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B Cell Subpopulations (b + cell_subpopulation)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Original Article: Clinical management of short children with low serum immunoglobulin but no immunodeficiency features

PEDIATRICS INTERNATIONAL, Issue 4 2010
Cristina Meazza
Abstract Background:, In children of different ages investigated for failure to thrive, low (below the cut-off for age) immunoglobulin (Ig) values can be detected, without any clinical evidence of humoral immunodeficiencies. To better characterize infants presenting with diminished immunoglobulin levels, we studied IgG subclasses, in vitro Ig production and B cell subpopulation. Methods:, We monitored 17 children (12 boys and five girls, age range 1,18 years) with low serum levels of one or more Ig isotypes but without any clinical or laboratory features of immunodeficiency. Results:, Low IgM levels were frequent (52.9%). During the follow up, six of 17 cases (35.3%) normalized their immunoglobulin levels. Frequently, in the observed patients, low levels of immunoglobulins were not limited to the period of infancy. In all patients, in vitro Ig production and B lymphocyte subpopulations were within normal ranges. Conclusions:, We suggest a quantification of serum Ig levels in children who fail to thrive in order to identify patients with low Ig levels. These children should be monitored until Ig levels normalize to exclude any immunodeficiency status. Early recognition of children with persistent hypogammaglobulinemia would allow prompt and appropriate clinical interventions. [source]

An orally bioavailable spleen tyrosine kinase inhibitor delays disease progression and prolongs survival in murine lupus

ARTHRITIS & RHEUMATISM, Issue 5 2008
Frances Rena Bahjat
Objective To assess whether R788, an orally bioavailable small molecule inhibitor of spleen tyrosine kinase (Syk),dependent signaling, could modulate disease in lupus-prone (NZB × NZW)F1 (NZB/NZW) mice via inhibition of Fc receptor (FcR) and B cell receptor signaling. Methods R788 was administered to NZB/NZW mice before and after disease onset. Proteinuria, blood urea nitrogen levels, and autoantibody titers were examined periodically, and overall survival and renal pathologic features were assessed following long-term treatment (24,34 weeks). The distribution and immunophenotype of various splenic T cell and B cell subpopulations were evaluated at the time of study termination. Arthus responses in NZB/NZW mice pretreated with R788 or Fc-blocking antibody (anti-CD16/32) were also examined. Results When R788 was administered prior to or after disease onset, it delayed the onset of proteinuria and azotemia, reduced renal pathology and kidney infiltrates, and significantly prolonged survival of lupus-prone NZB/NZW mice; autoantibody titers were minimally affected throughout the study. Dose-dependent reductions in the numbers of CD4+ activated T cells expressing high levels of CD44 or CD69 were apparent in spleens from R788-treated mice. Minimal effects on the numbers of naive T cells expressing CD62 ligand and total CD8+ T cells per spleen were observed following long-term drug treatment. R788 pretreatment resulted in reduced Arthus responses in NZB/NZW mice, similar to results obtained in mice pretreated with FcR-blocking antibody. Conclusion We demonstrate that a novel Syk-selective inhibitor prevents the development of renal disease and treats established murine lupus nephritis. These data suggest that Syk inhibitors may be of therapeutic benefit in human lupus and related disorders. [source]

Delayed memory B cell recovery in peripheral blood and lymphoid tissue in systemic lupus erythematosus after B cell depletion therapy

ARTHRITIS & RHEUMATISM, Issue 9 2007
Jennifer H. Anolik
Objective Recent data suggest that the reconstituting peripheral B cell compartment after B cell depletion therapy may be functionally immature, with a preponderance of transitional B cells and a paucity of memory B cells. This study was undertaken to determine the magnitude, duration, and cause of these defects in rituximab-treated systemic lupus erythematosus (SLE) patients. Methods Fifteen patients with SLE previously treated with rituximab as part of a phase I/II dose-escalation study were evaluated during a long-term followup (mean followup period 41 months). B cells from peripheral blood and tonsils were assessed using multicolor flow cytometry, and their developmental pathway was classified based on the expression of defined surface markers. Results Reconstitution of peripheral blood CD27+ memory B cells was delayed for several years after B cell depletion therapy in a subset of patients with prolonged clinical responses and autoantibody normalization. This delay correlated with the degree of expansion of B cells of a transitional phenotype during the B cell reconstitution phase (P = 0.005) and the absence of baseline autoantibodies directed against extractable nuclear antigens (RNP, Sm, Ro antigen, La antigen). Despite the paucity of peripheral blood memory cells and the prolonged expansion of functionally immature transitional B cells, tonsil biopsy tissues revealed active germinal center (GC) reactions, but with decreased Fc receptor homolog 4,positive memory B cells. Conclusion These results suggest heterogeneity in the B cell depletion and reconstitution process that impacts clinical and immunologic outcomes in SLE. The presence of GC reactions, but with altered memory B cell subpopulations in tonsils, suggests that peripheral blood memory cell reconstitution lags behind a slow secondary lymphoid tissue recovery, with important implications for immunologic competence and tolerance. [source]

Measurement of peripheral B cell subpopulations in common variable immunodeficiency (CVID) using a whole blood method

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2005
B. L. Ferry
Summary Recent reports have described reduced populations of CD27+ memory B cells and increased percentages of undifferentiated B cells in peripheral blood of patients with common variable immunodeficiency (CVID). This work has prompted two attempts to classify CVID based on rapid flow cytometric quantification of peripheral blood memory B cells and immature B cells. Evidence to support the hypothesis that such in vitro B cell classification systems correlate with clinical subtypes of CVID is being sought. For the classification to be useful in routine diagnosis, it is important that the flow cytometric method can be used without prior separation of peripheral blood mononuclear cells (PBMC). We have examined 23 CVID patients and 24 controls, using both PBMC and whole blood, and find an excellent correlation between these methods. The reproducibility of the method was excellent. We classified the CVID patients by all three of the existing classifications, including secretion of immunoglobulin by B cells in vitro as described by Bryant, as well as the more recent flow cytometric classification methods. Only one patient changed classification as a result of using whole blood. [source]