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1.
Case Reports Immunol ; 2023: 3977739, 2023.
Article in English | MEDLINE | ID: mdl-37260564

ABSTRACT

Patients with primary immunodeficiencies are especially vulnerable to developing severe coronavirus disease 2019 (COVID-19) after infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an important regulator of immune responses, and patients who suffer from CTLA4 haploinsufficiency have hyperactivation of effector T cells and infiltration of various organs. Overexpression of CTLA4 has been associated with a more severe disease course in patients with COVID-19, but there have only been a few reports on the disease course of COVID-19 in patients with CTLA4 haploinsufficiency. We report on a 33-year-old female with a history of immune thrombocytopenia, autoimmune haemolytic anaemia, granulomatous-lymphocytic interstitial lung disease, and common variable immunodeficiency who developed COVID-19. She was admitted and discharged from the hospital several times in the months thereafter and remained symptomatic and had a positive SARS-CoV-2 PCR for up to 137 days after the first symptoms. No SARS-CoV-2 antibodies were identified in the patients' serum. The disease was finally controlled after repeated infusions of convalescent plasma and treatment of concurrent bacterial and fungal infections. Genetic analysis revealed a likely pathogenic variant in CTLA4, and CTLA4 expression on regulatory T-cells was low. This case illustrates that patients with primary immunodeficiencies who have a protracted disease course of COVID-19 could benefit from convalescent plasma therapy.

2.
Transpl Immunol ; 72: 101599, 2022 06.
Article in English | MEDLINE | ID: mdl-35390480

ABSTRACT

Lung transplant recipients have an increased risk for severe coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A third dose of a SARS-CoV-2 vaccine has been recommended for all solid organ transplant recipients, but data from lung transplant recipients specifically are scarce. In this study, the serologic response to a third dose of an mRNA-based SARS-CoV-2 vaccine was measured in 78 lung transplant recipients. Sixty-two percent (n = 48) had a serological response to vaccination, which was significantly higher than after the second vaccine dose (27 patients (35%); p = 0.0013). A positive serologic response was associated with having had COVID-19 (p = 0.01), and higher serum IgG level and complement mannose binding lectin pathway activity prior to vaccination (p = 0.04 and p = 0.03, respectively). Serologic response was not associated with the dose of mycophenolate mofetil or prednisone or other immune status parameters. Eleven patients (14%) developed COVID-19 after the second or third vaccine dose, but this did not associate with serologic response after the second vaccine dose (9% in patients who developed COVID-19 versus 39% in patients who did not develop COVID-19 (p = 0.09)), or with serologic response above cut-off values associated with clinical protection in previous studies. In conclusion, the response to mRNA-based SARS-CoV-2 vaccines in lung transplant recipients improves significantly after a third vaccine dose. Factors associated with a positive serologic response are having had COVID-19 prior to vaccination, and serum IgG and complement mannose binding lectin pathway activity prior to vaccination. Serologic response did not associate with clinical protection against COVID-19 in this study.


Subject(s)
COVID-19 Vaccines , COVID-19 , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , Humans , Immunoglobulin G , Lung , Mannose-Binding Lectins , RNA, Messenger , SARS-CoV-2 , Transplant Recipients
4.
Lung ; 199(6): 667-676, 2021 12.
Article in English | MEDLINE | ID: mdl-34714393

ABSTRACT

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a severe fibrotic lung disease, in which inflammation is thought to only play a secondary role. Several factors associated with acute exacerbations of IPF (AE-IPF) have been identified, including infections. This study investigated whether humoral immunodeficiency or increased inflammatory markers at diagnosis were associated with AE-IPF and survival. METHODS: Four-hundred-and-nine patients diagnosed with IPF between 2011 and 2017 were retrospectively included. Immune status investigations at diagnosis included measurement of serum immunoglobulins (available in 38%), leukocyte and lymphocyte subsets in blood and bronchoalveolar lavage (BAL) fluid (available in 58%), as well as response to pneumococcal vaccination (available in 64%). RESULTS: Serum immunoglobulins or IgG subclass levels were below the lower limit of normal in 6%. The response to pneumococcal vaccination was severely impaired in 1%. Thirteen percent of patients developed an AE-IPF (4.7% per year). AE-IPF were associated with elevated lymphocytes in BAL fluid at diagnosis (p = 0.03). Higher serum IgA and IgG at diagnosis were associated with worse survival (p = 0.01; and p = 0.04), as were an increased BAL lymphocyte percentage (p = 0.005), and higher blood leukocytes and neutrophils (p = 0.01; and p = 0.0005). In a multivariate model, only BAL lymphocyte count retained statistical significance (p = 0.007). CONCLUSION: The prevalence of humoral immunodeficiencies was low in patients with IPF and not associated with AE-IPF or survival. Elevated lymphocytes in BAL were associated with the development of AE-IPF and worse survival. Higher serum immunoglobulins and immune cells in blood were also associated with worse survival. The local immune response in the lungs may be a target for future therapies.


