"A Person Like Me": Systemic Lupus Erythematosus, Gender, and Racial Immunity in the Twentieth-Century United States.

Systemic lupus erythematosus (SLE) is an autoimmune disorder that affects mostly women and disproportionately Black women. Until the 1940s, SLE was rarely diagnosed in Black Americans, reflecting racist medical beliefs about Black immunity. In the 1940s and 1950s, SLE and its treatment were part of a patriarchal narrative of American industrialization. By the 1960s, newer diagnostic techniques increased recognition of SLE, especially among Black women; medical thinking about SLE shifted from external causes like infection or allergy to autoimmunity, which emphasized biological, genetically determined racial difference. In the 1970s and 1980s, an advocacy structure crystalized around memoirs by women with SLE, which emphasized the experiences of able-bodied, economically privileged white women, while Black feminist health discourse and SLE narratives by Black authors grappled with SLE's more complicated intersections. Throughout the twentieth century, SLE embodied immunity as a gendered, racialized, and culturally invested process.

Graft-versus-host disease is associated with skewed γδ T-cell clonality after umbilical cord blood transplantation in children with nonmalignant diseases.

BACKGROUND AIMS: The γδ T-cells (GDT) are a subpopulation of lymphocytes expressing a distinct T-cell receptor coded by the TRG and TRD genes. GDTs may have immunoregulatory function after stem cell transplantation (SCT), but the relationship between GDT clonality and acute graft-versus-host disease (aGVHD) is not known. METHODS: We prospectively studied spectratype complex complexity of TCR Vγ (γ) and TCR Vδ (δ) pre-SCT and at approximately day 100 and day 180 post-SCT in a cohort of immunocompetent children receiving allogeneic umbilical cord blood SCT for nonmalignant diseases, with identical reduced-intensity conditioning and aGVHD prophylaxis. RESULTS: We studied 13 children undergoing SCT at a median age of 0.9 years (total range 0.4-16.6). In those with grade 0-1 aGVHD (N = 10), the spectratype complexity of most γ and δ genes was not significantly different from baseline at day 100 or day 180 post-SCT, and there was balanced expression of genes at the γ and δ loci. In those with grade 3 aGVHD (N = 3), spectratype complexity was significantly below baseline at day 100 and day 180, and there was relative overexpression of δ2. CD3+ cell counts were also lower in participants with grade 3 aGVHD. CONCLUSIONS: Recovery of a polyclonal GDT repertoire is an early part of immunological recovery after SCT. γ and δ gene expression is balanced in young children before and after SCT. Severe aGVHD is associated with GDT oligoclonality post-SCT and with skewed expression of δ2, which has not been previously reported. This association may reflect aGVHD therapy or aGVHD-associated immune dysregulation. Further studies of GDT clonality during the early post-SCT period may establish whether abnormal GDT spectratype precedes the clinical manifestations of aGVHD.

Managing the Cerebrovascular Complications of Sickle Cell Disease: Current Perspectives.

The importance of protecting brain function for people with sickle cell disease (SCD) cannot be overstated. SCD is associated with multiple cerebrovascular complications that threaten neurocognitive function and life. Without screening and preventive management, 11% of children at 24% of adults with SCD have ischemic or hemorrhagic strokes. Stroke screening in children with SCD is well-established using transcranial Doppler ultrasound (TCD). TCD velocities above 200 cm/s significantly increase the risk of stroke, which can be prevented using chronic red blood cell (RBC) transfusion. RBC transfusion is also the cornerstone of acute stroke management and secondary stroke prevention. Chronic transfusion requires long-term management of complications like iron overload. Hydroxyurea can replace chronic transfusions for primary stroke prevention in a select group of patients or in populations where chronic transfusions are not feasible. Silent cerebral infarction (SCI) is even more common than stroke, affecting 39% of children and more than 50% of adults with SCD; management of SCI is individualized and includes careful neurocognitive evaluation. Hematopoietic stem cell transplant prevents cerebrovascular complications, despite the short- and long-term risks. Newer disease-modifying agents like voxelotor and crizanlizumab, as well as gene therapy, may treat cerebrovascular complications, but these approaches are investigational.