Anticardiolipin and Anti-Beta₂ Glycoprotein I Antibodies in Infants Born to Mothers with Antiphospholipid Antibody-Positive Autoimmune Disease: A Follow-Up Study

ABSTRACT

Infants born from mothers with antiphospholipid antibody (aPL) -positive autoimmune disease were prospectively evaluated for anticardiolipin and anti-β2 glycoprotein I antibodies (group 1) and for growth and neurological development. The results were compared with those obtained from two age-matched control groups (group 2 and 3). All infants were negative for anticardiolipin at 12 months of life, whereas 14 (63.6%), eight (33.3%), and 10 (55.5%) of infants from group 1, 2, and 3, respectively, were positive for anti-beta₂ glycoprotein I. At follow-up, all infants had normal growth and neurological development. No thrombotic complication was observed. The negativity of anticardiolipin in all infants at 12 months suggests that anticardiolipin detection is the best assay to evaluate the disappearance of maternal aPL and to estimate the potential risk of thrombosis associated with these antibodies. The high rate of anti-beta₂ glycoprotein I positivity in all three groups of infants may indicate that the synthesis of this antibody is stimulated by aspecific factors.

Antiphospholipid antibodies - autoimmune disease - neonatal thrombosis

REFERENCES

• 1 Hughes G RV, Harris E N, Gharavi A E. The anticardiolipin syndrome.  J Rheumatol. 1986;  13 486-489
• 2 Wilson W A, Gharavi A E, 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
• 3 Pangborn M C. A new serologically active phospholipid from beef heart.  Proc Soc Exp Biol Med. 1941;  48 484-486
• 4 McNeil H P, Simpson R J, Chesterman C N, Krilis S A. Anti-phospholipid antibodies are directed against a complex antigen that includes a lipidbinding inhibitor of coagulation: β2-glycoprotein I (apolipoprotein H).  Proc Natl Acad Sci USA. 1990;  87 4120-4124
• 5 Galli M, Comfurius P, Maassen C et al.. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor.  Lancet. 1990;  335 1544-1547
• 6 Matsuura E, Igarashi Y, Fujimoto M et al.. Anticardiolipin cofactor(s) and differential diagnosis of autoimmune disease.  Lancet. 1990;  336 177-178
• 7 Galli M, Barbui T. Antiprothrombin antibodies: detection and clinical significance in the antiphospholipid syndrome.  Blood. 1999;  93 2149-2157
• 8 Balestrieri G, Tincani A, Spatola L et al.. Anti-β2- glycoprotein I antibodies: a marker of antiphospholipid syndrome?.  Lupus. 1995;  4 122-130
• 9 Viard J-P, Amoura Z, Bach J-F. Association of anti-b2 glycoprotein I antibodies with lupus-type circulating anticoagulant and thrombosis in systemic lupus erythematosus.  Am J Med. 1992;  93 181-186
• 10 Cabral A R, Amigo M C, Cabiedes J, Alarcón-Segovia D. The antiphospholipid/cofactor syndromes: a primary variant with antibodies to β2-glycoprotein-I but no antibodies detectable in standard antiphospholipid assays.  Am J Med. 1996;  101 472-481
• 11 Carreras L O, Forastiero R R, Martinuzzo M E. Which are the best biological markers of the antiphospholipid syndrome?.  J Autoimmun. 2000;  15 163-172
• 12 Miyakis S, Lockshin M D, Atsumi T et al.. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS).  J Thromb Haemost. 2006;  4 295-306
• 13 Branch D W, Khamashta M A. Antiphospholipid syndrome: obstetric diagnosis, management, and controversies.  Obstet Gynecol. 2003;  101 1333-1344
• 14 Pollard J K, Scott J R, Branch D W. Outcome of children born to women treated during pregnancy for the antiphospholipid syndrome.  Obstet Gynecol. 1992;  80 365-368
• 15 Botet F, Romera G, Montagut P, Figueras J, Carmona F, Balasch J. Neonatal outcome in women treated for the antiphospholipid syndrome during pregnancy.  J Perinat Med. 1997;  25 192-196
• 16 Ruffatti A, Dalla Barba B, Del Ross T et al.. Outcome of fifty-five newborns of antiphospholipid antibody-positive mothers treated with calcium heparin during pregnancy.  Clin Exp Rheumatol. 1998;  16 605-610
• 17 Brewster J A, Shaw N J, Farquharson R G. Neonatal and pediatric outcome of infants born to mothers with antiphospholipid syndrome.  J Perinat Med. 1999;  27 183-187
