Background Primary immunodeficiencies (PIDs) are inherited diseases associated with a considerable increase in susceptibility to infections. It is known that PIDs can also predispose to cancer and ...immune diseases, including allergy, autoimmunity, and inflammation. Objective We aimed at determining the incidence of autoimmunity and inflammation in patients with PIDs. Methods We have retrospectively screened 2183 consecutive cases of PID in the Centre de Référence Déficits Immunitaires Héréditaires registry (CEREDIH; the French national PID registry) for the occurrence of autoimmunity and inflammation. Results One or more autoimmune and inflammatory complications were noted in 26.2% of patients, with a risk of onset throughout the patient's lifetime. The risk of autoimmune cytopenia was at least 120 times higher than in the general population, the risk of inflammatory bowel disease in children was 80 times higher, and the risk of other autoimmune manifestations was approximately 10 times higher. Remarkably, all types of PIDs were associated with a risk of autoimmune and inflammatory complications, although the greatest risk was associated with T-cell PIDs and common variable immunodeficiency. The occurrence of autoimmune disease is a negative prognostic factor for survival. Conclusions Our results provide the basis for a detailed prospective evaluation of autoimmunity and inflammation in the context of PIDs, with a view to accurately assessing these risks and describing the possible effect of medical intervention.
Major histocompatibility complex (MHC) class II expression deficiency is a rare condition with autosomal recessive transmission. The defect of MHC class II leads to combined immunodeficiency with ...defective CD4(+) T-cell development and a lack of T helper cell-dependent antibody production by B cells. The clinical course of disease is characterized by the recurrence of bacterial, viral, fungal, and protozoan infections. The optimal symptomatic care that is available involves the prophylactic use of antibiotics and the administration of immunoglobulin with adequate nutritional support. Hematopoietic stem cell transplantation is the only known treatment available to cure MHC class II expression deficiency.
Advances in immunology have led to a breathtaking expansion of recognized primary immunodeficiency diseases (PID) with over 120 disease-related genes identified. In North America alone more than 1000 ...children have received allogeneic blood or marrow transplant over the past 30 years, with the majority surviving long term. This review presents results and highlights challenges and notable advances, including novel less toxic conditioning regimens, to transplant the more common and severe forms of PID. HLA-matched sibling donors remain the ideal option, however, advances in living donor unrelated HSCT and banked umbilical cord blood grafts provide hope for all children with severe PID.
Gene therapy for primary immunodeficiencies Fischer, Alain; Hacein-Bey-Abina, S; Cavazzana-Calvo, M ...
Immunology and allergy clinics of North America,
05/2010, Letnik:
30, Številka:
2
Journal Article
Recenzirano
The concept of gene therapy emerged as a way of correcting monogenic inherited diseases by introducing a normal copy of the mutated gene into at least some of the patients' cells. Although this ...concept has turned out to be quite complicated to implement, it is in the field of primary immunodeficiencies (PIDs) that proof of feasibility has been undoubtedly achieved. There is now a strong rationale in support of gene therapy for at least some PIDs, as discussed in this article.
Josiah F. Wedgwood (1950-2009) Diamond, Betty, MD; Cunningham-Rundles, Charlotte, MD, PhD; Fischer, Alain, MD ...
Journal of allergy and clinical immunology,
02/2010, Letnik:
125, Številka:
2
Journal Article
Recenzirano
Josiah was a steadfast proponent for research in PID, the driving force behind the establishment of the US Immunodeficiency Network, and an active member of the International Union of Immunological ...Societies Expert Committee on PID. Josiah is survived by his wife, Ruth Wedgwood, Burling Professor of International Law at Johns Hopkins University's School of Advanced International Studies; his 11-year-old son, Josiah, who accompanied him to the International Union of Immunological Societies conference in Dublin this past June; brothers Jeffrey and John; and his parents, Ralph Wedgewood, emeritus professor at the University of Washington, Seattle, and Ginny.
Background Hematopoietic stem cell transplantation remains the only treatment for most patients with severe combined immunodeficiencies (SCIDs) or other primary immunodeficiencies (non-SCID PIDs). ...Objective To analyze the long-term outcome of patients with SCID and non-SCID PID from European centers treated between 1968 and 2005. Methods The product-limit method estimated cumulative survival; the log-rank test compared survival between groups. A Cox proportional-hazard model evaluated the impact of independent predictors on patient survival. Results In patients with SCID, survival with genoidentical donors (n = 25) from 2000 to 2005 was 90%. Survival using a mismatched relative (n = 96) has improved (66%), similar to that using an unrelated donor (n = 46; 69%; P = .005). Transplantation after year 1995, a younger age, B+ phenotype, genoidentical and phenoidentical donors, absence of respiratory impairment, or viral infection before transplantation were associated with better prognosis on multivariate analysis. For non-SCID PID, in contrast with patients with SCID, we confirm that, in the 2000 to 2005 period, using an unrelated donor (n = 124) gave a 3-year survival rate similar to a genoidentical donor (n = 73), 79% for both. Survival was 76% in phenoidentical transplants (n = 23) and worse in mismatched related donor transplants (n = 47; 46%; P = .016). Conclusion This is the largest cohort study of such patients with the longest follow-up. Specific issues arise for different patient groups. Patients with B-SCID have worse survival than other patients with SCID, despite improvements in each group. For non-SCID PID, survival is worse than SCID, although more conditions are now treated. Individual disease categories now need to be analyzed so that disease-specific prognosis may be better understood and the best treatments planned.
Background Invasive aspergillosis is one of the most lethal airborne dangers for immune-suppressed subjects. Providing patient protection from such airborne threats requires costly and ...high-maintenance facilities. We herein evaluate a new self-contained mobile unit as an alternative for creating a patient protective environment. Methods Airborne contamination levels were monitored for different simulated scenarios and under actual clinical conditions. Functional tests were used to challenge the unit under adverse conditions, and a preliminary clinical study with patients and staff present was performed at 2 different French hospitals. Results Functional tests demonstrated that the unit can rapidly decontaminate air in the protected zone created by the unit and in the surrounding room. In addition, the protected zone is not sensitive to large disturbances that occur in the room. The clinical study included 4 patients with 150 accumulated days of testing. The protected zone created by the unit systematically provided an environment with undetectable airborne fungal levels (ie, <1 CFU/m3 ) regardless of the levels in the room or corridor ( P < .01). Conclusions These tests show that the unit can be used to create a mobile protective environment for immune-suppressed patients in a standard hospital setting.
A complete list of definite, as well as possible, indications for hemopoietic stem cell transplantation in primary immunodeficiency is provided. Included are: severe combined immunodeficiency, ...profound T cell defects, autoimmune and autoinflammatory syndromes, innate immune defects, hemophagocytic disorders, and other conditions. Some causes and limitations are included.
PDF
