KIL1 terminates fertility in maize by controlling silk senescence.

Plant flowers have a functional life span during which pollination and fertilization occur to ensure seed and fruit development. Once flower senescence is initiated, the potential to set seed or fruit is irrevocably lost. In maize, silk strands are the elongated floral stigmas that emerge from the husk-enveloped inflorescence to intercept airborne pollen. Here we show that KIRA1-LIKE1 (KIL1), an ortholog of the Arabidopsis NAC (NAM (NO APICAL MERISTEM), ATAF1/2 (Arabidopsis thaliana Activation Factor1 and 2) and CUC (CUP-SHAPED COTYLEDON 2)) transcription factor KIRA1, promotes senescence and programmed cell death (PCD) in the silk strand base, ending the window of accessibility for fertilization of the ovary. Loss of KIL1 function extends silk receptivity and thus strongly increases kernel yield following late pollination. This phenotype offers new opportunities for possibly improving yield stability in cereal crops. Moreover, despite diverging flower morphologies and the substantial evolutionary distance between Arabidopsis and maize, our data indicate remarkably similar principles in terminating floral receptivity by PCD, whose modulation offers the potential to be widely used in agriculture.

Distinguishing pathogenic mutations from background genetic noise in cardiology: The use of large genome databases for genetic interpretation.

Advances in clinical genetic testing have led to increased insight into the human genome, including how challenging it is to interpret rare genetic variation. In some cases, the ability to detect genetic mutations exceeds the ability to understand their clinical impact, limiting the advantage of these technologies. Obstacles in genomic medicine are many and include: understanding the level of certainty/uncertainty behind pathogenicity determination, the numerous different variant interpretation-guidelines used by clinical laboratories, delivering the certain or uncertain result to the patient, helping patients evaluate medical decisions in light of uncertainty regarding the consequence of the findings. Through publication of large publicly available exome/genome databases, researchers and physicians are now able to highlight dubious variants previously associated with different cardiac traits. Also, continuous efforts through data sharing, international collaborative efforts to develop disease-gene-specific guidelines, and computational analyses using large data, will indubitably assist in better variant interpretation and classification. This article discusses the current, and quickly changing, state of variant interpretation resources within cardiovascular genetic research, e.g., publicly available databases and ways of how cardiovascular genetic counselors and geneticists can aid in improving variant interpretation in cardiology.

Initiating transitional care for adolescents with cystic fibrosis at the age of 12 is both feasible and promising.

AIM: Adolescence is a vulnerable period in cystic fibrosis, associated with declining lung function. This study described, implemented and evaluated a transition programme for adolescents. METHODS: We conducted a single centre, nonrandomised and noncontrolled prospective programme at the cystic fibrosis centre at Copenhagen University Hospital Rigshospitalet from 2010 to 2011, assessing patients aged 12-18 at baseline and after 12 months. Changes implemented included staff training on communication, a more youth-friendly feel to the outpatient clinic, the introduction of youth consultations partly alone with the adolescent, and a parents' evening focusing on cystic fibrosis in adolescence. Lung function and body mass index (BMI) were measured monthly and adolescents were assessed for their readiness for transition and quality of life at baseline and 12 months. RESULTS: We found that 40 (98%) of the eligible patients participated and youth consultations were successfully implemented with no dropouts. The readiness checklist score increased significantly over the one-year study period, indicating increased readiness for transfer and self-care. Overall quality of life, lung function and BMI remained stable during the study period. CONCLUSION: A well-structured transition programme for cystic fibrosis patients as young as 12 years of age proved to be both feasible and sustainable.

Sinus surgery postpones chronic Gram-negative lung infection: cohort study of 106 patients with cystic fibrosis.

BACKGROUND: In patients with cystic fibrosis (CF) the sinuses are a bacterial reservoir for Gram-negative bacteria (GNB). From the sinuses the GNB can repeatedly migrate to the lungs. In a one-year follow-up study, endoscopic sinus surgery (ESS) with adjuvant therapy reduced the frequency of pulmonary samples positive for GNB. We investigated whether the effect is sustained. METHODOLOGY: We report the effect of ESS and adjuvant therapy three years postoperatively in a CF cohort participating in this prospective clinical follow-up study. The primary endpoint was the lung infection status defined by Leeds criteria. RESULTS: One hundred and six CF patients underwent ESS; 27 had improved lung infection status after three years. The prevalence of patients free of lung colonization with GNB significantly increased from 16/106 patients (15%) preoperatively to 35/106 patients (33%) after three years. The total cohort had decreasing lung function during follow-up; however, in 27 patients with improved lung infection status lung function was stable. Revision surgery was performed in 31 patients (28%). CONCLUSION: ESS with adjuvant therapy significantly improves the lung infection status for at least three years in our cohort of patients with CF and may postpone chronic lung infection with GNB and thus stabilize lung function.