Subject(s)
Idiopathic Pulmonary Fibrosis , Humans , Lung , Lymphocytes , Neutrophils , Retrospective Studies
5.
Expert Rev Vaccines ; 19(3): 227-234, 2020 03.
Article in English | MEDLINE | ID: mdl-32133883

ABSTRACT

Introduction: This review analyzes the efficacy of pneumococcal vaccinations in lung transplant patients before and after transplantation.Areas covered: This review addresses the risk for respiratory infections, in particular pneumococcal infections, in lung transplantation patients in the context of immunodeficiency and immunosuppressive medication. Vaccination is recommended to counteract the increased risk of pneumococcal infection, and the relevant guidelines are discussed in this review. The design of specific vaccination schedules is required because of the impaired antibody response in specific patient categories.Expert opinion: Lung transplantation candidates should be vaccinated with pneumococcal vaccines prior to transplantation. Currently, the 23-valent pneumococcal polysaccharide vaccine offers the broadest coverage, but the antibody response should be monitored. New generation pneumococcal conjugate vaccines with equally broad serotype coverage could be used in the future. During the post-transplantation period, the immune status of the patients should be monitored regularly, and vaccination should be repeated when indicated.


Subject(s)
Lung Transplantation , Pneumococcal Infections/prevention & control , Pneumococcal Vaccines/administration & dosage , Antibody Formation/immunology , Humans , Immunization Schedule , Pneumococcal Vaccines/immunology , Practice Guidelines as Topic , Vaccination/methods
6.
Transplant Proc ; 52(3): 958-966, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32146023

ABSTRACT

BACKGROUND: Lung transplantation (LTx) is a last treatment option for patients with an end-stage pulmonary disease. Chronic lung allograft dysfunction, which generally manifests as bronchiolitis obliterans syndrome (BOS), is a major long-term survival limitation. During injury, inflammation and BOS monocytes are recruited. We determined whether changes in count, subset distribution, and functionality by surface marker expression coincided with BOS development. METHODS: Fresh whole-blood samples were analyzed from 44 LTx patients, including 17 patients diagnosed with BOS, and compared with 10 age-matched healthy controls and 9 sarcoidosis patients as positive controls. Monocytes were quantified and analyzed using flow cytometry. Based on surface marker expression, classical, intermediate, and nonclassical subsets were determined, and functional phenotypes were investigated. RESULTS: The absolute count of monocytes was decreased in LTx and slightly increased in BOS patients. The relative count shifted toward classical monocytes at the expense of nonclassical monocytes in LTx and BOS. Surface marker expression was highest on intermediate monocytes. The expression of both CD36 and CD163 was significantly increased in the LTx and BOS cohort. The difference between the BOS cohort and the LTx cohort was only subtle, with a significant decrease in HLA-DR expression on nonclassical monocytes in BOS. CONCLUSIONS: Monocyte subsets and surface marker expression changed significantly in transplantation patients, while BOS-specific changes were understated. More research is needed to determine whether and how monocytes influence the disease process and how current immunosuppressants affect their normal function in vivo.


