Genetic screening of male patients with primary hypogammaglobulinemia can guide diagnosis and clinical management.

The precise diagnosis of an immunodeficiency is sometimes difficult to assess, especially due to the large spectrum of phenotypic variation reported among patients. Common variable immunodeficiency disorders (CVID) do not have, for a large part, an identified genetic cause. The identification of a causal genetic mutation is important to confirm, or in some cases correct, the diagnosis.

Protective effect of IgM against colonization of the respiratory tract by nontypeable Haemophilus influenzae in patients with hypogammaglobulinemia.

Background: Primary immunoglobulin deficiencies lead to recurrent bacterial infections of the respiratory tract and bronchiectasis, even with adequate immunoglobulin replacement therapy. It is not known whether patients able to secrete IgM (eg, those with hyper-IgM [HIgM] syndrome) are as susceptible to these infections as patients who lack IgM production (eg, those with panhypogammaglobulinemia [PHG]).

Objective: This study is aimed at identifying specific microbiological and clinical (infections) characteristics that distinguish immunoglobulin-substituted patients with PHG from patients with HIgM syndrome.

Parental consanguinity is associated with a severe phenotype in common variable immunodeficiency.

The DEFI study has collected clinical data and biological specimens from kindreds with CVID. Patients with demonstrated parental consanguinity (cCVID group) were compared to patients without parental consanguinity (ncCVID). A total of 24 of the 436 patients with CVID had consanguineous parents.

Autoimmunity in common variable immunodeficiency: correlation with lymphocyte phenotype in the French DEFI study.

Common variable immunodeficiency (CVID) is the most frequent clinically expressed primary immunodeficiency in adults and is characterized by primary defective immunoglobulin production. Besides recurrent infectious manifestations, up to 20% of CVID patients develop autoimmune complications. In this study, we took advantages of the French DEFI database to investigate possible correlations between peripheral lymphocyte subpopulations and autoimmune clinical expression in CVID adult patients.

B-cell and T-cell phenotypes in CVID patients correlate with the clinical phenotype of the disease.

Background: Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by recurrent infections and defective immunoglobulin production.

Methods: The DEFI French national prospective study investigated peripheral T-cell and B-cell compartments in 313 CVID patients grouped according to their clinical phenotype, using flow cytometry.

Results: In patients developing infection only (IO), the main B-cell or T-cell abnormalities were a defect in switched memory B cells and a decrease in naive CD4(+) T cells associated with an increase in CD4(+)CD95(+) cells.

Late-onset combined immune deficiency: a subset of common variable immunodeficiency with severe T cell defect.

Background: Common variable immunodeficiency (CVID) is a primary immune deficiency defined by defective antibody production. In most series, a small proportion of patients present with opportunistic infections (OIs).

Methods: The French DEFI study has enrolled patients with primary hypogammaglobulinemia and allows a detailed clinical and immunologic description of patients with previous OIs and/or at risk for OIs.

Infections in 252 patients with common variable immunodeficiency.

Background: Common variable immunodeficiency is characterized by recurrent infections and defective immunoglobulin production.

Methods: The DEFI French national study prospectively enrolled adult patients with primary hypogammaglobulinemia. Clinical events before inclusion were retrospectively analyzed at that time.

Hypoxia modulates HLA-G gene expression in tumor cells.

Human leukocyte antigen G (HLA-G) molecules are expressed in cytotrophoblasts and play a key role in maintaining immune tolerance at the maternal-fetal interface. HLA-G expression was also reported in inflammatory diseases, organ transplantation, and malignant tumors. The regulatory mechanisms of HLA-G gene expression differ from those of classical HLA class I genes and are still only partially elucidated.

Modulation of HLA-G expression in human neural cells after neurotropic viral infections.

HLA-G is a nonclassical human major histocompatibility complex class I molecule. It may promote tolerance, leading to acceptance of the semiallogeneic fetus and tumor immune escape. We show here that two viruses-herpes simplex virus type 1 (HSV-1), a neuronotropic virus inducing acute infection and neuron latency; and rabies virus (RABV), a neuronotropic virus triggering acute neuron infection-upregulate the neuronal expression of several HLA-G isoforms, including HLA-G1 and HLA-G5, the two main biologically active isoforms.

The 14 bp deletion-insertion polymorphism in the 3' UT region of the HLA-G gene influences HLA-G mRNA stability.

Human leukocyte antigen (HLA)-G molecules are generated by an alternative splicing of the primary transcript of the gene and display specialized function in regulating the immune response. Although HLA-G gene polymorphism is low, it may influence levels of protein expression and, in some cases, has been associated with pregnancy diseases. The HLA-G gene exhibits 14 alleles generating six proteins with minor variations and a null allele.

HLA-G gene repression is reversed by demethylation.

The HLA-G molecule plays an important role in immune tolerance, protecting the fetus from maternal immune attack, and probably contributes to graft tolerance and tumor escape from the host immune system. HLA-G expression is tightly regulated and involves mechanisms acting in part at the transcriptional level. Nevertheless, almost all regulatory sequences that govern constitutive and inducible HLA class I gene transcription are disrupted in the HLA-G gene promoter, suggesting an unusual regulatory process.