But anti-topo I, which also goes by anti-Scl-70, can be tricky, Dr. Medsger said.
“I think we have to be aware that of all of the autoantibodies which are tested these days by automated methods, Scl-70 is the one that produces the most frequent false positives,” he said.
The autoantibodies can sometimes be found together in the same patient—a change from older concepts of how these autoantibodies appear, Dr. Medsger said, mentioning dated literature that suggested anti-centromere and anti-topo I were mutually exclusive.
“There is some coexistence of these antibodies,” he said. Anti-Ku, anti-U3RNP, and anti-U1RNP are most commonly found with other antibodies, overlapping 37%, 21%, and 11% of the time, respectively.
“This is certainly in contrast to lupus, for example, where the rule is coexistence, rather than a patient having a single autoantibody,” he said. “The meaning of this difference between the two diseases is certainly not clear.”
From the point of view of planning clinical trials, one has to be aware that there are differences between SSc autoantibody subsets in the natural history of the disease and its complications.
Detecting Antibodies
SSc-associated antibodies are detected at the University of Pittsburgh using three methods: for anti-centromere, indirect immunofluorescence is used; anti-topo I, anti-U1RNP, and anti-PM-Scl are detected with double immunodiffusion; and the others with immunoprecipitation.
He said that today there is a reliable anti-RNA polymerase III enzyme-linked immunosorbent assay (ELISA). But ELISAs for anti-Th/To and anti-U3RNP that are offered by some laboratories have been disappointing because the results don’t compare well with his laboratory’s results using immunoprecipitation. He said there are new anti-U3RNP and anti-Th/To ELISAs being introduced.
“I’m hopeful that these will turn out to be good tests because I think these antibodies will be helpful in diagnosis and management of SSc patients,” he said.
Multiplex bead methods have recently been shown to be problematic, failing to identify 50% of SSc patients, particularly those with anti-RNA polymerase III and nucleolar indirect immunofluorescence antinuclear antibody testing, he noted.1
“Each of these SSc-associated antibodies has clinical associations,” he said, from anti-topo I’s link to interstitial lung disease to anti-PM-Scl’s link to myositis (see “Autoantibodies’ Links with Clinical Conditions,”).
The newest antibody his team has described, anti-U11/U12RNP, was found in 33 SSc patients, representing about 3% of all new SSc patients. Its most striking feature is a high frequency of interstitial lung disease, which is often very severe and progresses quickly. Its association to pulmonary fibrosis exceeds that of anti-topo I, which has previously been recognized as posing the greatest risk for pulmonary fibrosis.
