Genetic association of cutaneous neonatal lupus with HLA class II and tumor necrosis factor alpha: implications for pathogenesis.

Abstract

OBJECTIVE:

Cutaneous neonatal lupus resembles subacute cutaneous lupus erythematosus (SCLE), and photosensitivity is a common symptom. Tumor necrosis factor alpha (TNFalpha) release by ultraviolet light-exposed keratinocytes may be exaggerated in SCLE patients who have the haplotype TNFalpha -308A;DRB1*03. Accordingly, this study was undertaken to seek genetic and histologic evidence for a role of TNFalpha in the pathogenesis of cutaneous neonatal lupus.

METHODS:

DNA was isolated from 83 children (22 with rash, 35 with congenital heart block [CHB], 26 unaffected siblings) and 58 mothers from the Research Registry for Neonatal Lupus.

RESULTS:

The -308A allele (associated with higher TNFalpha production), HLA-DRQB1*02, and HLA-DRB1*03 were each present in the majority of children with rash (64%, 68%, and 64%, respectively). The frequency of all 3 6p alleles occurring together in 1 individual was greater in children with rash than in children who had either CHB or no manifestation of neonatal lupus (59% versus 30%; P = 0.02). This association with neonatal lupus rash was equivalent to published findings in a cohort of patients with SCLE, but significantly greater than the association in patients with discoid lupus erythematosus. Prominent TNFalpha staining in the epidermis was observed in lesional skin from 3 children with rash, but not in skin from a healthy neonate.

CONCLUSION:

Taken together, the finding of a genetic predisposition to generate increased levels of TNFalpha following tissue injury and the histologic demonstration of TNFalpha in the target organ support the notion that this inflammatory cytokine plays a role in the pathogenesis of cutaneous neonatal lupus. Furthermore, the results of these studies provide evidence of a biologic link between neonatal lupus and the rash of SCLE.

• Authors: Robert M Clancy, Chelsea B Backer, Xiaoming Yin, Mary Wu Chang, Steven R Cohen, Lela A Lee, Jill P Buyon
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 50 Issue 8 Pg. 2598-603 (Aug 2004) ISSN: 0004-3591 [Print] United States
• PMID: 15334474 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• HLA-DQ Antigens
• HLA-DQ beta-Chains
• HLA-DQB1 antigen
• HLA-DR Antigens
• Tumor Necrosis Factor-alpha

Topics

• Epidermis (chemistry)
• HLA-DQ Antigens (genetics)
• HLA-DQ beta-Chains
• HLA-DR Antigens (genetics)
• Heart Block (complications, congenital)
• Humans
• Infant, Newborn
• Lupus Erythematosus, Cutaneous (complications, genetics)
• Tumor Necrosis Factor-alpha (analysis)