Chest Radiographs for Distinguishing ADA-SCID from Other Forms of SCID.

PURPOSE: Early differentiation of adenosine deaminase deficient severe combined immunodeficiency (ADA-SCID) from other forms of SCID may initiate appropriate treatment interventions with the aim of metabolic detoxification and improved outcome. Our hypothesis was that previously described radiological features (inferior scapular angle squaring and spurring and costochondral cupping) can differentiate ADA-SCID from other forms of SCID. METHODS: Chest radiographs at clinical presentation between 2000 and 2017 of children with ADA-SCID were retrospectively included, provided that the radiological features were assessable. Random chest radiographs of children with other forms of SCID were included for comparison. Three paediatric radiologists (2 senior, 1 junior) assessed the radiographs for the specific radiological features and stated their diagnosis (ADA-SCID or non-ADA-SCID). An optimal threshold for test performance was defined using a ROC curve. RESULTS: Thirty-six patients with ADA-SCID and twenty-five patients with non-ADA-SCID were included (median age 3.8 months). The optimal threshold for test performance was at approximately < 7 months old: sensitivity 91.7%, specificity 80.7%, interreader agreement was k = 0.709, AUC 0.862. The positive likelihood ratio for scapular squaring, scapular spur, and costochondral cupping was 4.0, 54.6 and 7.8, respectively. The test was valid when performed by both senior and junior paediatric radiologists. CONCLUSION: Radiological features such as scapular spurring, scapular squaring and costochondral cupping can reliably differentiate between ADA-SCID and other forms of SCID. This is true for children aged approximately < 7 months, and this is reliable when assessed by both senior and junior paediatric radiologists.

Secondary hypogammaglobulinemia in Waldmann's disease treated with subcutaneous immunoglobulins.

Primary intestinal lymphangiectasia (PIL) is rare disorder characterized by congenital malformation or obstruction of intestinal lymphatic drainage; it is responsible for protein losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia. A low-fat diet associated with medium-chain triglyceride supplementation is the cornerstone of PIL management. The administration of intravenous immunoglobulins does not always lead to satisfactory plasma levels and therefore the replacement therapy with immunoglobulins is controversial. We describe here the case of a patient with PIL and severe hypogammaglobulinemia treated with immunoglobulins. The striking aspect of this case is the clinical and serological benefit obtained with the subcutaneous compared to the intravenous immunoglobulins administration.

[Reliability of the glutaraldehyde test to measure gamma-globulin levels in foals and the use of this test to check colostrum intake of foals]. / Een onderzoek naar de betrouwbaarheid van de glutaaraldehydetest voor de bepaling van het gammaglobulinegehalte in het serum van veulens en naar de bruikbaarheid van deze test in de praktijk bij het controleren van de colostrumopname bij veulens.

The glutaraldehyde coagulation test is a semi-quantitative test used to determine the gammaglobulin concentration in serum. The purpose of this study was to examine the reliability of the different modifications of this test by determining the sensitivity, specificity, positive and negative predictive value, and the prevalence of hypogammaglobulinemia in foals. The results of the glutaraldehyde coagulation test were compared with the serum gammaglobulin concentration as a reference value, determined by measuring total serum protein and the serum protein spectrum. It was concluded that the glutaraldehyde coagulation test is a suitable test to use in the field for determining the serum gammaglobulin concentration in foals. The test has good sensitivity, specificity, positive and negative predictive value when using a 5% glutaraldehyde solution and when results are evaluated at 30 minutes for a serum concentration of 8 g/l and at 50 minutes for a serum concentration of 5.5 g/l, a concentration below which therapy is recommended.

X-chromosome inactivation and mutation pattern in the Bruton's tyrosine kinase gene in patients with X-linked agammaglobulinemia. Italian XLA Collaborative Group.

BACKGROUND: The diagnosis of X-linked agammaglobulinemia (XLA) is not always clearcut. Not all XLA conform to the classic phenotype and less than 50% of affected boys have a family history of immunodeficiency. Mutations in the gene for Bruton's tyrosine kinase (BTK) are responsible for the majority of agammaglobulinemia cases. However, a certain proportion of patients may have mutations involving other genes, although they show with an XLA phenotype. We performed BTK gene mutation analysis in 37 males with presumed XLA and analyzed the pattern of X-chromosome inactivation (XCI) in 31 mothers to evaluate the relevance of these approaches to diagnosis and genetic counseling. MATERIALS AND METHODS: Twenty affected males with a sporadic occurrence and 17 familial cases belonging to nine families were enrolled within the framework of the Italian Multicenter Clinical Study on XLA. We used non-isotopic RNase cleavage assay (NIRCA), followed by cDNA sequence determination to screen for BTK mutations and X-chromosome inactivation analysis for carrier detection. RESULTS: Using the cDNA-based approach, the identification of BTK gene abnormalities confirmed the clinical diagnosis of XLA in 31 of 37 affected infants. Missense was the most frequent mutational event and the kinase domain was mostly involved. In addition, nine novel mutations were identified. In sporadic cases, BTK gene abnormalities were identified in 9 out of 10 patients whose mothers had a nonrandom pattern of XCI and in 5 out of 6 patients whose mother had a random pattern of XCI. With the exception of one family, all patients with a familial occurrence and born to mothers with a nonrandom pattern of XCI had mutations of the BTK gene. CONCLUSIONS: Our findings indicate that in sporadic cases BTK gene sequencing is the only reliable tool for a definitive diagnosis of XLA and support XCI as the first diagnostic tool in the mothers of affected males in multiple generations. Furthermore, our molecular analysis confirms that 10-20% of BTK-unaltered patients have disorders caused by defects in other genes.

