Patterns of organ involvement can differ by racial ancestry
Study into patterns in 385 patients of European ancestry, 987 African Americans
Patterns of multiorgan involvement in African Americans with sarcoidosis differ from those of Americans of European ancestry, a study suggests. But in both groups, certain genetic mutations are associated with specific patterns of organ involvement.
Collectively, its findings “support ancestry-specific differences likely resulting from distinct social, cultural, and environmental factors in the setting of unique genetic determinants,” the researchers wrote.
Sarcoidosis mainly affects lungs and skin in African American, white patients
Sarcoidosis is characterized by clumps of inflammatory immune cells, called granulomas, that can affect various organs. The specific patterns of organ involvement vary widely from person to person, and scientists are working to understand the underpinnings of this variability.
“Understanding the factors that influence the patterns of organ involvement and overall heterogeneity [variability] of the disease is important for opportune diagnosis, early management of potentially serious complications, and future targeted therapies,” the researchers wrote.
In prior research, scientists have used a statistical method called multiple correspondence analysis, or MCA, to identify ‘clusters’ of sarcoidosis patients — that is, groups of patients who have similar patterns of organ involvement.
Earlier studies suggested that patients within a cluster share certain genetic features, which may help to explain the differences in organ involvement patterns.
“The goal of methods such as MCA … is to reduce the noise present in data with a large number of variables while retaining the signal of interest and clarifying underlying patterns,” the researchers wrote. “As such, they serve to outline steps towards testing hypotheses and validating relationships by other means.”
While this type of research may help to better understand the underpinnings of sarcoidosis, prior studies have focused on people of European ancestry. It’s not clear whether these findings hold in other populations.
A team of U.S. scientists used similar MCA-based assessments to identify clusters of multiorgan involvement in sarcoidosis patients of European or African ancestry.
Their analyses included data from 385 patients of European ancestry (57.4% female) and 987 African Americans (72.5% female ) followed at the same U.S. institutions.
In both groups, the most frequently affected organs were the lungs (95.8% in European Americans and 98% in African Americans), followed by the skin (21.8% and 41%).
Ranking third was bone/joint involvement (22.1%) in the European ancestry group and eye involvement (28%) in the African American group. Lymph nodes located outside the chest were affected in about 21% of patients in both groups.
7 multiorgan clusters in European ancestry patients, 6 among African Americans
Analysis found seven multiorgan clusters among patients with European ancestry, with the largest cluster being of bone/joint/skin involvement. While there was some overlap between the different clusters, results suggested they could be separated fairly well.
For most of these clusters, there were statistically significant associations with variants in HLA-DRB1, a gene that is known to influence immune function.
These findings, overall, were comparable to those reported in earlier studies in patients of European ancestry, the researchers noted.
By contrast, six multiorgan clusters were identified among African American patients, with the largest being the calcium and the skin clusters. Higher-than-normal calcium levels in the blood and/or urine are common abnormalities in sarcoidosis patients, and may lead to severe complications and organ damage if untreated.
The six clusters showed greater overlap between them than the seven clusters of patients of European ancestry.
Despite these notable differences, most clusters in the African American analysis also showed significant associations with HLA-DRB1 gene variants.
Researchers noted that it’s not totally clear why these differences between patients of different ancestries exist. It’s possible that genetic differences could explain the results, but factors like socioeconomics also could be involved.
“These results further support the notion that genetically influenced immune risk profiles, which differ based on ancestry, play a role in [clinical profile variability],” the researchers wrote, adding that “dissecting such risk profiles will move us closer to personalized medicine for this complex disease.”
The scientists stressed a need for further research in people of all backgrounds to further understand the underpinnings of sarcoidosis.