Subject(s)
Bronchiolitis Obliterans/immunology , Lung Transplantation/adverse effects , Monocytes/immunology , Adult , Bronchiolitis Obliterans/pathology , Female , Humans , Male , Middle Aged , Phenotype
7.
Vaccine ; 35(37): 4886-4895, 2017 09 05.
Article in English | MEDLINE | ID: mdl-28802755

ABSTRACT

OBJECTIVES: The goal of this study is to investigate the immune response to the 13-valent pneumococcal conjugate vaccine (PCV13) in former pneumococcal CAP patients. We hypothesize that an impaired or suboptimal humoral immune response against (specific) pneumococcal serotypes might explain the vulnerability for pneumococcal disease. METHODS: Hospitalised adult CAP patients who participated in two trials (2004-2006 (n=201) and, 2007-2009 (n=304)) were screened. Patients eligible for inclusion had CAP caused by either S. pneumoniae (pneuCAP) or due to another well-defined pathogen (otherCAP). Serotype-specific pneumococcal antibody concentrations (total IgG and IgG2/IgG1) before and 3-4weeks after PCV13 administration were measured (Luminex) and compared between pneuCAP and otherCAP patients. RESULTS: We vaccinated 60 patients:i.e. 34 pneuCAP and 26 otherCAP patients. In the pneuCAP group, 74% of patients were categorized as good responders (≥9/13 serotypes with concentration≥1300ng/ml), versus 77% in the otherCAP group. Significantly fewer full responders (i.e. 13/13 serotypes with a concentration≥1300ng/mL) were identified in the pneuCAP group (15% vs 42% respectively, p=0.02). For serotype 1, total IgG and IgG2/IgG1 subset post-vaccination concentrations were significantly lower among pneuCAP patients. Our additional case-series showed that of 16 pneuCAP patients who were infected by a serotype included in PCV13 three patients did not respond against the serotype originally responsible for their CAP episode, including one former bacteraemic pneumococcal CAP patient who also failed to show a response against the serotype responsible for CAP during infection. Thirteen patients did respond to the previously infecting serotype following PCV13 including three patients who had bacteraemic pneumococcal pneumonia and did not show a response during infection against the serotype responsible for CAP. CONCLUSIONS: Our results confirm the immunogenic properties of PCV13 in former pneumococcal CAP patients including patients previously regarded as potential hyporesponders. A slightly diminished overall humoral response to polysaccharides characterizes the former pneumococcal CAP patients. ClinicalTrials.gov Identifier: NCT02141009.


Subject(s)
Pneumococcal Vaccines/therapeutic use , Pneumonia, Pneumococcal/prevention & control , Streptococcus pneumoniae/pathogenicity , Adult , Aged , Antibodies, Bacterial/immunology , Community-Acquired Infections/immunology , Community-Acquired Infections/prevention & control , Female , Heptavalent Pneumococcal Conjugate Vaccine/therapeutic use , Humans , Immunotherapy , Male , Middle Aged , Pneumococcal Vaccines/immunology , Pneumonia, Pneumococcal/immunology , Serogroup , Streptococcus pneumoniae/immunology
8.
Case Rep Pulmonol ; 2016: 1310862, 2016.
Article in English | MEDLINE | ID: mdl-27088026

ABSTRACT

Pulmonary fibrosis is a frequent manifestation of telomere syndromes. Telomere gene mutations are found in up to 25% and 3% of patients with familial disease and sporadic disease, respectively. The telomere gene TINF2 encodes an eponymous protein that is part of the shelterin complex, a complex involved in telomere protection and maintenance. A TINF2 gene mutation was recently reported in a family with pulmonary fibrosis. We identified a heterozygous Ser245Tyr mutation in the TINF2 gene of previously healthy female patient that presented with progressive cough due to pulmonary fibrosis as well as panhypogammaglobulinemia at age 52. Retrospective multidisciplinary evaluation classified her as a case of possible idiopathic pulmonary fibrosis. Telomere length-measurement indicated normal telomere length in the peripheral blood compartment. This is the first report of a TINF2 mutation in a patient with sporadic pulmonary fibrosis, which represents another association between TINF2 mutations and this disease. Furthermore, this case underlines the importance of telomere dysfunction and not telomere length alone in telomere syndromes and draws attention to hypogammaglobulinemia as a manifestation of telomere syndromes.

