PT - JOURNAL ARTICLE AU - Cecilia P Chung AU - Gul Karakoc AU - Ge Liu AU - Jorge L Gamboa AU - Jonathan D Mosley AU - Nancy J Cox AU - C Michael Stein AU - Vivian Kawai TI - Ancestry, <em>ACKR1</em> and leucopenia in patients with systemic lupus erythematosus AID - 10.1136/lupus-2022-000790 DP - 2022 Nov 01 TA - Lupus Science &amp; Medicine PG - e000790 VI - 9 IP - 1 4099 - http://lupus.bmj.com/content/9/1/e000790.short 4100 - http://lupus.bmj.com/content/9/1/e000790.full SO - Lupus Sci Med2022 Nov 01; 9 AB - Objective SLE is more prevalent in populations of African (AA) than European ancestry (EA) and leucopenia is common. A homozygous variant in ACKR1 (rs2814778-CC) is associated with lower white cell counts; the variant is common in AA but not EA populations. We hypothesised that in SLE: (1) leucopenia is more frequent in patients of AA than EA, and (2) the ACKR1-CC genotype accounts for the higher frequency of leucopenia in AA patients.Methods We performed a retrospective cohort study in patients with SLE at a tertiary care system. Ancestry was defined by genetic principal components. We compared the rate of leucopenia, thrombocytopenia and anaemia between (a) EA and AA patients, and (b) ACKR1-CT/TT and CC genotype in AA patients.Results The cohort included 574 patients of EA and 190 of AA; ACKR1-CC genotype was common in AA (70%) but not EA (0%) patients. Rates of leucopenia for ancestry and genotype were AA 60.0% vs EA 36.8 % (p=1.9E-08); CC 67.7% vs CT/TT 42.1% (p=9.8E-04). The rate of leucopenia did not differ by ancestry comparing EA patients versus AA with CT/TT genotype (p=0.59). Thrombocytopenia (22.2% vs 13.2%, p=0.004) and anaemia (88.4% vs 66.2%, p=3.7E-09) were more frequent in AA patients but were not associated with ACKR1 genotype (p=0.82 and p=0.84, respectively).Conclusions SLE of AA had higher rates of anaemia, leucopenia, and thrombocytopenia than those of EA; only the difference in leucopenia was explained by ACKR1-CC genotype. This genotype could affect clinical practice.Data are available upon reasonable request. All data and materials used in the analysis are available upon request to the corresponding author, in accordance with the funders and institutional guidance and legal requirements.