medwireNews: Gene expression profiles are associated with rituximab response among people of African or Asian ancestry with systemic lupus erythematosus (SLE), but not in those of European ancestry, research suggests.
As outlined at the British Society for Rheumatology 2022 Annual Conference in Glasgow, UK, the study included a total of 213 patients with active SLE who were enrolled in the BILAG biologics registry.
Lucy Carter, from the University of Leeds in the UK, said that among patients of African (13%), subcontinental Asian (13%), or Chinese or other Asian (5%) ancestry, analysis of gene expression signatures identified three clusters that were significantly associated with differential response to rituximab.
Specifically, the nine patients in the “interferon (IFN) low–neutrophil inflammation high” cluster had the lowest rate of response to rituximab according to BILAG-2004 criteria at 6 months, at 12.5%. This response rate increased to 41.2% for the 21 patients in the “IFN high–neutrophil inflammation low” cluster, and was highest for the 25 patients in the “all signatures high” cluster, at 85.0%.
Carter emphasized that other variables such as age, BILAG score, and rates of active renal disease did not significantly differ across gene expression clusters in these ancestry groups.
Conversely, for patients of European ancestry (White British or Irish; 60% of study population), gene expression clusters were not significantly associated with rituximab response, but were significantly associated with BILAG score and renal involvement.
Rituximab response rates were 81.2% in the “all signatures low” group (n=25), 72.2% in the “IFN high–neutrophil inflammation low” group (n=24), and 57.6% in the “all signatures high” group (n=33) for patients of European ancestry.
In these people, the median BILAG score and proportion of patients with renal disease were lowest in the “all signatures low” group (13 points and 16.0%, respectively), followed by the “IFN high–neutrophil inflammation low” group (21 points and 20.8%), and were highest in the “all signatures high” group (22 points and 60.6%).
The presenter concluded that “ancestry is central to the clinical and immunological heterogeneity in SLE,” and “ancestry-specific interpretation appears essential” for the development of gene expression profiles as biomarkers of disease activity, renal involvement, and treatment response.
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BSR Annual Conference 2022; Glasgow, UK: 25–27 April