Chapter 16 : Molecular Mimicry: Lessons from Experimental Models of Systemic Lupus Erythematosus and Antiphospholipid Syndrome

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The immunogenicity of self-like microbial molecules is strikingly illustrated in several cases of murine and human systemic lupus erythematosus (SLE). Several indirect arguments support the idea that microbial agents influence the course of antiphospholipid syndrome (APS). An association between APS and pathogens was documented, such as hepatitis C virus, lipopolysaccharide, and , a rare bacterium that has so far only been found in human immunodeficiency virus (HlV)-infected persons and that was isolated from the blood and throat of a non-HIV-infected patient with primary APS. The molecular basis of antigen mimicry by anti-idiotypic antibodies was studied extensively. On the basis of Jerne's theory, after immunization with an autoantibody that carries a specific idiotype (Abl), naive mice develop an antiautoantibody (anti-Id; which is also known as Ab2) and then generate anti-anti-Id (Ab3) a few weeks later. Immunization of naive mice with anticardiolipin βGPI-dependent MAbs and polyclonal antibodies or their corresponding scFv, such as Abl, resulted in the production in the inoculated mice of autoantibody directed to cardiolipin and to the cardiolipin βGPI-dependent antibody Ab3. Studies on experimental lupus and experimental APS prove the existence of molecular mimicry between pathogens and the autoantigens involved in experimental lupus and APS. Recognition of multiple antigens and epitopes is evident in insulin-dependent diabetes mellitus, SLE, APS, rheumatoid arthritis, PBC, and probably most autoimmune diseases, with spreading of the named epitope leading to autoantibody spread.

Citation: Blank M, Krause I, Shoenfeld Y. 2000. Molecular Mimicry: Lessons from Experimental Models of Systemic Lupus Erythematosus and Antiphospholipid Syndrome, p 223-233. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch16

Key Concept Ranking

Bacterial Proteins
Systemic Lupus Erythematosus
Immune Systems
Major Histocompatibility Complex
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Table 1

Major examples of molecular mimicry in association with autoimmune diseases

Citation: Blank M, Krause I, Shoenfeld Y. 2000. Molecular Mimicry: Lessons from Experimental Models of Systemic Lupus Erythematosus and Antiphospholipid Syndrome, p 223-233. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch16
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Table 2

Homolosv between the studied peptides and bacteria, viruses, and yeast

Citation: Blank M, Krause I, Shoenfeld Y. 2000. Molecular Mimicry: Lessons from Experimental Models of Systemic Lupus Erythematosus and Antiphospholipid Syndrome, p 223-233. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch16
Generic image for table
Table 3

Presence of autoantibodies in the sera of mice immunized with bacteria or yeast homologous to the relevant peptides

Citation: Blank M, Krause I, Shoenfeld Y. 2000. Molecular Mimicry: Lessons from Experimental Models of Systemic Lupus Erythematosus and Antiphospholipid Syndrome, p 223-233. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch16
Generic image for table
Table 4

Clinical manifestations in mice infused with mouse Abs directed to the peptide homologous to the bacterium or yeast

Citation: Blank M, Krause I, Shoenfeld Y. 2000. Molecular Mimicry: Lessons from Experimental Models of Systemic Lupus Erythematosus and Antiphospholipid Syndrome, p 223-233. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch16

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