Dataset Information

Characterization of circulating and cultured Tfh-like cells in sickle cell disease in relation to red blood cell alloimmunization status.

ABSTRACT:

Background

People living with sickle cell disease (SCD) are prone to red blood cell (RBC) alloimmunization. We hypothesized that subjects with alloantibodies (responders) would have differences in circulating T-follicular helper (Tfh)-like cells compared to subjects without alloantibodies (non-responders).

Materials and methods

Peripheral blood mononuclear cells were collected from 28 subjects, including those with SCD and controls. Circulating CD4 T-cell subsets were first evaluated at baseline. CD4 T-cell subsets were also evaluated after naïve CD4 T-cells were differentiated into Tfh-like cells following in vitro culture with CD3/CD28 beads, IL-7, IL-12, and Activin A. Transfusion and alloantibody histories were extracted from the electronic medical record.

Results

Non-responders had a lower percentage of CD45RA negative Tmemory cells than responders or controls (p<0.05). Notably, there were no differences in circulating Tfh-like cells between any group. However, naïve CD4 T-cells from subjects with SCD were more likely to express CXCR5 after in vitro culture than cells from controls. After culture, CXCR5 expressing cells from responders were more likely to express PD1 and ICOS (16.43 %, sd. 20.23) compared to non-responders (3.69 %, s.d. 3.09) or controls (2.78 %, s.d. 2.04).

Discussion

The tendency for naïve CD4 T-cells from responders to differentiate into Tfh-like cells after in vitro culture may suggest these cells are prepared to assist B-cells with antibody production regardless of antigen specificity. Further studies are needed, but it is possible that these results may explain why some responders form RBC alloantibodies with multiple specificities, in addition to RBC autoantibodies and HLA alloantibodies.

SUBMITTER: Balbuena-Merle R

PROVIDER: S-EPMC7483805 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Key Points • Transfusion during proinflammatory events increases alloimmunization in patients with sickle cell disease, which is not mitigated by HU.• High transfusion burden and HbSS and HbSβ0–thalassemia genotypes are additional risk factors for alloimmunization. Visual Abstract Abstract We examined risk factors for red blood cell (RBC) alloimmunization in pediatric patients with sickle cell disease, focusing on the recipients’ inflammatory state at the time of transfusion and anti-inflammatory role of hydroxyurea (HU). Among 471 participants, 55 (11.70%) participants were alloimmunized and formed 59 alloantibodies and 17 autoantibodies with an alloimmunization rate of 0.36 alloantibodies per 100 units. Analysis of 27 participants in whom alloantibodies were formed with specificities showed 23.8% (30/126) of units transfused during a proinflammatory event resulting in alloantibody formation compared with 2.8% (27/952) of units transfused at steady state. Therefore, transfusion during proinflammatory events increased the risk for alloimmunization (odds ratio [OR], 4.22; 95% confidence interval [CI], 1.64-10.85; P = .003). Further analysis of all the 471 participants showed that alloimmunization of patients who received episodic transfusion, mostly during proinflammatory events, was not reduced with HU therapy (OR, 6.52; 95% CI, 0.85-49.77; P = .071), HU therapy duration (OR, 1.13; 95% CI, 0.997-1.28; P = .056), or HU dose (OR, 1.06; 95% CI, 0.96-1.16; P = .242). The analysis also identified high transfusion burden (OR, 1.02; 95% CI, 1.003-1.04; P = .020) and hemoglobin S (HbSS) and HbSβ0–thalassemia genotypes (OR, 11.22, 95% CI, 1.51-83.38; P = .018) as additional risk factors for alloimmunization. In conclusion, the inflammatory state of transfusion recipients affects the risk of RBC alloimmunization, which is not modified by HU therapy. Judicious use of transfusion during proinflammatory events is critical for preventing alloimmunization.