Vancomycin-resistant Enterococcus faecium: impact of ending screening and isolation in a Danish University hospital.

BACKGROUND: Substantial resources are used in hospitals worldwide to counteract the ever-increasing incidence of vancomycin-resistant and vancomycin-variable Enterococcus faecium (VREfm and VVEfm), but it is important to balance patient safety, infection prevention, and hospital costs. AIM: To investigate the impact of ending VREfm/VVEfm screening and isolation at Odense University Hospital (OUH), Denmark, on patient and clinical characteristics, risk of bacteraemia, and mortality of VREfm/VVEfm disease at OUH. The burden of VREfm/VVEfm bacteraemia at OUH and the three collaborative hospitals in the Region of Southern Denmark (RSD) was also investigated. METHODS: A retrospective cohort study was conducted including first-time VREfm/VVEfm clinical isolates (index isolates) detected at OUH and collaborative hospitals in the period 2015-2022. The intervention period with screening and isolation was from 2015 to 2021, and the post-intervention period was 2022. Information about clinical isolates was retrieved from microbiological databases. Patient data were obtained from hospital records. FINDINGS: At OUH, 436 patients were included in the study, with 285 in the intervention period and 151 in the post-intervention period. Ending screening and isolation was followed by an increased number of index isolates. Besides a change in van genes, only minor non-significant changes were detected in all the other investigated parameters. Mortality within 30 days did not reflect the VREfm/VVEfm-attributable deaths, and in only four cases was VREfm/VVEfm infection the likely cause of death. CONCLUSION: Despite an increasing number of index isolates, nothing in the short follow-up period supported a reintroduction of screening and isolation.

Clinical effects of sinus surgery and adjuvant therapy in cystic fibrosis patients - can chronic lung infections be postponed?

BACKGROUND: The paranasal sinuses can be a bacterial reservoir for pulmonary infections in patients with cystic fibrosis (CF) METHODOLOGY: In this prospective, non-randomised, uncontrolled, intervention cohort study, the clinical effect of sinus surgery followed by two weeks` intravenous antibiotics, 6 months` antibiotic nasal irrigations was assessed in 106 CF patients. RESULTS: One year after sinus surgery, the prevalence of intermittently colonised patients had decreased by 38%, while the prevalence of non-colonised patients had increased by 150%. The frequency of pulmonary samples with CF pathogens was reduced after surgery. Specific IgG against P. aeruginosa decreased after six months. Additionally, the self reported symptoms of chronic rhinosinusitis and quality of life improved. CONCLUSION: Combined sinus surgery and postoperative systemic and topical antibiotic treatment significantly reduced the frequency of pulmonary samples positive for CF pathogens in the first year after sinus surgery.

Identification of CTX-M15-, SHV-28-producing Klebsiella pneumoniae ST15 as an epidemic clone in the Copenhagen area using a semi-automated Rep-PCR typing assay.

Rapid molecular typing methods can be a valuable aid in the investigation of suspected outbreaks. We used a semi-automated repetitive sequence-based polymerase chain reaction (Rep-PCR) typing assay and pulsed field gel electrophoresis (PFGE) to investigate the relationship between local Klebsiella pneumoniae (K. pneumoniae) producing extended spectrum ß-lactamases (ESBLs) and their relation to recognized Danish outbreak strains. PFGE and Rep-PCR produced similar clustering among isolates. Individual isolates from each cluster were further characterized by PCR amplification and sequencing of bla (TEM), bla (SHV), and bla (CTX-M), and multilocus sequence typing (MLST). Thirty-five out of 52 ESBL-producing K. pneumoniae isolates were ST15 and bla (CTX-M15), bla (SHV-28), and bla (TEM-1) positive by PCR. Ten out of 52 were ST16 and tested positive for bla (CTX-M15), bla (SHV-1), and bla (TEM-1). Isolates from previously recognized hospital outbreaks were also ST15 and PCR positive for bla (CTX-M15), bla (SHV-28), and bla (TEM-1), and typed within the main cluster by both Rep-PCR and PFGE. In conclusion, K. pneumoniae ST15 containing bla (CTX-M15) and bla (SHV-28) constitutes an epidemic clone in the Copenhagen area and this clone can be rapidly recognized by semi-automated Rep-PCR.

