Serum type I interferon activity is dependent on maternal diagnosis in anti-SSA/Ro-positive mothers of children with neonatal lupus.
OBJECTIVE
The type I interferon (IFN) pathway is activated in many patients with systemic lupus erythematosus (SLE), and high serum levels of IFN are associated with anti-SSA/Ro autoantibodies. To investigate the clinical features associated with type I IFN production in vivo, we compared serum IFN activity in individuals with anti-SSA/Ro antibodies who were asymptomatic with that in individuals with clinical manifestations of SLE or Sjögren's syndrome (SS).


METHODS
Antibody-positive sera from 84 mothers of children with manifestations of neonatal lupus were studied for type I IFN activity, using a functional reporter cell assay. Maternal health status was characterized as asymptomatic, SS, SLE, pauci-SLE, or pauci-SS, based on a screening questionnaire, telephone interview, and review of medical records. The prefix "pauci-" indicates symptoms insufficient for a formal classification of the disease.


RESULTS
Only 4% of asymptomatic mothers had high serum type I IFN activity, compared with 73% with pauci-SLE (P = 5.7 x 10(-5)), 35% with SLE (P = 0.011), and 32% of patients with SS (P = 0.032). One of the 4 patients with pauci-SS had high levels of IFN. The majority of patients for whom longitudinal data were available had stable type I IFN activity over time, and changes in IFN activity were not clearly accompanied by changes in the clinical diagnosis.


CONCLUSIONS
Patients with SLE, patients with pauci-SLE, and patients with SS are more likely to have high serum IFN activity than asymptomatic individuals with SSA/Ro autoantibodies, suggesting that these autoantibodies are insufficient for activation of the type I IFN pathway, and that disease-specific factors are important for type I IFN generation in vivo.
Niewold
Timothy B
TB
University of Chicago, Section of Rheumatology, Chicago, Illinois 60637, USA. tniewold@medicine.bsd.uchicago.edu
Rivera
Tania L
TL
Buyon
Jill P
JP
Crow
Mary K
MK
D000328:Adult; D000974:Antibodies, Antinuclear / Q000097:blood* / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000276:immunology*; D007370:Interferon Type I / Q000097:blood* / Q000276:immunology; D008137:Longitudinal Studies; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000276:immunology*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology*; D012042:Registries; D012859:Sjogren's Syndrome / Q000175:diagnosis / Q000276:immunology
D000974:Antibodies, Antinuclear; D007370:Interferon Type I; C035356:SS-A antibodies