[Anti-SSA/Ro and anti-SSB/La antibodies. What's new?]

Anti-SSA/Ro and anti-SSB/La autoantibodies recognize different epitopes on polypeptides associated with small RNAs called scYRNA situated mostly in the cytoplasmic compartment (70%) and few in the nuclear compartment (30%). These hYRNPs (h=human) can be found on the cytoplasmic membrane or in small blebs during apoptosis after various stimuli such as UVB, 17-beta-estradiol, viral infection, TNF alpha and other cellular apoptosis inducing molecules. At least two major different proteins are called SSA/Ro: a 52 kDa Ro (with two subtypes alpha and beta) and a 60 kDa Ro. There is only one SSB/La protein of 48 kDa. In some circumstances, other proteins such as calreticuline (MW 57 kDa) join Ro/SSA proteins on some YRNAs. Anti-SSA/Ro antibodies are detected in the sera of 30% of patients with SLE, even during preclinical setting; anti-Ro/SSA are strongly associated (90%) with some subtypes of SLE such as old-onset (>50 y) SLE, subacute lupus erythematosus, drug-induced subacute lupus erythematosus and in patients with hereditary C2 or C4 or C1q deficiency with lupus or lupus-like disease. Anti-SSA/Ro are also associated with primary Sjögren syndrome (50% to 60%) and with undifferenciated connective tissue disease (UCTD). Anti-SSA/Ro antibodies are almost always present in sera of mothers with babies with neonatal lupus syndrome (NNL) and with complete congenital heart block (CCHB). This last event is very unusual in pregnant patients with anti-Ro/SSA antibodies (1% to 2% of primigeste women). Some good evidences such as experimental models in vitro or ex-vivo, argue for the responsibility of maternal anti-Ro/SSA 52 kDa and/or anti-La/SSB antibodies (or associated IgG antibodies) as major etiologic factor of CCHB and NNL. IgG anti-Ro 52 beta kDa has been shown able to interrupt the atrioventricular conduction as well as the L calcium channel influx of fetal cardiocytes. Other factors must be taken into account to explain discordant twins (with and without CCHB). More recently anti-Ro/SSA antibodies were associated with QT interval prolongation in newborns without CCHB.