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Background: Primary ciliary dyskinesia (PCD) is a rare genetic disorder caused by the malfunction of motile cilia and a specific etiology of adult bronchiectasis of unknown prevalence. A better understanding of the clinical phenotype of adults with PCD is needed to identify individuals for referral to diagnostic testing., Research Question: What is the frequency of PCD among adults with bronchiectasis; how do people with PCD differ from those with other etiologies; and which clinical characteristics are independently associated with PCD?, Study Design and Methods: We investigated the proportion of PCD among the participants of the Prospective German Non-CF-Bronchiectasis Registry (PROGNOSIS) study; applied multiple imputation to account for missing data in 64 (FEV 1 ), 58 (breathlessness), 26 (pulmonary exacerbations), and two patients (BMI), respectively; and identified predictive variables from baseline data using multivariate logistic regression analysis., Results: We consecutively recruited 1,000 patients from 38 centers across all levels of the German health care system. Overall, PCD was the fifth most common etiology of bronchiectasis in 87 patients (9%) after idiopathic, postinfective, COPD, and asthma. People with PCD showed a distinct clinical phenotype. In multivariate regression analysis, the chance of PCD being the etiology of bronchiectasis increased with the presence of upper airway disease (chronic rhinosinusitis and/or nasal polyps; adjusted OR [aOR], 6.3; 95% CI, 3.3-11.9; P < .001), age < 53 years (aOR, 5.3; 95% CI, 2.7-10.4; P < .001), radiologic involvement of any middle and lower lobe (aOR, 3.7; 95% CI, 1.3-10.8; P = .016), duration of bronchiectasis > 15 years (aOR, 3.6; 95% CI, 1.9-6.9; P < .001), and a history of Pseudomonas aeruginosa isolation from respiratory specimen (aOR, 2.4; 95% CI, 1.3-4.5; P = .007)., Interpretation: Within our nationally representative cohort, PCD was a common etiology of bronchiectasis. We identified few easy-to-assess phenotypic features, which may promote awareness for PCD among adults with bronchiectasis., Clinical Trial Registration: ClinicalTrials.gov; No.: NCT02574143; URL: www., Clinicaltrials: gov., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: I. P. reports grants from COFONI-2FF4 and COFONI-6LZF23 by the Ministry of Science and Culture of Lower Saxony paid to her institution and personal lecture fees from AstraZeneca and Boehringer Ingelheim. S. S. reports fees for clinical trial participation from Celtaxsys, Corbus, Galapagos, Insmed, Proteostasis, and Vertex Pharmaceuticals paid to his institution; and personal fees for consulting and lectures from Boehringer Ingelheim, Insmed, and Vertex Pharmaceuticals. S. P. A. reports personal consulting fees from AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, and GlaxoSmithKline. A. G. reports personal fees for consulting, advisory board participation, and lectures from Boehringer Ingelheim and GlaxoSmithKline. A. S. reports personal fees for consulting and lectures from Ethris, Insmed, Spirovant, and Translate Bio; and is involved in the European Respiratory Society (ERS) Clinical Research Collaborations AMR-Lung, BEAT-PCD, and EMBARC. S. W. reports fees for clinical trial participation from Insmed paid to her institution and personal honoraria from Vertex Pharmaceuticals. P. M. reports fees for clinical trial participation from Boehringer Ingelheim and Insmed paid to his institution; reports personal fees for lectures from AstraZeneca, MAÄF eV, ResMed, and streamedup! GmbH; reports travel support from the German Society for Internal Medicine (DGIM), CSL Behring, and Insmed; and is honorary co-chair of the German Bronchiectasis Registry PROGNOSIS. J. R. reports grants from the German Center for Lung Research (DZL), the German Center for Infection Research (DZIF), the Federal Ministry of Education and Research (BMBF), the Federal Ministry of Health (BMG), Novartis, and Insmed paid to her institution; reports personal fees for consulting or advisory board participation and honoraria for lectures from AstraZeneca, Brahms GmbH, ERS, Grifols, Insmed, MedUpdate, MSD, Pfizer, Shionogi, and streamedup! GmbH; and is honorary co-chair of the German Bronchiectasis Registry PROGNOSIS and chair of the Respiratory Infections and Tuberculosis Assembly of the German Respiratory Society (DGP). F. C. R. reports grants from the German Center for Lung Research (DZL), the German Center for Infection Research (DZIF), IMI (EU/EFPIA), and the Innovative Medicines Initiative (IMI) and EFPIA companies under the European Commission funded project, iABC [Grant 115721], Novartis, and Insmed Germany paid to his institution; reports personal fees for consulting or advisory board participation and honoraria for lectures from Parion, Grifols, Zambon, Insmed, Helmholtz-Zentrum für Infektionsforschung, i!DE Werbeagentur GmbH, Interkongress GmbH, streamedup! GmbH, AstraZeneca, Insmed, Shionogi, and Grifols; reports travel support from the German Kartagener Syndrome and Primary Ciliary Dyskinesia patient advocacy group, which he serves as the unpaid co-speaker of its medical advisory board; and is honorary co-chair of the German Bronchiectasis Registry PROGNOSIS, a member of the steering committee of the European Bronchiectasis Registry EMBARC, and a member of the Protocol Review Committee of the PCD-Clinical Trials Network. None declared (R. E., U. S., B. O. S.)