Dr. Bernstein and her colleagues collected survival rates for 3,763 adults with SSC, PAH and interstitial lung disease (ILD) from the UNOS database. After fully adjusting the rates to account for other factors that may influence mortality, they found that SSc patients had a 48% higher risk of death than ILD patients, but comparable risk to PAH patients. Further stratified analyses showed that SSc patients who did not take preoperative corticosteroids also showed a higher mortality rate than those with ILD or PAH. “One possible explanation for this finding is that corticosteroid use might attenuate the risk associated with the diagnosis of systemic sclerosis,” said Dr. Bernstein. The analysis was limited due to the lack of some information, such as phenotypic profiles, in this database, but may help identify modifiable risk factors for SSc patients who seek lung transplants in the future, she said.
Anti-Ro52 & Innate Immunity
Interaction between anti-Ro52 antibodies and innate immunity may play a critical role in Sjögren’s syndrome induction, according to research presented by Umesh S. Deshmukh, PhD, an associate at the Oklahoma Medical Research Foundation in Oklahoma City. The presence of anti-Ro52 antibodies is associated with a higher severity of disease in Sjögren’s syndrome in mice, he said. How does the immune response against Ro52 influence disease pathogenesis? That’s not yet known, he said.
One injection of alum causes a significant reduction in saliva production in mice, Dr. Deshmukh noted. His team found that immunizing New Zealand Mixed 2758 mice, bred with a genetic susceptibility for a Sjögren’s-like disease, against Ro52 with alum generated a robust Ro52 antibody response compared to mice injected with maltose-binding protein and alum or alum alone, he said. Salivary gland function was diminished. “If you measure pilocarpine-induced saliva production in these mice, the Ro52-immunized mice show the highest significant drop in their ability to make saliva,” Dr. Deshmukh said. “Also, the mice with the highest anti-Ro52 reactivity had the lowest ability to make saliva.”
Both the Ro52-immunized mice and the mice receiving the MBP and alum showed mild sialoadenitis. Immunoglobulin gamma (IgG) deposits were seen in the salivary glands of the Ro52-immunized mice, but not in the other two groups, “suggesting that maybe some of these autoantibodies were actually penetrating the ductal cells” of the glands, he said. “Maybe you need prior action of innate immunity, and then maybe the antibodies become pathogenic.”
IDO & Neurotoxicity
Interferon-induced expression of the IDO gene is associated with neurotoxicity and may be one cause of severe fatigue and depression in primary Sjögren’s syndrome patients, said Naomi I. Maria, a graduate student at Erasmus MC in Rotterdam, The Netherlands.