9.
Am J Transplant ; 16(3): 987-98, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26517734

ABSTRACT

Complement activation leads primarily to membrane attack complex formation and subsequent target cell lysis. Protection against self-damage is regulated by complement regulatory proteins, including CD46, CD55, and CD59. Within their promoter regions, single-nucleotide polymorphisms (SNPs) are present that could influence transcription. We analyzed these SNPs and investigated their influence on protein expression levels. A single SNP configuration in the promoter region of CD59 was found correlating with lower CD59 expression on lung endothelial cells (p = 0.016) and monocytes (p = 0.013). Lung endothelial cells with this SNP configuration secreted more profibrotic cytokine IL-6 (p = 0.047) and fibroblast growth factor ß (p = 0.036) on exposure to sublytic complement activation than cells with the opposing configuration, whereas monocytes were more susceptible to antibody-mediated complement lysis (p < 0.0001). Analysis of 137 lung transplant donors indicated that this CD59 SNP configuration correlates with impaired long-term survival (p = 0.094) and a significantly higher incidence of bronchiolitis obliterans syndrome (p = 0.046) in the recipient. These findings support a role for complement in the pathogenesis of this posttransplant complication and are the first to show a deleterious association of a donor CD59 promoter polymorphism in lung transplantation.


Subject(s)
CD59 Antigens/genetics , Graft Rejection/diagnosis , Lung Transplantation , Polymorphism, Genetic/genetics , Postoperative Complications , Promoter Regions, Genetic/genetics , Tissue Donors , Adolescent , Adult , Complement Activation , Female , Follow-Up Studies , Graft Rejection/etiology , Graft Survival , Humans , Male , Middle Aged , Monocytes/cytology , Monocytes/metabolism , Prognosis , Survival Rate , Young Adult
11.
J Cyst Fibros ; 14(1): 42-5, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25096855

ABSTRACT

Autoantibodies against endothelin-1 type A receptor (ETAR) are present in systemic sclerosis complicated by lung fibrosis and pulmonary hypertension. As increased serum levels and local overproduction of endothelin-1 in the airways are reported in cystic fibrosis (CF) patients, we reasoned that anti-ETAR antibodies could be prevalent in endstage CF patients prior to lung transplantation (LTx). Also, ETAR autoantibodies are frequently associated with autoantibodies against the angiotensin II type 1 receptor (AT1R). We analyzed the presence of anti-ETAR and anti-AT1R autoantibodies in 43 LTx patients (chronic obstructive pulmonary disease (COPD), n=20; CF, n=13; interstitial lung disease (ILD), n=1). We observed overall higher anti-ETAR and anti-AT1R autoantibody titers in sera taken prior to LTx in the CF patient group as compared to COPD. No difference was found in autoantibody levels between patients with CF versus ILD. In sera taken post-LTx we found the same difference in anti-ETAR and anti-AT1R autoantibody titers between patients with CF versus COPD. No difference was found in antibody titers between sera taken prior to or 6 months after LTx. There was no association between autoantibody levels and other relevant demographic parameters, and we found no association between autoantibody titers and the development of the bronchiolitis obliterans syndrome. Both autoantibody titers were strongly correlated. We hypothesize that due to prolonged exposure to bacterial infection, increased levels of AT1R and ETAR result in a deregulated immune response causing autoantibody formation. Further research is expedient to elucidate the occurrence of autoantibodies against ETAR and AT1R and their role in disease progression.


Subject(s)
Autoantibodies/immunology , Cystic Fibrosis/immunology , Cystic Fibrosis/surgery , Receptor, Angiotensin, Type 1/metabolism , Receptor, Endothelin A/metabolism , Adolescent , Adult , Biomarkers/blood , Cohort Studies , Cystic Fibrosis/blood , Enzyme-Linked Immunosorbent Assay , Female , Humans , Lung Diseases, Interstitial/blood , Lung Diseases, Interstitial/immunology , Lung Transplantation/methods , Male , Middle Aged , Patient Selection , Pilot Projects , Prognosis , Pulmonary Disease, Chronic Obstructive/blood , Pulmonary Disease, Chronic Obstructive/immunology , Receptor, Angiotensin, Type 1/immunology , Receptor, Endothelin A/blood , Retrospective Studies , Risk Assessment , Severity of Illness Index , Young Adult
12.
Clin Exp Immunol ; 177(1): 272-9, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24547957

