Flow cytometric assessment of leukocyte kinetics for the monitoring of tissue damage.

Leukocyte populations quickly respond to tissue damage, but most leukocyte kinetic studies are not based on multiparameter flow cytometry. We systematically investigated several blood leukocyte populations after controlled tissue damage. 48 patients were assigned to either an anterior or posterolateral total hip arthroplasty.

Clinical heterogeneity can hamper the diagnosis of patients with ZAP70 deficiency.

One of the severe combined immunodeficiencies (SCIDs), which is caused by a genetic defect in the signal transduction pathways involved in T-cell activation, is the ZAP70 deficiency. Mutations in ZAP70 lead to both abnormal thymic development and defective T-cell receptor (TCR) signaling of peripheral T-cells. In contrast to the lymphopenia in most SCID patients, ZAP70-deficient patients have lymphocytosis, despite the selective absence of CD8+ T-cells.

Two patients with complete defects in interferon gamma receptor-dependent signaling.

Unusual susceptibility to mycobacterial infections can be caused by deleterious mutations in genes that encode the interferon-gamma receptor 1 chain. Such mutations hamper the activation of macrophages by a type 1 immune response and result in enhanced survival of intracellular pathogens. We here report two patients with unusual mycobacterial infections, both diagnosed with homozygous deleterious interferon-gamma receptor 1 gene mutations.

Radiosensitive SCID patients with Artemis gene mutations show a complete B-cell differentiation arrest at the pre-B-cell receptor checkpoint in bone marrow.

Severe combined immunodeficiency disease (SCID) can be immunologically classified by the absence or presence of T, B, and natural killer (NK) cells. About 30% of T(-)B(-)NK(+) SCID patients carry mutations in the recombination activating genes (RAG). Some T(-)B(-)NK(+) SCID patients without RAG gene mutations are sensitive to ionizing radiation, and several of these radiosensitive (RS) SCID patients were recently shown to have large deletions or truncation mutations in the Artemis gene, implying a role for Artemis in DNA double-strand break (dsb) repair.

XLA patients with BTK splice-site mutations produce low levels of wild-type BTK transcripts.

X-linked agammaglobulinemia is caused by mutations in the BTK gene, which result in a precursor B-cell differentiation arrest in the bone marrow and the absence of or strongly reduced B lymphocytes in blood. We identified a patient with a mild clinical phenotype, low numbers of B lymphocytes, and a splice-site mutation in the BTK gene. The precursor B-cell compartment in the bone marrow of this patient was almost identical to that in healthy children.

The immunophenotypic and immunogenotypic B-cell differentiation arrest in bone marrow of RAG-deficient SCID patients corresponds to residual recombination activities of mutated RAG proteins.

The protein products of the recombination activating genes (RAG1 and RAG2) initiate the formation of immunoglobulin (Ig) and T-cell receptors, which are essential for B- and T-cell development, respectively. Mutations in the RAG genes result in severe combined immunodeficiency disease (SCID), generally characterized by the absence of mature B and T lymphocytes, but presence of natural killer (NK) cells. Biochemically, mutations in the RAG genes result either in nonfunctional proteins or in proteins with partial recombination activity.

Composition of precursor B-cell compartment in bone marrow from patients with X-linked agammaglobulinemia compared with healthy children.

X-linked agammaglobulinemia (XLA) is characterized by a severe B-cell deficiency, resulting from a differentiation arrest in the bone marrow (BM). Because XLA is clinically and immunologically heterogeneous, we investigated whether the B-cell differentiation arrest in BM of XLA patients is heterogeneous as well. First, we analyzed BM samples from 19 healthy children by flow cytometry.