Ribosomal protein SA haploinsufficiency in humans with isolated congenital asplenia.

Isolated congenital asplenia (ICA) is characterized by the absence of a spleen at birth in individuals with no other developmental defects. The patients are prone to life-threatening bacterial infections. The unbiased analysis of exomes revealed heterozygous mutations in RPSA in 18 patients from eight kindreds, corresponding to more than half the patients and over one-third of the kindreds studied. The clinical penetrance in these kindreds is complete. Expression studies indicated that the mutations carried by the patients-a nonsense mutation, a frameshift duplication, and five different missense mutations-cause autosomal dominant ICA by haploinsufficiency. RPSA encodes ribosomal protein SA, a component of the small subunit of the ribosome. This discovery establishes an essential role for RPSA in human spleen development.

Olecranon bursitis secondary to Mycobacterium kansasii infection in a patient receiving infliximab for Behcet's disease.

We present a case of Mycobacterium kansasii olecranon bursitis in a woman with known immunosuppression secondary to the treatment received for her Behçet's disease. We found only one other case report of olecranon bursitis caused by M. kansasii in the literature, which, unlike our case, presented in an immunocompetent adult following trauma. This case extends the range of opportunistic mycobacterial infections that are associated with anti-tumour necrosis factor therapy.

T-cell immunodeficiency in CHARGE syndrome.

UNLABELLED: CHARGE syndrome comprises coloboma of the eye, heart defects, choanal atresia, growth and developmental retardation, genitourinary anomalies and ear and hearing defects. The association between CHARGE syndrome and T-cell immunodeficiency is recognized, but has not been reported widely in the literature. We report four patients meeting the diagnostic criteria for CHARGE syndrome, who had moderate or severe T-cell lymphopenia complicated by infections. The patients presented in Leicester, UK, between 2000 and 2007. All patients were negative for 22q11.2 deletions by FISH analysis, but mutations in the CHD7 gene were identified in three patients in whom the analysis was performed. Our cases indicate that patients with CHARGE syndrome may have a spectrum of T-cell immune deficiency, and that this association may be more common than has previously been appreciated. We recommend that all patients diagnosed with CHARGE syndrome should have lymphocyte subsets evaluated as part of their initial investigation. CONCLUSION: Thymic hypoplasia should be included in the clinical features associated with CHARGE syndrome. All patients with CHARGE syndrome should have lymphocyte subset analysis performed, to exclude T-cell immunodeficiency.

Vaccination with polysaccharide-conjugate-vaccines in adult patients with specific antibody deficiency.

We report on a cohort of seven adult patients with specific antibody deficiency, defined by failure to respond to 23-valent Streptococcus pneumoniae vaccine while being able to respond to tetanus toxoid. Antibodies to Hemophilus influenzae (HiB) polysaccharides either pre-existed or were readily induced by a single vaccination with the HiB-tetanus toxoid conjugate. By contrast a single vaccination with the S. pneumoniae-diphtheria conjugate failed to induce a response to any of the seven serotypes in any of the seven patients. After a second vaccination in six patients, two patients continued to show no response but four showed a 3- to 45-fold response with development of >1 microg/ml of IgG to 2-4 of the serotypes, respectively. The data show that conjugate vaccines can enforce a response in adult patients with selective antibody deficiency but, dependent on the type of polysaccharide-conjugate, repeated immunisation and monitoring of the response is required.

Lymphocyte subpopulations from patients with primary antibody deficiency do not show increased telomere erosion.

Telomere erosion and residual replicative capacity can be used as markers of the replicative history of somatic cells. We have investigated telomere length, in vitro replicative capacity and rate of telomere erosion in T and B lymphocyte populations from patients with primary antibody deficiency requiring immunoglobulin replacement therapy. We found no significant differences in telomere lengths of B cells, or of CD4+, CD8+, CD45RA+ (naive) and CD45RO+ (memory) T cell populations between patients and age matched controls. Overall, telomere length correlated inversely with age, and was reduced in memory (CD45RO+) as compared with naive (CD45RA+) T cells. In vitro long-term (6 months) cell cultures showed no differences between patients and controls in the mitogen-stimulated replicative potential of T cell subpopulations (CD4+, CD8+, CD45RA+, CD45RO+), or in the rates of telomere erosion with cellular replication in these cell populations. The rate of telomere erosion per population doubling in CD45RA+ cells, however, was greater than in CD45RO+ cells in both patients and controls. These data suggest that premature immune exhaustion is unlikely to represent a long-term complication of primary antibody deficiency.