ABSTRACT

Mannose-binding lectin (MBL)-deficiency is associated with an increased susceptibility to pneumococcal infections and other forms of disease. Pneumococcal vaccination is recommended in MBL-deficient patients with recurrent respiratory tract infections (RRTI). The response to pneumococcal vaccination in MBL-deficient individuals has not yet been studied in detail. An impaired response to pneumococcal polysaccharides in MBL-deficient patients might explain the association between MBL deficiency and pneumococcal infections. This study investigates the antibody response to pneumococcal vaccination in MBL-deficient adult patients with RRTI. Furthermore, we investigated whether there was a difference in clinical presentation between MBL-deficient and -sufficient patients with RRTI. Eighteen MBL-deficient and 63 MBL-sufficient adult patients with RRTI were all vaccinated with the 23-valent pneumococcal polysaccharide vaccine and antibodies to 14 pneumococcal serotypes were measured on a Luminex platform. There were no differences observed in the response to pneumococcal vaccination between MBL-sufficient and -deficient patients. Forty-three MBL-sufficient patients could be classified as responders to pneumococcal vaccination and 20 as low responders, compared to 15 responders and three low responders in the MBL-deficient patients. We found no clear difference in clinical, radiological, lung function and medication parameters between MBL-sufficient and -deficient patients. In conclusion, our study suggests that MBL-deficient adults with RRTI have a response to a pneumococcal capsular polysaccharide vaccine comparable with MBL-sufficient patients. Moreover, we did not find a clear clinical role of MBL deficiency in adults with RRTI. As MBL deficiency is associated with an increased susceptibility to pneumococcal infections, pneumococcal vaccination might be protective in MBL-deficient patients with RRTI.


Subject(s)
Mannose-Binding Lectin/deficiency , Metabolism, Inborn Errors/immunology , Pneumococcal Infections/immunology , Pneumococcal Vaccines/immunology , Respiratory Tract Infections/immunology , Streptococcus pneumoniae/immunology , Adult , Antibodies, Bacterial/blood , Female , Genotype , Humans , Immunity, Humoral , Male , Mannose-Binding Lectin/immunology , Metabolism, Inborn Errors/complications , Middle Aged , Pneumococcal Infections/etiology , Pneumococcal Infections/prevention & control , Pneumococcal Vaccines/administration & dosage , Practice Patterns, Physicians' , Recurrence , Respiratory Function Tests , Respiratory Tract Infections/etiology , Respiratory Tract Infections/prevention & control
13.
Sarcoidosis Vasc Diffuse Lung Dis ; 30(1): 28-35, 2013 Mar.
Article in English | MEDLINE | ID: mdl-24003532

ABSTRACT

BACKGROUND AND OBJECTIVE: The development of bronchiolitis obliterans syndrome (BOS) after lung transplantation is characterized by inflammation, remodeling and fibrosis. Both YKL-40 and matrix metalloproteinase (MMP)-9 have shown to be involved in these processes. We measured serial YKL-40 and MMP-9 serum levels in lung transplant recipients and assessed their usefulness as biomarker for BOS. Furthermore, we investigate the relationship between these two potential biomarkers of BOS and MMP-7. DESIGN: Ten patients with BOS (BOS(pos)) and 10 matched patients without BOS (BOS(neg)) were included. Serial serum samples were collected after lung transplantation and prior to BOS. YKL-40, MMP-9 and MMP-7 serum levels were determined by ELISA. RESULTS: The median concentrations of YKL-40 did not differ between BOS(pos) and BOS(neg) patients (p > 0.05). The median concentration of MMP-9 in BOS(pos) patients was significantly higher than in BOS(neg) patients (p < 0.0001). For MMP-9 as possible risk factor for BOS, a cut off value of 145 ng/ml has a sensitivity of 90% and a negative predictive value of 83%. Longitudinal analysis of YKL-40 and MMP-9 serum levels from the early post-transplant period onwards did not reveal a significant trend in time in both serum levels preceding BOS. In BOS(neg) patients MMP-9 showed an inverse relationship with MMP-7, that was absent in BOS(pos) patients. CONCLUSIONS: From the moment of transplantation onwards, patients who eventually developed BOS had significantly increased MMP-9 serum levels in comparison with patients who did not develop BOS. Therefore, increased MMP-9 serum levels might be useful as risk factor for BOS.