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Sotorasib is a first-in-class KRAS p.G12C-inhibitor that has entered clinical trials in pretreated patients with non-small cell lung cancer (NSCLC) in 2018. First response rates were promising in the CodeBreaK trials. It remains unclear whether response to sotorasib and outcomes differ in a real-world setting when including patients underrepresented in clinical trials., Methods: Patients with KRAS p.G12C-mutated advanced or metastatic NSCLC received sotorasib within the German multicenter sotorasib compassionate use program between 2020 to 2022. Data on efficacy, tolerability, and survival were analyzed in the full cohort and in subgroups of special interest such as co-occurring mutations and across PD-L1 expression levels., Results: We analyzed 163 patients who received sotorasib after a median of two treatment lines (range, 0 to 7). Every fourth patient had a poor performance status and 38% had brain metastases (BM). The objective response rate was 38.7%. The median overall survival was 9.8 months (95% CI, 6.5 to not reached). Median real-world (rw) progression-free survival was 4.8 months (9% CI, 3.9 to 5.9). Dose reductions and permanent discontinuation were necessary in 35 (21.5%) and 7 (4.3%) patients, respectively. Efficacy seems to be influenced by PD-L1 expression and a co-occurring KEAP1 mutation. KEAP1 was associated with an inferior survival. Other factors such as BM, STK11, and TP53 mutations had no impact on response and survival., Conclusion: First results from a real-world population confirm promising efficacy of sotorasib for the treatment of advanced KRAS p.G12C-mutated NSCLC. Patients with co-occurring KEAP1 mutations seem to derive less benefit., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JAS reports personal fees from Boehringer Ingelheim, personal fees from AstraZeneca, personal fees from Roche, personal fees from BMS, personal fees from Amgen, personal fees from LEO pharma, personal fees from Novartis, personal fees from Takeda, outside of the submitted work. FCA has received a research grant from Novartis, support for attending meetings and/or travel from Amgen, and consultant fees from IQVIA.PD has nothing to disclose. JR has nothing to disclose. AT has nothing to disclose. ANH has nothing to disclose. NF reports personal fees from AbbVie, Amgen, AstraZeneca, BeiGene, Berlinchemie, Boehringer Ingelheim, Bristol Myers&Squibb, Lilly, Merck Sharp&Dohme, Merck, Novartis, Pfizer, Roche, Sanofi, Takeda, outside of the submitted work. HY has nothing to disclose. PC has received research funding from AstraZeneca, Amgen, Boehringer Ingelheim, Novartis, Roche, and Takeda, speaker’s honoraria from AstraZeneca, Janssen, Novartis, Roche, Pfizer, Thermo Fisher, Takeda, support for attending meetings from AstraZeneca, Eli Lilly, Daiichi Sankyo, Gilead, Novartis, Pfizer, Takeda, and personal fees for participating to advisory boards from Boehringer Ingelheim, Chugai, Pfizer, Novartis, MSD, Takeda and Roche, all outside the submitted work. OB has nothing to disclose. CMB has nothing to disclose. ABVD has nothing to disclose. JA has nothing to disclose. SPA as nothing to disclose. MW has nothing to disclose. SK has nothing to disclose. MU has nothing to disclose. GT has nothing to disclose. CFW has nothing to disclose. AR reports grants from AbbVie, grants from AstraZeneca, grants from BMS, grants from Boehringer Ingelheim, grants from Daichi Sankyo, grants from Eli Lilly, grants from GSK, grants from MSD, grants from Novartis, grants from Pfizer, grants from Roche, outside the submitted work. PH has nothing to disclose. JB has nothing to disclose. HGK has nothing to disclose. CG has nothing to disclose. MSch has nothing to disclose. CSch has nothing to disclose. FG reports personal fees from AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Siemens, Amgen, Ariad, Abbvie, Tesaro / GSK, Sanofi, Daiichi-Sankyo, Beigene, outside of the submitted work. MSch has nothing to disclose. MS reports personal fees from Lilly, Astra-Zeneca, Bristol-Myers & Squibb, Merck Sharp & Dohme, Pfizer, Takeda, Roche, AbbVie, Boehringer-Ingelheim, Celgene, Novartis, grants from Astra Zeneca outside the submitted work. NR reports personal fees from Amgen, personal fees from AstraZeneca, personal fees from Bristol-Myers Squibb, personal fees from Boehringer-Ingelheim, personal fees from Daiichi Sankyo, personal fees from GSK, personal fees from Hoffmann-La Roche, personal fees from Janssen, personal fees from MSD, personal fees from Merck, personal fees from Lilly, personal fees from Pfizer, personal fees from Takeda, outside the submitted work., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Major life-threatening complications secondary to cisplatin-based chemotherapy are rare in patients with testicular germ cell tumour (GCT). The incidence of complications increases with dosage of chemotherapy and with a variety of patient-related as well as disease-related conditions. We here report the first case of GCT experiencing as many as four major complications most of which can be explained by the conjunction of several predispositions., Case Presentation: A 48 year old patient with testicular seminoma and bulky retroperitoneal and mediastinal metastases underwent cisplatin based chemotherapy. During the third cycle of chemotherapy, he developed thrombosis of the central venous port device, subtotal splenic infarction, and Bleomycin induced pneumonitis (BIP). Three months after completion of therapy, he was struck by thalamic infarction. Genetic testing then revealed heterozygote mutation of Factor V Leiden (FVL). He received full-dose warfarin anticoagulation treatment and steroid treatment for BIP. 18 months thereafter, the patient is still disease-free, oncologically. Neurological symptoms have disappeared, but pulmonary dysfunction persists with a vital capacity of 50%., Conclusion: The unique co-incidence of four major complications occurring in this patient were obviously triggered by the genetically determined predisposition of the patient to thrombotic events (FVL). Additionally, several patient-related and disease-related conditions contributed to the unique pattern of complications, i.e. (1) the slightly advanced age (48 years), (2) the prothrombotic condition caused by the disease of cancer, (3) the central venous port device, (4) retroperitoneal bulky metastasis, and (5) cisplatin chemotherapy. Whether or not FVL contributed to the pulmonary fibrosis as well, remains elusive. Practically, in the case of one major vascular complication during cisplatin chemotherapy at standard dose, genetic testing for hereditary thrombophilia should be considered. Thus, precautions for preventing further complications could be initiated.

