The European internet-based patient and research database for primary immunodeficiencies: update 2011.

In order to build a common data pool and estimate the disease burden of primary immunodeficiencies (PID) in Europe, the European Society for Immunodeficiencies (ESID) has developed an internet-based database for clinical and research data on patients with PID. This database is a platform for epidemiological analyses as well as the development of new diagnostic and therapeutic strategies and the identification of novel disease-associated genes. Since its start in 2004, 13,708 patients from 41 countries have been documented in the ESID database.

Antiviral and regulatory T cell immunity in a patient with stromal interaction molecule 1 deficiency.

Stromal interaction molecule 1 (STIM1) deficiency is a rare genetic disorder of store-operated calcium entry, associated with a complex syndrome including immunodeficiency and immune dysregulation. The link from the molecular defect to these clinical manifestations is incompletely understood. We report two patients with a homozygous R429C point mutation in STIM1 completely abolishing store-operated calcium entry in T cells.

Fatal hemophagocytic syndrome in a patient with a previously well-controlled asymptomatic HIV infection after EBV reactivation.

We present a rare case of hemophagocytic lymphohistiocytosis (HLH) in a 70 year-old male patient with previously well-controlled HIV infection. We could confirm HLH in different organs post mortem. Since the diagnosis of HLH was delayed, the patient died despite initiation of chemotherapy.

Vascular damage in the central nervous system: a multifaceted role for vascular-derived TGF-β.

The brain function depends on a continuous supply of blood. The blood-brain barrier (BBB), which is formed by vascular cells and glia, separates components of the circulating blood from neurons and maintains the precisely regulated brain milieu required for proper neuronal function. A compromised BBB alters the transport of molecules between the blood and brain and has been associated with or shown to precede neurodegenerative disease.

Histopathological patterns of nephrocalcinosis: a phosphate type can be distinguished from a calcium type.

Background: The etiology of nephrocalcinosis is variable. In this study, we wanted to elucidate whether the histopathological appearance of calcium phosphate deposits provides information about possible etiology.

Methods: Autopsy cases from the years 1988 to 2007 and native kidney biopsies from a 50-year period (1959-2008) with nephrocalcinosis were identified.

Major histocompatibility complex-dependent cytotoxic T lymphocyte repertoire and functional avidity contribute to strain-specific disease susceptibility after murine respiratory syncytial virus infection.

Susceptibility to respiratory syncytial virus (RSV) infection in mice is genetically determined. While RSV causes little pathology in C57BL/6 mice, pulmonary inflammation and weight loss occur in BALB/c mice. Using major histocompatibility complex (MHC)-congenic mice, we observed that the H-2(d) allele can partially transfer disease susceptibility to C57BL/6 mice.

Clinical and immunological manifestations of patients with atypical severe combined immunodeficiency.

Hypomorphic mutations in genes associated with severe combined immunodeficiency (SCID) or Omenn syndrome can also cause milder immunodeficiencies. We report 10 new patients with such "atypical" SCID and summarize 63 patients from the literature. The patient groups with T(low)B(low) (n=28), T(low)B(+) (n=16) and ADA (n=29) SCID variants had similar infection profiles but differed in the frequency of immune dysregulation, which was observed predominantly in patients with recombination defects.

ORAI1-mediated calcium influx is required for human cytotoxic lymphocyte degranulation and target cell lysis.

Lymphocytes mediate cytotoxicity by polarized release of the contents of cytotoxic granules toward their target cells. Here, we have studied the role of the calcium release-activated calcium channel ORAI1 in human lymphocyte cytotoxicity. Natural killer (NK) cells obtained from an ORAI1-deficient patient displayed defective store-operated Ca(2+) entry (SOCE) and severely defective cytotoxic granule exocytosis leading to impaired target cell lysis.

Macrophages recognize streptococci through bacterial single-stranded RNA.

Group B streptococcus (GBS) is a leading cause of both neonatal sepsis and meningitis, two diseases that are characterized by inflammation. However, the manner in which GBS organisms are recognized by monocytes and macrophages is poorly understood. In this study, we report that the recognition of GBS and other Gram-positive bacteria by macrophages and monocytes relies on bacterial single-stranded RNA (ssRNA).

Clinical features and outcome of patients with IRAK-4 and MyD88 deficiency.

Autosomal recessive interleukin-1 receptor-associated kinase (IRAK)-4 and myeloid differentiation factor (MyD)88 deficiencies impair Toll-like receptor (TLR)- and interleukin-1 receptor-mediated immunity. We documented the clinical features and outcome of 48 patients with IRAK-4 deficiency and 12 patients with MyD88 deficiency, from 37 kindreds in 15 countries.The clinical features of IRAK-4 and MyD88 deficiency were indistinguishable.

Common variable immunodeficiency at the end of a prospering decade: towards novel gene defects and beyond.

Purpose Of Review: Patients with a primary antibody deficiency of unknown cause are usually allotted the diagnosis of common variable immunodeficiency (CVID), thus creating a genetically, immunologically, and clinically highly heterogeneous study population, that focuses the attention of many clinicians and researchers worldwide. The purpose of this review is to highlight the most important publications of the past year with an emphasis on novel findings in genetics and the immunophenotype of CVID.

Recent Findings: New gene defects associated with a CVID phenotype have been described in BAFF-R, CD81, and CD20 in single consanguineous families.

Clinical and immunological overlap between autoimmune lymphoproliferative syndrome and common variable immunodeficiency.

Autoimmune lymphoproliferative syndrome (ALPS) is mainly caused by defects in the CD95 pathway. Raised CD3+TCRαβ+CD4-CD8- double negative T cells and impaired T cell apoptosis are hallmarks of the disease. In contrast, the B cell compartment has been less well studied.

B cell receptor-mediated calcium signaling is impaired in B lymphocytes of type Ia patients with common variable immunodeficiency.

Several lines of evidence have demonstrated B cell intrinsic activation defects in patients with common variable immunodeficiency (CVID). The rapid increase of intracellular free calcium concentrations after engagement of the BCR represents one crucial element in this activation process. The analysis of 53 patients with CVID for BCR-induced calcium flux identified a subgroup of patients with significantly reduced Ca2+ signals in primary B cells.

Protective effect of human leukocyte antigen B27 in hepatitis C virus infection requires the presence of a genotype-specific immunodominant CD8+ T-cell epitope.

Unlabelled: Human leukocyte antigen B27 (HLA-B27) is associated with protection in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection. This protective role is linked to single immunodominant HLA-B27-restricted CD8+ T-cell epitopes in both infections. In order to define the relative contribution of a specific HLA-B27-restricted epitope to the natural course of HCV infection, we compared the biological impact of the highly conserved HCV genotype 1 epitope, for which the protective role has been described, with the corresponding region in genotype 3 that differs in its sequence by three amino acid residues.

Circulating CD21low B cells in common variable immunodeficiency resemble tissue homing, innate-like B cells.

The homeostasis of circulating B cell subsets in the peripheral blood of healthy adults is well regulated, but in disease it can be severely disturbed. Thus, a subgroup of patients with common variable immunodeficiency (CVID) presents with an extraordinary expansion of an unusual B cell population characterized by the low expression of CD21. CD21(low) B cells are polyclonal, unmutated IgM(+)IgD(+) B cells but carry a highly distinct gene expression profile which differs from conventional naïve B cells.