Der neonatale Lupus erythematodes (NLE) umfasst vorrangig den kutanen NLE und den angeborenen AV-Block und wird durch eine antikörpervermittelte Entzündungsreaktion ausgelöst, wobei transplazentar übertragenen mütterlichen Autoantikörpern gegen den RNA-Proteinkomplex Ro(SS-A)/La(SS-B) eine pathogenetische Bedeutung zukommt. Die Krankheitsmanifestationen des NLE sind mit Ausnahme des kompletten kongenitalen Herzblockes (CCHB) durch den Abbau der mütterlichen Antikörper in der Zirkulation des Neugeborenen limitiert. Dabei gilt der CCHB als eine vital bedrohliche Komplikation, die insbesondere bei Müttern mit subklinischem Sjögren-Syndrom und koinzidenten Autoantikörpern gegen Ro(SS-A) und La(SS-B) auftreten kann. Die Arbeit gibt einen aktuellen Überblick zu diagnostischen und differenzialtherapeutischen Aspekten des angeborenen atrioventrikulären (AV-)Blockes, der enger mit einem mütterlichen Sjögren-Syndrom als mit einem systemischen Lupus erythematodes (SLE) assoziiert ist.
Abstract
Neonatal lupus erythematosus (NLE) comprises predominantly cutaneous neonatal lupus erythematosus and congenital atrioventricular block and is triggered by an inflammatory reaction mediated by antibodies. In this regard, pathogenetic significance is ascribed to transplacentally transfered maternal auto-antibodies against the RNA protein complex Ro(SS-A) / La(SS-B). The manifestations of NLE are limited due to degradation of the maternal antibodies, except, however, the manifestations of complete congenital heart block (CCHB). It must be beared in mind that CCHB is rated a life-threatening complication that can occur especially in mothers suffering from sub-clinical Sjögren’s syndrome co-incidentally with auto-antibodies against Ro(SS-A) and La(SS-B). The following article is an update review of the diagnostic and differential therapeutic aspects of neonatal atrioventricular block that is more closely associated with a maternal Sjögren’s syndrome than with systemic lupus erythematosus.
Literatur
1
Buyon J P.
Neonatal lupus syndromes.
Curr Opin Rheumatol.
1994;
6
523-529
3
Eronen M, Siren M K, Ekblad H. et al .
Short- and long-term outcome of children with congenital complete heart block diagnosed in utero or as a newborn.
Pediatrics.
2000;
106
86-91
4
Buyon J P, Hiebert R, Copel J. et al .
Autoimmune-associated congenital heart block: demographics, mortality, morbidity and recurrence rates obtained from a national neonatal lupus registry.
J Am Coll Cardiol.
1998;
31
1658-1666
6
Franco H L, Weston W L, Peebles C. et al .
Autoantibodies directed against sicca syndrome antigens in the neonatal lupus syndrome.
J Am Acad Dermatol.
1981;
4
67-72
9
Ishibashi-Ueda H, Yutani C, Imakita M. et al .
An autopsy case of congenital complete heart block in a newly born of a mother with systemic lupus erythematosus.
Pediatr Cardiol.
1988;
9
157-161
11
Scott J S, Maddison P J, Taylor P V. et al .
Connective tissue disease, antibodies to ribonucleoprotein and congenital heart block.
N Engl J Med.
1983;
309
209-212
13
Silverman E D, Mamula M, Hardin J A. et al .
Importance of the immune response to the Ro/La particle in the development of congenital heart block and neonatal lupus erythematosus.
J Rheumatol.
1991;
18
120-124
14
Buyon J P, Ben-Chetrit E, Karp S. et al .
Acquired congenital heart block. Pattern of maternal antibody response to biochemically defined antigens of the SSA/Ro-SSB/La system in neonatal lupus.
J Clin Invest.
1989;
84
627-634
16
Buyon J P, Waltuck J, Caldwell K. et al .
Relationship between maternal and neonatal levels of antibodies to 48 kD SSB(La), 52 kD SSA(Ro), and 60 kD SSA(Ro) in pregnancies complicated by congenital heart block.
J Rheumatol.
1994;
21
1943-1950
17
Taylor P V, Taylor K F, Norman A. et al .
Prevalence of maternal Ro(SS-A) and La(SS-B) autoantibodies in relation to congenital heart block.
Br J Rheumatol.
1988;
27
128-132
18
Dörner T, Chaoui R, Feist E. et al .
Significantly increased maternal and fetal IgG autoantibody levels to 52 kD Ro(SS-A) and La(SS-B) in complete congenital heart block.
J Autoimm.
1995;
8
675-684
19
Carreira P E, Gutierrez L arraya F, Gomez R eino JJ.