Background: Despite antibiotic treatment, the mortality of severe community-acquired pneumonia (CAP), especially in patients with severe comorbidity, remains high. Innate defense mechanisms including polymorphonuclear neutrophil (PMN) activation and survival, orchestrated by cytokines, are primarily responsible for the elimination of bacterial organisms from the alveolus., Objectives: The aim of this study was to evaluate the effect of granulocyte colony-stimulating factor (G-CSF) on PMN activation, apoptosis and cytokine response in patients with CAP., Methods: Patients received a single dose of G-CSF (1 x 300 or 480 microg s.c.) prior to standard antibiotic treatment (n=8) or standard treatment only (n=8). Apoptosis rate and expression of CD11b, CD66b, CD64 and CD114 surface molecules on systemic PMN were assessed using fluorescence-activated cell sorter analysis. Levels of the interleukin-1 receptor antagonist (IL-1 RA), the soluble tumor necrosis factor receptor inhibitor (sTNF-p55) and G-CSF were measured by ELISA., Results: In the treatment group, 12 h after G-CSF application, neutrophil count increased, neutrophil activation marker CD11b was stimulated (CD11b: 48.6+/-9.7 vs. 71.2+/-17.7, p<0.01), neutrophil apoptosis decreased (apoptosis: 1.36+/-0.27 vs. 0.2+/-0.12%, p <.01) and the concentration of IL-1RA and sTNF-p55 increased (IL-1RA 136.4+/-72.2 vs. 340.1+/-194.6 ng/ml, p<0.01; sTNF-p55,382+/-4,243 vs. 632+/-4,714 ng/ml, p<0.01; control group nonsignificant). These effects were not seen in the control group., Conclusions: The application of a single dose of G-CSF in patients with CAP caused a prolonged survival and increased activation of neutrophils combined with a sustained release of anti-inflammatory cytokines.

