Limiting dilution analysis of Epstein-Barr virus infectable B cells secreting anti-Ro/SSA and anti-La/SSB antibodies in neonatal lupus erythematosus and systemic lupus erythematosus

Abstract

Neonatal lupus erythematosus (NLE) is associated with the transplacental passage of maternal anti-Ro and anti-La antibodies. In order to better determine the risk of delivery of a child with NLE, we examined the frequency of anti-Ro and anti-La antibody secreting cells in mothers of children with NLE and in mothers at risk to deliver a child with NLE. We established limiting dilution experiments, using EBV-infected peripheral blood mononuclear cells, from 10 mothers following delivery of a child with NLE and from six mothers with anti-Ro and anti-La antibodies who delivered an unaffected child. Supernatants were assessed, by Poisson analysis, to determine the frequency of IgG and IgM anti-Ro and anti-La antibody-secreting B cells. We found that the frequency of anti-Ro and anti-La IgM antibody secreting B cells was greater than the frequency of IgG antibody secreting B cells of the same autoantibody specificity. We found no correlation between serum IgM and IgG anti-Ro or anti-La antibody titres and their respective precursor cell frequencies. We found that the mothers of children with NLE who later developed SLE tended to have higher anti-Ro and anti-La antibody-committed B cells than did the mothers who remained well. Although anti-Ro and anti-La antibody precursor frequencies were similar within a patient, they varied significantly from patient to patient. We found that most of the experiments with a precursor frequency of < 1 per million were from mothers of children with NLE rather than the mother with SLE who delivered normal children. Overall, we found that, in anti-Ro and anti-La antibody-positive women, a low anti-Ro or anti-La antibody B cell precursor frequency tended to be associated with the birth of a child with NLE.