Autoimmune Diseases

• SYSTEMIC LUPUS ERYTHEMATOSUS


  Chronic inflammatory autoimmune disease which include swelling in joints

  Characterized with a classic butterfly rash across the nose and cheeks. This is what is responsible for the name lupus, derived from the Latin term meaning “wolflike.”

  The most common cause of death in lupus patients are renal failure and infection, followed by heart disease
• STRONGLY ASSOCIATED WITH HLA-DR 3

  SYSTEMIC LUPUS ERYTHEMATOSUS
• LE Cells


  a neutrophil that has engulfed the antibody- coated nucleus of another neutrophil. NEUTROPHIL with round homogenous body
• Fluorescent antinuclear antibody (FANA) test


  uses a substrate such as mouse kidney or human epithelial HEp-2 cells
• Fluorescent antinuclear antibody (FANA) testing


  has been the most widely used and accepted test because it is highly sensitive, detects a wide range of antibodies, and is inexpensive and easy to perform
• Interpretation for FANA testing

  A titer of ≥160 is generally considered to be clinically significant
• Homogenous /Diffuse


  Characterized by uniform staining of the entire nucleus in interphase cells and of the condensed chromosomal region in metaphase cells
• Peripheral/Shaggy/ rim/ outerline


  Diffuse staining is seen throughout the nucleus, but there is a greater staining intensity around the outer circle surrounding the nucleus in interphase cells. Dividing cells show strong staining of the condensed chromatin
• Peripheral/Shaggy/ rim/ outerline


  The pattern results from antibodies to DNA Associated with SLE in the active stage of the disease and in Sjogren’s syndrome
• Mottled/Speckled/ Pepper Dot


  *Characterized by discrete, fluorescent specks throughout the nuclei of interphase cells. Staining is absent in the nucleolus and in the chromatin region in dividing cells
• Mottled/Speckled/ Pepper Dot


  Pattern occurs in the presence of antibody to any extractable nuclear antigen devoid of DNA or histone
• Anti- Sm antibodies


  have been shown to be specific for SLE
• Anti-RNP


  been found in patients with wide variety of rheumatic diseases including SLE, RA, Sjogren’s syndrome, progressive systemic sclerosis, MCTD and dermatomyositis
• Nucleolar


  Prominent staining of the nucleoli within the nuclei of interphase cells is seen in this pattern.
• Nucleolar


  Present In about 50% patients with scleroderma (progressive systemic sclerosis), Sjogren’s syndrome and in SL
• Centromere


  Numerous discrete speckles are seen in the nuclei of interphase cells and the chromatin of dividing cells
• Centromere


  Antibody reacts with the centromeric chromatin of metaphase and interphase cells

  Appears to be highly selective for the CREST variant of progressive systemic sclerosis
• Double-stranded DNA (dsDNA) antibodies


  the most specific for SLE because they are mainly seen in patients with lupus and their levels correlate with disease activity
• CREST

  CALCINOSIS, RAYNAUD’S SYNDROME, ESOPHAGEAL DYSMOTILITY, SCLERODACTYL, & TELANGIECTASIA
• RHEUMATOID ARTHRITIS


  RA can be characterized as a chronic, symmetric, and erosive arthritis of the peripheral joints that can also affect multiple organs such as the heart and the lungs
• RHEUMATOID ARTHRITIS


  It is strongly associated with HLA-DR4
• Rheumatoid factor


  an IgM directed to the Fc region of IgG
• 80 OR GREATER


  is generally considered a positive reaction
• a titer of 20 to 40 is considered


  a weakly positive reaction
• no agglutination at 1:20


  negative
• Detection of Anti- CCP (cyclic citrullinated peptide)


  Anti-keratin antibody, anti-perinuclear antibody, anti-filaggrin, and anti-Sa antibody are all directed against citrullinated proteins thus called anti –CCP which is more specific than RF.
• Detection of Anti-Nuclear Antibodies (ANA)


  Low titers of ANAs are present in about 40% of patients. The pattern most frequently identified is the speckled pattern directed against RNP
• Type 1 diabetes


  Selective destruction of the insulin producing B cells of the islets of Langerhans in the pancreas
• Grave’s Disease


  Unregulated secretion of T3 and T4 due to stimulation of TSH receptor by antibody
• Hashimoto’s Thyroiditis


  Destruction of the thyroid gland
• Pernicious Anemia


  Destruction of the parietal cells of the stomach mucosa leading to intrinsic factor deficiency
• Multiple Sclerosis


  an immune-mediated inflammatory disease that attacks myelinated axons in the central nervous system, destroying the myelin and the axon in variable degrees and producing significant physical disability
• Good pasture’s syndrome


  Combination of glomerulonephritis with alveolar hemorrhage and anti-GBM antibodies.
• Primary Biliary Cirrhosis


  An autoimmune cholestatic liver disease characterized by a breakdown of immune tolerance to mitochondrial and nuclear antigens, causing injury to the biliary epithelial cells (BEC) lining the small intrahepatic bile ducts
• Chronic active hepatitis


  Liver disease that is characterized by diffuse parenchymal inflammation and hepatic cell necrosis
• Myasthenia Gravis


  Disease of the neuromuscular junction (NMJ) caused by antibodies that attack components of the postsynaptic membrane, impair neuromuscular transmission, and lead to weakness and fatigue of skeletal muscle.
• Wegener’s Granulomatosi


  Granuloma formation, "pauci-immune" vasculitis and glomerulonephritis (= renal vasculitis) are the histologic hallmarks
• Sjogren’s syndrome


  Keratoconjunctivitis sicca (dryness of eyes) and xerostomia (dry mouth) due to lymphocytic infiltrates of lachrymal and salivary glands
• Scleroderma


  Involves the hardening and tightening of the skin and connective tissues