Thrombotic thrombocytopenic purpura and autoimmunity: a tale of shadows and suspects.
OBJECTIVE
The key pathogenic feature of TTP is the formation of platelet aggregates within the microcirculation; however, the etiology of such aggregates has been elusive for years. A large amount of evidence points to an abnormal interaction between damaged vascular endothelium and platelets, although the cause of the primary microvascular endothelial cell injury is seldom clear. The autoimmune hypothesis often recurs, and this is based on a number of observations: the claimed superiority of plasma-exchange over plasma infusion, the anecdotal report of the presence of immunocomplexes and autoantibodies in TTP patients, the efficacy of the administration of corticosteroids and other immunosuppressant agents, and the concomitant occurrence of TTP in association with autoimmune diseases, especially systemic lupus erythematosus (SLE). This review will focus on the complex relationships between TTP and humoral autoimmunity; in particular, similarities and differences between TTP, SLE and antiphospholipid (aPL) antibodies syndrome, as well as the putative role of several other antibodies directed towards endothelial cells and/or platelets, including the recently discovered anti-CD36 antibodies and antivWF-cleaving metalloprotease, will be discussed.


METHODS
The authors have been involved in the study and treatment of TTP and autoimmune diseases for years; furthermore, the PubMed data base of the National Library of Congress has been extensively searched using the Internet.


CONCLUSIONS
Although over the years evidence has increased in favor of the autoimmune hypothesis for TTP etiopathogenesis, TTP should not yet be considered an autoimmune disease. Autoantibodies should be regarded as only one of the many different insults which can trigger microvascular thrombosis even though the autoimmune theory of the pathogenesis of TTP is gaining more and more strength. As far as concerns the relationship between TTP, SLE and aPL antibodies-related disorders, these diseases should be distinguished on the basis of both different clinical presentations and accurate antibody screening, although this approach should definitely not delay the prompt start of treatment.
Porta
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Medicina Interna ed Oncologia Medica, I.R.C.C.S. Policlinico San Matteo, p.le Camillo Golgi, I-27100 Pavia, Italy. cporta@tin.it.
Caporali
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Montecucco
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D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; D000328:Adult; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology; D000918:Antibody Specificity; D016824:Antigens, Human Platelet / Q000276:immunology; D016736:Antiphospholipid Syndrome / Q000150:complications / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000150:complications / Q000276:immunology; D015551:Autoimmunity; D018955:CD36 Antigens / Q000276:immunology; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology; D005169:Factor VIII / Q000276:immunology; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000276:immunology; D008297:Male; D008666:Metalloendopeptidases / Q000276:immunology; D018448:Models, Immunological; D010951:Plasma Exchange; D010974:Platelet Aggregation; D011697:Purpura, Thrombotic Thrombocytopenic / Q000453:epidemiology / Q000209:etiology / Q000276:immunology* / Q000628:therapy; D014841:von Willebrand Factor / Q000378:metabolism
D019268:Antibodies, Antineutrophil Cytoplasmic; D016824:Antigens, Human Platelet; D001323:Autoantibodies; D001324:Autoantigens; D018955:CD36 Antigens; D014841:von Willebrand Factor; D005169:Factor VIII; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human