We thank Dr. Ruffatti and colleagues for their interest in our work. They report on a family in which CHB is present in 2 generations. Two points are notable, one related to maternal and fetal genetics and the risk of CHB, and the other to the progression of AV nodal dysfunction subsequent to the clearance of maternal autoantibodies.
The family they describe illustrates that the risk of CHB comprises both maternal and fetal components. The mother contributes a “necessary” factor, i.e., anti-SSA/Ro antibodies, the synthesis of which is linked to her own HLA–DRB1*03 (Harley JB, Alexander EL, Bias WB, Fox OF, Provost TT, Reichlin M, et al. Anti–Ro (SS-A) and anti–La (SS-B) in patients with Sjögren's syndrome. Arthritis Rheum 1986;29:196–206). The fetal contribution is less clear, but does not appear to rely solely on HLA–DRB1*03. HLA class II molecules were analyzed across 3 generations, and there was inheritance of DRB1*03 in 6 of 6 mother/child pairs. However, 2 of the 6 children did not develop autoantibodies or incur CHB, suggesting that the role of HLA in immunologic events related to CHB is difficult to assign. In contrast, in our study the majority of children with neonatal lupus rash had the −308A promoter allele of tumor necrosis factor α (TNFα). This allele was associated with the presence of both HLA–DQB1*02 and HLA–DRB1*03 in children with rash significantly more often than in anti-SSA/Ro–exposed children without rash (both with CHB and unaffected). Clinically, the cutaneous manifestation resembles subacute cutaneous lupus erythematosus (SCLE). Neonatal lupus rash and SCLE share the extended DQB1*02;DRB1*03 haplotype, which, in the case of neonatal lupus rash, contributes a “double hit”: the maternal component is the predisposition to autoantibody, and the child's component is the TNFα portion (−308A) of 6p.
The deterioration of block to third degree at 27 months was also noted in several children enrolled in the US Research Registry for Neonatal Lupus (Askanase AD, Friedman DM, Dische MR, Dubin A, Starc T, Katholi MC, et al. Spectrum and progression of conduction abnormalities in infants born to mothers with anti-SSA/Ro-SSB/La antibodies. Lupus 2002;11:145–51). These cases suggest that events initiated in utero (despite transient clinical benefit with dexamethasone) can progress to further scarring. Understanding the fetal/neonatal contribution to this unleashed fibrotic process may lead to novel therapeutic approaches.