We report a case of acute renal failure due to proximal tubular necrosis associated with tenofovir treatment in a patient with acquired immunodeficiency syndrome.

Background: Pulmonary sarcoidosis is characterised by a mononuclear alveolitis with a predominance of CD4+ T cells and macrophages. We determined the intracellular expression of interferon (IFN)gamma, interleukin (IL)-2, tumour necrosis factor (TNF)alpha, IL-4, IL-5 and IL-10 in CD4+ and CD8+, naive and memory lymphocytes from blood and bronchoalveolar lavage (BAL) fluid using three colour flow cytometry., Methods: Eighteen untreated patients with pulmonary sarcoidosis were evaluated and stratified according to whether they had acute or chronic disease., Results: Significantly more T cells expressed Th1 than Th2 type cytokines in both BAL fluid and peripheral blood samples, regardless of clinical presentation. Significantly greater proportions of T cells secreted Th1 type cytokines in BAL fluid than in peripheral blood. Th1 type cytokines were more frequently expressed by peripheral and alveolar T cells in acute disease than in chronic disease. There were no significant differences between CD4+ and CD8+ T cells. Concerning naive and memory lymphocytes, significantly higher CD45RO:CD45RA ratios were found in BAL fluid than in blood, and increased expression of Th2 type cytokines was found in peripheral compared with alveolar memory T cells., Conclusions: Our data support the immunopathogenetic concept of Th1/Th2 imbalance and compartmentalisation in pulmonary sarcoidosis and suggest that the cytokine patterns change during the course of disease. Expression of Th2 type cytokines in memory lymphocytes is decreased in the alveolar compartment compared with peripheral blood.

Hypersensitivity pneumonitis (HP) represents an immunologic reaction of the pulmonary parenchyma to an inhaled agent. Since tumor necrosis factor (TNF)-alpha is thought to be involved in the pathogenesis of HP, and polymorphisms in the TNF genes have been associated with variations in the production of TNF-alpha, we investigated the serum bioactivity and genotype of TNF in HP. TNF bioactivity was measured after hay dust challenge in eight patients with farmer's lung (Group A) and in 12 healthy, sensitized (antibody-positive) controls (Group B). Genotyping for the -308 TNF-alpha promoter polymorphism and the TNF-beta intron 1 gene polymorphism was performed in 20 patients with farmer's lung, 25 patients with pigeon breeder's lung, and 216 controls. TNF bioactivity increased in Group A at 4 to 10 h after hay dust challenge, but not in Group B (p < 0.05). The frequency for the TNFA2 allele, a genotype associated with high TNF-alpha production in vitro, was significantly higher in farmer's lung patients (frequency [f] = 0.43, p = 0.0012) than in controls (f = 0.19) or patients with pigeon breeder's lung (f = 0.16). Genotyping for TNF-beta revealed no significant abnormalities. Thus, increased production of TNF-alpha after hay contact, and a genetic predisposition to TNF-alpha production, are implicated in the pathogenesis of alveolitis in farmer's lung.

Aims/hypothesis: Patients treated with human immunodeficiency virus-1 protease inhibitors often develop impaired glucose tolerance or diabetes, most likely due to an induction of insulin resistance. We therefore investigated whether the protease inhibitor indinavir alters insulin signalling., Methods: We incubated HepG2 cells for 48 h without or with indinavir (100 micromol/l). Subsequently 125I-insulin binding to the cells and the effects of insulin stimulation on insulin-receptor substrate-1-phosphorylation, association of phosphatidylinositol 3-kinase with insulin-receptor substrate-1 and Akt-Thr308-phosphorylation were measured., Results: In cells not exposed to indinavir, insulin (100 nmol/l) led to rapid increases of insulin-receptor substrate-1-phosphorylation, association of phosphatidylinositol 3-kinase with insulin-receptor substrate-1 and Akt-phosphorylation during the first 75 s, followed by subsequent decreases. In indinavir-treated cells, these insulin-stimulated increases during the first 75 s were reduced by 30-60% and this was not associated with alterations in cell number or viability, insulin binding to the cells or cellular insulin-receptor substrate-1-content., Conclusion/interpretation: Effects of indinavir on initial insulin signalling could cause, or contribute to, the metabolic effects of human immunodeficiency virus-1 protease inhibitors.

