
  • Good pasture's syndrome
  • Systemic lupus erythematosus (SLE)
  • Sjogren's syndrome
  • Rheumatic fever & glomerulonephritis
  • Polyarteritis Nodosa
• Rheumatoid arthritis (RA)


  • A symmetric polyarthritis with muscle wasting, subcutaneous nodules with serositis, myocarditis, vasculitis and other disseminated lesions
  • Crippling inflammation in the joints, especially in hands, wrists & knees
  • Cartilage and bones are damaged
  • Presence of a circulating autoantibody - IgM called the rheumatoid factor (RF)
  • The RF acts as an antibody against the Fc fragment of IgG
• Rheumatoid arthritis (RA)


  • ESR is raised
  • RA factor is positive
  • Anti CCP is Positive
  • Cryoglobulins is present
  • Fibrinogen is raised
  • CRP is raised
  • Increased complement levels
  • Increased level of complement breakdown products
• Good pasture's syndrome


  • Antibodies appear against the non-collagenous basement membrane of kidney glomerular capillary and lung alveoli
  • Antibodies cause inflammation with complement and Fc portion of antibody mediated inflammation and lead to bleeding from the lungs and kidney failure
  • Thought to attack the alpha-3 subunit of type IV collagen, which has therefore been referred to as Goodpasture's antigen
• Systemic lupus erythematosus (SLE)


  • A chronic & multisystem disease with remissions, exacerbations and fatal
  • Patients have a variety of autoantibodies directed against cell nuclei, intracytoplasmic cell constituents, immunoglobulins, thyroid and other organ specific antigens
  • Our body's immune system mistakenly attacks healthy tissues in many parts of the body
  • Symptoms vary between people and may be mild to severe
  • Immunologically damaged nucleus of a leukocyte is called LE body
• Non-Organ Specific AID Symptoms in SLE

  • Malar Rash (butterfly shaped rash on face)
  • Discoid rash (circular, coin- or disk-shaped red patches that are thick and scaly)
  • Photosensitivity
  • Oral ulcers
  • Non erosive arthritis (>2 peripheral joints)
  • Pleuritis or pericarditis
  • Renal proteinuria or cellular casts
  • Neurological disorders: Psychosis/seizures
  • Hematologic disorder: Hemolytic anemia, leukopenia
  • Antibodies to double stranded DNA, Positive Anti-nuclear antibodies
• Sjogren's syndrome


  • A triad of conjuncitivitis sicca, dryness of the mouth with or without salivary gland enlargement and rheumatoid arthritis
  • May occur in association with other collagen diseases
  • Antinuclear antibodies & rheumatoid factor commonly occur in sera
• Frequency of Positive Laboratory Test Results in Primary Sjögren Syndrome


  • Anti-SSA (Ro)
  • Anti-SSB (La)
  • Antinuclear antibody
  • Rheumatoid factor
• Rheumatic fever & glomerulonephritis

  • Antibodies against Streptococcal antigens present in the blood may cross react with heart valve
  • Antibodies & self antigens have reacted, form complexes and localised in the kidney's glomeruli - causes glomerulonephritis - kidney failure
• Polyarteritis Nodosa


  Necrotizing angiitis involving medium-sized arteries
• Transitory Autoimmune Diseases


  • Follow certain infections or drug therapy
  • Infecting agent or drug induces antigenic alteration in some self Ags
  • Transient
  • Undergo spontaneous cure when the infection is controlled or the drug is withdrawn
  • Includes anaemia, thrombocytopenia or nephritis
• Autoimmune skin diseases


  • Offer a striking demonstration of the remarkable specificity of autoimmune responses
  • Vary from life-threatening disruption of the integrity of the skin to patchy loss of pigmentation
  • Autoantibodies can be detected in many of these disorders
  • Both B & T-cells probably mediate tissue damage in these disorders
• Bullous skin diseases


  The bullous skin diseases (pemphigus vulgaris, bullous pemphigoid, pemphigoid gestationis & dermatitis herpetiformis) are not common but are serious and, so far as pemphigus vulgaris is concerned, may occasionally prove fatal
• Pemphigus vulgaris (PV)


  • The most serious of the bullous skin disorders
  • The most common type of pemphigus in adults between the ages of 40 - 60
  • Begins with ulceration of the oral mucosa, followed by widespread flaccid, weepy bullae
  • Characterized by big, flaccid bullae that burst easily
  • Autoantibodies against Desmoglein-3, Desmoglein 1 & Plakoglobin
  • Desmosomes are cell-cell junctions between epithelial, myocardial, and certain other cell types
  • Blisters occur within the epidermis
  • Desmoglein 3 is a calcium-binding transmembrane glycoprotein component of desmosomes in vertebrate epithelial cells
  • Primary autoantibodies to desmoglein 3 causes cell death in keratinocytes
  • Keratinocyte shrinkage, detachment & death via apoptosis
• Treatment for pemphigus vulgaris includes plasmapheresis and corticosteroids
• Immune skin diseases


