Improved Outcome Following Busulfan-Based Conditioning in Children with Functional Neutrophil Disorders Undergoing Hematopoietic Stem Cell Transplant from HLA-Matched Donors.

Hematopoietic stem-cell transplantation (HSCT) is the only curative treatment for chronic granulomatous disease (CGD) and leukocyte-adhesion deficiency (LAD), but both diseases have high rates of graft failure in transplant and patients with these diseases are often referred to HSCT with significant comorbidity. The intensity of the conditioning regimen should be balanced between the need to ensure durable engraftment and to minimize toxicity when transplanting young children with infections and organ damage. We report on 26 children transplanted at our institution with CGD and LAD over 24 years.

B lymphocytes in treatment-naive paediatric patients with lupus are epigenetically distinct from healthy children.

Background: SLE is likely triggered by gene-environment interactions. We have shown that most SLE-associated haplotypes encompass genomic regions enriched for epigenetic marks associated with enhancer function in lymphocytes, suggesting genetic risk is exerted through altered gene regulation. Data remain scarce on how epigenetic variance contributes to disease risk in paediatric SLE (pSLE).

FcγRIIB regulates autoantibody responses by limiting marginal zone B cell activation.

FcγRIIB is an inhibitory receptor expressed throughout B cell development. Diminished expression or function is associated with lupus in mice and humans, in particular through an effect on autoantibody production and plasma cell (PC) differentiation. Here, we analyzed the effect of B cell-intrinsic FcγRIIB expression on B cell activation and PC differentiation.

Context-dependent induction of autoimmunity by TNF signaling deficiency.

TNF inhibitors are widely used to treat inflammatory diseases; however, 30%-50% of treated patients develop new autoantibodies, and 0.5%-1% develop secondary autoimmune diseases, including lupus. TNF is required for formation of germinal centers (GCs), the site where high-affinity autoantibodies are often made.