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Article ; Online: A flow cytometry-based assay to determine the ability of anti-Streptococcus pyogenes antibodies to mediate monocytic phagocytosis in human sera.

Boero, Elena / Carducci, Martina / Keeley, Alexander J / Berlanda Scorza, Francesco / Iturriza-Gómara, Miren / Moriel, Danilo Gomes / Rossi, Omar

Journal of immunological methods

2024 Volume 528, Page(s) 113652

Abstract: Streptococcus pyogenes, commonly referred to as Group A Streptococcus (Strep A), causes a spectrum of diseases, with the potential to progress into life-threatening illnesses and autoimmune complications. The escalating threat of antimicrobial resistance, ...

Abstract	Streptococcus pyogenes, commonly referred to as Group A Streptococcus (Strep A), causes a spectrum of diseases, with the potential to progress into life-threatening illnesses and autoimmune complications. The escalating threat of antimicrobial resistance, stemming from the prevalent reliance on antibiotic therapies to manage Strep A infections, underscores the critical need for the development of disease control strategies centred around vaccination. Phagocytes play a critical role in controlling Strep A infections, and phagocytosis-replicating assays are essential for vaccine development. Traditionally, such assays have employed whole-blood killing or opsonophagocytic methods using HL-60 cells as neutrophil surrogates. However, assays mimicking Fcγ receptors- phagocytosis in clinical contexts are lacking. Therefore, here we introduce a flow cytometry-based method employing undifferentiated THP-1 cells as monocytic/macrophage model to swiftly evaluate the ability of human sera to induce phagocytosis of Strep A. We extensively characterize the assay's precision, linearity, and quantification limit, ensuring robustness. By testing human pooled serum, the assay proved to be suitable for the comparison of human sera's phagocytic capability against Strep A. This method offers a valuable complementary assay for clinical studies, addressing the gap in assessing FcγR-mediated phagocytosis. By facilitating efficient evaluation of Strep A -phagocyte interactions, it may contribute to elucidating the mechanisms required for the prevention of infections and inform the development of future vaccines and therapeutic advancements against Strep A infections.
MeSH term(s)	Humans ; Flow Cytometry/methods ; Phagocytosis ; Antibodies, Bacterial ; Neutrophils ; Streptococcus pyogenes ; Streptococcal Infections
Chemical Substances	Antibodies, Bacterial
Language	English
Publishing date	2024-03-06
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	120142-6
ISSN	1872-7905 ; 0022-1759
ISSN (online)	1872-7905
ISSN	0022-1759
DOI	10.1016/j.jim.2024.113652
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Zs.A 795: Show issues

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Article ; Online: Natural history and impact of irritable bowel syndrome-type symptoms in inflammatory bowel disease during 12 months of longitudinal follow-up.

Barberio, Brigida / Fairbrass, Keeley M / Gracie, David J / Ford, Alexander C

Neurogastroenterology and motility

2023 Volume 36, Issue 2, Page(s) e14713

Abstract: Background: Little is known about the natural history and impact of irritable bowel syndrome (IBS)-type symptoms on psychological health and quality of life in inflammatory bowel disease (IBD). We aimed to address this in a 12-month longitudinal follow- ... ...

Abstract	Background: Little is known about the natural history and impact of irritable bowel syndrome (IBS)-type symptoms on psychological health and quality of life in inflammatory bowel disease (IBD). We aimed to address this in a 12-month longitudinal follow-up study of secondary care patients. Methods: We collected demographic, Rome III IBS-type symptom, psychological, and quality of life data, with questionnaires at 3-month intervals, over 12 months of follow-up in patients with IBD in clinical remission at baseline. We assessed the natural history of Rome III IBS-type symptoms over the 12 months of the study and compared psychological and quality of life data between those reporting Rome III IBS-type symptoms at each of the points of follow-up with those not reporting such symptoms. Key results: Among 206 patients with IBD in clinical remission at baseline (104 [50.5%] women, mean age 56.9 years [range 18-83 years], 79 [38.3%] Crohn's disease), 33 (16.0%) reported Rome III IBS-type symptoms at baseline and 72 (35.0%) reported Rome III IBS-type symptoms at one or more time points. Among the 33 patients with Rome III IBS-type symptoms at baseline, symptoms resolved in 6 (18.2%) patients, were present throughout in 6 (18.2%) patients, and fluctuated in the remaining 21 (63.6%) patients. Among the 39 patients with new onset of Rome III IBS-type symptoms after baseline, 24 (65.1%) had symptoms at one point in time only, 10 (25.6%) at two points, four (10.3%) at three points, and one (2.6%) at four points. At each point in time, reporting IBS-type symptoms was associated with significantly higher anxiety, depression, or somatoform symptom-reporting scores, and/or lower quality of life scores. Conclusions & inferences: In this 12-month follow-up study, one-third of patients with IBD reported presence of Rome III IBS-type symptoms at any point in time. Reporting such symptoms was associated with significant impacts on psychological health and/or quality of life.
MeSH term(s)	Humans ; Female ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Male ; Irritable Bowel Syndrome/diagnosis ; Follow-Up Studies ; Quality of Life ; Inflammatory Bowel Diseases/psychology ; Crohn Disease/complications ; Surveys and Questionnaires
Language	English
Publishing date	2023-11-22
Publishing country	England
Document type	Journal Article
ZDB-ID	1186328-6
ISSN	1365-2982 ; 1350-1925
ISSN (online)	1365-2982
ISSN	1350-1925
DOI	10.1111/nmo.14713
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Article ; Online: Healthy Mind, Healthy Body: Chronic Depression May Predate the Development of Inflammatory Bowel Disease by up to 9 Years.

