Clara cell protein in serum and bronchoalveolar lavage

The 10 kDa Clara cell protein was measured in serum and bronchoalveolar lavage (BAL) from 39 healthy subjects (14 smokers, 25 nonsmokers) and from 41 patients with respiratory disease (chronic obstructive pulmonary disease (COPD), sarcoidosis, lung cancer). Clara cell protein appears as one of the most abundant respiratory tract derived proteins, with values averaging 7% of the total protein content of lung lavages from healthy nonsmokers. A significant reduction of Clara cell protein was found in BAL from smokers and patients with COPD or lung cancer. The same pattern of change was found in the concentrations of Clara cell protein in serum. Pulmonary sarcoidosis did not affect absolute values of Clara cell protein in lung lavages but was associated with elevated levels in serum. Changes in lung lavage Clara cell protein differed from that of albumin, beta 2-microglobulin or the secretory component, since the latter were unaffected by smoking or COPD but increased in sarcoidosis and lung cancer. These results indicate that Clara cell protein in BAL or serum might serve as a sensitive indicator of nonciliated bronchial cell dysfunction

Bronchoalveolar lavage immunoglobulin A and G and antiproteases correlate with changes in diffusion indices during the natural course of pulmonary sarcoidosis.

We wanted to determine whether cell populations and soluble components in bronchoalveolar lavage (BAL) could be useful in predicting the outcome of lung function and chest radiography in patients with untreated pulmonary sarcoidosis. Analysis of soluble proteins in BAL fluid, included the levels of immunoglobulins and the two major antiproteases, alpha 2-macroglobulin (alpha 2-M) and alpha 1-protease inhibitor (alpha 1-PI), expressed as a relative coefficient of excretion (RCE). Thirty one nonsmoking patients with biopsy proven sarcoidosis, who remained untreated, had reassessment of lung function tests after 6-54 months (median 21 months). No correlation was observed between initial BAL data and changes in lung volumes and radiographic opacities. By contrast, the initial BAL immunoglobulin A and G (IgA and IgG) RCE correlated inversely with the change in transfer factor for carbon monoxide (TLCO) in the whole group and in patients with sarcoidosis of recent origin (estimated disease duration 24 months, or radiographic Stage 4), the change in carbon monoxide transfer coefficient (KCO) correlated negatively with the initial alpha 1-PI RCE and positively with the initial helper to suppressor T-cell (T4/T8) ratio. By contrast, no significant difference in BAL cellular and protein data was found between patients with recent and longstanding sarcoidosis.(ABSTRACT TRUNCATED AT 250 WORDS

Serum Immunoglobulin Levels in Heterozygous Subjects With Immunoglobulin Heavy-chain Constant-region Gene Deletions

The immunoglobulin heavy chain constant region locus is a multigene family composed of nine genes and two pseudogenes, whose high homology is often responsible for meiotic mispairings leading to deleted and duplicated haplotypes. These rearrangements have a population frequency of about 1.5% and 4.5% respectively, with a significant difference between deletions and duplications (P < 0.001). Both positive selection of duplications or negative selection against deletions can account for this imbalance. Serum levels of IgG and IgA subclasses, of IgE, of isohemagglutinins and of IgG antibodies to tetanus toroid and pneumococcal antigens were evaluated in 11 heterozygous carriers of constant region deletions. There was no gross abnormality in serum IgG and IgA subclass levels, with the possible exception of G1-deleted individuals; furthermore, isohemagglutinins and anti-tetanus toroid and pneumococcal IgG antibodies are in the normal range, suggesting that the humoral immune response is normal in these carriers. The influence of single and multiple immunoglobulin heavy chain constant region gene deletions on the humoral response is discussed

Latex gloves with a lower protein content reduce bronchial reactions in subjects with occupational asthma caused by latex.

Latex gloves have been documented as causing rhinitis and asthma. Using inhalation challenges, we evaluated the bronchial response to hypoallergenic gloves in eight health care workers with latex-induced asthma. The subjects were exposed to the powdered latex gloves causing asthma at work and various brands of gloves with a lower protein content, either low-powdered, nonpowdered, or powdered. Exposure to hypoallergenic gloves resulted in the absence (in six subjects) or a significant reduction (in two subjects) of bronchial response. The effects of repeated exposure to hypoallergenic gloves was assessed in two subjects who did not demonstrate changes in peak expiratory flow rates and nonspecific bronchial responsiveness to histamine. This study on a limited number of patients suggests that the use of hypoallergenic gloves could be an effective means of reducing the risk of asthmatic reactions in health care workers with latex-induced asthma when complete avoidance cannot be achieved. The long-term effect of exposure as well as the widespread use of hypoallergenic gloves warrant further investigation on larger cohorts of subjects

Validation of IgA1 and IgA2 measurements by a solid-phase immunoradiometric assay in serum and secretions