Faunal mediated carbon export from mangroves in an arid area.

The outwelling paradigm argues that mangrove and saltmarsh wetlands export much excess production to downstream marine systems. However, outwelling is difficult to quantify and currently 40-50% of fixed carbon is unaccounted for. Some carbon is thought outwelled through mobile fauna, including fish, which visit and feed on mangrove produce during tidal inundation or early life stages before moving offshore, yet this pathway for carbon outwelling has never been quantified. We studied faunal carbon outwelling in three arid mangroves, where sharp isotopic gradients across the boundary between mangroves and down-stream systems permitted spatial differentiation of source of carbon in animal tissue. Stable isotope analysis (C, N, S) revealed 22-56% of the tissue of tidally migrating fauna was mangrove derived. Estimated consumption rates showed that 1.4% (38 kg C ha-1 yr-1) of annual mangrove litter production was directly consumed by migratory fauna, with <1% potentially exported. We predict that the amount of faunally-outwelled carbon is likely to be highly correlated with biomass of migratory fauna. While this may vary globally, the measured migratory fauna biomass in these arid mangroves was within the range of observations for mangroves across diverse biogeographic ranges and environmental settings. Hence, this study provides a generalized prediction of the relatively weak contribution of faunal migration to carbon outwelling from mangroves and the current proposition, that the unaccounted-for 40-50% of mangrove C is exported as dissolved inorganic carbon, remains plausible.

Core genome multi-locus sequence typing as an essential tool in a high-cost livestock-associated meticillin-resistant Staphylococcus aureus CC398 hospital outbreak.

BACKGROUND: Livestock-associated meticillin-resistant Staphylococcus aureus (LA-MRSA) clonal complex (CC) 398 may be transmitted and cause morbidity and mortality in hospitals. The economic cost of stopping hospital transmission of LA-MRSA CC398 is poorly described. Early detection of transmission may limit the extent of the intervention. AIM: To evaluate core genome multi-locus sequence typing (cgMLST) for detecting transmission chains and to estimate the costs for interventions to prevent further spread after discovery of hospital transmission of LA-MRSA CC398. METHODS: Five patients were involved in two episodes of transmission of LA-MRSA CC398 in a hospital. Standard interventions including MRSA screening of patients and healthcare workers were initiated. Whole genome sequences of the five isolates and 17 epidemiologically unrelated MRSA CC398 isolates from other hospitalized patients were analysed by single nucleotide polymorphism (SNP) comparisons and cgMLST. The economic costs of constraining transmission were calculated from relevant sources. FINDINGS: The five isolates suspected to be involved in hospital transmission clustered with ≤2 SNPs in the draft genome sequences with some distance to other isolates. cgMLST allocated the five isolates to the same type, which was different from all but two of the sporadic isolates. Furthermore, cgMLST separated the five transmission isolates from all other isolates. The economic costs of the outbreak interventions exceeded €11,000 per patient. CONCLUSION: LA-MRSA CC398 is transmittable in hospitals, and intervention against transmission may reach considerable costs. cgMLST is useful in surveillance of hospital transmission of LA-MRSA.

Antibody response against Mycobacterium avium complex in cystic fibrosis patients measured by a novel IgG ELISA test.

