A diagnosis of an autoimmune disease (AID) in patients with sickle cell disease (SCD) seems to be associated with both a severe phenotype of AID and a worsening of SCD, according to an article published in the American Journal of Hematology.

The researchers conducted an observational study with retrospective data analysis of medical files from 304 adult patients with SCD followed up from January 2012 to July 2020.

They analyzed the prevalence of biological autoimmunity and the occurrence of an AID diagnosis. The SCD clinical severity score was used to compare the condition of each patient before and after the AID diagnosis. The researchers also analyzed the course and treatment of both conditions.

According to the results, 58% of tested participants had indicators of biological autoimmunity in their sera. However, only 15 of 154 patients with biological autoimmunity were diagnosed with an AID.

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“We found a particularly high prevalence of anti-liver autoimmunity, 16% of the autoimmune tests performed being positive for at least one anti-liver antibody. Interestingly, the presence of these antibodies seems to be associated with a more severe SCD phenotype and most often a homozygous genotype,” Mausoléo and colleagues wrote.

No specific SCD features correlated with the risk of developing an AID, except for a past history of splenectomy. More than half of the patients with SCD diagnosed with an AID presented with a flare after the diagnosis was established.

The evolution of AIDs while receiving immunosuppressive therapy was mostly unfavorable as 41.6% of patients had persistent disease activity and 16.7% died during follow-up.

“One hypothesis is that during active AID, the production of pro-inflammatory cytokines (IL-1β, IL-6, TNFα) can stimulate the vascular endothelium, induce erythrocyte adhesion, and lead to the occurrence of vaso-occlusive crises. The other hypothesis is an exacerbation related to the immunosuppressive therapy, particularly corticosteroids.”

The association between SCD and AIDs has been reported in the context of a difficult and delayed diagnosis due to similarities in clinical manifestations of both conditions.


Mausoléo A, Fredeau L, Chrétien P, et al. Autoimmunity in sickle cell disease: analysis of a large cohort of adult patients. Am J Hematol. Published online August 21, 2023. doi:10.1002/ajh.27061