Correspondence
The Antiphospholipid Syndrome
N Engl J Med 2002; 347:145-146July 11, 2002
- Article
To the Editor:
In their review article, Levine et al. (March 7 issue)1 state that the prevalence of antiphospholipid antibodies increases with age and is especially high in the elderly population. This statement overlooks data on the prevalence of antiphospholipid antibodies in children. In particular, anticardiolipin antibodies can be found in a high percentage of children without any discernible disease. We observed positive values for anticardiolipin antibodies in 11.4 percent of 61 apparently healthy children at their regular preventive visits.2 In addition, Rapizzi et al. found anticardiolipin antibodies in 28 percent of 100 healthy children.3 It has generally been assumed that such naturally occurring anticardiolipin antibodies could be the result of previous infections or vaccinations that are common in this population.4
Furthermore, recent evidence suggests that alternative responses of the developing immune system to dietary antigens can result in the production of specific antiphospholipid antibodies during childhood. We showed that the mean value of IgG anti–β2-glycoprotein I antibodies is highest in preschool children and that, in this group, it is significantly higher than in adolescents and healthy adults.2 Moreover, IgG anti–β2-glycoprotein I antibodies can be found in a high percentage of infants with atopic dermatitis who have exaggerated immune responses to nutritional antigens. These findings indicate that dietary β2-glycoprotein I may act as an oral immunization agent and induce transitory production of anti–β2-glycoprotein I antibodies in infants, whose intestinal mucosa is more permeable to large molecules than that of adolescents and healthy adults.4,5
5 ReferencesTadej Avcin, M.D.
Tanja Kveder, Ph.D.
Bla Rozman, M.D., Ph.D.
University Medical Center Ljubljana, Ljubljana SI-1000, Slovenia
tadej.avcin@siol. net 1
Levine JS ,Branch DW ,Rauch J . The antiphospholipid syndrome. N Engl J Med 2002;346:752-763
Full Text | Web of Science | Medline2
Avcin T ,Ambrozic A ,Kuhar M ,Kveder T ,Rozman B . Anticardiolipin and anti-β(2)-glycoprotein I antibodies in sera of 61 apparently healthy children at regular preventive visits. Rheumatology (Oxford) 2001;40:565-573
CrossRef | Web of Science | Medline3
Rapizzi E ,Ruffatti A ,Tonello M , et al. Correction for age of anticardiolipin antibodies cut-off points. J Clin Lab Anal 2000;14:87-90
CrossRef | Web of Science | Medline4
Avcin T ,Cimaz R ,Meroni PL . Recent advances in antiphospholipid antibodies and antiphospholipid syndromes in pediatric populations. Lupus 2002;11:4-10
CrossRef | Web of Science | Medline5
Avcin T ,Cimaz R ,Meroni PL . Do we need an international consensus statement on classification criteria for the antiphospholipid syndrome in the paediatric population? Lupus 2001;10:897-898
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Author/Editor Response
The authors reply:
To the Editor: Dr. Avcin and colleagues note that we omitted mention of the prevalence of antiphospholipid antibodies in children. They also suggest that the relatively high prevalence of anticardiolipin antibodies in this population may be the result of previous infections, vaccinations, or exposure to dietary antigens, including dietary sources of β2-glycoprotein I.1
Our review focused on adults, in whom the prevalence of antiphospholipid antibodies increases with age. However, the implication that we should have made specific reference to the problem of antiphospholipid antibodies and the antiphospholipid syndrome in children has merit. As summarized by Dr. Avcin and colleagues, the prevalence of antiphospholipid antibodies may be biphasic with respect to age, with an initial peak occurring before adolescence. Although the presence of antiphospholipid antibodies does not mean that a patient has the antiphospholipid syndrome, the current diagnostic criteria2 may be deficient with respect to their application in children.1
Though worthy of speculation, the potential link between oral antigens and antiphospholipid antibodies has not, to our knowledge, been proved. Another attractive theory, for which there is experimental evidence, is that there is an infectious trigger for the production of antiphospholipid antibodies. Viral3 and bacterial4 peptides induced antiphospholipid antibodies in murine models. In fact, the antiphospholipid antibodies induced in response to a cytomegalovirus peptide caused thrombosis and endothelial-cell activation in mice.3 In adults, high levels of antiphospholipid antibodies have been described in association with cytomegalovirus infection in recipients of allogeneic stem-cell transplants.5 Finally, cytomegalovirus infection is found in approximately 1 percent of newborns and is common in young children.
5 ReferencesD. Ware Branch, M.D.
University of Utah, Salt Lake City, UT 84132Jerrold S. Levine, M.D.
University of Chicago, Chicago, IL 60637Joyce Rauch, Ph.D.
McGill University Health Centre, Montreal, QC H3G 1A4, Canada
joyce.rauch@mcgill. ca 1
Avcin T ,Cimaz R ,Meroni PL . Recent advances in antiphospholipid antibodies and antiphospholipid syndromes in pediatric populations. Lupus 2002;11:4-10
CrossRef | Web of Science | Medline2
Wilson WA ,Gharavi AE ,Koike T , et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum 1999;42:1309-1311
CrossRef | Web of Science | Medline3
Gharavi AE ,Pierangeli SS ,Espinola RG ,Liu X ,Colden-Stanfield M ,Harris EN . Antiphospholipid antibodies induced in mice by immunization with a cytomegalovirus-derived peptide cause thrombosis and activation of endothelial cells in vivo. Arthritis Rheum 2002;46:545-552
CrossRef | Web of Science | Medline4
Blank M ,Krause I ,Fridkin M , et al. Bacterial induction of autoantibodies to β2-glycoprotein-I accounts for the infectious etiology of antiphospholipid syndrome. J Clin Invest 2002;109:797-804
CrossRef | Web of Science | Medline5
Mengarelli A ,Minotti C ,Palumbo G , et al. High levels of antiphospholipid antibodies are associated with cytomegalovirus infection in unrelated bone marrow and cord blood allogeneic stem cell transplantation. Br J Haematol 2000;108:126-131
CrossRef | Web of Science | Medline
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