Subject(s)
Adipokines/blood , Biomarkers/blood , Bronchiolitis Obliterans/blood , Lectins/blood , Matrix Metalloproteinase 9/blood , Adult , Bronchiolitis Obliterans/epidemiology , Chitinase-3-Like Protein 1 , Female , Humans , Lung Diseases/blood , Lung Transplantation , Male , Matrix Metalloproteinase 7/blood , Middle Aged , Risk Factors
14.
Diabet Med ; 29(8): e159-62, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22486317

ABSTRACT

AIMS: The aims of the study are to investigate the prevalence of diabetes in patients with cystic fibrosis compared with patients without cystic fibrosis, and its impact on the outcome after lung transplantation. METHODS: Data were reviewed from 77 lung transplantation recipients in our centre between 2001 and 2010; 43 patients had cystic fibrosis and 34 patients had other lung diseases (no cystic fibrosis). To define diabetes, we used the American Diabetes Association definition. RESULTS: Before lung transplantation, diabetes was diagnosed in 63% of patients with cystic fibrosis and 6% of patients without cystic fibrosis (P<0.001). In both groups, approximately 60% of the patients at risk developed new-onset diabetes after transplantation. The mortality in patients with cystic fibrosis was higher in patients with diabetes diagnosed before lung transplantation compared with those without (44 vs. 6%, P=0.04). Diabetes remained an independent factor in multivariate analyses. CONCLUSIONS: Diabetes diagnosed before lung transplantation has a negative effect on survival after lung transplantation in patients with cystic fibrosis. Pre-existing diabetes is common in patients with cystic fibrosis, in contrast to patients without cystic fibrosis. Development of new-onset diabetes after transplantation is similar in both groups.


Subject(s)
Cystic Fibrosis/complications , Diabetes Mellitus/diagnosis , Lung Transplantation/statistics & numerical data , Adult , Cohort Studies , Cystic Fibrosis/mortality , Cystic Fibrosis/surgery , Diabetes Complications/epidemiology , Diabetes Complications/mortality , Diabetes Mellitus/mortality , Female , Humans , Incidence , Lung Diseases/complications , Lung Diseases/mortality , Lung Diseases/surgery , Male , Postoperative Complications/mortality , Preoperative Period , Prevalence , Risk Factors , Treatment Outcome , United States/epidemiology , Young Adult
15.
Clin Exp Immunol ; 166(1): 103-9, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21910727

ABSTRACT

Alloreactive T cells that infiltrate the graft after lung transplantation (LTx) play a role in chronic rejection. Chemokines such as thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC) and monocyte chemotactic protein-1 (MCP-1) are produced locally in the lung and attract T cells via chemokine receptor 4 (CCR4). In a TARC gradient, cells expressing CCR4(++) migrate more efficiently than CCR4(+) -expressing cells. In this study, we compared the CCR4 expression of T cells in blood from 20 lung transplant recipients to healthy controls. We then examined whether CCR4 expression is associated with the occurrence of chronic rejection. The CCR4(++) expression was decreased on CD4 T cells from LTx patients (P < 0·0001) when compared to healthy controls. The analysis of CD4 T cell subsets showed that this decrease was present on central memory, effector memory and terminally differentiated T cells (P = 0·0007, P < 0·0001 and P = 0·05, respectively), while a trend was found for naive CD4 T cells (P = 0·06). Also, the expression of CCR4(+) on regulatory T cells (T(regs) ) was decreased in LTx patients when compared to healthy controls (P = 0·02). Interestingly, the CCR4(++) expression on CD4 effector memory T cells was decreased in patients developing chronic rejection sometimes more than a year before the clinical diagnosis when compared to patients who did not (P = 0·04). The analysis of CD8 T cell subsets only showed the CCR4(+) expression to be increased significantly on effector memory and terminally differentiated CD8 T cells (P = 0·02, P = 0·03, respectively) in LTx patients, but no relation was found in chronic rejection. In conclusion, the expression of CCR4 on T cell subsets was altered after LTx and appears to be related to chronic rejection.


Subject(s)
Bronchiolitis Obliterans/immunology , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/metabolism , Graft Rejection/blood , Lung Transplantation/immunology , Receptors, CCR4 , Adult , Biomarkers/blood , Bronchiolitis Obliterans/blood , Bronchiolitis Obliterans/etiology , Bronchiolitis Obliterans/pathology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Case-Control Studies , Cell Movement/immunology , Cells, Cultured , Chemokine CCL17/biosynthesis , Chemokine CCL17/immunology , Chemokine CCL2/biosynthesis , Chemokine CCL2/immunology , Chemokine CCL22/biosynthesis , Chemokine CCL22/immunology , Female , Flow Cytometry , Graft Rejection/immunology , Graft Rejection/pathology , Humans , Lung Transplantation/adverse effects , Lung Transplantation/pathology , Male , Middle Aged , Receptors, CCR4/biosynthesis , Receptors, CCR4/blood , Receptors, CCR4/immunology , Syndrome , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Time Factors
16.
Clin Exp Immunol ; 165(3): 410-6, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21707593