Study Objectives: The central role of apoptosis in the regulation of lung inflammation is increasingly recognized. The aim of this study was to determine the parameters of cell activation and apoptosis on neutrophils from the circulation and the pulmonary compartment in patients with community-acquired pneumonia (CAP), and to assess the role of the Fas system and of complement-regulating molecules in this context., Design and Methods: The study population consisted of nine patients with CAP (group 1) and six age-matched control patients without evidence of bronchopulmonary inflammation (group 2). Apoptosis rate and expression of CD11b, CD16, CD55, CD59, CD95, and CD114 surface molecules on systemic and bronchoalveolar neutrophils were assessed ex vivo using fluorescence-activated cell sorter analysis., Results: In patients with CAP, we found a significant decrease of the mean apoptosis rate in pulmonary neutrophils compared to systemic neutrophils, without concomitant changes in Fas expression. In contrast, cell activation markers were significantly increased on pulmonary cells (CD11b, 288 +/- 98.2 relative mean fluorescence intensity [rMFI] vs 53.8 +/- 10.8 rMFI on peripheral cells), and similar changes were observed with respect to the expression of complement-regulating molecules. Pulmonary polymorphonuclear neutrophils of the control group showed analogous changes, compared to systemic neutrophils, but a significantly higher rate of apoptosis and a lower increase of activation-marker expression were found, compared to pulmonary neutrophils of patients with pneumonia., Conclusions: Pulmonary neutrophils from patients with CAP show a decreased rate of apoptosis and increased activation status in the alveolar compartment, which may be important for effective control of pulmonary inflammation.

Background: Pulmonary inflammation in bronchiectasis, pneumonia and idiopathic pulmonary fibrosis (IPF) is dominated by neutrophils. Pathophysiologic differences are seen in the degree of airway and tissue destruction. Neutrophil activation and neutrophil proteolytic activity might differ between bronchiectasis, pneumonia and IPF., Objective: The aim of this study was to determine whether levels of inflammatory and protective markers in bronchoalveolar lavage (BAL) differed among cases of bronchiectasis, pneumonia and IPF., Methods: We studied 11 bronchiectasis patients (group 1), 30 pneumonia patients (group 2), 15 IPF patients (group 3) and 12 healthy volunteers (group 4). In the bronchoalveolar lavage fluid, concentrations of alpha(1)-proteinase inhibitor, myeloperoxidase (MPO) and elastase-alpha(1)PI complex were determined using immunoluminometric assays. Elastase inhibition capacity (EIC) and elastase activity were determined using a colorimetric assay., Results: No EIC, but free elastase activity, was found in 82% of group 1, 20% of group 2, 20% of group 3 and 0% of group 4. Median MPO concentration was highest in group 1: 7,951 ng/ml (16th-84th percentile [16-84%]: 256-36,342) vs. 692 ng/ml (106-2,279; group 2), 332 ng/ml (98-1,657; group 3), and 0.12 ng/ml (0.08-0.26; group 4). Bronchiectasis patients with bronchial Pseudomonas infection showed higher amounts of neutrophils (p < 0.01) and higher elastase activity (p < 0.05) than patients with sterile lavage., Conclusion: Bronchiectasis patients show a severe imbalance between neutrophil activity and protective molecules leading to possible lung destruction. Chronic Pseudomonas infection might trigger neutrophil activation. Future research and treatment strategies should focus on increased bacterial clearance and inhibition of neutrophil toxicity., (Copyright 2000 S. Karger AG, Basel)

Granulocyte colony-stimulating factor (G-CSF) has immunomodulating properties that could be beneficial for adjunctive treatment of severe infections. Cytokine release from stimulated whole blood and expression of neutrophil surface and apoptosis markers in response to G-CSF were studied in human volunteers under physiologic conditions and after ethanol pretreatment. Levels of interleukin (IL)-1 receptor antagonist and soluble tumor necrosis factor (TNF) receptor-1 were significantly increased after G-CSF, whereas TNF-alpha and IL-10 concentrations were reduced, and IL-1beta and IL-8 remained unchanged. There was a significant inhibition of neutrophil apoptosis and increased expression of complement regulatory protein CD55 without changes in CD11b, CD14, and CD59 expression. These effects were well preserved after ethanol pretreatment, which per se led to an increase in apoptosis and decreased CD55 expression. Thus, G-CSF treatment was associated with a reduction of the proinflammatory cytokine response and enhanced neutrophil survival in vivo, suggesting a therapeutic potential of G-CSF for severe infections in the nonneutropenic host.

