Evaluation of CD103 as a cellular marker for the diagnosis of pulmonary sarcoidosis

A high CD4(+)/CD8(+) ratio in bronchoalveolar lavage fluid is indicative for the diagnosis pulmonary sarcoidosis but this ratio only does not fully discriminate pulmonary sarcoidosis from other interstitial lung diseases. Recently, the integrin CD103 has been implicated in the diagnostic evaluation of sarcoidosis. CD103 is expressed on intraepithelial lymphocytes in mucosal areas, including bronchi, and is possibly involved in the retention of lymphocytes to the mucosa. The Dutch BAL working party initiated an investigation to evaluate the diagnostic value of relative number of CD103 expressing CD4(+) T-lymphocytes in the BAL fluid of patients with a variety of interstitial lung diseases. The expression of CD103 was examined on bronchoalveolar lavage cells from 119 patients including 56 patients with pulmonary sarcoidosis. We redefined criteria for alveolar CD4(+) T-cell lymphocytosis and for the relative enumeration of CD103 expressing CD4(+) T-lymphocytes in the BAL fluid. Our data demonstrate that the combined use of the CD103(+)CD4(+)/CD4(+) ratio ( 3) or the relative alveolitis CD4(+)/CD8(+) BAL/PB ratio (> 2) provides a specific tool for discriminating sarcoidosis, also without a clear CD4(+) alveolitis, from other interstitial lung diseases. (c) 2007 Elsevier Inc. All rights reserved

Clinical and virologic response to combination treatment with indinavir, zidovudine, and lamivudine in children with human immunodeficiency virus-1 infection: A multicenter study in The Netherlands

Objective: To evaluate the clinical, immunologic, and virologic response to indinavir, zidovudine, and lamivudine in children with human immunodeficiency virus-1 (HIV-1) infection. Study design: Twenty-eight HIV-1 infected children (3 months to 16 years of age) with or without prior treatment with reverse-transcriptase inhibitors and a HIV-1 RNA >5000 copies/mL and/or a CD4 cell count less than the lower limit of the age- specific reference value were treated with indinavir, zidovudine, and lamivudine. Pharmacokinetics of indinavir were determined in each child. Results: The combination treatment was well tolerated in the majority of patients. Clinical improvement was seen in all patients. After 6 months of therapy, 70% of the patients had an HIV-1 RNA load below 500 copies/mL, whereas 48% of the children had a vital load below 40 copies/mL. Relative CD4 cell counts in relation to the lower limit of the age-specific reference value increased significantly from a median value of 79% at baseline to 106% after 6 months of therapy. The doses of indinavir necessary to achieve area under the curve values comparable to adult values varied from 1250 mg/m2/d to 2450 mg/m2/d. Conclusions: Highly active antiretroviral therapy consisting of indinavir, zidovudine, and lamivudine in children reduced HIV-1 RNA to less than 500 copies/mL in 70% of the children within 6 months. Improved CD4 cell counts were observed in most patients, as was a better clinical condition (no invasive or opportunistic infections, increased weight gain). Side effects of the triple therapy were mild. Highly active antiretroviral therapy can be used as successfully in children as in adults