BACKGROUND: Early signs of Mycobacterium avium complex pulmonary disease can be missed in patients with cystic fibrosis due to subclinical infection or delays in mycobacterial culture. The aim of this study was to determine the diagnostic accuracy of a novel enzyme linked immunosorbent assay for immunoglobulin G against Mycobacterium avium complex, which could help stratify patients according to risk. METHODS: A retrospective cross sectional analysis of serum samples from the Copenhagen Cystic Fibrosis Center was performed. Corresponding clinical data were reviewed and patients with cystic fibrosis were assigned to one of four groups based on their mycobacterial culture results. In addition, anti-Mycobacterium avium complex immunoglobulin G levels were measured longitudinally before and after first positive culture in the period 1984-2015. RESULTS: Three-hundred and five patients with cystic fibrosis were included with a median of five nontuberculous mycobacterial cultures. Four individuals had Mycobacterium avium complex pulmonary disease at the time of cross sectional testing and their median antibody level was 22-fold higher than patients with no history of infection (1820 vs. 80 IgG units; p < 0.001). Test sensitivity was 100% (95% CI 40-100) and specificity 77% (95% CI 72-81). Longitudinal kinetics showed rising antibodies prior to first positive culture suggesting diagnostic delay. CONCLUSIONS: Antibody screening for Mycobacterium avium complex may be used as a supplement to culture. Although confirmation in a larger cohort is needed, our findings suggest that stratifying a cystic fibrosis population into high- and low-risk groups based on antibody levels may help clinicians identify patients in need of more frequent culture.

Transmission of Salmonella between wildlife and meat-production animals in Denmark.

AIMS: To investigate the transmission of Salmonella spp. between production animals (pigs and cattle) and wildlife on production animal farms in Denmark. METHODS AND RESULTS: In the winter and summer of 2001 and 2002, 3622 samples were collected from Salmonella-infected and noninfected herds of pigs and cattle and surrounding wildlife. Salmonella was detected in wildlife on farms carrying Salmonella-positive production animals and only during the periods when Salmonella was detected in the production animals. The presence of Salmonella Typhimurium in wild birds significantly correlated to their migration pattern and food preference. CONCLUSIONS: Salmonella was transmitted from infected herds of production animals (cattle and pigs) to wildlife that lived amongst or in close proximity to them. SIGNIFICANCE AND IMPACT OF THE STUDY: Salmonella in animal food products is associated with the occurrence of Salmonella in primary animal production. Strategies to control the introduction and spread of infection should include wildlife management, as the nearby wildlife may act as reservoirs for Salmonella spp. and/or may be passive carriers of the bacteria.

Shiga toxin-producing Escherichia coli: incidence and clinical features in a setting with complete screening of patients with suspected infective diarrhoea.

OBJECTIVES: Shiga toxin-producing Escherichia coli (STEC) causes diarrhoeal disease, bloody diarrhoea, and haemolytic uraemic syndrome. The aim of this study was to describe the incidence of STEC and the clinical features of STEC patients from a well-defined Danish population in which all fecal samples of patients with suspected infective gastroenteritis were analysed for STEC. METHODS: In this population-based cohort study, all stool samples referred to two clinical microbiology laboratories were screened for STEC by culture and/or PCR. Epidemiological (n=170) and clinical (n=209) characteristics were analysed using data from local and national registries. RESULTS: Overall, 75,132 samples from 30,073 patients were screened resulting in 217 unique STEC-isolates. The epidemiological analysis showed an incidence of 10.1 cases per 100,000 person-years, which was more than twofold higher than the incidence in the rest of Denmark (3.4 cases per 100,000 person-years, p <0.001). Three groups were associated with a higher incidence: age <5 years (n=28, p <0.001), age ≥65 years (n=38, p 0.045), and foreign ethnicity (n=27, p 0.003). In the clinical analysis, patients with STEC harbouring only the Shiga toxin 1 gene (stx1-only isolates) showed a lower frequency of acute (n=11, p <0.05) and bloody diarrhoea (n=5, p <0.05) and a higher frequency of gastrointestinal symptoms for ≥3 months (n=8, p <0.05) than the other STEC patients. CONCLUSIONS: We report a more than twofold higher incidence in the project area compared with the rest of Denmark, indicating that patients remain undiagnosed when selective STEC screening is used. We found an association between patients with stx1-only isolates and long-term gastrointestinal symptoms.

Selecting PCR for the Diagnosis of Intestinal Parasitosis: Choice of Targets, Evaluation of In-House Assays, and Comparison with Commercial Kits.

