Autoimmune Diseases II - System

• Autoimmunity

  Immune system's recognition apparatus break down and begin to produce antibodies & T-cells directed against the body's own components - an attack on self antigen / self cell
• Causes of autoimmune diseases

  • An abnormal immune response to normal self antigen
  • A normal immune response to an abnormal self antigen
  • 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
• Autoimmune diseases

  • Occurrence of more than one type in an individual
  • Higher incidence among females
  • Usually non-reversible (chronic)
• Predisposing factors for autoimmune diseases

  • Familiar history
  • Certain HLA haplotypes - Rheumatoid Arthritis - HLA DR4
• Mechanisms of autoimmunisation

  • Molecular mimicry - Cross reacting foreign Ags
  • Polyclonal B cell activation
  • Breakdown of immunological homeostasis (tolerance)
  • 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
  • Transitory diseases
  • Autoimmune skin diseases

  
• Rheumatoid arthritis (RA)

  A symmetric polyarthritis with muscle wasting, subcutaneous nodules with serositis, myocarditis, vasculitis - other disseminated lesions. It is a common disease, produces crippling inflammation in the joints especially in hands, wrists & knees. Cartilage and bones are damaged. The presence of a circulating autoantibody - IgM called the rheumatoid factor (RF)
• Investigations for rheumatoid arthritis

  • 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
  • Plain X-ray of the joints
• Good pasture's syndrome

  Antibodies are appeared against to non-collagenous basement membrane of kidney glomerular capillary & lung alveoli. Antibodies cause inflammation with complement and Fc portion of antibody mediated inflammation and lead to bleeding from the lungs and kidney failure. It is 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 leucocyte is called LE body.

  
• Diagnostic criteria for systemic lupus erythematosus (SLE)

  • Malar Rash
  • Discoid rash
  • 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 standard 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. This syndrome 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

  When antibodies against Streptococcal antigens present in the blood may cross react with heart valve by those antibodies. It is commonly occur in children at the age of 5 -15. The antibodies may cross react with different host tissues and causes inflammation of joints, heart, brain and skin. The cardiac involvement is the most serious sign of acute rheumatic fever. 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


  The autoimmune 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

  
• 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 Desmoglin-3, Desmoglobin 1 & Plakoglobin. Desmosomes are cell-cell junctions between epithelial, myocardial, and certain other cell types.

  
• 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.

  
• 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 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


  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. Systemic sclerosis – called as scleroderma. It is classified into limited systemic sclerosis with cutaneous & internal involvement limited, and diffuse systemic sclerosis with skin & visceral involvement usually extensive and sometimes life-threatening. Systemic sclerosis usually presents between the ages of 45- 65 years; women are affected four times more frequently than men. 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)

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