Search

Chronic rhinosinusitis (CRS) is one of the most common long-term illnesses in the United States. The etiology of CRS is unknown, and no effective treatment has been established.We investigated the hypothesis that abnormal immunologic responses to ubiquitous airborne fungi contribute to the pathogenesis of this disease.The proliferative and cytokine responses of PBMCs to extracts from 4 common airborne fungi-including Alternaria , Aspergillus , Cladosporium , and Penicillium -were examined by in vitro culture. Serum specimens were tested for specific IgE and IgG to these fungi.PBMCs from approximately 90% of the patients with CRS, but not those from normal individuals, produced both IL-5 and IL-13 when exposed to Alternaria. Furthermore, PBMCs from patients with CRS produced significantly more IFN-gamma than PBMCs from normal individuals in response to Alternaria (median, 553 pg/mL vs 98 pg/mL; P.01). Levels of serum IgG antibodies to Alternaria and Cladosporium were clearly increased in patients with CRS compared with normal individuals ( P.01). Less than 30% of the patients with CRS had specific IgE antibodies to Alternaria or Cladosporium. The increased humoral (serum IgG) response strongly correlated with the increased cellular (IL-5 production) response to Alternaria ( r = 0.619; P.01).Patients with CRS show exaggerated humoral and cellular responses, both T(H)1 and T(H)2 types, to common airborne fungi, particularly Alternaria. The anomalous immune and inflammatory responses to ubiquitous fungi may explain the chronicity of airway inflammation in CRS.

Rationale We developed a quantitative immunoassay using microsphere photometry to enable simultaneous, quantitative measurement of IgG antibodies to 24 Streptococcus pneumoniae serotypes as an aid in evaluating the immune response to pneumococcal vaccination in children and adults. Methods Pneumococcal polysaccharide antigens (24 serotypes, ATCC, Rockville, MD) were coupled covalently to polystyrene microspheres (Luminex Corp., Austin, TX). Each polysaccharide was coupled to a different fluorescent microsphere, and the microspheres were mixed to create a single immunosorbent reagent. This reagent was used to capture antibodies to S. pneumoniae in patient's sera, standards and controls. After incubating with the immunosorbent, bound antibodies were detected with R-phycoerythrin conjugated, goat anti-human IgG antibody using a flow microfluorometer (Luminex Corp.). The concentrations of IgG antibodies to each serotype were determined from standard curves using a primary reference material (10 serotypes, US Reference Pneumococcal Antiserum, FDA, Bethesda, MD)or a secondary reference material (14 serotypes, in-house preparation). Testing for antibodies to all 24 serotypes was completed in 2 hours. Results Measurements of anti-pneumococcal antibodies in sera from 80 healthy adults agreed with published data for the 10 standardized serotypes. The immunoassay detected concentrations ranging from 0.005 to 7.8 micrograms/ml. Interassay reproducibility across different serotypes ranged from 4.8 to 11.9%. Conclusions The microsphere immunoassay we describe is accurate and reproducible, and is suitable for clinical evaluation of patients treated with pneumococcal vaccines. Quantitative results are available for all serotypes in current vaccines.

We describe the development of specific immunoassays for IgG4 protein and for allergen-specific IgG4 antibodies. We also measured the concentrations of IgG4 protein and determined the frequencies of detectable IgG4 antibodies to several common allergens in sera from adults and children with asthma and from nonallergic subjects. Serum concentrations of IgG4 protein increase with age but are not different in children with asthma and nonallergic children, nor does a raised serum concentration predict a severe clinical course in childhood asthma. IgG4 antibodies to milk and egg are common in children and adults and are more common in children with asthma than in nonallergic children less than 3 years of age. The presence of detectable IgG4 antibodies or a raised concentration of IgG4 protein in serum is not useful empirically as a diagnostic indicator of asthma but more likely results from antigen exposure occurring at mucosal surfaces.

Two employees developed allergic rhinitis and bronchial asthma which was occupationally related to raising crickets. Skin tests, bronchial challenge, radioallergosorbent test (RAST), in vitro histamine release and a passive transfer test supported the presence of type I hypersensitivity to cricket allergens. Skin tests of other employees and patients of an allergy clinic suggested that cricket emanations are potent allergens.

To assess the etiologic role of cockroach antigen in bronchial asthma, 46 asthmatic subjects were studied using in vitro assays for total and cockroach-specific IgE antibodies (IgEcr) and the responsiveness of the skin and bronchial tree to the antigen challenge in vivo. Asthmatic subjects were divided into skin test-positive (PCR) and skin test-negative (NCR) groups according to immediate skin response to cockroach antigen. The 28 in the PCR group showed high total IgE (1,901 ng/ml) and a high cockroach-specific IgE antibody level (329%) in the serum compared to the 10 in the NCR group (IgE: 915 ng/ml, IgEcr: 84%) (p < 0.001). Bronchial challenge with the antigen revealed immediate asthmatic reaction (3033) and late asthmatic reaction (1633) in the PCR asthmatics, whereas the NCR asthmatics showed neither immediate asthmatic reaction (213 showed questionable decrease in FEV1) nor late asthmatic reaction (p < 0.001). A marked increase in peripheral eosinophils (758% vs 121%) was noted following antigen inhalation in the skin test-positive asthmatics (p < 0.025). The results indicate that cockroach antigen causes antigen-specific IgE-mediated bronchial asthma and peripheral eosinophilia in specifically sensitized asthmatic subjects.

On epidemiologic grounds, respirable particles from chilled-water air-conditioning systems in textile production plants have been implicated as a cause of hypersensitivity pneumonitis. We have purified the antigen from scum growing in this chilled water by antibody-affinity chromatography by use of IgG isolated from a pool of serum obtained from three workers with disease. Two patients with the disease, three coworkers without the disease, and two unexposed control subjects inhaled a dose of the purified antigen approximately equivalent to that amount calculated to be inhaled during an 8-hour work shift. Both workers with disease experienced fever, malaise, cough, and dyspnea 6 to 8 hours after the aerosol challenge. In these two patients the exposure evoked a transient decrease in circulating lymphocytes, predominately T cells. Before challenge the patients' peripheral blood mononuclear cells demonstrated a blastogenic response to the antigen. The responding cells had disappeared from the circulation 24 hours after the challenge. Seventy-two hours after the challenge, mononuclear cells that were producing large amounts of specific IgG antibody appeared in the circulation. We conclude that the same antigen(s) that react with IgG antibody produced an acute episode of the disease, that specific antigen-recognition cells disappear from the peripheral blood after exposure to the antigen (presumably because they are attracted to the lung), and that antibody-forming cells appear in the peripheral blood approximately 2 days after a challenge. These antigen-specific reactions of circulating mononuclear cells may be specific for the disease, but studies on a larger number of cases are needed to be certain.