Defective Treg generation and increased type 3 immune response in leukocyte adhesion deficiency 1.

In 15 Turkish LAD-1 patients and controls, we assessed the impact of pathogenic ITGB2 mutations on Th17/Treg differentiation and functions, and innate lymphoid cell (ILC) subsets. The percentage of peripheral blood Treg cells, in vitro-generated induced Tregs differentiated from naive CD4+ T cells were decreased despite the elevated absolute counts of CD4+ cells in LAD-1 patients. Serum IL-23 levels were elevated in LAD-1 patients. Post-curdlan stimulation, LAD-1 patient-derived PBMCs produced more IL-17A. Additionally, the percentages of CD18-deficient Th17 cells expanded from total or naïve CD4+ T cells were higher. The blood ILC3 subset was significantly elevated in LAD-1. Finally, LAD-1 PBMCs showed defects in trans-well migration and proliferation and were more resistant to apoptosis. Defects in de novo generation of Tregs from CD18-deficient naïve T cells and elevated Th17s, and ILC3s in LAD-1 patients' peripheral blood suggest a type 3-skewed immunity and may contribute to LAD-1-associated autoimmune symptoms.

Outcome of treosulfan-based reduced-toxicity conditioning regimens for HSCT in high-risk patients with primary immune deficiencies.

INTRODUCTION: HSCT is the curative therapeutic option in PIDs. Due to the increase in survival rates, reduced-toxicity conditioning regimens with treosulfan have become another alternative. The purpose of this retrospective study was to analyze the outcome of treosulfan-based conditioning before HSCT for patients with PID. METHOD: A total of 15 patients that received a treosulfan-based conditioning regimen for HSCT were recruited. Type of diagnosis, donor and stem cell source, pretransplant organ damage, infections, engraftment, chimerism, and transplant-related toxicities were analyzed. RESULTS: At a median follow-up time of 32 months, the overall survival was 86.7%. Following HSCT, 14 of 15 patients had engraftment, with 86.7% of the cohort having full-donor chimerism. The most common toxicity was seen on the skin (53.3%). Acute GVHD and chronic GVHD were documented in 53% and 20% of the study population, respectively. Although the cohort consisted of patients with pretransplant liver damage, SOS manifestations were documented in 20%. CONCLUSION: Treosulfan-based conditioning regimens before HSCT are associated with lower toxicity compared to myeloablative regimens, are safe, and have high engraftment rates with full-donor chimerism in patients having PID, regardless of the specified genetic diagnosis and donor type.

Spinal epidural abscess associated with IgG4 deficiency.

The objective is to present the possibility of an association between spinal epidural abscess and IgG deficiency. Spinal epidural abscess is a rare but potentially devastating condition. Review of the literature showed no reported acknowledgment about the relationship between spinal epidural abscess and IgG deficiency. This report discusses the case of a 16-year-old boy who developed progressive paraplegia within 24 hours. Clinical and neuroradiologic features are reported. Serum quantitative total IgG, IgA, and IgM concentrations were measured by nephelometry. Thoracic magnetic resonance imaging showed epidural abscess between T6 and T11 compressing the cord posteriorly. IgG subclasses (IgG ) were found abnormal. The possible importance of immunologic evaluation in the patients with spinal epidural abscess when no source of infection could be find is discussed.(4) (4) (4)