Several lines of evidence suggest that Fas-mediated apoptosis is involved in the CD4 T-cell depletion in human immunodeficiency virus-1 (HIV-1) infection. To investigate this, we studied changes in peripheral blood, early T-cell apoptosis and Fas expression after initiation of antiretroviral therapy (ART) in 18 HIV-1-infected individuals. Flow cytometric analysis was performed with Apostain and CD4, CD8 and Fas staining. Fas expression was quantified by standardized beads. The levels of CD4 and CD8 T cells with early apoptosis were increased comparably in HIV-1-infected individuals. Despite elevated CD4 T cell counts, no decline in early T-cell apoptosis could be detected during the first 8 weeks of ART. However, after 26 weeks of ART in five patients that showed a sustained reduction of viral replication there was a marked decrease in T cells with features of early apoptosis. No difference was found for Fas expression on early apoptotic T cells. Fas expression on CD4 and CD8 T cells was reduced after initiation of ART; this was independent of the CD4 T-cell trend and indicates that the immediate CD4 T-cell expansion during ART is probably not the result of a decreased rate of early apoptosis among peripheral blood CD4 T cells. However, preliminary data imply a long-term reduction of early T-cell apoptosis and Fas expression in patients who show a sustained reduction of viral replication.

Several lines of evidence suggest a dysregulation of the complement system in human immunodeficiency virus-1 (HIV-1) infected patients. The aim of this study was to elucidate whether CD4+ alveolar lymphocytes from HIV-1 infected patients show a loss of complement regulatory proteins that would render these cells susceptible to antibody-dependent complement-mediated cytotoxicity. We investigated the expression of complement regulatory (CD46, CD55, CD59) and complement receptor (CR1, CR2, CR3, CR4) proteins on alveolar cells by flow cytometry. Cells were obtained by bronchoalveolar lavage from 17 HIV-1 infected and 12 HIV-1 negative individuals. Expression of adhesion molecules (leucocyte functional associated antigen-1 (LFA-1), intercellular adhesion molecule-1 (ICAM-1)) and CD30 were evaluated in patient subgroups. In addition, interleukin (IL)-1beta, tumour necrosis factor alpha (TNF-alpha), IL-4 and interferon gamma (IFN-gamma) concentrations were measured in supernatants of alveolar cells. We found a significantly reduced expression of CD46 and CD59 on CD4+ alveolar lymphocytes from HIV-1 infected individuals, whereas the expression of CR3, CR4, ICAM-1 and CD30 was increased. IL-1beta and TNF-alpha concentration in supernatants of alveolar cells was augmented in HIV-1 infected patients, but did not correlate with the expression of surface molecules. IFN-gamma concentration was also increased and showed an inverse relationship to the surface expression of CD30 on CD4+. Our data suggest that in human immunodeficiency virus-1 infection an increased level of activation is associated with a diminished expression of complement regulatory proteins on CD4+ alveolar lymphocytes. This phenomenon might contribute to the depletion of CD4+ lymphocytes and the local immunodeficiency in the pulmonary compartment.

Active T cell suicide (apoptosis) is supposed to be involved in the CD4+ T cell depletion in the course of HIV infection. We investigated the expression of the apoptosis-related antigen Fas on CD4+ T cells from 25 HIV-positive individuals (CDC I-III) and 8 HIV-negative controls by two-colour flowcytometry. In addition, we evaluated: total CD4 count, HIV p24 antigen concentration in serum after immune complex dissociation, and clinical course of infection in HIV-positive individuals. We found a significant increase in mean Fas expression on CD4+ T cells from HIV-positive individuals compared to HIV-negative individuals (85.84 +/- 14.92% vs. 64.28 +/- 7.59%, P < 0.001). Within the HIV-positive group the increase in Fas expression was correlated with the decline in CD4 count (r = -0.76, P < 0.001), p24 antigen concentration in serum, after immune complex dissociation (r = 0.67, P < 0.001), and CDC stage (r = 0.73, P < 0.001). The upregulation of Fas antigen on CD4 cells is associated with CD4 depletion and other virological and clinical marker of disease progression in HIV infection.