  • Offer a striking demonstration of the remarkable specificity of autoimmune responses
  • The disease varies from life-threatening disruption of the integrity of the skin to patchy loss of pigmentation
  • Autoantibodies can be detected in many of these disorders
  • Both B & T-cells probably mediate tissue damage in these disorders
• Bullous skin diseases


  • pemphigus vulgaris
  • bullous pemphigoid
  • pemphigoid gestationis
  • dermatitis herpetiformis
• Bullous skin diseases


  Not common but serious, and pemphigus vulgaris may occasionally prove fatal
• Autoantigens in bullous skin disease

  BMZ, basement membrane zone
• Pemphigus vulgaris (PV)


  • The most serious of the bullous skin disorders
  • The most common type of pemphigus in adults between the ages of 40 - 60
  • Begins with ulceration of the oral mucosa, followed by widespread flaccid, weepy bullae
  • Characterized by big, flaccid bullae that burst easily
  • Autoantibodies against Desmoglein-3, Desmoglein 1 & Plakoglobin
  • Desmosomes are cell-cell junctions between epithelial, myocardial, and certain other cell types
• Pemphigus vulgaris


  1. Blisters occur within the epidermis

  2. Desmoglein 3 is a calcium-binding transmembrane glycoprotein component of desmosomes in vertebrate epithelial cells

  3. Primary autoantibodies to desmoglein 3 causes cell death in keratinocytes

  4. Keratinocyte shrinkage, detachment & death via apoptosis
• Treatment for Pemphigus Vulgaris

  Plasmapheresis, Corticosteroids, Immunosuppressant, Rituximab (Target – CD20 – Lymphoma cells/Leukemia)
• Bullous pemphigoid (BP)


  • Shows close clinical similarity to PV but the blisters are subepidermal not in the intraepidermal
  • It is most common in people over the age of 60 years
  • It is characterized by the presence of large, tense bullae, usually on the thighs, arms and abdomen
  • Auto-antibodies to basement membrane zone (BMZ) that bind to hemi-desmosomal proteins (BP180 (type XVII collagen) & BP230) localized in the lamina lucida
  • Tense blisters
• Diagnosis of Bullous Pemphigoid


  IgG & C3 deposits in the dermal epidermal junction against BP230, BP180 (IFA)
• Dermatitis herpetiformis


  • DH is characterized by groups of extremely itchy, small vesicles on extensor surfaces such as the elbows, knees, buttocks, neck and shoulders
  • Most patients are aged 20–40 years at diagnosis
  • Like bullous pemphigoid, the bullae are subepidermal
  • Deposition of IgA in the dermal papillae
  • Men and women are equally affected
  • Associated with coeliac disease and gluten sensitivity
  • Auto-antibodies - to tissue transglutaminase is the enzyme in the epidermis
• Vitiligo


  • Consists of patches of skin depigmentation anywhere on the body
  • Loss of melanocytes from the epidermis via a process that is thought to be autoimmune
  • IgG antibodies to melanocytes, in particular, to tyrosinase, a key enzyme in melanin synthesis, have been found in about 80% of patients with vitiligo
  • There are strong clinical associations with organ-specific autoimmune diseases - thyroid disease, diabetes mellitus, pernicious anaemia and idiopathic Addison's disease
• Systemic sclerosis


  • A chronic fibrosing disease of unknown aetiology
  • Affects the skin, blood vessels, musculoskeletal system and many internal organs
  • Indurated & thickened skin is the most striking feature of the disease
  • Classified into Limited systemic sclerosis - cutaneous & internal involvement is limited, and Diffuse systemic sclerosis - skin & visceral involvement is usually extensive and sometimes life-threatening
  • Limited systemic sclerosis is known as the CREST syndrome
  • Systemic sclerosis usually presents between the ages of 45- 65 years; women are affected four times more frequently than men
  • It is a rare disorder (around 1/10 000)
  • Renal failure & malignant hypertension the major causes of death
  • Pulmonary fibrosis has now become the most feared complication in diffuse disease
  • Diagnosis of systemic sclerosis is clinical, & biopsy of skin and other organs
  • Several autoantibody production - Autoantibodies to Scl-70 (enzyme, topoisomerase 1, important in controlling coiling of DNA superhelices)
• IFA for Autoimmune bullous dermatoses

  • Indication: autoimmune bullous dermatoses
  • The BIOCHIP Mosaic consists of 6 substrates: Primate oesophagus, Salt-split skin, Desmoglein-1-expressing cells, Desmoglein-3-expressing cells, BP230-expressing cells (gc) and BP180 (EUROPLUS)
  • A single analysis, allowing targeted serological diagnosis
• ELISA for Autoimmune bullous dermatoses

  Microplate ELISA: Anti-Desmoglein 1, Anti-Desmoglein 3, Anti-Envoplakin, Anti-BP180-NC16A-4X, Anti-BP230-CF