SLE, particularly drug related; various rheumatic diseases

Mixed connective tissue disease SLE

Primary Sjögrens syndrome; cutaneous LE; fetal heartblock

Primary Sjögrens syndrome; SLE

Scleroderma, CREST variant

Scleroderma, systemic sclerosis

Systemic sclerosis; undifferentiated rheumatic diseases

SLE (rarely)

Pempiphigus vulgaris, pemphigus foliaceus Bullous pemphigoid Myasthenia gravis, with thymoma Myocarditis, rheumatic carditis Rheumatoid arthritis Glomerulonephritis (Goodpasture type) Uveitis

Male infertility; orchitis (?) Ulcerative colitis (?)

Antiphospholipid syndrome, thromboembolism

Atrophic gastritis, pernicious anemia Rheumatoid arthritis

Atrophic hypothyroidism; Hashimotos thyroiditis Type I diabetes mellitus

Table 1 Continued Autoantigen

Neural products Glutamic acid decarboxylase Calcium channels, synaptotagmin Purkinje cell cytoplasm (Yo) Cerebellar neuronal nuclei

(?) Indicates incomplete consensus.

of several epitopes on autoantigens, and/or the existence of conformational epitopes, could limit the appeal of the molecular mimicry hypothesis because it is unlikely that the several epitopes of the autoantigen would be conformationally similar, or that the extrinsic antigen would have multiple mimicry epitopes; however, mimicry could exist for a single shared or cross-reactive epitope recognized by the CD4 helper T cell that could then recruit successive B cell epitopes into the autoimmune response, a process known as epitope spreading.

3. The epitope recognized by autoantibody is frequently associated with an active site of an enzyme or other functional molecule, and the antibody can be shown to inhibit the function in vitro of the cognate autoantigenic enzyme. For example, the major epitope of PDC-E2, the M2 autoantigen of PBC, is the functional lipoyl domain, and the reaction of PBC serum with this domain specifically abrogates the catalytic function of the PDC enzyme in vitro.

4. There is a possibility that autoantigens may have 'disease-specific' epitopes that differ in site or structure from epitopes that are reactive with non-disease-specific natural autoantibodies.

5. Various intracellular antigenic molecules have been functionally characterized at the molecular genetic level by the use of autoantibodies as research reagents. Examples, of which there are many, include the U-ribonucleoproteins which splice out introns from mRNA, the La ribonucleoprotein which participates in the termination of transcription of RNA polymerase III, and the Ku antigen which participates in recombination and repair of DNA.

One major need at present is to verify T cell responses to autoantigens and map the relevant epitopes, noting that autoepitope-responsive T cells have a low representation among peripheral blood cells and, even in affected tissues, will be 'diluted' by nonspecifically reactive cells in inflammatory exudates. Another need is to understand why particular molecules or related groups of molecules are singled out among numerous others as autoantigenic reac-

Related diseases

Stiff man syndrome

Lambert-Eaton myasthenic syndrome

Paraneoplastic (PN) cerebellar degeneration

PN sensorimotor neuropathy

PN midbrain encephalitis/ataxia/myelopathy tants, i.e. why there is failure of tolerance to these particular tissue constituents. This will require better understanding of how 'nascent' self reactive T or B lymphocytes are deleted in the thymus or bone marrow respectively during ontogeny, and how self reactive lymphocytes that escape this process are tolerized in the periphery in postnatal life.

See also: Adrenal autoimmunity; Anemia, autoimmune hemolytic in human; Anemia, pernicious; Antiglobulin (Coombs') test; Antinuclear antibodies; Autoantibodies, tests for; Autoimmune disease, Induced experimental models; Autoimmune disease, pathogenesis; Autoimmune disease, spontaneous experimental models; Autoimmune diseases; Autoimmunity; Cardiac disease, autoimmune; Epitopes; Experimental autoimmune encephalomyelitis (EAE); Eye, autoimmune disease; Goodpasture's syndrome; Idiopathic thrombocytopenic purpura; Insulin-dependent diabetes mellitus, animal models; Insulin-dependent diabetes mellitus, human; Molecular mimicry; Neuromuscular junction autoimmunity; Neurological autoimmune diseases; Polyendocrine autoimmunity; Rheumatoid arthritis, animal models; Rheumatoid arthritis, human; Sjögrens syndrome; Skin, autoimmune diseases; Systemic iupus erythematosus, experimental models; Systemic lupus erythematosus (SLE), human; Thyroid autoimmunity, expecUneotal models; Thyroid autoimmunity, human; Vitiligo; Primary biliary cirrhosis; Chronic active and autoimmune hepatitis.

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