English abstract
Sickle cell disease (SCD) is a group of inherited red blood cell disorders, which is highly prevalent in Oman where 0.3% of the population is affected. As a result of repeated cycles of inflammation, infection and tissue damage, SCD patients are at an increased risk of developing connective tissue disorders (CTD) such assystemic lupus erythematous (SLE). This latter is the most common CTD inOman whereby the incidence of SLE in SCD patients is 3.09%, which is higher than the general population. Although the underlying mechanisms are not fully understood, recent findings suggest that B regulatory (Breg) cells may play a vital role in maintaining immune homeostasis and self-tolerance. It has been shown that any dysregulation of Breg cells may lead to the development of CTD. Therefore, this study aims at exploring alterations of Breg cells in the peripheral blood of SCD patients with SLE. To this end, four groups were studied including SCD patients with SLE (n=21), patients with SCD only (n=24), patients with SLE only (n=24) and healthy controls (n=24). The American College of Rheumatology (ACR) criteria was used to classify and diagnose SLE patients. SickleDex® test was used to screen for Hbs while HPLC was used to confirm whether the participants had SCD. Circulating levels of Breg cells were assessed by immuno-phenotyping using specific surface markers and flow cytometry. The functional properties were evaluated by interleukin-10 (IL-10) production and STAT3 phosphorylation after stimulation and cell culture. Correlations of demographic, hematological and clinical parameters with the numerical and functional properties of Breg cells were evaluated. The demographic data were similar among the study groups. All participants were free of infections such as human immunodeficiency virus, hepatitis B and C virus and syphilis. SCD patients with SLE and patients with SLE only were positive for autoimmune markers and showed an average ACR score of five and six respectively. The frequency of Breg cells ranged between 1.5-8% in healthy controls. The circulating levels of Breg cells were significantly reduced in SCD patients with or without SLE and patients with SLE only when compared to the healthy controls (p<0.0001). Similarly, compared to healthy controls, Breg cells from SCD patients with or without SLE and patients with SLE only produced significantly lower amount of IL-10 (p<0.0001). Likewise, STAT3 phosphorylation was also decreased in Breg cells from SCD patients with or without SLE and patients with SLE only compared to the healthy controls (p<0.0001). Demographic and hematological data along with the treatments did not affect the levels and functions of Breg cells. Most of the associations did not reach a statistical significance, except a moderate correlation was evidenced between production of IL-10 by Breg cells and antinuclear a lear antibody titer (p=0.52, p=0.009). Collectively, these findings showed numerical and functional deficits of Breg cells in SCD patients with or without SLE and patients with SLE only. This implies that Breg cell capacity to maintain tolerance and control inflammation is imbalanced in SCD patients therefore favoring development of SLE.
