[Show abstract][Hide abstract] ABSTRACT: Inherited deficiency of major histocompatibility complex (MHC) class II molecules impairs antigen presentation to CD4(+) T cells and results in combined immunodeficiency (CID). Autosomal-recessive mutations in the RFXANK gene account for two-thirds of all cases of MHC class II deficiency. We describe here the genetic, clinical, and immunologic features of 35 patients from 30 unrelated kindreds from North Africa sharing the same RFXANK founder mutation, a 26-bp deletion called I5E6-25_I5E6 + 1), and date the founder event responsible for this mutation in this population to approximately 2250 years ago (95% confidence interval [CI]: 1750-3025 years). Ten of the 23 patients who underwent hematopoietic stem cell transplantation (HSCT) were cured, with the recovery of almost normal immune functions. Five of the patients from this cohort who did not undergo HSCT had a poor prognosis and eventually died (at ages of 1-17 years). However, 7 patients who did not undergo HSCT (at ages of 6-32 years) are still alive on Ig treatment and antibiotic prophylaxis. RFXANK deficiency is a severe, often fatal CID for which HSCT is the only curative treatment. However, some patients may survive for relatively long periods if multiple prophylactic measures are implemented.
[Show abstract][Hide abstract] ABSTRACT: Background
The recent demonstration of the cure of HIV infection following CCR Δ32/Δ32 stem cell transplantation in a German patient (Berlin patient) paves the way to new therapeutic options.
Allogeneic haematopoietic stem cell transplantation (HSCT) have been used since many years during HIV infection and is associated with major toxicity concerns. Several tools have been developed (siRNA, shRNA, Zinc finger proteins) in order to disrupt CCR5 expression in hematopoietic stem cell progenitors. They have been evaluated both in humans and in animal models.
Results showed that CCR5 knockout strategies do not impair immune reconstitution. They also suggest that the effect of long-term control of HIV in the Berlin patient is related to both CCR5 down regulation and the effects of myeloablative and immunosuppressive therapies used during HSCT.
In the event of a large use of genetic therapies during HIV infection, beside the context of HSCT, it will be necessary to target several cellular factors in order to obtain a long term control of HIV as observed in the Berlin patient.
[Show abstract][Hide abstract] ABSTRACT: During primary systemic vasculitides gastrointestinal (GI) involvement is associated with a poor outcome, leading to the use of immunosuppressive therapy. The significance of GI involvement during hepatitis C virus (HCV)-related systemic vasculitis has never been evaluated.
To evaluate the significance of GI involvement during HCV-related systemic vasculitis in the antiviral therapy era.
Data from 163 patients were retrospectively reviewed to describe the presentation and outcome of patients with HCV-related systemic vasculitis with GI involvement (GI+), and to compare them with patients without GI involvement (GI-).
GI manifestations were present in 12 (7.4%) patients. Abdominal pain was consistently present in GI+ patients, and half of patients presented with surgical abdomen and/or intestinal bleeding. GI+ compared to GI- patients had more frequent renal (75% vs 30%; p=0.003) and cardiac involvement (25% vs 2%; p=0.006), medium-vessel vasculitis (67% vs 22%; p=0.003) and higher mixed cryoglobulinaemia levels (2.2 g/l vs 1.2 g/l; p=0.07). After treatment, GI+ and GI- patients had similar rates of overall clinical response of the vasculitis and immunological and virological responses. HCV-MC vasculitis patients with GI involvement did not have poorer overall survival than those without.
GI involvement is a rare manifestation of HCV-related vasculitis, associated with acute-onset and life-threatening manifestations. In contrast with primary vasculitides, GI+ patients do not seem to have poorer overall survival than GI- patients.
Gut 12/2010; 59(12):1709-15. · 10.73 Impact Factor