[The oldest case with X-linked agammaglobulinemia in Japan lacking Bruton-type tyrosine kinase protein detected by flow cytometry].

We report a case of sporadic X-linked agammaglobulinemia previously diagnosed as variable immunodeficiency (VID). An 39-year-old male had recurrent episodes of respiratory tract infection since his early childhood. At the age of four, he developed partial paresis of the left limbs after polio immunization. After diagnosis of VID based on marked decrease of serum IgG, IgA and IgM levels and no antibody production against antigenetic stimuli at age 22 years old, he received intravenous immunoglobulin supplementation irregularly. We reexamined him and found marked decrease in B cells in the peripheral blood. In addition, we investigated the expression of Bruton-type tyrosine kinase on monocytes by flow cytometry and confirmed its deficiency. His mother was diagnosed as a carrier of XLA. The patient is probably the oldest case with XLA in Japan.

Diarréia crônica e infecçöes repetidas em adulto / Chronic diarrhea and repeated infections in an adult

Um caso de infecçäo por Shigella flexneri em uma mulher de 34 anos de idade com hipogamaglobulinemia e diarréia é apresentado; o problema diagnóstico representado por diarréia no paciente com hipogamaglobulinemia é discutido. A revisäo de 7 outros pacientes com hipogamaglobulinemia tratados no HCRP é apresentado e é enfatizado que vários agentes patogênicos podem causar diarréia nesses pacientes

[Importance of studying deficiencies of IgG subclasses (IgG2 and IgG4) in immuno-allergologic practice]. / Intérêt de la recherche d'un déficit en sous-classes d'IgG (IgG2 et IgG4) en pratique immuno-allergologique.

Levels of the sub-classes of immunoglobulins IgG2 and IgG4 have been established by radial diffusion with monoclonal antibodies in 150 subjects. 49 (42 adults and 7 children) showed either a low level of IgG2 (less than 0.42 g/l n = 11) or a reduced level of IgG4 (less than 0.05 g/l n = 38). A single patient had a double deficit, 38 subjects had a superinfection of which 17 had a severe form and in 77% of these cases a level of IgG4 of less than 0.05 g/l.

[Rectocolic lymph node appearance in adults (author's transl)]. / Aspect nodulaire lymphoïde rectocolique chez l'adulte.

A very characteristic rectocolic "lymph follicle appearance" was observed on radiological examination by double contrast enemas in 3.5 p. cent of 480 cases explored. The usual typical appearance is that of small lacunae of 1 to 3 mm in diameter, with indistinct borders, extending through several colon segments. The frequency with which these images are observed is probably a function of the double contrast technique employed, particularly the adherence of the barium. In most cases, the "lymph follicle appearance" is a variation of the normal, but several rare forms could result from a partial immunity deficiency. Differential diagnosis includes colon wall oedema and most polyposis disorders in their initial stages. Coloscopy with biopsy is necessary when diagnosis is uncertain.

Hypogammaglobulinaemia in foals: prevalence on Victorian studs and simple methods for detection and correction in the field.

The prevalence of hypogammaglobulinaemia in 82 young foals was determined. Twelve foals were considered clinically abnormal at birth and ten died within two weeks. All of these foals were hypogammaglobulinaemic. Seven (10%) of the other 70 apparently normal foals were hypogammaglobulinaemic despite having suckled normally. Three of these foals developed significant disease and one died at one month of age. Rapid detection of foals with low serum immunoglobulin levels was achieved by adapting the zinc sulphate turbidity test to partially evacuated blood collection tubes. This permitted test to be conducted on the stud or in the veterinarian's own laboratory. Plasma concentrated twofold by a freeze thaw technique was administered intravenously to supplement the immunoglobulin levels of two colostrum deprived foals. The simplicity of the concentration procedure eliminated the need for laboratory preparation of equine immunoglobulin.

Evaluation for immune system failures in horses and ponies.

Between January 1973 and September 1979, 2,092 horses and ponies were evaluated for immunologic disorders. A total of 418 abnormalities were detected in 416 (20%) of the animals tested. Disorders encountered were failure or partial failure of colostral immunoglobulin transfer from mare to foal (228 cases), combined immunodeficiency (159 cases), selective immunoglobulin M deficiency (19 cases), agammaglobulinemia (3 cases), transient hypogammaglobulinemia (2 cases), and lymphosarcoma (7 cases). Four conclusions were drawn from the study. (1) Immunologic abnormalities occur commonly in horses and ponies. (2) Failure and partial failure of passive transfer were the most common disorders, involving 19.7% of surveyed foals at risk. (3) Combined immunodeficiency remains a disease limited to Arabian horses. (4) Considering the high frequency of immunologic disorders in horses and the availability of diagnostic tests for the disorders, older animals with recurrent infections as well as all newborn foals should be evaluated for immune disorders.