We describe specific, sensitive and reproducible immunoradiometric assays to measure total IgA and IgA subclass levels in biological fluids, which take into account the problem that polymeric forms are differently recognized in immunoassays. Sera from subjects totally deficient in one of the IgA subclasses allowed us to ensure the specificity of the subclass assays and to define the proportions of IgA1 (84%) and IgA2 (16%) in the normal pooled serum (from 30 blood donors) used as standard. With purified milk 11-S secretory IgA1 and 11-S secretory IgA2, we determined a correction factor for the corresponding polymeric forms using, respectively, monomeric IgA1 and monomeric IgA2 from pooled serum as standards. With the monoclonal antibodies used, purified 11-S secretory IgA1 was similarly recognized by both the total IgA assay and the IgA1 assay; both total IgA and IgA1 concentrations were underestimated compared with monomeric IgA or monomeric IgA1. In contrast, 11-S secretory IgA2 was better recognized by the IgA2 assay than by the total IgA assay and the values were thus overestimates. Considering this problem of recognition, we fractionated saliva and lung secretions by sucrose density gradient ultracentrifugation before measuring their IgA1 and IgA2 levels

IgA subclasses and molecular size in children with vertically transmitted HIV infection.

SCOPUS: cp.jinfo:eu-repo/semantics/publishe

Fc alpha-receptor expression on the myelomonocytic cell line THP-1: comparison with human alveolar macrophages

Immunoglobulin A (IgA) and alveolar macrophages are two important components of the immune system in the respiratory tract. Fc alpha-receptors (Fc alpha R) are present on neutrophils, eosinophils and a series of human mononuclear phagocytes, including monocytes, alveolar macrophages and leukaemia cell lines (U-937). In the present study, using idiotypes and anti-idiotypic antibodies, we report that THP-1 cells, a myelomonocytic cell line, constitutively express Fc alpha R and that all IgA preparations used bind the receptor. Of the stimuli used (phorbol myristate acetate, retinoic acid, calcitriol), only calcitriol can induce differentiation of THP-1 cells, as assessed by CD14 expression. The expression of Fc alpha R appears to be independent of cell differentiation, since calcitriol pretreatment has no effect on IgA-binding. Finally, My43, a monoclonal antibody recognizing the Fc alpha R on U-937 cells, does not bind to THP-1 cells or to human alveolar macrophages. In addition, preincubation of THP-1 cells or human alveolar macrophages with My43 does not diminish IgA-binding to these cells. Ribonucleic acid (RNA) encoding the Fc alpha R isolated from U-937 is expressed, although possibly at a lower level, in alveolar macrophages and THP-1 cells. In conclusion, Fc alpha R are constitutively expressed on THP-1 cells and share some characteristics with the Fc alpha R described in human alveolar macrophages. THP-1 cells, therefore, may represent a reasonable model for further investigation of the interaction of immunoglobulin A and tissue macrophages

Structural and immunologic analysis of gene triplications in the Ig heavy chain constant region locus

The Ig H chain C region is a multigene family often involved in genomic rearrangements leading to deleted and duplicated haplotypes, most probably through unequal crossing over between homologous regions within the locus. The frequency of these haplotypes in Italy is around 2.7% each. Using PFGE analysis in two unrelated Italian families we found an abnormal high m.w. band, inherited in a Mendelian fashion. To assess the extension of the haplotype we performed Southern blot analysis using several specific Ig H chain C probes. In both cases, the haplotype turned out to be triplicated, with three copies of the genes from A1 to E. In one family segregation of a duplication from EP to G4 was also observed. Analysis of polymorphic loci suggests that the two triplications are of independent origin. Serological detection of IgA2 allotypes demonstrated the functional activity of the genes at the 3' end of the triplicated locus, ruling out any major effect of these large genomic rearrangements on Ig class switching. Furthermore, the triplicated haplotype does not seem to give rise to any clinically significant immunological impairment or increase in Ig serum concentrations

Reduced Cancer Incidence in Huntington's Disease: Analysis in the Registry Study

Background: People with Huntington's disease (HD) have been observed to have lower rates of cancers. Objective: To investigate the relationship between age of onset of HD, CAG repeat length, and cancer diagnosis. Methods: Data were obtained from the European Huntington's disease network REGISTRY study for 6540 subjects. Population cancer incidence was ascertained from the GLOBOCAN database to obtain standardised incidence ratios of cancers in the REGISTRY subjects. Results: 173/6528 HD REGISTRY subjects had had a cancer diagnosis. The age-standardised incidence rate of all cancers in the REGISTRY HD population was 0.26 (CI 0.22-0.30). Individual cancers showed a lower age-standardised incidence rate compared with the control population with prostate and colorectal cancers showing the lowest rates. There was no effect of CAG length on the likelihood of cancer, but a cancer diagnosis within the last year was associated with a greatly increased rate of HD onset (Hazard Ratio 18.94, p < 0.001). Conclusions: Cancer is less common than expected in the HD population, confirming previous reports. However, this does not appear to be related to CAG length in HTT. A recent diagnosis of cancer increases the risk of HD onset at any age, likely due to increased investigation following a cancer diagnosis