Fairbrass, Keeley M / Gracie, David J / Ford, Alexander C

Gastroenterology

2021 Volume 160, Issue 7, Page(s) 2611–2613

Language	English
Publishing date	2021-02-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	80112-4
ISSN	1528-0012 ; 0016-5085
ISSN (online)	1528-0012
ISSN	0016-5085
DOI	10.1053/j.gastro.2021.02.004
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Article ; Online: Editorial: natural history of irritable bowel syndrome in inflammatory bowel disease-authors' reply.

Fairbrass, Keeley M / Hamlin, P John / Gracie, David J / Ford, Alexander C

Alimentary pharmacology & therapeutics

2022 Volume 56, Issue 8, Page(s) 1302–1303

MeSH term(s)	Chronic Disease ; Diarrhea ; Humans ; Inflammatory Bowel Diseases ; Irritable Bowel Syndrome
Language	English
Publishing date	2022-09-24
Publishing country	England
Document type	Editorial ; Comment
ZDB-ID	639012-2
ISSN	1365-2036 ; 0269-2813 ; 0953-0673
ISSN (online)	1365-2036
ISSN	0269-2813 ; 0953-0673
DOI	10.1111/apt.17215
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Article ; Online: Relative Contribution of Disease Activity and Psychological Health to Prognosis of Inflammatory Bowel Disease During 6.5 Years of Longitudinal Follow-Up.

Fairbrass, Keeley M / Gracie, David J / Ford, Alexander C

Gastroenterology

2022 Volume 163, Issue 1, Page(s) 190–203.e5

Abstract: Background & aims: Symptoms of common mental disorders, such as anxiety or depression, are common in inflammatory bowel disease (IBD) and may affect prognosis. However, unlike clinical or biochemical markers of disease activity, psychological health is ... ...

Abstract	Background & aims: Symptoms of common mental disorders, such as anxiety or depression, are common in inflammatory bowel disease (IBD) and may affect prognosis. However, unlike clinical or biochemical markers of disease activity, psychological health is not a recommended therapeutic target. We assessed relative contribution of poor psychological health and clinical or biochemical activity to prognosis. Methods: Demographic features, IBD subtype, treatments, and anxiety and depression scores were recorded at baseline for 760 adults, with clinical activity determined using validated scoring systems. Fecal calprotectin was analyzed in 379 (49.9%) patients (≥250 μg/g used to define biochemical activity). Glucocorticosteroid prescription or flare, escalation, hospitalization, intestinal resection, or death were assessed during 6.5 years of follow-up. Occurrence was compared using multivariate Cox regression across 4 patient groups according to presence of disease remission or activity, with or without symptoms of a common mental disorder, at baseline. Results: In total, 718 (94.5%) participants provided data. Compared with clinical remission without symptoms of a common mental disorder at baseline, need for glucocorticosteroid prescription or flare (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.58-3.54), escalation (HR, 1.65; 95% CI, 1.14--2.40), and death (HR, 4.99; 95% CI, 1.80-13.88) were significantly higher in those with clinical activity and symptoms of a common mental disorder. Rates in those with clinical remission and symptoms of a common mental disorder at baseline or those with clinical activity without symptoms of a common mental disorder were not significantly higher. Similarly, with biochemical activity and symptoms of a common mental disorder, rates of glucocorticosteroid prescription or flare (HR, 2.48; 95% CI, 1.38-4.46), escalation (HR, 2.97; 95% CI, 1.74-5.06), hospitalization (HR, 3.10; 95% CI, 1.43-6.68), and death (HR, 6.26; 95% CI, 2.23-17.56) were significantly higher. Conclusions: Psychological factors are important determinants of poor prognostic outcomes in IBD and should be considered as a therapeutic target.
MeSH term(s)	Adult ; Anxiety/epidemiology ; Chronic Disease ; Follow-Up Studies ; Humans ; Inflammatory Bowel Diseases/diagnosis ; Inflammatory Bowel Diseases/drug therapy ; Leukocyte L1 Antigen Complex ; Prognosis
Chemical Substances	Leukocyte L1 Antigen Complex
Language	English
Publishing date	2022-03-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80112-4
ISSN	1528-0012 ; 0016-5085
ISSN (online)	1528-0012
ISSN	0016-5085
DOI	10.1053/j.gastro.2022.03.014
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Article ; Online: Development and characterization of a hemolysis inhibition assay to determine functionality of anti-Streptolysin O antibodies in human sera.

