Antibodies vary by race, but don’t explain differences in scleroderma

Outcomes differ for patients of different races, meaning antibodies play a role
by Marisa Wexler, MS | September 17, 2024

Some types of disease-specific antibodies are more common in Black patients with scleroderma than white patients, a study shows.

Differences in antibody profiles may help explain why clinical outcomes tend to differ for patients of different races, but the data suggest these variations can’t fully account for all the clinical differences between races, meaning other factors must also factor in.

“Distinct autoantibody types are enriched in Black [scleroderma] patients compared with those observed in white patients; these specificities associate with more aggressive clinical manifestations of the disease. However, differences in autoantibody distributions explain only a fraction of the racial effects on clinical outcomes,” the researchers wrote.

The study, “Racial variability in immune responses only partially explains differential systemic sclerosis disease severity,” was published in the Annals of the Rheumatic Diseases.
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Scleroderma, also called systemic sclerosis, or SSc, is marked by uncontrolled fibrosis (scarring) that can affect various organs. Several specific types of autoantibodies, that is, antibodies that attack healthy tissue and are thought to be a main driver of the disease, have been linked to the disease. The biological consequences of individual autoantibody types are poorly understood, however.

​Differences in scleroderma by race
Scleroderma more often affects Black people over white people and Black patients tend to have more severe disease and higher rates of scleroderma-related mortality. It’s not clear if these are due to biological differences, sociological effects, or some combination, leading scientists to analyze autoantibody profiles from nearly 3,000 scleroderma patients (803 Black, 2,178 white) to gain more insight on the role of autoantibodies and their association with race. Consistent with known racial variations, the Black patients tended to be younger at the disease’s onset and have more severe disease across a range of measures.

“We sought to examine whether self-identified Black and white individuals with [scleroderma] have distinct autoantibody profiles and whether autoantibodies influence the association between self-reported race and clinical outcomes,” the researchers wrote, noting theirs was the largest study to perform this type of analysis.

Certain types of autoantibodies were more common in Black patients and others were more common in white patients. Significantly more Black patients were positive for anti-Scl70, anti-U1RNP, anti-U3RNP, anti-Th/To, anti-Ku and anti-NOR90. White patients had significantly higher rates of anti-centromere, anti-POLR3 and anti-PM/Scl.

“We observed that the frequency of [scleroderma]-specific autoantibodies varies significantly between self-identified black and white patients,” the researchers wrote.

Several autoantibody types that varied by race showed statistically significant associations with clinical outcomes. For example, anti-Scl70 autoantibodies were associated with a significantly increased likelihood of severe lung disease. Anti-centromere autoantibodies were linked with a lower risk, however.

Antibodies and clinical outcomes
While rates of specific autoantibodies varied by race, associations between autoantibodies and clinical manifestations were largely independent of race, the researchers said. For example, white patients with anti-Scl70 autoantibodies had higher risk of severe lung disease, even though this autoantibody type was on average more common in Black patients.

The researchers then constructed statistical models to predict the rates of serious scleroderma manifestations. As expected, they showed Black patients were at a significantly higher risk of complications, including severe lung disease, severe skin disease, and severe digestive issues. The researchers then looked at how the models were affected when they were mathematically adjusted to take into account differences in autoantibodies.

Here, the differences in race became less pronounced, suggesting antibody differences play some role in influencing overall differences between races. There were still significant differences between white and Black patients even after accounting for autoantibodies, however, indicating other factors must be at play.
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“Our data suggest that while autoantibody status identifies risk for specific organ manifestations and outcomes, other factors, such as genetics, socioeconomic and environmental exposures, may also contribute to differential disease severity between these self-reported racial groups,” wrote the scientists, who said more research is needed to untangle the complex role that race plays in scleroderma.