Déficits immunitaires primaires: diagnostic, prise en charge, quelques perspectives.

Severe primary immunodeficiencies (PID) are rare; their global incidence is comparable to that of childhood leukemia; they include more than 100 different entities. Clinical manifestations are: unusually severe or frequent infections or infections that do not respond to adequate treatment; an increased risk of certain malignancies; sometimes auto-immune manifestations. Delayed diagnosis and management of PID can lead to severe and irreversible complications or to death. PID can become manifest only in the adult; in common variable immune deficiency, the median age at diagnosis is between the 2nd and the 3rd decade of life. PID are often transmitted genetically; recent progresses in molecular biology have allowed more precise and earlier, including antenatal, diagnosis. Molecular treatment of 3 infants with a severe immunodeficiency has recently been achieved in April 2000. Those progresses were mostly based on the study of immunodeficiency databases. We present here the work of a Belgian group specialized in PID; meetings have started in June 1997. This group establishes guidelines for the diagnosis and treatment of PID, adapted to the local situation. The elaboration of a national register of PID is also underway; this has to provide all guaranties of anonymity to patients and families. Such a register already exists at the European level; it has provided the basis for new diagnostic and therapeutic possibilities. The inclusion of Belgian data in this register should allow essential progresses essential for our patients.

La greffe de moelle dans les maladies héréditaires.

Since 1968, bone marrow transplantation became the first line therapy for selected metabolic and immunological hereditary disorders. Actually, advances in the supportive care in bone marrow transplantation and a better knowledge of the immunology of BMT complications has been associated with a better disease correction and an increase in long term survival. New approaches are under investigation and include: hematopoietic growth factors, enzymatic replacement and gene therapy. However at the present time BMT is still the only curative treatment for selected hereditary disorders.

Evaluation of a WHO-Validated Serotype-Specific Serological Assay for the Diagnosis of Pneumococcal Etiology in Children with Community-Acquired Pneumonia.

BACKGROUND: The etiologic diagnosis of community-acquired pneumonia (CAP) remains challenging in children because blood cultures have low sensitivity. Novel approaches are needed to confirm the role of Streptococcus pneumoniae. METHODS: In this study, pneumococcal aetiology was determined by serology using a subset of blood samples collected during a prospective multicentre observational study of children <15 years of age hospitalised in Belgium with X-ray-confirmed CAP. Blood samples were collected at admission and 3-4 weeks later. Pneumococcal (P)-CAP was defined in the presence of a positive blood or pleural fluid culture. Serotyping of Streptococcus pneumoniae isolates was done with the Quellung reaction. Serological diagnosis was assessed for nine serotypes using World Health Organization validated IgG and IgA serotype-specific enzyme-linked immunosorbent assays (ELISAs). RESULTS: Paired admission/convalescent sera from 163 children were evaluated by ELISA (35 with proven P-CAP and 128 with non proven P-CAP). ELISA detected pneumococci in 82.8% of patients with proven P-CAP. The serotypes identified were the same as with the Quellung reaction in 82% and 59% of cases by IgG ELISA and IgA ELISA, respectively. Overall, ELISA identified a pneumococcal aetiology in 55% of patients with non-proven P-CAP. Serotypes 1 (51.6%), 7F (19%), and 5 (15.7%) were the most frequent according to IgG ELISA. CONCLUSIONS: In conclusion, the serological assay allows recognition of pneumococcal origin in 55% of CAP patients with negative culture. This assay should improve the diagnosis of P-CAP in children and could be a useful tool for future epidemiological studies on childhood CAP etiology.

Cutaneous lesions as a clue to severe combined immunodeficiency.

A 2-month-old boy experienced cutaneous lesions that revealed an underlying severe, combined immunodeficiency (SCID). It is important to recognize cutaneous manifestations of primary immunodeficiency disorders, as they may provide the earliest clue to a defect in immune function.

Characterization of serum anti-gliadin IgA in childhood coeliac diseases versus other gastrointestinal diseases and controls.

info:eu-repo/semantics/nonPublished

NF-KB Activation and Severity of Gastritis in Helicobacter pylori-Infected Children and Adults.

In contrast to adults, Helicobacter pylori gastritis in children is reported as milder and ulcer disease as uncommon, but unequivocal data are lacking.

Antibody deficiency due to a missense mutation in CD19 demonstrates the importance of the conserved tryptophan 41 in immunoglobulin superfamily domain formation.

Immunoglobulin superfamily (IgSF) domains are conserved structures present in many proteins in eukaryotes and prokaryotes. These domains are well-capable of facilitating sequence variation, which is most clearly illustrated by the variable regions in immunoglobulins (Igs) and T cell receptors (TRs). We studied an antibody-deficient patient suffering from recurrent respiratory infections and with impaired antibody responses to vaccinations. Patient's B cells showed impaired Ca(2+) influx upon stimulation with anti-IgM and lacked detectable CD19 membrane expression. CD19 sequence analysis revealed a homozygous missense mutation resulting in a tryptophan to cystein (W52C) amino acid change. The affected tryptophan is CONSERVED-TRP 41 located on the C-strand of the first extracellular IgSF domain of CD19 and was found to be highly conserved, not only in mammalian CD19 proteins, but in nearly all characterized IgSF domains. Furthermore, the tryptophan is present in all variable domains in Ig and TR and was not mutated in 117 Ig class-switched transcripts of B cells from controls, despite an overall 10% amino acid change frequency. In vitro complementation studies and CD19 western blotting of patient's B cells demonstrated that the mutated protein remained immaturely glycosylated. This first missense mutation resulting in a CD19 deficiency demonstrates the crucial role of a highly conserved tryptophan in proper folding or stability of IgSF domains.

Echovirus meningoencephalitis in X-linked hypogammaglobulinemia.

Echovirus meningoencephalitis and polymyositis are classical complications of X-linked agammaglobulinemia (1). The treatment of meningoencephalitis is troublesome since intravenous (2), intrathecal (3) and intraventricular (4) administration of gammaglobulins have been reported successful, but failure also occurred in some cases (5). We report our experience of high dose intravenous treatment.