CD3δ deficiency was first identified a decade ago by using differential expression libraries derived from thymocytes of patients with severe combined immunodeficiency. The phenotype was surprisingly severe unlike the mouse model or other human CD3 deficiencies known at that time.

Immunodeficiencies of most T-cell receptor (TCR) components (TCRID) have been reported in almost 40 patients worldwide who have also, at times, shown signs of autoimmunity. We updated their clinical, immunological, and molecular features with an emphasis on practical diagnosis, as the range of the disorder grows in complexity with new partial defects. Cellular and animal models are also reviewed and in some cases reveal their limitations for predicting TCRID immunopathology.

Background: IVIG-SN is a modern intravenous immunoglobulin with multiple pathogen elimination steps. This clinical trial in patients with primary immunodeficiency (PID) was designed to evaluate the safety, efficacy, and tolerability of this product in adults and children. Methods: Forty-four patients with PID were treated with IVIG-SN for 12 months. IgG trough levels and pharmacokinetics of IVIG-SN were evaluated as well as efficacy and safety according to standard FDA guidelines. Results: Overall, a total of 572 IVIG-SN infusions were administered according to either a 21- or a 28-day schedule. IgG trough levels during the treatment period ranged from 823.00 to 902.77 mg/dL, respectively, and half-life in serum of the administered IgG was 43.45 ± 30.25 days. There were no deaths and no adverse events leading to withdrawal from the study. Of all infusions administered, only 137 (24%) were temporally associated with an adverse event (AE). The upper bound for the 95% CI for the frequency of infusions temporally associated with an AE was 29.2%. Drug-related AEs were predominantly mild, and there were no acute serious bacterial infections during the study. Efficacy was also demonstrated by low rates of missed work, school, or daycare days (mean 2.6 days); unscheduled visits to physicians (mean 1.7); and therapeutic antibiotic use (mean 15 days). Conclusion: IVIG-SN is effective in preventing infections and is safe and well tolerated. Statement of novelty: This efficacy and toxicity trial was conducted using a new IVIG preparation.

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare primary immunodeficiency caused by inherited defects in the FOXP3 gene that impair regulatory T cells. IPEX syndrome can be cured by hematopoietic stem cell transplantation (HSCT) from HLA-matched unrelated donors (MUD); however, the best conditioning prior to HSCT for IPEX syndrome is not known. Here we report on a patient suffering from IPEX syndrome, including immune-mediated colitis and membranous nephropathy, without polyendocrinopathy, caused by a novel mutation in the Forkhead domain of the FOXP3 gene. The patient's symptoms resolved following MUD HSCT after myeloablative conditioning performed at 16 months of age. The patient is clinically well, 3 years after HSCT, with robust immune reconstitution and fully engrafted. The lack of extensive autoimmune damage might have contributed to the patient's favourable outcome following MUD HSCT with myeloablative conditioning. Statement of novelty: We describe a novel mutation in the FOXP3 gene causing IPEX syndrome and the correction of IPEX syndrome with bone marrow transplant from a HLA-matched unrelated donor following myeloablative conditioning.

Patients with severe combined immunodeficiency (SCID) typically present with profoundly reduced T cells. In some cases, however, T cells may be affected by defects that allow some T-cell development but compromise T-cell function such as in Omenn syndrome (OS), which is characterized by impaired T cell differentiation in the presence of abnormal self-reactive cells. One distinctive feature of SCID patients, which can sometimes resemble the clinical picture of OS, is the presence of alloreactive cells that originated from transplacentally acquired maternal T lymphocytes. The traditional view is that self-reactive cells and transplacentally acquired maternal T cells cannot occur concomitantly in the same OS patient. This review provides an updated functional characterization of transplacentally acquired maternal T cells and compares them with the T cells of an OS patient. An unusual case of an immunodeficient SCID patient with a mild OS phenotype is also presented. This patient had both self-reactive cells and transplacentally acquired maternal T cells, allowing us to simultaneously evaluate the function and tolerance capacities of both cell types. We propose that coexistence of autologous and maternal T cells in patients exhibiting mild OS symptoms was rejected because it had not been studied before and not because the cells are mutually exclusive. Moreover, taking into consideration the milder clinical phenotype associated with transplacentally acquired maternal T cells in SCID patients, we believe that these cells may provide some degree of immunity and prevent autoimmunity, even though they do not actually function to protect against infections. Statement of novelty: Autologous and transplacental-acquired maternal T cells can coexist in the same SCID patient. Although both cell types are nonfunctional for protecting against infections, maternal cells provide some degree of immunity and therefore are associated with only mild GVHD symptoms.