Induction of IgG2 and IgG4 B-cell memory following sublingual immunotherapy for ryegrass pollen allergy

Background: While treatment for atopic rhinitis is aimed mostly to relieve symptoms, only allergen-specific immunotherapy (AIT) is targeted to modify the natural history of allergic diseases. This results in sustained clinical tolerance, even when treatment has stopped. The immunomodulatory effects of AIT are attributed mainly to increased regulatory T-cell function and increased allergen-specific IgG4, yet little is known about the effect on the memory B-cell compartment. Objective: We aimed to examine the effects of AIT on the IgE- and IgG subclass-expressing memory B cells. Methods: We recruited 29 patients with atopic seasonal rhinoconjunctivitis and performed a longitudinal analysis of the peripheral immune compartment before, during, and after sublingual immunotherapy (SLIT) for allergy to temperate grass pollen, predominantly to ryegrass pollen (RGP; Lolium perenne). Using flow cytometry on peripheral blood mononuclear cells and serum immunoassays, we analyzed the effects of a 4 months preseasonal treatment regimen comprising two or three courses in consecutive years on circulating IgE+ and IgG+ memory B cells and allergen-specific Ig levels. Results: SLIT increased RGP-specific serum IgG2 and IgG4, as well as the frequencies of IgG2 + and IgG4 + memory B cells, whereas no effect was observed on the IgE+ memory B-cell compartment. Furthermore, SLIT enhanced proportions of regulatory T cells specific to RGP. These changes were associated with clinical improvement. Conclusion: Our data provide evidence for immunological effects of SLIT on B-cell memory. Skewing responses toward IgG2 and IgG4 subclasses might be a mechanism to suppress IgE-mediated allergic responses

Knee extensor torque and perceived discomfort during symmetrical biphasic electromyostimulation

BACKGROUND: During follow-up of children with a brain tumor, traditionally surveillance-imaging studies are done in addition to clinical evaluations. The purpose of this study was to determine the role of clinical evaluations by a multidisciplinary team for the detection of recurrent tumor. PROCEDURE: We retrospectively assessed the predictive value of clinical evaluation, using subsequent neuroimaging as the gold standard. Ninety-eight children with a newly diagnosed primary brain tumor were included in the study. In these patients, 393 imaging studies were done, 75 because of clinical suspicion of recurrence, and 318 for routine surveillance only. RESULTS: In 28 of these 75 imaging studies on clinical indications, a radiologic diagnosis of recurrence was made. Only 9 out of 318 routine surveillance imaging studies resulted in an unexpected diagnosis of recurrence. Thus, the overall positive predictive value of clinical evaluation was 37%; the overall negative predictive value was 97%. The negative predictive values for specific brain tumors varied from 91% (optical glioma) to 99% (primitive neuroectodermal tumors). CONCLUSIONS: An accurate multidisciplinary clinical evaluation has a very high negative predictive value. Consequently, the added value of surveillance imaging studies is limited. The role of such studies during the follow-up of children with brain tumors should be reconsidered

De rol van routinematig beeldvormend onderzoek bij de follow-up van kinderen met een hersentumor

Item does not contain fulltext1 p

Calcineurin inhibitors in the treatment of adult autoimmune hepatitis: a systematic review

Background and Aims: A considerable number of au-toimmune hepatitis (AIH) patients completely or partially fail on first-line treatment. Several studies on the use of calcineurin inhibitors (CNIs) in the treatment of AIH have been published without focusing on indication. The aim was to assess the efficacy of CNIs in the treatment of adult AIH patients, specifically focusing on indication: first-line intolerant and with first-line insufficient response (failure to achieve or maintain remission), and with second versus third-line treatment. Methods: A literature search included studies on the use of CNIs in adult AIH. Patients with past or present use of CNIs from the Dutch AIH group cohort were added. The primary endpoint was biochemical remission while using CNIs. Secondary endpoints were biochemical response, treatment failure, and adverse effects. Results: Twenty studies from the literature and nine Dutch patients were included describing the use of cyclosporine in 59 and tacrolimus in 219 adult AIH patients. The CNI remission rate was 53% in patients with insufficient response to first-line treatment and 67% in patients intolerant to first-line treat-ment. CNIs were used as second-line treatment in 73% with a remission rate of 52% and as third-line treatment in 22% with a remission rate of 26%. Cyclosporine was discontin-ued in 13% and tacrolimus in 11% of patients because of adverse events. Conclusions: CNIs as rescue treatment in adult AIH patients are reasonably effective and safe both with insufficient response or intolerance to previous treat-ment. Prospective studies are needed