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)α, 869T/C transforming growth factor (TGF)β and −889C/T interleukin (IL)1α. 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 TGFβT/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.

A comprehensive review of the clinical approach to pregnancy and systemic lupus erythematosus

“…Neonatal lupus (NL) is a passively acquired autoimmune disease mediated by maternal autoantibodies and was reported in about 1e2% of babies born to mothers with antibodies to Ro/SSA and/or La/SSB with autoimmune disease (mainly SLE and primary Sj€ ogren's syndrome, pSS) [78]. However, some cases occur in children of mothers who have the same autoantibodies, but who do not have any symptoms of SLE nor autoimmune diseases at the time of pregnancy; about one-half of these mothers could develop autoimmune disease in the future [79]. Neonatal Lupus includes benign forms such as cutaneous manifestations and asymptomatic elevation of liver function tests, but also cytopenia and central nervous system involvement.…”

Prevention of complete heart block in children of mothers with anti-SSA/Ro and anti-SSB/La autoantibodies: detection and treatment of first-degree atrioventricular block

“…Neonatal lupus manifestations did not predict disease progression in an asymptomatic mother. Mothers with anti-SSA/Ro and anti-SSB/La were nearly twice as likely to develop an autoimmune disease as mothers with anti-SSA/Ro only [16]. The authors recommended continued follow-up of asymptomatic neonatal lupus.…”

Neonatal Lupus

“…In a review of the RRNL, 50 % of mothers had progression of autoimmune symptoms. The probability of an asymptomatic mother developing SLE or SS by 10 years is roughly 19 and 28 %, respectively [ 26 ]. The NL manifestation of the child was not predictive of maternal disease progression [ 26 ].…”

“…Studies show that presence of maternal rheumatic disease does not appear to infl uence the recurrence of the NL [ 12 , 25 ]. However, about half of asymptomatic mothers of NL offspring will go on to later develop an autoimmune disease, the most common being SS [ 26 ].…”