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Splenectomy has been used in patients with common variable immunodeficiency disorders ( CVID), mainly in the context of refractory autoimmune cytopenia and suspected lymphoma, but there are understandable concerns about the potential of compounding an existing immunodeficiency. With increasing use of rituximab as an alternative treatment for refractory autoimmune cytopenia, the role of splenectomy in CVID needs to be re-examined. This retrospective study provides the largest cohesive data set to date describing the outcome of splenectomy in 45 CVID patients in the past 40 years. Splenectomy proved to be an effective long-term treatment in 75% of CVID patients with autoimmune cytopenia, even in some cases when rituximab had failed. Splenectomy does not worsen mortality in CVID and adequate immunoglobulin replacement therapy appears to play a protective role in overwhelming post-splenectomy infections. Future trials comparing the effectiveness and safety of rituximab and splenectomy are needed to provide clearer guidance on the second-line management of autoimmune cytopenia in CVID. [ABSTRACT FROM AUTHOR]

We studied the efficacy, safety and pharmacokinetic profiles of Intratect®, a recently developed polyvalent intravenous immunoglobulin (IVIG) preparation. Fifty-one patients (aged 6–48 years) with primary immunodeficiencies (PID) and established replacement therapy using a licensed IVIG were enrolled and treated for 12 months with Intratect®. Retrospective patient data served as prestudy controls. The primary efficacy variable was the annual rate of acute serious bacterial infection (ASBI) per patient. Secondary parameters were annual rate of acute relevant infection (ARI), days with antibiotic use, fever, absence from school/work and hospitalization. The average IVIG dose was 0·49 g/kg, with an average infusion rate of 2·4 ml/kg/h. The annual ASBI rate/patient was 0·02 and ARIs were detected 128 times during the 630 adverse events in 40 patients, specified mainly as bronchitis, sinusitis, respiratory tract infection, rhinitis and pharyngitis. The annual rate of respiratory ARIs/patient was 2·0 and the rates/patient for days with fever >38°C, school/work absence and hospitalization were 1·81, 3·99 and 0·36, respectively. A total of 630 adverse events (AEs) were observed in 50 of 51 (98·0%) of patients. In 46 of 51 patients the AEs were not related to infusion. Pharmacokinetic studies after the first infusion revealed a mean elimination half-life of 50·8 ± 30·3 days. During this study, 19 of 649 (2·9%) IgG trough levels were below 6 g/l, better than that of reference IVIGs during the 6 months before study start (10 of 201). These data suggest that Intratect® is a well tolerated, safe and effective IgG concentrate for the treatment of patients with PID. [ABSTRACT FROM AUTHOR]

X-linked agammaglobulinaemia (XLA) is a B cell humoral abnormality arising from mutations in the gene encoding Bruton’s tyrosine kinase (Btk). The phenotype of XLA can be variable, with some individuals having a less severe immunophenotype, although in most cases this cannot be correlated with the Btk mutation or expression of Btk protein. In this study we describe clinical and immunological heterogeneity within the same pedigree. Analysis of the genetic defect identified a missense mutation in the kinase domain of Btk which, unusually, preserved Btk protein expression but at reduced levels, and also considerably diminished autophosphorylation activity. Structural analysis of the effect of this mutation on the kinase domain suggests that this mutation is not an integral part of the ATP or substrate binding domains but may affect the interaction of the kinase domain with its own kinase domain and other substrates. Together, these data may provide an explanation for the variable XLA phenotype. [ABSTRACT FROM AUTHOR]

The low lymphocyte response to phytohaemagglutinin in patients undergoing tonsillectomy is associated with anaesthesia. There is no serum blocking factor, and the lymphocytes responded normally after washing. [ABSTRACT FROM AUTHOR]