Session Title: ACR/ARHP Combined Abstract Session: Pediatric Rheumatology
Session Type: ACR Concurrent Abstract Session
Session Time: 9:00AM-10:30AM
Background/Purpose: Neonatal Lupus (NL) is a model of passively acquired autoimmunity conferred by exposure to maternal anti-Ro antibodies. This study was initiated to address the development of de novo autoimmunity in these children and identify associated genetic risk factors. Of relevance, the initial NL congenital heart block (CHB) GWAS revealed associations with HLA class I genes of the PSORS1 region that are linked to psoriasis.
Methods: In a retrospective cohort study of enrollees in the Research Registry for Neonatal Lupus, 346 children exposed to anti-Ro in utero responded to a follow up questionnaire focused on symptoms of autoimmunity. Self-reported diseases were confirmed via medical record review. Bivariate analyses were performed with potential risk factors for autoimmune disease development including NL manifestation, a disease severity score based on mortality risk factors, and maternal diagnosis of systemic lupus erythematosus (SLE) or Sjogren’s syndrome (SS). In a substudy of these children (188 with CHB and their parents), DNA was interrogated using the Immunochip, a 196,806 SNP array that maps 200 regions containing known autoimmune diseases. Findings were compared to published SNPs outside of the HLA region in cohorts of rheumatoid arthritis (RA), Type 1 Diabetes (T1D) and psoriasis.
Results: Of the respondents, 134 had CHB, 74 cutaneous NL and 138 were unaffected siblings. Females comprised 54% and 81% were Caucasian. The mean age was 11.3±8.3; 10% age 0-2 years, 49% 2-13, and 40% > 13. An autoimmune disease developed in 24; 17 had CHB, 2 cutaneous NL and 5 unaffected (Table 1). The most prevalent disease was psoriasis. The presence of CHB was significantly associated with autoimmunity vs the cutaneous or unaffected children (12% vs 3%, p=0.002). An association between higher NL severity score and autoimmune disease was also found (5.0±4.7 vs 2.5±4.2, p= 0.003). The development of autoimmunity was not significantly different in children whose mother had SLE or SS vs those with asymptomatic mothers (7% vs 7%, p=1.0). No mother had psoriasis. Genetic analysis revealed that for significant associations of CHB vs. controls (p<0.01), overlaps were observed with other autoimmune diseases: 2 SNPs associated with RA, 0 T1D, and 178 psoriasis. For the latter, gene regions at B3GNT2-TMEM17, TRAF31P2 and KEAP-SLC9A8-SPATA2-RNF114 were of particular interest as these were significant in CHB offspring but not mothers.
Conclusion: Genetic risks factors in NL may predispose affected offspring to autoimmune diseases later in life, including psoriasis. That the development of an autoimmune disease is most apparent in those with CHB and more severe disease may relate to an inherent susceptibility to inflammation, manifest both in utero and later in life. The absence of certain SNPs in the mothers and independence of maternal clinical disease suggests that NL offspring may occupy a unique place in the spectrum of autoimmunity.
To cite this abstract in AMA style:Garza Romero A, Izmirly PM, Ainsworth HC, Marion M, Langefeld C, Clancy R, Buyon JP, Saxena A. Development of Autoimmune Diseases and Genetic Predisposition in Children with Neonatal Lupus and Their Unaffected Siblings [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/development-of-autoimmune-diseases-and-genetic-predisposition-in-children-with-neonatal-lupus-and-their-unaffected-siblings/. Accessed August 4, 2021.
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