Abstract: Anti-52 kDa Ro, Anti-60 kDa Ro, and Anti-La Antibody Profiles in Neonatal Lupus

Anti-52 kDa Ro, Anti-60 kDa Ro, and Anti-La Antibody Profiles in Neonatal Lupus

PATRICK GORDON, MUNTHER A. KHAMASHTA, ERIC ROSENTHAL, JOHN M. SIMPSON, GURLEEN SHARLAND, ANTONIO BRUCATO, FRANCO FRANCESCHINI, KATRIEN DE BOSSCHERE, LYDIE MEHEUS, PIER LUIGI MERONI, GRAHAM R.V. HUGHES, and JILL BUYON

ABSTRACT.

Objective. Studies suggest that anti-52 kDa Ro antibodies are more sensitive and specific than anti-60 kDa Ro antibodies for neonatal lupus. However, these studies mainly used immunoblot or ELISA using recombinant protein, which have poor sensitivity for anti-60 kDa Ro antibodies. In addition, the control patients were not disease matched. We reassessed the sensitivity and specificity of anti-52 kDa Ro, anti-60 kDa Ro, and anti-La, addressing these limitations.

Methods and Results. To assess sensitivity, 125 mothers of children with neonatal lupus (NLM) were recruited. All maternal sera were assessed using a commercial line immunoassay that uses natural 60 kDa Ro protein (Inno-Lia^TM ANA Update, Innogenetics NV, Gent, Belgium). By this method, 96% of the sera had antibodies to 60 kDa Ro, 86% to 52 kDa Ro, and 78% to 48 kDa La. Immunoblot of 65 NLM showed significantly fewer positive results for anti-60 kDa Ro (p < 0.001) and anti-52 kDa Ro (p < 0.05). Sensitivity of the 3 antibodies was assessed in the symptomatic mothers of children with congenital heart block (CHB) (78 women) and disease matched controls with unaffected children (65 women) using Inno-Lia^TM ANA Update. The sensitivity of each antibody was compared by multiple logistic regression to adjust for maternal disease. There was no significant difference between the groups for 60 kDa Ro or for anti-52 kDa Ro antibody. However, there was a significant difference for the anti-La antibody (p = 0.001), with an odds ratio of 3.59. This translates to an increase in risk from a published 2% for CHB in an anti-Ro-positive mother to 3.1% if the woman is also anti-La antibody-positive, and to a decrease in risk to 0.9% if anti-La-negative.

Conclusion. Contrary to previous reports, 52 kDa Ro as detected by Inno-Lia^TM ANA Update is not more specific for or frequent in CHB than 60 kDa Ro. However, the presence of anti-La antibodies significantly increases the risk for CHB. (J Rheumatol 2004;31:2480-7)

Key Indexing Terms:

CONGENITAL HEART BLOCK
NEONATAL LUPUS RASH

From King's College Hospital, London, UK; St. Thomas' and Guy's Hospitals, London, UK; Ospedale Niguarda, Milan, Italy; Spedali Civili, Brescia, Italy; Innogenetics NV, Gent, Belgium; IRCCS Istituto Auxologico Italiano, University of Milan, Milan, Italy; and the Hospital for Joint Diseases, New York University School of Medicine, New York, NY, USA.

Supported by Innogenetics NV, Gent, Belgium. Dr. Gordon was supported by the British Heart Foundation. Many of the sera were provided by the Research Registry for Neonatal Lupus, which is supported by the US National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH Contract AR-4-2220 for the Research Registry for Neonatal Lupus, directed by Dr. Buyon). Prof. Meroni and Dr. Brucato were supported by a grant from MURST, Cofin 2000, and Ricerca Corrente 2000-02 IRCCS Istituto Auxologico Italiano.

P.A. Gordon, MRCP, Consultant Physician and Rheumatologist, King's College Hospital, London, UK; M.A. Khamashta, MD, FRCP, PhD, Senior Lecturer/Consultant Physician, Lupus Research Unit, The Rayne Institute, St. Thomas' Hospital, London, UK; E. Rosenthal, MD, FRCP, Consultant in Paediatric Cardiology, Department of Paediatric Cardiology; J.M. Simpson, MD, FRCP, Consultant in Fetal and Paediatric Cardiology, Fetal Cardiology Unit; G. Sharland, BSc, MD, FRCP, Reader in Fetal Cardiology, Fetal Cardiology Unit, Guy's Hospital, London, UK; A. Brucato, MD, Ospedale Niguarda, Milan, Italy; F. Franceschini, MD, Allergy, Clinical Immunology and Rheumatology Service, Spedali Civili, Brescia, Italy; K. De Bosschere, Bio-engineer (ir.); L. Meheus, PhD, Innogenetics NV, Gent, Belgium; P.L. Meroni, MD, Professor of Medicine, Department of Internal Medicine, University of Milan, Allergy, Clinical Immunology and Rheumatology Unit, IRCCS, Istituto Auxologico Italiano, Milan, Italy; G.R.V. Hughes, MD, FRCP, Head, Lupus Research Unit, The Rayne Institute, St. Thomas' Hospital, London, UK; J. Buyon, MD, Professor of Medicine, Hospital for Joint Diseases, New York University School of Medicine, New York, NY, USA.

Address reprint requests to Dr. P. Gordon, Department of Rheumatology, King's College Hospital, London SE5 9RS, United Kingdom. E-mail: Patrick.Gordon@kcl.ac.uk

Submitted February 17, 2004; revision accepted July 4, 2004.