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.

Figures

Figure 1

Assignment of rheumatological classification of mothers at enrolment and follow-up (n = 229). A. Group I: mothers enrolled in the Research Registry for Neonatal Lupus (RRNL) within 1 year of birth of affected child (n = 103). B. Group II: mothers enrolled in the RRNL more than 1 year after birth of affected child (n = 126). SLE, systemic lupus erythematosus; SS, Sjögren syndrome; UAS, undifferentiated autoimmune syndrome.

Figure 2

Time to disease progression for mothers initially asymptomatic or diagnosed with pauci-undifferentiated autoimmune syndrome (pauci-UAS). A. Estimated distribution of time to disease progression (development of any symptom for initially asymptomatic mothers). B. Estimated distribution of time to development of systemic lupus erythematosus (SLE) in initially asymptomatic mothers. C. Estimated distribution of time to development of probable or definite Sjögren syndrome (SS) in initially asymptomatic mothers. D. Kaplan–Meier disease-free survival curve for time to progression in initially pauci-UAS mothers.

Figure 3

Estimates of the distribution of time to disease progression by antibody status.