• 18 Tincani A, Lojacono A, Taglietti M et al.. Pregnancy and neonatal outcome in primary antiphospholipid syndrome.  Lupus. 2002;  11 649
• 19 Finazzi G, Cortelazzo S, Viero P, Galli M, Barbui T. Maternal lupus anticoagulant and fatal neonatal thrombosis.  Thromb Haemost. 1987;  57 238
• 20 Sheridan-Pereira M, Porreco R P, Hays T, Burke M S. Neonatal aortic thrombosis associated with the lupus anticoagulant.  Obstet Gynecol. 1988;  71 1016-1018
• 21 Silver R K, Mac Gregor S N, Pasternak J F, Neely S E. Fetal stroke associated with elevated maternal anticardiolipin antibodies.  Obstet Gynecol. 1992;  80 497-499
• 22 Contractor S, Hiatt M, Kosmin M, Kim H C. Neonatal thrombosis with anticardiolipin antibody in baby and mother.  Am J Perinatol. 1992;  9 409-410
• 23 Tabbutt S, Griswold W R, Ogino M T, Mendoza A E, Allen J B, Reznik V M. Multiple thromboses in a premature infant associated with maternal phospholipid antibody syndrome.  J Perinatol. 1994;  14 66-70
• 24 Hage M L, Liu R, Marcheschi D G, Bowie J D, Allen N B, Macik B G. Fetal renal vein thrombosis, hydrops fetalis, and maternal lupus anticoagulant: a case report.  Prenat Diagn. 1994;  14 873-877
• 25 Teyssier G, Gautheron V, Absi L, Galambrun C, Ravni C, Lepetit J C. Anticorps anticardiolipine, ischémie cérébrale et hémorragie surrénalienne chez un nouveau-né.  Arch Pediatr. 1995;  2 1086-1088
• 26 de Klerk O L, de Vries T W, Sinnige L GF. An unusual cause of neonatal seizures in a newborn infant.  Pediatrics. 1997;  100 E8
• 27 Navarro F, Dona-Naranjo M A, Villanueva I. Neonatal antiphospholipid syndrome.  J Rheumatol. 1997;  24 1240-1241
• 28 Akanli L F, Trasi S S, Thuraisamy K et al.. Neonatal middle cerebral artery infarction: association with elevated maternal anticardiolipin antibodies.  Am J Perinatol. 1998;  15 399-402
• 29 Chow G, Mellor D. Neonatal cerebral ischemia with elevated maternal and infant anticardiolipin antibodies.  Dev Med Child Neurol. 2000;  42 412-413
• 30 Tincani A, Allegri F, Sanmarco M et al.. Anticardiolipin antibody assay-a methodological analysis for a better consensus in routine determinations: a cooperative project of the European Antiphospholipid Forum.  Thromb Haemost. 2001;  86 575-583
• 31 Balestrieri G, Tincani A, Spatola L et al.. Anti-beta 2-glycoprotein I antibodies: a marker of antiphospholipid syndrome?.  Lupus. 1995;  4 122-130
• 32 Capute A J, Shapiro B K. The motor quotient: a method for early determination of motor delay.  Am J Dis Child. 1985;  139 940-942
• 33 Zurgil N, Bakimer R, Tincani A et al.. Detection of anti-phospholipid and anti-DNA antibodies and their idiotypes in newborns of mothers with anti-phospholipid syndrome and SLE.  Lupus. 1993;  2 233-237
• 34 Cohen S B, Goldenberg M, Rabinovici J et al.. Anti-cardiolipin antibodies in fetal blood and amniotic fluid derived from patients with the anti-phospholipid syndrome.  Hum Reprod. 2000;  15 1170-1172
• 35 Chamley L W, Allen J L, Johnson P M. Synthesis of β2-glycoprotein 1 by the human placenta.  Placenta. 1997;  18 403-407
• 36 Fialová L, Malbohan I, Mikulíková L, Benešová O, Zwinger A. Antibodies against β2-glycoprotein I (β2-GP I) and their relationship to fetoplacental antigens.  Physiol Res. 2002;  51 449-455
• 37 di Simone N, Meroni P L, Del Papa N et al.. Antiphospholipid antibodies affect trophoblast gonadotropin secretion and invasiveness by binding directly and through adhered beta2-glycoprotein I.  Arthritis Rheum. 2000;  43 140-150
• 38 Avcin T, Cimaz R, Meroni P L. Recent advances in antiphospholipid antibodies and antiphospholipid syndromes in pediatric populations.  Lupus. 2002;  11 4-10
• 39 Avcin T, Ambrozic A, Kuhar M, Kveder T, Rozman B. Anticardiolipin and anti-β2 glycoprotein I antibodies in sera of 61 apparently healthy children at regular preventive visits.  Rheumatology (Oxford). 2001;  40 565-573
• 40 Shoenfeld Y, Krause I, Kvapil F et al.. Prevalence and clinical correlations of antibodies against six beta2-glycoprotein-I-related peptides in the antiphospholipid syndrome.  J Clin Immunol. 2003;  23 377-383

1 Deceased