Virginia Monafo

Clinical spectrum of X-linked hyper-IgM syndrome

We report the clinical and immunologic features and outcome in 56 patients with X-linked hyper-IgM syndrome, a disorder caused by mutations in the CD40 ligand gene. Upper and lower respiratory tract infections (the latter frequently caused by Pneumocystis carinii), chronic diarrhea, and liver involvement (both often associated with Cryptosporidium infection) were common. Many patients had chronic neutropenia associated with oral and rectal ulcers. The marked prevalence of infections caused by intracellular pathogens suggests some degree of impairment of cell-mediated immunity. Although lymphocyte counts and in vitro proliferation to mitogens were normal, a defective in vitro proliferative response to antigens was observed in some patients, and additional defects of cell-mediated immunity may be presumed on the basis of current knowledge of CD40-ligand function. All patients received regular infusions of immunoglobulins. Four patients underwent liver transplantation because of sclerosing cholangitis, which relapsed in there. Three patients underwent bone marrow transplantation. Thirteen patients (23%) died of infection and/or liver disease. X-linked hyper-IgM syndrome, once considered a clinical variant of hypogammaglobulinemia, is a severe immunodeficiency with significant cellular involvement and a high mortality rate.

Serum IgG subclass concentrations in healthy subjects at different age: Age normal percentile charts

IgG subclass levels were determined in 448 normal children from 6 months to 18 years of age and in 141 healthy adults by radial immunodiffusion using monoclonal antibodies. Age-normal percentile values were calculated for each year of age up to 18 years for IgG1, IgG2, IgG3 and in adults for all four subclasses. The broad spread of IgG4 values in children did not permit calculation of reference values.

Selective IgA deficiency: Clinical and immunological evaluation of 50 pediatric patients

Fifty children with IgA deficiency were followed for 1 to 4 years from 1975 to 1978. Thirty-five had complete deficiency of serum IgA (<2.5 IU/ml) and 15 partial deficiency (serum IgA below the 10th centile for age). Patients with another associated immunodeficiency, such as ataxia-telangiectasia, were not included. Most children with complete deficiency of IgA had recurrent respiratory and/or gastrointestinal infections, about half with onset in the first year of life, while partial deficiency of IgA has probably little if any importance for anti-infectious immunity but is important in the pathogenesis of atopy. Atopic diseases were frequent in both groups. Chromosomal abnormalities were found in 2 patients: trisomy 21 in one and in the other a ring chromosome 18. No important defects in cellular immunity were detected but some isolated, borderline abnormalities were often present.

A comparison of secretory antibodies in breast-fed and formula-fed infants over the first six months of life

In the present study salivary IgA, anti‐Escherichia coli, anti‐β‐lactoglobulin and anti‐poliovirus type 1 IgA and IgM in serum and saliva were evaluated longitudinally in 13 breast‐fed and 14 formula‐fed infants over the first six months of life. Salivary IgA was quantified by electroimmunodiffusion; specific IgA and IgM antibodies were determined in serum and saliva by ELISA. Salivary IgA was significantly lower at age one month in breast‐fed compared with formula‐fed infants but in breast‐fed infants salivary IgA increased with age and was significantly higher at six months than at one month. In both groups of infants, at the age of six months, salivary IgA levels were significantly lower than in adult controls. No significant differences in secretory anti‐E. coli were observed between the two groups of infants. Salivary anti‐poliovirus IgA and IgM antibodies increased transiently only to disappear in most babies at age six months, while anti‐β lactoglobulin IgA and IgM, present in saliva at all ages, showed a wide scatter. No important differences in specific serum IgA or IgM antibodies were observed either between the groups or at different times within the groups.

