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


CONCLUSIONS
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.
Clancy
Robert M
RM
Department of Rheumatology, Hospital for Joint Diseases, New York University School of Medicine, New York, New York 10003, USA. bobdclancy@aol.com
Backer
Chelsea B
CB
Yin
Xiaoming
X
Chang
Mary Wu
MW
Cohen
Steven R
SR
Lee
Lela A
LA
Buyon
Jill P
JP
D004817:Epidermis / Q000737:chemistry; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D006327:Heart Block / Q000150:complications / Q000151:congenital; D006801:Humans; D007231:Infant, Newborn; D008178:Lupus Erythematosus, Cutaneous / Q000150:complications / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D014409:Tumor Necrosis Factor-alpha