ABSTRACT

Despite the use of immunosuppressives mainly influencing T and B cell responses, the prevalence of the bronchiolitis obliterans syndrome (BOS) after lung transplantation is high. Mannose-binding lectin (MBL) is a pattern recognition molecule of complement and an important component of the innate immunity. MBL is associated with rejection, infection and survival in other solid organ transplantations. In this study the relation between functional MBL levels and cytomegalovirus (CMV) reactivations and the development of BOS and survival after lung transplantation was investigated. MBL levels were measured in 85 patients before and in 57 of these patients after lung transplantation. The relation of MBL on survival, CMV reactivation and the development of BOS were investigated with Kaplan-Meier (log-rank) survival analysis. MBL levels decreased on average by 20% (P < 0·001) after transplantation and eventually returned to pretransplant levels. Fourteen of the 85 patients had deficient pretransplant MBL levels and these patients had a tendency towards a better survival compared to those with normal MBL levels (P = 0·08). Although no correlation was found between MBL deficiency and the development of BOS, more CMV reactivations occurred in recipients with deficient versus normal levels of MBL (P = 0·03). Our results suggest that MBL deficiency is associated with CMV reactivations and a longer overall survival, but not with the development of BOS.


Subject(s)
Cytomegalovirus/physiology , Lung Transplantation/mortality , Mannose-Binding Lectin/deficiency , Virus Activation , Adolescent , Adult , Bronchiolitis Obliterans/diagnosis , Cytomegalovirus/immunology , Cytomegalovirus/isolation & purification , Female , Ganciclovir/analogs & derivatives , Ganciclovir/therapeutic use , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Kaplan-Meier Estimate , Lung Transplantation/immunology , Male , Mannose-Binding Lectin/blood , Middle Aged , Postoperative Complications/diagnosis , Postoperative Complications/virology , Retrospective Studies , Risk Factors , Survival Rate , Valganciclovir , Young Adult
17.
Case Rep Infect Dis ; 2011: 460313, 2011.
Article in English | MEDLINE | ID: mdl-22567471

ABSTRACT

Scedosporium/Pseudallescheria species are frequently seen in cystic fibrosis patients. However, disseminated forms after lung transplantation in these patients are rarely seen, but often with poor outcome. In this case report we describe a lung transplant recipient with cystic fibrosis who developed a spondylodiscitis that was caused by Scedosporium apiospermum. The patient was treated with anti-fungal treatment by voriconazole for over three years with a clinical good response and without the need for surgical intervention. To our opinion this is the first anti-fungal treated case of invasive disease caused by Scedosporium/Pseudallescheria in a cystic fibrosis (CF) patient who underwent lung transplantation that survived.

18.
Clin Exp Immunol ; 154(2): 202-8, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18785972

ABSTRACT

The main reason for mortality after lung transplantation is the bronchiolitis obliterans syndrome (BOS), which represents chronic rejection. As soluble CD30, which is produced mainly by activated T helper 2 (Th2) cells, was shown to be related to development of BOS, we aimed to investigate the relation between development of BOS and Th2 chemoattractant thymus and activation regulated chemokine (TARC/CCL17). In 54 patients we measured serum TARC levels prior to transplantation by enzyme-linked immunosorbent assay, and in 44 of these patients sera were analysed at months 1, 2 and 3 after lung transplantation. In addition, longitudinal measurements were performed in sera from eight healthy controls and 14 patients, the latter taken over a period of 2 years post-transplantation from seven patients developing BOS plus seven clinically matched BOS-free patients. Median serum TARC levels post-transplantation of patients who developed BOS were significantly lower than those of the matched BOS-free patients (P = 0.05). A receiver operating characteristics analysis (area under the curve 0.77), together with a Kaplan-Meyer analysis, showed that serum TARC levels below 325 pg/ml in the first month post-transplantation can predict development of BOS post-transplantation (P = 0.001). In contrast, pretransplant serum TARC levels were not significantly different between patients developing BOS, BOS-free patients or healthy controls. In conclusion, pretransplantation serum TARC levels do not predict the development of BOS post-transplantation, but measurement of the serum TARC levels in the first month directly after transplantation can provide us with a tool to identify the group at risk of developing BOS.