Immunodeficiency in Down's syndrome: Relationship between presence of human thyroglobulin antibodies and HBsAg carrier status

The relationship between the presence of hepatitis B surface antigen (HBsAg) and antibodies to human thyroglobulin (HTgAb) has been studied in 110 subjects with Downs syndrome (DS) from 4 months to 50 years of age and in 122 controls carefully matched for sex, age and socio-environmental conditions. The overall percentage of HBsAg carriers was 22.7 in DS and 6.6 in controls and that of HTgAb-positive subjects was 41.8 in DS and 19.7 in controls. In DS the frequency of HTgAb-positive subjects was very high, even in the youngest age groups in which the percentage of HBsAg carriers was relatively low; the latter thereafter showed a marked increase with age. A positive association between the presence of HBsAg and HTgAb was found only in the oldest age group of DS subjects. It is thus concluded that in DS the high frequency of HTgAb cannot be attributed to chronic hepatitis B virus infection. On the contrary, the presence of HTgAb might well represent an early “marker” of immunodeficiency and increased susceptibility to infection with hepatitis B virus.

Increased frequency of RAG-expressing, CD4+CD3low peripheral T lymphocytes in patients with defective responses to DNA damage

Accumulating evidence indicates that peripheral lymphocyte variants with altered antigen receptor expression may be capable of expressing recombination‐activating genes (RAG). We and others recently observed functional RAG gene products in mature T cells with defective TCR expression (MacMahan and Fink, Immunity 1998. 9: 637 – 647; Lantelme et al., J. Immunol., 2000. 164: 3455 – 3459). Here, the association between TCR expression and RAG activity was assessed further in lymphocytes from patients with defective responses to DNA damage. We show that T cells with altered TCR surface expression are present in increased numbers in these patients and that they express RAG genes. The finding of RAG gene expression by TCR variants suggests the possibility that secondary V(D)J rearrangements could be induced in these cells to rescue their defective phenotype and cellular function. Moreover, as V(D)J recombination has been implicated in chromosome translocations involving antigen receptor genes, we discuss a possible relationship between altered TCR expression, RAG activity and the frequent lymphoma‐specific translocations observed in these patients.

An enzyme-linked immunosorbent assay for cow's milk protein-specific IgE using biotinylated antigen. Avoidance of interference by specific IgG

Detection of specific IgE by the radioallergosorbent test (RAST) which uses labelled antibody can be hampered by the presence of antibodies other than IgE but with the same specificity and may limit usefulness of the RAST for diagnosis of IgE-mediated milk allergy in infancy when high titres of cows milk protein-specific IgG antibodies are known to be present. This can be avoided by using a system employing labelled antigen, such as the enzyme-linked immunosorbent assay (ELISA) described here, where IgE in the test serum is immunoadsorbed to anti-human IgE coated to microtitre plates. Biotinylated antigen, in this case cows milk proteins, binds to specific IgE and the reaction is revealed colorimetrically by adding horseradish peroxidase (HRP)-avidin conjugate.

Asymptomatic persistent pulmonary infiltrates in an immunocompetent boy with cat-scratch disease.

We describe here an immunocompetent boy with fever, regional adenopathy, multifocal hepatosplenic granulomas, and high and increasing serum antibody titers for Bartonella henselae in whom diffuse bilateral reticulonodular pulmonary infiltrates developed in the absence of respiratory symptoms.

A new immunoperoxidase assay for Lolium perenne-specific IgE in serum based on the biotin/avidin system (BAS).

A new solid‐phase immunoassay based on the biotin/avidin system (BAS) for measuring scrum Lolium perenne (LP)‐specific IgE antibody is described. LP‐specific IgE was assayed by the BAS assay and RAST for comparison in the sera of thirty‐two normal asymptomatic subjects R AST‐negative for LP and of twenty‐six subjects with hay fever and R AST‐positive for LP. The specificity of the BAS assay for LP‐specific IgE was demonstrated by absorption experiments. An overall agreement of 91% (53/58) was observed between the BAS and RAST and a high correlation (r= 0.87. P < 0.001) was found between the LP‐specific IgE determined by the two methods. The advantages of ihe BAS assay as compared to both the RAST and classical ELISA arc discussed.

Different role of secretory IgA in the pathogenesis of RAST-positive and RAST-negative atopic dermatitis

Secretory‐IgA (SIgA) concentrations were determined in whole saliva, unstimulated or stimulated by lemon juice, of thirty‐eight children with atopic dermatitis, which comprised three adolescents, sixteen with IgE detected by RAST to one or more common allergen and twenty‐two without specific IgE by RAST. There were thirty healthy controls matched for age and sex.