Diagnosis and treatment of primary immunodeficiency disease in patients with gastrointestinal symptoms.

An estimated 250,000 individuals in the Unites States have been diagnosed with a primary immunodeficiency disease (PIDD). Early diagnosis and treatment of PIDD are critical to minimizing morbidity and improving quality of life. Patients with certain subtypes of PIDD may present with gastrointestinal complaints such as chronic or acute diarrhea, malabsorption, gastrointestinal pain, and inflammatory bowel diseases. Therefore, gastroenterologists are well positioned to help identify patients with PIDD. The hallmarks of PIDD include recurrent or persistent infections, infections due to microorganisms that rarely cause significant disease in immunocompetent people, unusually severe or life-threatening infections, and either low or persistently high white blood cell counts. An assessment for PIDD involves detailed patient and family histories, a physical examination, and diagnostic screening tests. Immunoglobulin replacement therapy is the cornerstone of treatment for most subtypes of PIDD.

Trisomy 22 and facioauriculovertebral (Goldenhar) sequence.

We report on an infant girl born with complete trisomy 22 and left hemifacial microsomia, ear anomaly, and limbal and epibulbar complex choristoma. Trisomy 22 was confirmed by prometaphase chromosome analysis and in situ hybridization. This patient extends the list of chromosome abnormalities associated with apparent Golenhar sequence and emphasizes the importance of chromosome analysis in the investigation of patients with this condition. A detailed ophthalmopathological investigation is reported.

Enlargement of the thymus in a child with chronic granulomatous disease receiving interferon gamma therapy.

Both an enlarged thymus (with normal results on histologic examination) and an increase in the percentage of peripheral CD4+CD45RA+ (naive) T lymphocytes developed in a child with chronic granulomatous disease receiving long-term interferon gamma therapy. The thymic regrowth may be secondary to interferon gamma therapy or to overstimulation of his compromised immune system by recurrent infections. To our knowledge, an association between enlargement of the thymus and either chronic granulomatous disease or interferon gamma has not been previously reported.

A comparison of electrochemiluminescence and flow cytometry for the detection of natural latex-specific human immunoglobulin E.

In vitro correlates of type 1 hypersensitivity to natural latex (NL) proteins continue to be limited by both sensitivity and specificity. Methods which have detection limits in the picogram range, namely, radioallergosorbent assays (RAST) and enzyme-linked immunosorbent assays (ELISA), are inadequate for the identification of NL hypersensitivity in certain at-risk groups, such as health care workers. A flow cytometry assay (FCA), previously shown to be comparable to RAST and ELISA in the identification of NL-sensitized pediatric patients with spina bifida, was compared with electrochemiluminescence (ECL) in the evaluation of pediatric patients with spina bifida and NL-sensitized adult health care workers. As with RAST and ELISA, ECL is capable of detecting picogram amounts of specific analyte. The ECL assay detected NL-specific immunoglobulin E (NL-IgE) in three of six health care workers with strong histories of NL hypersensitivity. All six patients were negative by FCA. Further, 2 of 11 spina bifida patients found to be NL-IgE negative by FCA were NL-IgE positive by ECL. These findings suggest that in sensitivity the ECL assay is an improvement over the FCA for the identification of NL-sensitive individuals.

Production of T-helper cell subsets and cytokines by lymphocytes from patients with chronic mucocutaneous candidiasis.

Chronic mucocutaneous candidiasis (CMC) is a heterogeneous group of disorders characterized by recurrent and persistent superficial candidal infections. Cytokine-induced dysregulation of T-helper cell function has been described in other immune-deficient states but has not been studied in CMC patients. We studied T-helper cell subsets by flow cytometry and cytokine production by stimulated lymphocytes in six CMC patients, two healthy pediatric controls, and five healthy adult controls. Peripheral blood lymphocytes were stimulated in vitro with phytohemagglutinin or Candida albicans extract, and the production of interleukin-2R (IL-2R), IL-4, IL-10, and gamma interferon in the supernatants was measured by enzyme-linked immunosorbent assay. CMC patients had a decrease in the CD29+/CD29+ cell population compared with the numbers in controls (P < 0.02). The percentage of CD4+/CD45RA+ cells was greater in patients than in controls, but the difference was not significant. There was no difference in the production of IL-10 or gamma interferon by the patient lymphocytes. CMC patients produced more IL-4 than the controls (P < 0.001), whereas the controls tended to produce more IL-2R than the patients (P = 0.19). These findings support the concept that a decrease in CD4+/CD29+ T-helper inducer cells along with T-helper cell dysregulation may lead to defective memory responses to antigens in CMC patients and a decrease in cell-mediated immunity due to inhibition of TH1 cells by increased levels of IL-4.