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 cow's 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 cow's milk proteins, binds to specific IgE and the reaction is revealed colorimetrically by adding horseradish peroxidase (HRP)-avidin conjugate.

Electrophysiologic study of central motor pathways in ataxia-telangiectasia.

To date, corticospinal tract functional integrity in ataxia-telangiectasia has not been studied. Thorough evaluation of central motor pathways is also lacking in neuropathologic and clinical studies. Using electromagnetic stimulation, we assessed the integrity of the corticospinal tracts in eight patients with ataxia-telangiectasia. Cortical and peripheral compound motor action potentials were recorded from the abductor pollicis brevis muscle. Recordings of the shortest F-wave latency and of the compound motor action potential distal latency were made from the abductor pollicis brevis muscle after electrical stimulation of the median nerve at the wrist. A significant increase in central motor conduction time was observed in four patients, two of whom had clinical findings compatible with a pyramidal lesion. This study demonstrates involvement of the central motor pathways in ataxia-telangiectasia, which appears to be more frequent late in the course of the disease.

[Phadiatop-Paediatric, a new screening test for atopy: a comparison with RAST results]. / Phadiatop-pediatrico, un nuovo test di screening per atopia: confronto con i risultati del RAST.

The results obtained using a new in vitro screening test for atopy Phadiatop-paediatric (Phad-P) and RAST for multiple food and inhalant allergens in 132 children (82 with atopic dermatitis and 50 with a negative history of atopic symptoms are compared. 64% of the subjects were RAST-positive for food allergens (55/82) in those with dermatitis and only 5/50 in those without atopic symptoms. The only difference between the new test and the RAST is that a mixture of food and inhalant allergens, rather than a single allergen, is conjugated to the paper disk and the results are expressed as positive or negative so as to identify atopic subjects for further allergologic evaluation. The sensibility and specificity of Phad-P as compared to RAST were respectively 87% and 85% with an efficiency of 86%. On the basis of these data, assuming a 20% prevalence of atopy, in the general population the predictive value of negative results of the new test would be 97% and of positive results 59% with an expected efficiency of 86% values similar to those observed in other studies and at the moment considered satisfactory for a screening test fo atopy.

[Buschke's scleredema and carditis: a clinical case]. / Scleredema di Buschke e cardite: un caso clinico.

An 11-year old girl who presented non-pitting edema of the face and neck, shoulder pain and a gallop rhythm about 10 days after a febrile episode with sore throat is described. The mask-like facial appearance and limited movement of the neck led to suspect scleredema which may be accompanied by carditis. Skin and muscle biopsy findings confirmed the diagnosis. Cardiac involvement included a gallop rhythm persisting for 6 months, ECG changes consisting in transitory T-wave inversion in leads II and V2 - V4, a transitory pericardial function rub and hepatomegaly due to right-sided failure which responded to digitalization. In this case the presence of a gallop rhythm and elevated ASLO titer led to an initial diagnosis of acute rheumatic fever; dermatomysitis and sclerodermia are also to be considered in the differential diagnosis of scleredema of Buschke. In our patient the edema resolved completely within 12 months, the gallop rhythm within 6 months and the ECG became normal after 8 months.

[Granulocyte disorders]. / Anomalie dei granulociti.

The various "in vitro" tests for evaluating polymorphonuclear leucocyte function in children with recurrent infections are described and the different clinical conditions caused or accompanied by defects in polymorphonuclear function are summarized briefly. The necessity of correct interpretation of the results of the laboratory tests used in the diagnostic evaluation of patients with suspected immunodeficiency is stressed.

Infectious mononucleosis fifty years after the discovery of the Paul-Bunnell test.

The Paul-Bunnell test, now 50 years old, is still of fundamental importance in the diagnosis of infectious mononucleosis, even though various immunologic methods have been developed in clinical practice to identify constituents of the Epstein-Barr virus (EBV). The demonstration of sheep red cell agglutinins in infectious mononucleosis (Paul-Bunnell) was in fact the first observation of the presence of heterophil antibodies in this viral disease which was later shown to evoke a polyclonal antibody response to a wide spectrum of autoantigens as well. The selective tropism of EBV for B lymphocytes and the reactivity of T lymphocytes to these infected B lymphocytes are the pathophysiological elements characteristic of infectious mononucleosis, and are the reason for this massive antibody response.

Recurrent infections with IgG2 deficiency.

An 11 year old girl with retarded growth, recurrent infections, bronchiectasis, and normal serum immunoglobulin concentrations had a combined deficit of the IgG2 subclass and IgG and IgM specific antibodies. Immunoglobulin replacement was followed by clinical improvement. The importance of determining both IgG subclasses and antibody activity in patients with recurrent infections and normal serum immunoglobulin values is emphasised.

Rapidly reversible depression of delayed hypersensitivity in two children with visceral leishmaniasis.

