Cytokine profile in two siblings with neonatal lupus erythematosus.

We studied the cytokine profile of two siblings with neonatal lupus erythematosus (NLE) born to a mother positive for serum anti-Ro and -La antibodies, who did not receive any medication during the two pregnancies. The first sibling was found to have complete atrioventricular block in utero and became severely ill after birth. He fulfilled the diagnostic criteria for hemophagocytic lymphohistiocytosis on day 2. The second sibling did not have any fetal symptoms. He was generally stable after birth, but with typical skin rash. Laboratory data suggested that they both had hypercytokinemia during the neonatal period, requiring corticosteroid treatment. Interleukin (IL)-6, interferon-γ, IL-8 and monocyte chemotactic protein-1 were elevated in both cases, while IL-12, IL-13 and IL-17 were elevated only in the second sibling. Comparison of the cytokine profiles suggests the potential roles of different cytokines in the onset and clinical manifestations of NLE.

The importance of the level of maternal anti-Ro/SSA antibodies as a prognostic marker of the development of cardiac neonatal lupus erythematosus a prospective study of 186 antibody-exposed fetuses and infants.

OBJECTIVES: The purpose of this study was to determine whether cardiac complications of neonatal lupus erythematosus (NLE) are related to maternal anti-Ro and anti-La autoantibody-levels. BACKGROUND: Autoantibody-positive mothers are frequently referred for serial echocardiography because of the elevated fetal risk of developing immune-mediated heart block. Little is known why only some and not all offspring are affected. METHODS: All cases referred since 2000 for serial fetal echocardiography or cardiac complications related to maternal antibodies were included. Patients without cardiac NLE (group 1) and with cardiac NLE (group 2) were compared. Antibody levels were measured by enzyme-linked immunosorbent assay with a cutoff value of 8 U/ml for a positive test result. RESULTS: Group 1 included 146 serially screened fetuses with normal pregnancy outcomes. Group 2 consisted of 40 fetuses/neonates with a diagnosis of heart block or endocardial fibroelastosis or both, and included 4 fetuses diagnosed during serial screening. All cardiac complications were associated with moderate (>or=50 U/ml; 15%) or high (>or=100 U/ml; 85%) maternal anti-Ro levels, independently of anti-La antibody titres. The event rate of complete heart block was 5% for prospectively screened fetuses with Ro-values >or=50 U/ml (odds ratio: 7.8) and 0% for fetuses with lower titres (p < 0.0001). Infants with pre-natal exposure to high-titre anti-La levels >or=100 U/ml were the most likely to have noncardiac features of NLE (event rate: 57%; odds ratio: 4.7). CONCLUSIONS: Our findings support that the amount of maternal antibodies, rather than their presence, is associated with fetal tissue injury. As anti-Ro levels correlate with the risk of cardiac complications, serial echocardiography should be limited to women with high anti-Ro-titres.

[Rheumatic diseases in pregnancy]. / Rheumatische Erkrankungen in der Schwangerschaft.

Rheumatic diseases can influence the reproduction, the course of pregnancy and the development of the fetus. The inflammatory rheumatic disease itself can be modulated in its activity in terms of amelioration or exacerbation of the rheumatic symptoms. The associations between rheumatic diseases and pregnancy will be illustrated with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and systemic lupus erythematosus as examples. Antirheumatic drug therapy during pregnancy and the breast feeding period has to be adapted critically.

Microchimeric cells in systemic lupus erythematosus: targets or innocent bystanders?

During pregnancy maternal and fetal cells commute back and forth leading to fetal microchimerism in the mother and maternal microchimerism in the child that can persist for years after the birth. Chimeric fetal and maternal cells can be hematopoietic or can differentiate into somatic cells in multiple organs, potentially acting as targets for 'autoimmunity' and so have been implicated in the pathogenesis of autoimmune diseases that resemble graft-versus-host disease after stem cell transplantation. Fetal cells have been found in women with systemic lupus erythematosus, both in the blood and a target organ, the kidney, suggesting that they may be involved in pathogenesis. Future studies will address how the host immune system normally tolerates maternal and fetal cells or how the balance may change during autoimmunity.

From antibody insult to fibrosis in neonatal lupus - the heart of the matter.

Few diseases exemplify the integration of research from bench to bedside as well as neonatal lupus, often referred to as a model of passively acquired autoimmunity. In essence, this disease encompasses two patients, both the mother and her child. The signature histologic lesion of autoimmune-associated congenital heart block is fibrosis of the conducting tissue, and in some cases the surrounding myocardium. It is astounding how rapid and, in most cases, irreversible is the fibrotic response to injury. The mechanism by which maternal anti-SSA/Ro-SSB/La antibodies initiate and perpetuate inflammation, and eventuate in scarring of the atrioventricular node, is not yet defined. In vitro and in vivo studies suggest that one pathologic cascade leading to scarring may be initiated via apoptosis, resulting in translocation of SSA/Ro-SSB/La antigens and subsequent surface binding by maternal autoantibodies. These opsonized cardiocytes are phagocytosed by macrophages, which secrete factors that transdifferentiate fibroblasts into myofibroblasts, a scarring phenotype. Dissecting the individual components in this fibrotic pathway should provide insights into the rarity of irreversible injury and should form the basis of rational approaches to prevention and treatment.

Cutting edge: the orphan chemokine receptor G protein-coupled receptor-2 (GPR-2, CCR10) binds the skin-associated chemokine CCL27 (CTACK/ALP/ILC).

We recently reported the identification of a chemokine (CTACK), which has been renamed CCL27 according to a new systematic chemokine nomenclature. We report that CCL27 binds the previously orphan chemokine receptor GPR-2, as detected by calcium flux and chemotactic responses of GPR-2 transfectants. We renamed this receptor CCR10. Because of the skin-associated expression pattern of CCL27, we focused on the expression of CCL27 and CCR10 in normal skin compared with inflammatory and autoimmune skin diseases. CCL27 is constitutively produced by keratinocytes but can also be induced upon stimulation with TNF-alpha and IL-1beta. CCR10 is not expressed by keratinocytes and is instead expressed by melanocytes, dermal fibroblasts, and dermal microvascular endothelial cells. CCR10 was also detected in T cells as well as in skin-derived Langerhans cells. Taken together, these observations suggest a role for this novel ligand/receptor pair in both skin homeostasis as well as a potential role in inflammatory responses.

Systemic lupus erythematosus and human development.

The symptoms of systemic lupus erythematosus (SLE) suggest that the manifestations of the disorder are related to known or plausible control mechanisms in embryogenesis. It is suggested that homo sapiens has, in the course of evolution, developed novel processes controlling development.