Scientists at Bristol-Myers Squibb have uncovered mechanisms explaining why African-Americans with systemic lupus erythematosus (SLE) experience more serious symptoms and become sick at earlier ages than American patients of European descent.
The difference lies in B-cells according to the study “B cells from African American lupus patients exhibit an activated phenotype,” published in JCI Insight
In an attempt to understand what factors drive the disease differently among African-American people, the research team enrolled 68 lupus patients with low to moderate disease activity and 69 normal healthy volunteers, then isolated B-cells from their blood.
A thorough mapping of the molecules expressed on the cells’ surfaces — largely determining the activity of the immune cells — revealed that patients of African-American descent had, in part, a different set of molecules on their surfaces. The differences could not be explained by other factors such as sex, age, duration of disease, disease severity, other health issues of individual patients (comorbidities), and drug treatment.
The research team also compared individuals who recently experienced disease flares with those who did not; and people with and without lupus kidney disease. Those factors also did not explain the difference in B-cell appearance.
Comparing a subset of 21 African-American patients with 21 European descendants, the team additionally observed that African-Americans had lower numbers of naıve, non-activated B-cells, and higher numbers of activated cells in their blood. When looking at African-American healthy controls, activated B-cells were more common. further supporting the idea that descendance, or familial lineage, may determine the difference.
Researchers also deduced that activated B-cells could trigger activation in neighboring cells and creating a feed-forward loop.
B-cells from African-American patients did not respond differently when stimulated in a lab dish but the patients had higher levels of certain autoantibodies. Except for slightly lower numbers of a certain type of T-cell among African-Americans, the team could find no difference in other types of immune cells, such as monocytes, NK-cells and other subsets of T-cells, between the two descendant groups.