Anti-Ro(SS-A) HLA-DR3-Positive Women: The Interrelationship Between Some ANA Negative, SS, SCLE, and NLE Mothers and SS/LE Overlap Female Patients

During the past 15 years, the clinical spectrum associated with the anti-Ro(SS-A) antibody response has been defined. Various clinical presentations, including subacute cutaneous lupus erythematosus, the neonatal lupus syndrome, the Sjogren's syndrome/ lupus erythematous overlap syndrome, and primary Sjogren's syndrome, have been detected in association with the anti-Ro(SS-A) response. The anti-Ro(SS-A) antibody response is associated with the HLA-DR2 and HLA-DR3 phenotypes. There is now a good deal of evidence to suggest that many anti-Ro(SS-A) -positive HLA-DR3 women are genetically closely related, sharing in common an enriched frequency of the HLA-DR3-linked B8, DQw2, and DRW52 phenotypes. DNA sequence studies have confirmed this genetic relationship. These studies have led us to the following conclusions. (1) The HLA-DR2 and HLA-DR3 associations with systemic lupus erythematosus and the HLA-DR3 association with Sjogren's syndrome are related to the anti-Ro(SS-A) antibody response and not to the clinical disease expression. (2) HLA-DR3 anti Ro-positive female patients with first-degree Sjogren's syndrome, subacute cutaneous lupus erythematosus, or Sjogren's syndrome, or who are asymptomatic, are immunogenetically closely related even though the clinical presentations are strikingly different. All these HLA-DR3 anti-Ro(SS-A) antibody-positive women are at risk to give birth to a child with the neonatal lupus syndrome.