Autoimmune Diseases

"The fancier the plumbing, the easier it is to stop up the drain" -- The human immune system is very complex and, hence, there are numerous ways it can malfunction. There are a number of diseases that can result, and many of these have similarities. It is sometimes difficult to separate them. They are also often called "connective tissue" disorders because many of them are manifested in a variety of tissues.

Hypersensitivity reactions involved in autoimmunity are primarily types II and III, though type IV reactions can also be present.

Mechanisms proposed for development of autoimmunity include:

Bypass of CD4+ T-cell tolerance of "self" antigens by:

• complex of antigen with a hapten (such as a drug or infectious agent) or infectious degradation of an antigen

• cross-reaction with a hapten on an infectious agent that is similar to tissue proteins--classic for poststreptoccocal glomerulonephritis and rheumatic heart disease

• direct activation of B-cells via bacterial endotoxin and via Epstein-Barr virus receptors on B-cells

Idiotype bypass through ligand mimicry, as seen in antireceptor antibody mediated disease, and cross-reactivity with infectious agents:

• T-suppressor/helper imbalance

• emergence of a sequestered antigen through tissue trauma or inflammatory destruction. Examples include: lens crystalline of eye, spermatozoa in testis, and myelin in CNS

Antinuclear Antibodies

Many autoimmune diseases have serologic evidence for antibodies directed at components of "self" cell nuclei. Though these antibodies may not be the direct cause of, or evidence for, tissue injury, they are very useful for diagnosis and categorization of autoimmune diseases. The types include:

ANA (antinuclear antibody): seen in many autoimmune diseases and not diagnostic of any. In general, the higher the titer, the worse the disease. There are some characteristic fluorescent staining patterns for ANA:

• homogenous (diffuse) - not very specific for anything

• rim - may be indicative of anti-double stranded DNA, seen in SLE

• speckled - indicative of antibody to extractable nuclear antigens, often seen in MCTD

• nucleolar - antibody to nucleolar RNA, seen often in PSS

• centromere - antibody to centromeric protein, seen in CREST syndrome

Autoantibody Panels

Though indirect immunofluorescence is a reference method to detect autoantibides, methods using enzyme immunoassay can be utilized that are faster and less prone to interpretive variables. For general screening for a systemic autoimmune disease, the venerable antinuclear antibody (ANA) test is employed, but for more specific classification of autoimmune conditions, a panel of autoantibodies is obtained. A titer or a numeric value may be reported for each autoantibody.

The autoantibodies called "extractable nuclear antigens" (ENA) are so named because they represent antigens that can be extracted from the cell nucleus with saline. Such antibodies include: SS-A, SS-B, U1-RNP, Scl-70, Jo-1, and Sm.

Though no autoantibody is completely sensitive or specific for a particular autoimmune disease, some of the strongest associations include:

• Anti-double stranded DNA (native DNA antibody): SLE

• Anti-Smith: SLE

• anti-histone: drug-induced SLE

• anti SS-A and anti SS-B: Sjogren's syndrome

• anti DNA-topoisomerase I (Scl-70): PSS

• anti-histidyl-tRNA synthetase (Jo-1): polymyositis

• anti-RNP (ribonucleoprotein): MCTD

• anti-phospholipid antibody (anti-cardiolipin antibody): SLE and others