Two cases of visceral leishmaniasis in children are described. In both "in vitro" lymphocyte response to mitogens and allogeneic cells was initially markedly depressed, but returned to normal within a few days after six days of treatment with N-methylglucamine antimonate; in one the candidin skin test reverted from negative to positive after treatment and in the other a circulating serum factor was found which strongly inhibited phytohemagglutinin--and mixed--responsiveness of normal lymphocytes, but disappeared after therapy.

[Clinical implications of sensitization to inhalants in atopic dermatitis]. / Implicazioni cliniche della sensibilizzazione ad inalanti nella dermatite atopica.

In 104 children with atopic dermatitis (AD) and RAST tests for 2 inhalant and 9 food allergen mixtures, RAST results, severity of skin involvement and presence of respiratory symptoms by history were analyzed in addition to total serum IgE values available in 66 children. Overall frequency of sensibilization was high (74%) with more positive RAST results for foods than inhalants, although of the latter the only two tested were among the more frequently positive. When the subjects positive for inhalants were considered alone, the frequency of respiratory symptoms was significantly higher in those sensitized to both inhalant mixtures tested (dermatophagoides and graminaceae) and the presence of more severe skin lesions was more common among those sensitized to graminaceae.

X-linked agammaglobulinemia and isolated growth hormone deficiency.

No further reports of associated X-linked hypogammaglobulinemia and isolated growth hormone deficiency have appeared in the literature since the description of the first affected family, two brothers and two maternal uncles, by Fleisher et al. in 1980. We report here a 13-year-old boy with X-linked agammaglobulinemia and isolated growth hormone deficiency, also probably inherited as an X-linked trait. The height of an older agammaglobulinemic brother who died at 6 years of age was below the third percentile.

Pulmonary hypertrophic osteoarthropathy in a child with late-onset agammaglobulinemia.

A case of hypertrophic osteoarthropathy is described in an 8-year-old child with late-onset agammaglobulinemia, bronchiectasis and clubbing of the fingers and toes. The child presented with pain of recent onset in the legs, ankles, and knees and a diagnosis of hypertrophic osteoarthropathy was made on the basis of the radiologic findings. Therefore the differential diagnosis of bone and joint pain in agammaglobulinemic subjects must take into account hypertrophic osteoarthropathy.

Increased frequency of RAG-expressing, CD4(+)CD3(low) 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.

Selective IgA deficiency: clinical and immunological evaluation of 50 pediatric patients.

Fifty children with IgA deficiency were folllowed for 1 to 4 years from 1975 to 1978. Thirty-five had complete deficiency of serum IgA (less than 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.

Clinical heterogeneity and reversibility of selective immunoglobulin A deficiency in 80 children.

80 children with selective immunoglobulin A (IgA) deficiency--40 with severe deficiency (serum IgA less than 5 mg/dl) and 40 with partial deficiency (serum IgA greater than 5 mg/dl but less than minus 2 SD of the age-normal mean)--were followed up for 1.5 to 9 years; during which their serum and salivary IgA levels were measured periodically and the number and type of infections they had were recorded. In the partial deficiency group serum IgA rose to normal levels in half the group at a median age of 14 years and at a median time of 4 years after diagnosis, but they did not reach the normal range in the severe deficiency group. Pneumonia occurred more frequently in the severe than in the partial deficiency group. In addition, 11 of the 12 severely IgA deficient patients who had pneumonia had levels of both serum and salivary IgA of less than 0.5 mg/dl, and only 1 had detectable serum IgA levels. These data indicate that in childhood severe IgA deficiency is persistent and predisposed to pneumonia, whereas partial IgA deficiency is often transient and only occasionally associated with pneumonia.

Prolidase deficiency: biochemical study of erythrocyte and skin fibroblast prolidase activity in Italian patients.

BACKGROUND AND METHODS: Prolidase deficiency (PD), a rare, autosomally inherited disorder causing iminodipeptiduria is associated with a number of clinical manifestations, the principle feature being chronic skin ulceration. The enzyme prolidase cleaves iminodipeptides containing C-terminal prolyl or hydroxyprolyl residues and is important in the final stages of protein catabolism. We report clinical and biochemical findings in 8 Italian patients with proven prolidase deficiency. There was considerable heterogeneity in age at onset of symptoms (varying from 3-17 years), mental retardation and clinical manifestations (asymptomless to very severe). Prolidase activity was determined in hemolysates of patient erythrocytes and cultured dermal fibroblasts. RESULTS: Prolidase activity was found to be deficient, especially against gly-pro. Erythrocyte and fibroblast enzyme was also separated into two forms, a major isoform (I) and a minor one (II) by fast protein liquid chromatography, and activity against different iminodipeptide substrates was tested. Isoform I activity was markedly reduced in all patients as compared to normal controls, while isoform II activity appeared to be unaltered. CONCLUSIONS: We were unable to find any correlation between degree of enzyme activity loss and severity of symptoms.