Successful intrauterine therapy with dexamethasone for fetal myocarditis and heart block in a woman with systemic lupus erythematosus.
J Rheumatol.
1993;
20
1204-1207
21
Julkunen H, Kurki P, Kaaja R. et al .
Isolated congenital heart block: long-term outcome of mothers and characterization of the immune response to SS-A/Ro and SS-B/La.
Arthritis Rheum.
1993;
36
1588-1598
22
Ramsey-Goldman R, Hom D, Deng J S. et al .
Anti-SS-A antibodies and fetal outcome in maternal systemic lupus erythematosus.
Arthritis Rheum.
1986;
10
1269-1273
23
Derksen R H, Meilof J F.
Anti-Ro/SS-A and anti-La/SS-B autoantibody levels in relation to systemic lupus erythematosus disease activity and congenital heart block. A longitudinal study comprising two consecutive pregnancies in a patient with systemic lupus erythematosus.
Arthritis Rheum.
1992;
35
953-959
24
Meilof J F, Frohn-Mulder I M, Stewart P A. et al .
Maternal autoantibodies and congenital heart block: no evidence for the existence of a unique heart block-associated anti-Ro/SS-A autoantibody profile.
Lupus.
1993;
2
239-246
25
Miranda-Carus M E, Askanase A D, Clancy R M. et al .
Anti-SSA/Ro and anti-SSB/La autoantibodies bind the surface of apoptotic fetal cardiocytes and promote secretion of TNF-alpha by macrophages.
J Immunol.
2000;
165
5345-5351
26
Buyon J P, Tseng C E, Di Donato F. et al .
Cardiac expression of 52beta, an alternative transcript of the congenital heart block-associated 52-kd SS-A/Ro autoantigen, is maximal during fetal development.
Arthritis Rheum.
1997;
40
655-660
27
Miranda-Carus M E, Boutjdir M, Tseng C E. et al .
Induction of antibodies reactive with SSA/Ro-SSB/La and development of congenital heart block in a murine model.
J Immunol.
1998;
161
5886-5892
28
Alexander E L, Buyon J P, Lane J. et al .
Anti-SS-A/Ro SS-B/La antibodies bind to neonatal rabbit cardiac cells and preferentially inhibit in vitro cardiac repolarization.
J Autoimmun.
1989;
2
463-469
29
Garcia S, Nascimento H M, Bonfa E. et al .
Cellular mechanisms of the conduction abnormalities induced by serum from anti-Ro/SSA-positive patients in rabbit hearts.
J Clin Invest.
1994;
93
718-724
30
Julkunen H, Kaaja R, Siren M K. et al .
Immune-mediated congenital heart block (CHB): identifying and counseling patients at risk for having children with CHB.
Semin Arthritis Rheum.
1998;
28
97-106
32
Reichlin M, Friday K, Harley J B.
Complete congenital heart block followed by anti-Ro/SS-A in adult life. Studies of an informative family.
Am J Med.
1988;
2
339-344
36
Julkunen H, Siren M K, Kaaja R. et al .
Maternal HLA antigens and antibodies to SS-A/Ro and SS-B/La -comparison with systemic lupus erythematosus and primary Sjögren’s syndrome.
Br J Rheumatol.
1995;
34
901-907
37
Bierman F Z, Baxi L, Jaffe I. et al .
Fetal hydrops and congenital complete heart block: response to maternal steroid therapy.
J Pediatr.
1988;
112
646-648
39
Herreman G, Sauvaget F, Genereau T. et al .
Congenital atrioventricular block and maternal autoimmune diseases.
Ann Med Interne Paris.
1990;
141
234-238
41
Zemlin M, Bauer K, Dorner T. et al .
Intrauterine therapy and outcome in four pregnancies of one mother with anti ro-autoantibody positive Sjoegren’s syndrome.
Z Geburtshilfe Neonatol.
2002;
206
22-25
42
Buyon J P, Swersky S H, Fox H E. et al .
Intrauterine therapy for presumptive fetal myocarditis with acquired heart block due to systemic lupus erythematosus. Experience in a mother with a predominance of SS-B (La) antibodies.
Arthritis Rheum.
1987;
30
44-49
43
Feist E, Dörner T, Wagenmann A. et al .
Erfolgreiches therapeutisches Management einer Risikoschwangerschaft bei primärem Sjögren-Syndrom mit Plasmapherese und Dexamethason.
Z Rheumatol.
1996;
55
127-132
44
Kaaja R, Julkunen H, Ämmälä P. et al .
Congenital heart block: Successful prophylactic treatment with intravenous gamma globulin and corticosteroid therapy.
Am J Obstet Gynecol.
1991;
165
1333-1334
