In utero and early life exposures to smoking are associated with systemic autoimmune rheumatic diseases

Systemic autoimmune rheumatic diseases (SARDs) are influenced by genetic and environmental factors. We examined pregnancy complications, early life events (birth season, birth order, feeding), and exposures to tobacco smoking in relation to SARD diagnosis.

In a case-control study, probands with SARDs were compared to same-sex close-in-age unaffected siblings (US), and demographically-matched unrelated controls (UC); 329 children (probands=124, US=115, UC=90) and 184 adults (probands=76, US=63, UC=45) were included. Conditional and unconditional logistic regression were used to examine proband-US and proband-UC comparisons. We examined associations between SARDs and exposures to smoking while adjusting for HLA-DRB1*03:01 in White probands and UC.

No specific pregnancy complication was associated with SARDs; however, the total number of pregnancy complications was greater in juvenile probands. A higher proportion of juvenile-onset probands than UC were exposed to tobacco smoking, both in utero and after birth (prenatal, 20 % vs 4 %, OR=4.04, 95 %CI=1.20-17.7; household smoking before age 3, 14 % vs 3 %, OR=4.83, 95 %CI=1.31-26.1). Among adult-onset probands and US, household smoking exposure before age 10 was associated with SARDs (60 % vs 42 %, OR=10.06, 95 %CI=1.23-82.0). Among White subjects, HLA-DRB1*03:01 was associated with SARDs (juvenile-onset OR=2.03, 95 %CI=1.04-4.10; adult-onset OR=7.67, 95 %CI=2.72-26.4). After adjusting for HLA-DRB1*03:01, household smoking exposure was associated with juvenile- and adult-onset SARDs (OR=5.49, 95 %CI=1.22-39.7, and OR=4.01, 95 %CI=1.11-17.2).

Early life exposure to tobacco smoking is associated with SARDs; the effect remained after adjusting for the genetic risk of HLA. These findings support a role for early environmental exposures in autoimmune diseases.