TY - JOUR
T1 - Genetic association of cutaneous neonatal lupus with HLA class II and tumor necrosis factor α
T2 - Implications for pathogenesis
AU - Clancy, Robert M.
AU - Backer, Chelsea B.
AU - Yin, Xiaoming
AU - Chang, Mary Wu
AU - Cohen, Steven R.
AU - Lee, Lela A.
AU - Buyon, Jill P.
PY - 2004/8
Y1 - 2004/8
N2 - Objective. Cutaneous neonatal lupus resembles subacute cutaneous lupus erythematosus (SCLE), and photosensitivity is a common symptom. Tumor necrosis factor α (TNFα) release by ultraviolet light-exposed keratinocytes may be exaggerated in SCLE patients who have the haplotype TNFα -308A;DRB1*03. Accordingly, this study was undertaken to seek genetic and histologic evidence for a role of TNFα 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 TNFα 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 TNFα 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 TNFα following tissue injury and the histologic demonstration of TNFα 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.
AB - Objective. Cutaneous neonatal lupus resembles subacute cutaneous lupus erythematosus (SCLE), and photosensitivity is a common symptom. Tumor necrosis factor α (TNFα) release by ultraviolet light-exposed keratinocytes may be exaggerated in SCLE patients who have the haplotype TNFα -308A;DRB1*03. Accordingly, this study was undertaken to seek genetic and histologic evidence for a role of TNFα 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 TNFα 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 TNFα 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 TNFα following tissue injury and the histologic demonstration of TNFα 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.
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U2 - 10.1002/art.20442
DO - 10.1002/art.20442
M3 - Article
C2 - 15334474
AN - SCOPUS:4043121901
SN - 2326-5191
VL - 50
SP - 2598
EP - 2603
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
IS - 8
ER -