Subject(s)
Bronchiolitis Obliterans/diagnosis , Chemokine CCL17/blood , Lung Transplantation/adverse effects , Adolescent , Adult , Biomarkers/blood , Bronchiolitis Obliterans/etiology , Enzyme-Linked Immunosorbent Assay/methods , Female , Follow-Up Studies , Humans , Immunosuppression Therapy , Male , Middle Aged , Postoperative Care/methods , Postoperative Period , Prognosis
19.
Eur Respir J ; 25(3): 482-9, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15738292

ABSTRACT

As a defective anti-polysaccharide response can exist in the absence of an immunoglobulin deficiency, a series of 26 patients with bronchiectasis of unknown aetiology was vaccinated with a 23-valent pneumococcal polysaccharide vaccine. All patients suffered from recurrent respiratory tract infections. When measuring total antibody levels to pneumococcal serotypes 3, 4 and 9, a normal polysaccharide antibody response was found in 22 patients. However, only 11 of these subjects showed a normal pneumococcal antibody response within the IgA and/or IgG2 subclass, and thus could be classified as true responders, while 15 patients did not respond in either the IgA class or in the IgG2 subclass. When analysing differences between the responder (n = 11) and nonresponder (n = 15) groups, the latter demonstrated higher frequencies of respiratory tract infections and more severe lung pathology, as revealed by the presence of more bronchi visualised in the peripheral third of the lung by high-resolution computed tomography scanning. Moreover, nonresponders needed extensive lung surgery more often in order to control their disease (number of resected segments eight versus five). In conclusion, an important fraction of patients presenting with idiopathic bronchiectasis is associated with a selective anti-polysaccharide response deficiency and this subgroup appears to represent a more severe clinical phenotype. Therefore, it can be regarded as a separate clinical entity with possible therapeutic targets. In order to identify IgA and IgG2 anti-polysaccharide nonresponders, all patients presenting with bronchiectasis of unknown aetiology should be immunised with a pneumococcal polysaccharide vaccine, and IgA and IgG2 isotype responses should be evaluated as well as the total antibody response.


Subject(s)
Bronchiectasis/immunology , Bronchiectasis/prevention & control , Immunoglobulin A/blood , Immunoglobulin G/blood , Pneumococcal Vaccines/therapeutic use , Polysaccharides, Bacterial/immunology , Bronchiectasis/diagnostic imaging , Female , Humans , Male , Pneumococcal Vaccines/immunology , Radiography , Reference Values , Respiratory Tract Infections/immunology , Respiratory Tract Infections/prevention & control , Titrimetry
20.
Clin Exp Immunol ; 118(1): 102-7, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10540166

ABSTRACT

Serum IgG subclass concentrations were determined in patients visiting, the pulmonology out-patient clinic with chronic respiratory tract problems. A total of 24 patients with a serum IgG1 concentration < 4.9 g/l (i.e. below the reference range) and normal values for IgG2, IgM and IgA were included. Patients with a selective IgG1 deficiency were vaccinated with a 23-valent pneumococcal polysaccharide vaccine. There were nine patients with a poor antibody response to pneumococcal capsular polysaccharide antigens. Responsiveness to protein antigens was intact in all patients. Patients with pneumonia showed a significantly lower anti-polysaccharide response in the IgG2 subclass than patients without pneumonia. Patients with recurrent sinusitis showed a significantly lower response in the IgA isotype after vaccination with pneumococcal polysaccharide vaccine compared with non-sinusitis patients. It can be concluded that patients with recurrent sinopulmonary infections and a mild IgG1 subclass deficiency have an impaired IgG1 anti-polysaccharide response, which can extend to decreased IgG2 and IgA anti-polysaccharide responses.


Subject(s)
IgG Deficiency/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Adult , Aged , Antibodies, Bacterial/blood , Bacterial Vaccines/therapeutic use , Female , Humans , IgG Deficiency/complications , Immunization , Immunoglobulin A/blood , Immunoglobulin M/blood , Male , Middle Aged , Pneumococcal Vaccines , Polysaccharides, Bacterial/immunology , Respiratory Tract Infections/blood , Respiratory Tract Infections/complications , Respiratory Tract Infections/immunology , Respiratory Tract Infections/prevention & control , Serologic Tests
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