title: Disease progression in mothers of children enrolled in the Research Registry for Neonatal Lupus.
abstract: OBJECTIVE
  To evaluate autoimmune disease progression in asymptomatic and pauci-symptomatic mothers of children with neonatal lupus (NL).
  
  
  METHODS
  Clinical information on mothers enrolled in the Research Registry for NL (RRNL) was obtained from medical records. Genotyping was performed for -308A/G tumour necrosis factor (TNF)alpha, 869T/C transforming growth factor (TGF)beta and -889C/T interleukin (IL)1alpha.
  
  
  RESULTS
  Of the 321 mothers enrolled, 229 had at least 6 months of follow-up. Of the 51 mothers who were asymptomatic at the NL child's birth, 26 progressed: 12 developed pauci-undifferentiated autoimmune syndrome (pauci-UAS), 2 poly-UAS, 7 SS, 4 SLE and 1 SLE/SS. The median time to develop any symptom was 3.15 years. Of the 37 mothers classified as pauci-UAS at the NL child's birth, 16 progressed: 5 developed poly-UAS, 6 Sjögren syndrome (SS), 4 systemic lupus erythematosus (SLE) and 1 SLE/SS. Of the pauci-UAS mothers enrolled within 1 year, the median time to progression was 6.7 years. Four mothers developed lupus nephritis (two asymptomatic, two pauci-UAS). The probability of an asymptomatic mother developing SLE by 10 years was 18.6%, and developing probable/definite SS was 27.9%. NL manifestations did not predict disease progression in an asymptomatic mother. Mothers with anti-Sjögren syndrome A antigen (SSA/)Ro and anti-Sjögren syndrome B antigen (SSB)/La were nearly twice as likely to develop an autoimmune disease as mothers with anti-SSA/Ro only. Only TGFbetaT/T was significantly higher in SLE mothers compared to asymptomatic mothers (p = 0.03).
  
  
  CONCLUSIONS
  Continued follow-up of asymptomatic NL mothers is warranted since nearly half progress, albeit few develop SLE. While the anti-SSB/La antibodies may be a risk factor for progression, further work is needed to determine reliable biomarkers in otherwise healthy women with anti-SSA/Ro antibodies identified solely because of an NL child.
authors.affiliation: New York University School of Medicine, New York, 10016, USA. tania.rivera@nyumc.org
authors.forename: T L
authors.initials: TL
authors.lastname: Rivera
authors.forename: P M
authors.initials: PM
authors.lastname: Izmirly
authors.forename: B K
authors.initials: BK
authors.lastname: Birnbaum
authors.forename: P
authors.initials: P
authors.lastname: Byrne
authors.forename: J B
authors.initials: JB
authors.lastname: Brauth
authors.forename: M
authors.initials: M
authors.lastname: Katholi
authors.forename: M Y
authors.initials: MY
authors.lastname: Kim
authors.forename: J
authors.initials: J
authors.lastname: Fischer
authors.forename: R M
authors.initials: RM
authors.lastname: Clancy
authors.forename: J P
authors.initials: JP
authors.lastname: Buyon
mesh_terms: D000974:Antibodies, Antinuclear / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D008180:Lupus Erythematosus, Systemic / Q000151:congenital* / Q000235:genetics / Q000276:immunology; D009035:Mothers; D011110:Polymorphism, Genetic; D012042:Registries; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; C035356:SS-A antibodies; C035357:SS-B antibodies; D014409:Tumor Necrosis Factor-alpha