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Anti-β2-glycoprotein I IgG antibodies from 1-year-old healthy children born to mothers with systemic autoimmune diseases preferentially target domain 4/5: might it be the reason for their ‘innocent’ profile?
  1. Laura Andreoli1,
  2. Cecilia Nalli1,
  3. Mario Motta2,
  4. Gary L Norman3,
  5. Zakera Shums3,
  6. Susan Encabo3,
  7. Walter L Binder3,
  8. Monica Nuzzo1,
  9. Micol Frassi1,
  10. Andrea Lojacono4,
  11. Tadej Avcin5,
  12. Pier-Luigi Meroni6,
  13. Angela Tincani1
  1. 1Rheumatology and Clinical Immunology, Spedali Civili, University of Brescia, Brescia, Italy
  2. 2Neonatology and NICU, Spedali Civili, Brescia, Italy
  3. 3INOVA Diagnostics Inc, San Diego, California, USA
  4. 4Obstetrics and Gynecology, Spedali Civili, Brescia, Italy
  5. 5Allergology, Rheumatology and Clinical Immunology, Children's Hospital, University Medical Center Ljubljana, Ljubljana, Slovenia
  6. 6Rheumatology, Department of Internal Medicine, University of Milan, Istituto Ortopedico Gaetano Pini, IRCCS Istituto Auxologico Italiano, Milan, Italy
  1. Correspondence to Dr Angela Tincani, Rheumatology and Clinical Immunology, A.O. Spedali Civili, Piazzale Spedali Civili, 1, 25123 Brescia, Italy; tincani{at}


Background Anti-β2-glycoprotein-I (anti-β2GPI) were demonstrated to be pathogenic in the antiphospholipid syndrome (APS). However, they can be detected in patients with no features of APS, especially those affected by systemic autoimmune diseases (SAD), and so in healthy children. It has been suggested that anti-β2GPI against domain 1 (D1) associate with thrombosis, while those recognising domain 4/5 (D4/5) are present in non-thrombotic conditions.

Objective To evaluate the fine specificity of anti-β2GPI in adults and infants.

Methods Three groups were examined—group A: 57 1-year-old healthy children born to mothers with SAD; group B: 33 children with atopic dermatitis; group C: 64 patients with APS. Subjects were selected based on positive anti-β2GPI IgG results. Serum samples were tested for anti-β2GPI IgG D1 and D4/5 using research ELISAs containing recombinant β2GPI domain antigens.

Results Children (A and B) displayed preferential IgG reactivity for D4/5, whereas patients with APS were mainly positive for D1. No thrombotic events were recorded in groups A and B.

Conclusions The specificity for D4/5 suggests that anti-β2GPI IgG production in children born to mothers with SAD is a process neither linked to systemic autoimmunity nor related to the maternal autoantibody status. This unusual fine specificity might, at least partially, account for the ‘innocent’ profile of such antibodies.

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  • Competing interests GLN, ZS, SE and WLB are employees of INOVA Diagnostics Inc.

  • Ethics approval This study was conducted with the approval of the local ethics committees.

  • Provenance and peer review Not commissioned; externally peer reviewed.