Genetic association of cutaneous neonatal lupus with HLA class II and tumor necrosis factor α: Implications for pathogenesis

Robert M. Clancy, Chelsea B. Backer, Xiaoming Yin, Mary Wu Chang, Steven R. Cohen, Lela A. Lee, Jill P. Buyon

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2598-2603
Number of pages6
JournalArthritis and Rheumatism
Volume50
Issue number8
DOIs
StatePublished - Aug 2004
Externally publishedYes

Fingerprint

Exanthema
Cutaneous Lupus Erythematosus
Tumor Necrosis Factor-alpha
Skin
Alleles
Discoid Lupus Erythematosus
HLA-DRB1 Chains
Genetic Predisposition to Disease
Ultraviolet Rays
Neonatal Systemic lupus erythematosus
Keratinocytes
Epidermis
Haplotypes
Registries
Siblings
Mothers
Newborn Infant
Staining and Labeling
Cytokines
DNA

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Cite this

Genetic association of cutaneous neonatal lupus with HLA class II and tumor necrosis factor α : Implications for pathogenesis. / Clancy, Robert M.; Backer, Chelsea B.; Yin, Xiaoming; Chang, Mary Wu; Cohen, Steven R.; Lee, Lela A.; Buyon, Jill P.

In: Arthritis and Rheumatism, Vol. 50, No. 8, 08.2004, p. 2598-2603.

Research output: Contribution to journalArticle

Clancy, Robert M. ; Backer, Chelsea B. ; Yin, Xiaoming ; Chang, Mary Wu ; Cohen, Steven R. ; Lee, Lela A. ; Buyon, Jill P. / Genetic association of cutaneous neonatal lupus with HLA class II and tumor necrosis factor α : Implications for pathogenesis. In: Arthritis and Rheumatism. 2004 ; Vol. 50, No. 8. pp. 2598-2603.
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abstract = "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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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.

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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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