Microscopy of stool samples is a labour-intensive and inaccurate technique for detection of intestinal parasites causing diarrhoea and replacement by PCR is attractive. Almost all cases of diarrhoea induced by parasites over a nine-year period in our laboratory were due to Giardia lamblia, Cryptosporidium species, or Entamoeba histolytica detected by microscopy. We evaluated and selected in-house singleplex real-time PCR (RT-PCR) assays for these pathogens in 99 stool samples from patients suspected of having intestinal parasitosis tested by microscopy. The strategy included a genus-specific PCR assay for C. parvum and C. hominis, with subsequent identification by a PCR that distinguishes between the two species. G. lamblia was detected in five and C. parvum in one out of 68 microscopy-negative samples. The performance of the in-house RT-PCR assays was compared to three commercially available multiplex test (MT-PCR) kit systems in 81 stool samples, collected in 28 microscopy-positive and 27 microscopy-negative samples from individuals suspected of intestinal parasitosis and in 26 samples from individuals without suspicion of parasitic infection. The in-house assays detected parasites in more samples from patients suspected of having parasitosis than did any of the kits. We conclude that commercial kits are targeting relevant parasites, but their performance may vary.

Whole-genome sequencing for identification of the source in hospital-acquired Legionnaires' disease.

Acquisition of Legionnaires' disease is a serious complication of hospitalization. Rapid determination of whether or not the infection is caused by strains of Legionella pneumophila in the hospital environment is crucial to avoid further cases. This study investigated the use of whole-genome sequencing to identify the source of infection in hospital-acquired Legionnaires' disease. Phylogenetic analyses showed close relatedness between one patient isolate and a strain found in hospital water, confirming suspicion of nosocomial infection. It was found that whole-genome sequencing can be a useful tool in the investigation of hospital-acquired Legionnaires' disease.

Associations between adherence, depressive symptoms and health-related quality of life in young adults with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a life shortening disease, however prognosis has improved and the adult population is growing. Most adults with cystic fibrosis live independent lives and balance the demands of work and family life with a significant treatment burden. The aim of this study was to examine the relationships among treatment adherence, symptoms of depression and health-related quality of life (HRQoL) in a population of young adults with CF. METHODS: We administered three standardized questionnaires to 67 patients with CF aged 18-30 years; Morisky Medication Adherence Scale, Major Depression Inventory, and Cystic Fibrosis Questionnaire-Revised. RESULTS: There was a response rate of 77 % and a majority of the young adults (84 %) were employed or in an education program. Most participants (74 %) reported low adherence to medications. One third (32.8 %) of the participants reported symptoms of depression. HRQoL scores were especially low on Vitality and Treatment Burden, and symptoms of depression were associated with low HRQoL scores (p < 0.01) with medium to large deficits across on all HRQoL domains (Cohen's d 0.60-1.72) except for the domain treatment burden. High depression symptom scores were associated with low adherence (r = -0.412, p < 0.001). CONCLUSIONS: Despite improved physical health, many patients with CF report poor adherence, as well as impaired mental wellbeing and HRQoL. Thus, more attention to mental health issues is needed.

Erratum to: Associations between adherence, depressive symptoms and health-related quality of life in young adults with cystic fibrosis.

[This corrects the article DOI: 10.1186/s40064-016-2862-5.].

A longitudinal study of lung bacterial pathogens in patients with primary ciliary dyskinesia.

In patients with primary ciliary dyskinesia (PCD), impaired mucociliary clearance leads to an accumulation of secretions in the airways and susceptibility to repeated bacterial infections. The primary aim of this study was to investigate the bacterial flora in non-chronic and chronic infections in the lower airways of patients with PCD. We retrospectively reviewed the presence of bacteria from patients with PCD during an 11-year period and genotyped 35 Pseudomonas aeruginosa isolates from 12 patients with chronic infection using pulsed-field gel electrophoresis. We identified 5450 evaluable cultures from 107 patients with PCD (median age 17 years, range 0-74 years) (median age at diagnosis 7.8 years, range 0-63 years). Haemophilus influenzae was the most frequent microorganism. Other common pathogens were P. aeruginosa, Streptococcus pneumoniae, Moraxella catarrhalis and Staphylococcus aureus. The number of patients colonized with P. aeruginosa at least once varied from 11 to 44 patients (15-47%) annually, and 42 patients (39%) met the criteria for chronic infection at least once. Pseudomonas aeruginosa was more frequently isolated in teenagers and adults than children (p 0.02) and the prevalence was significantly lower in patients with preschool (<6 years) PCD diagnosis (p 0.04). Ten out of 12 patients (83%) were chronically infected with a unique clone-type of P. aeruginosa. No sharing of clone-types or patient-to-patient transmission was observed. In conclusion, PCD patients were infected by a unique set of bacteria acquired in an age-dependent sequence. Pseudomonas aeruginosa frequently colonizes the lower respiratory tract and the incidence of chronic infection was higher than previously reported.

