母体对52-kd SSA/RO p200肽的抗体反应与胎儿传导缺陷的发生

Maternal antibody responses to the 52-kd SSA/RO p200 peptide and the development of fetal conduction defects.

作者信息

Clancy Robert M, Buyon Jill P, Ikeda Keigo, Nozawa Kazuhisa, Argyle Dionne A, Friedman Deborah M, Chan Edward K L

机构信息

Department of Rheumatology, Hospital for Joint Diseases, New York University School of Medicine, New York, New York 10003, USA.

出版信息

Arthritis Rheum. 2005 Oct;52(10):3079-86. doi: 10.1002/art.21289.

DOI:10.1002/art.21289

PMID:16200587

Abstract

OBJECTIVE

To identify a finer level of antibody specificity for risk of congenital heart block (CHB) than reactivity to 52-kd SSA/Ro (Ro 52).

METHODS

Serum from mothers enrolled in the Research Registry for Neonatal Lupus and the observational PR Interval and Dexamethasone Evaluation (PRIDE) study was evaluated for reactivity against peptide aa200-239 of Ro 52 (p200), recently reported to be associated with a higher risk of CHB.

RESULTS

The majority of 156 Ro 52-positive sera tested were reactive with p200 (>3 SD above control), irrespective of the clinical status of the child. Optical density (OD) values of p200 did not differ significantly among mothers of children with CHB (mean +/- SD 0.187 +/- 0.363), mothers of children with rash (mean +/- SD 0.176 +/- 0.356), and mothers of children without neonatal lupus (mean +/- SD 0.229 +/- 0.315). Reactivity against p200 was found in 80 of 104 mothers of children with CHB (77%), 24 of 30 mothers of children with rash (80%), and 21 of 22 mothers who delivered healthy children and had no children with neonatal lupus (95%) (P not significant for all comparisons). Sera from 4 mothers of children with CHB with varied p200 titers (OD range 0.025-1.818) bound to the surface of non-permeabilized apoptotic, but not proliferating, human fetal cardiocytes. In 32 Ro 52-positive women who completed the PRIDE study (22 with no child with neonatal lupus, 7 with a child with CHB, and 3 with a child with rash) in whom p200 levels were determined during pregnancy, the correlation between level of p200 (OD range 0.000-1.170) and maximal fetal PR interval (range 115-168 msec) was not significant (rho = 0.107, P = 0.58).

CONCLUSION

Reactivity to p200 is a dominant but not uniform anti-Ro 52 response in women whose children have CHB. Since exposure to this antibody specificity was observed with a similar frequency in children without CHB born to mothers with anti-Ro 52, additional factors are necessary to convert risk to disease expression.

摘要

目的

确定比针对52-kd SSA/Ro（Ro 52）的反应性更精细的先天性心脏传导阻滞（CHB）风险抗体特异性水平。

方法

对参加新生儿狼疮研究登记处和观察性PR间期与地塞米松评估（PRIDE）研究的母亲的血清进行评估，以检测其对Ro 52的aa200-239肽段（p200）的反应性，最近报道该肽段与较高的CHB风险相关。

结果

所检测的156份Ro 52阳性血清中的大多数与p200反应（高于对照3个标准差以上），无论孩子的临床状况如何。CHB患儿母亲（平均±标准差0.187±0.363）、皮疹患儿母亲（平均±标准差0.176±0.356）和无新生儿狼疮患儿母亲（平均±标准差0.229±0.315）的p200光密度（OD）值无显著差异。104例CHB患儿母亲中有80例（77%）、30例皮疹患儿母亲中有24例（80%）以及22例分娩健康儿童且无新生儿狼疮患儿的母亲中有21例（95%）对p200有反应（所有比较P均无显著性）。4例CHB患儿母亲的血清，其p200滴度各异（OD范围0.025-1.818），能结合未通透的凋亡人胎儿心肌细胞表面，但不能结合增殖的心肌细胞表面。在32例完成PRIDE研究的Ro 52阳性女性中（22例无新生儿狼疮患儿，7例有CHB患儿，3例有皮疹患儿），在孕期测定了p200水平，p200水平（OD范围0.000-1.170）与胎儿最大PR间期（范围115-168毫秒）之间的相关性不显著（rho = 0.107，P = 0.58）。