PMID- 15334474
OWN - NLM
STAT- MEDLINE
DCOM- 20040924
LR  - 20111117
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 50
IP  - 8
DP  - 2004 Aug
TI  - Genetic association of cutaneous neonatal lupus with HLA class II and tumor 
      necrosis factor alpha: implications for pathogenesis.
PG  - 2598-603
AB  - 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.
FAU - Clancy, Robert M
AU  - Clancy RM
AD  - Department of Rheumatology, Hospital for Joint Diseases, New York University 
      School of Medicine, New York, New York 10003, USA. bobdclancy@aol.com
FAU - Backer, Chelsea B
AU  - Backer CB
FAU - Yin, Xiaoming
AU  - Yin X
FAU - Chang, Mary Wu
AU  - Chang MW
FAU - Cohen, Steven R
AU  - Cohen SR
FAU - Lee, Lela A
AU  - Lee LA
FAU - Buyon, Jill P
AU  - Buyon JP
LA  - eng
GR  - AR-42220/AR/NIAMS NIH HHS/United States
GR  - AR-42455/AR/NIAMS NIH HHS/United States
GR  - AR-48409/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQB1 antigen)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
CIN - Arthritis Rheum. 2005 May;52(5):1623-5; author reply 1625-6. PMID: 15880834
MH  - Epidermis/chemistry
MH  - HLA-DQ Antigens/*genetics
MH  - HLA-DQ beta-Chains
MH  - HLA-DR Antigens/*genetics
MH  - Heart Block/complications/congenital
MH  - Humans
MH  - Infant, Newborn
MH  - Lupus Erythematosus, Cutaneous/complications/*genetics
MH  - Tumor Necrosis Factor-alpha/*analysis
EDAT- 2004/08/31 05:00
MHDA- 2004/09/25 05:00
CRDT- 2004/08/31 05:00
PHST- 2004/08/31 05:00 [pubmed]
PHST- 2004/09/25 05:00 [medline]
PHST- 2004/08/31 05:00 [entrez]
AID - 10.1002/art.20442 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2004 Aug;50(8):2598-603. doi: 10.1002/art.20442.