Genomic lineage of Salmonella enterica serotype Gallinarum.

Forty-eight strains of Salmonella enterica serotype Gallinarum of biotypes Gallinarum and Pullorum were characterised by three chromosomally based typing methods. The patterns obtained were compared with those of strains of eight other serotypes of Salmonella of O serogroup D. The same PvuII and PstI IS200 patterns were commonly observed among strains of both biotypes and the three SmaI ribotypes of serotype Gallinarum strains differed in only one or two bands, supporting the view that members of these two biotypes are closely related. The same IS200 patterns were also commonly observed among strains of serotype Enteritidis, indicating its evolutionary relationship with serotype Gallinarum. NotI pulsed-field gel electrophoresis (PFGE) patterns divided strains into 24 types. Based on a similarity analysis, two clusters were formed. One contained the majority of biotype Gallinarum strains and two atypical strains of Pullorum; the other contained strains of biotype Pullorum and an otherwise typical strain of biotype Gallinarum. Two atypical strains of biotype Pullorum remained unclustered by PFGE analysis. The grouping of strains differed according to the typing method used, but the majority of strains within each of the biotypes Gallinarum and Pullorum were very similar by the chromosomal markers analysed.

Clonal lines of Salmonella enterica serotype Enteritidis documented by IS200-, ribo-, pulsed-field gel electrophoresis and RFLP typing.

Sixty-two selected strains of Salmonella serotype Enteritidis of 33 phage types (PTs), and one strain classified as RDNC, were characterised by four different chromosomally based typing methods to elucidate genetic relationships among strains of different phage types. Based on IS200-hybridisation patterns, two major groups, containing strains of the most commonly encountered phage types, and six minor groups (seven with the RDNC strain included) were observed. IS200 pattern was a stable epidemiological marker in strains of all phage types except PT 6a and 14b. Ribotyping separated strains of the phage types into one major and five minor groups; the pattern of the RDNC strain was not seen with other strains. More than one ribotype was observed among strains of Enteritidis PTs 6, 7, 14b and 21. By pulsed-field gel electrophoresis, strains of 21 of the 33 phage types formed one large cluster when bands > 125 kb were used as the criterion for separation. Among strains belonging to PTs 1, 6, 7 and 14b, more than one pattern was observed by this method. By probing with five random cloned fragments of the Enteritidis chromosome, strains from 27 of 31 phage types examined showed the same hybridisation pattern. With the combined use of four genotypic methods, two groups of strains, representing eight and seven of 33 Enteritidis phage types, were formed; these two groups may be considered as the main evolutionary lines of Enteritidis. Strains of the remaining phage types, and the RDNC strain, belonged to separate groups.

Immunoglobulin allotypes and IgG subclass antibody response to Aspergillus fumigatus in cystic fibrosis patients.

BACKGROUND: A majority of patients with cystic fibrosis (CF) become colonised with Aspergillus fumigatus (Af.), but only a minority develops allergic bronchopulmonary aspergillosis (ABPA). ABPA is associated with increased levels of specific immunoglobulin G (IgG) anti-Af. antibodies with a characteristic IgG subclass distribution. We examined whether this characteristic immune response was under the influence of GM and KM allotypes, which are genetic markers (antigenic determinants) on gamma- and kappa-light chains, respectively. METHODS: Sera from 233 CF patients were typed for seven GM determinants and two KM determinants. The types were correlated to IgG subclass anti-Af. antibody levels and to the presence or absence of Af. colonisation as well as ABPA. RESULTS: The IgG2 antibody level was significantly higher in heterozygous GM (1,2,17 23 5,21 and 1,3,17 23 5,21) compared to homozygous GM allotypes (p = 0.02). Patients with the same allotypes tended to have higher IgG1 (p = 0.051). In patients with ABPA, being heterozygous for G1M and G3M was linked to higher IgG4 and lower IgG3 as compared to the other genotypes. The KM markers did not influence the antibody levels. The allotype GM(3 23 5), associated with atopic bronchial asthma, tended to make a relatively larger group in ABPA patients compared to non-ABPA and patients not colonised with Af. (p = 0.09). CONCLUSIONS: An influence of the GM allotypes on the immune response to Af. and on the development of ABPA in patients with CF is suggested.