Carducci, Martina / Whitcombe, Alana / Rovetini, Luca / Massai, Luisa / Keeley, Alexander J / de Silva, Thushan I / Bennett, Julie / Berlanda Scorza, Francesco / Iturriza, Miren / Moreland, Nicole J / Moriel, Danilo G / Rossi, Omar

Journal of immunological methods

2024 Volume 526, Page(s) 113618

Abstract: The high burden of disease and the long-lasting sequelae following Streptococcus pyogenes (Strep A) infections make the development of an effective vaccine a global health priority. Streptolysin O (SLO), is a key toxin in the complex pathogenesis of ... ...

Abstract	The high burden of disease and the long-lasting sequelae following Streptococcus pyogenes (Strep A) infections make the development of an effective vaccine a global health priority. Streptolysin O (SLO), is a key toxin in the complex pathogenesis of Strep A infection. Antibodies are elicited against SLO after natural exposure and represent a key target for vaccine-induced immunity. Here we present the setup and characterization of a hemolysis assay to measure functionality of anti-SLO antibodies in human sera. Assay specificity, precision, linearity, reproducibility, and repeatability were determined. The assay was demonstrated to be highly sensitive, specific, reproducible, linear and performed well in assessing functionality of anti-SLO antibodies induced by exposed individuals. Moreover, different sources of critical reagents, in particular red- blood cells, have been compared and had minimal impact on assay performance. The assay presented here has throughput suitable for evaluating sera in vaccine clinical trials and sero-epidemiological studies to gain further insights into the functionality of infection- and vaccine-induced antibodies.
MeSH term(s)	Humans ; Streptococcus pyogenes ; Hemolysis ; Reproducibility of Results ; Streptolysins/pharmacology ; Bacterial Proteins ; Antibodies/pharmacology ; Streptococcal Infections/diagnosis ; Vaccines
Chemical Substances	Streptolysins ; Bacterial Proteins ; Antibodies ; Vaccines
Language	English
Publishing date	2024-01-16
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120142-6
ISSN	1872-7905 ; 0022-1759
ISSN (online)	1872-7905
ISSN	0022-1759
DOI	10.1016/j.jim.2024.113618
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Zs.A 795: Show issues

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Article ; Online: Asymptomatic SARS-CoV-2 infection: the tip or the iceberg?

Keeley, Alexander J / Evans, Cariad M / de Silva, Thushan I

Thorax

2020 Volume 75, Issue 8, Page(s) 621–622

MeSH term(s)	Betacoronavirus ; COVID-19 ; Coronavirus Infections ; Humans ; Pandemics ; Pneumonia, Viral ; SARS Virus ; SARS-CoV-2 ; Washington
Keywords	covid19
Language	English
Publishing date	2020-06-24
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	204353-1
ISSN	1468-3296 ; 0040-6376
ISSN (online)	1468-3296
ISSN	0040-6376
DOI	10.1136/thoraxjnl-2020-215337
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Article ; Online: Novel symptom clusters predict disease impact and healthcare utilisation in inflammatory bowel disease: Prospective longitudinal follow-up study.

Riggott, Christy / Fairbrass, Keeley M / Black, Christopher J / Gracie, David J / Ford, Alexander C

Alimentary pharmacology & therapeutics

2023 Volume 58, Issue 11-12, Page(s) 1163–1174

Abstract: Background: Predicting adverse disease outcomes and high-volume users of healthcare amongst patients with inflammatory bowel disease (IBD) is difficult.: Aims: The aim of this study is to use latent class analysis to create novel clusters of patients ...

Abstract	Background: Predicting adverse disease outcomes and high-volume users of healthcare amongst patients with inflammatory bowel disease (IBD) is difficult. Aims: The aim of this study is to use latent class analysis to create novel clusters of patients and to assess whether these predict outcomes during 6.5 years of longitudinal follow-up. Methods: Baseline demographic features, disease activity indices, anxiety, depression, and somatoform symptom-reporting scores were recorded for 692 adults. Faecal calprotectin (FC) was analysed at baseline in 348 (50.3%) patients (<250 mcg/g defined biochemical remission). Using baseline gastrointestinal and psychological symptoms, latent class analysis identified specific patient clusters. Rates of glucocorticosteroid prescription or flare, escalation, hospitalisation, or intestinal resection were compared between clusters using multivariate Cox regression. Results: A three-cluster model was the optimum solution; 132 (19.1%) patients had below-average gastrointestinal and psychological symptoms (cluster 1), 352 (50.9%) had average levels of gastrointestinal and psychological symptoms (cluster 2), and 208 (30.1%) had the highest levels of both gastrointestinal and psychological symptoms (cluster 3). Compared with cluster 1, cluster 3 had significantly increased risk of flare or glucocorticosteroid prescription (hazard ratio (HR): 2.13; 95% confidence interval (CI): 1.46-3.10), escalation (HR: 1.92; 95% CI: 1.34-2.76), a composite of escalation, hospitalisation, or intestinal resection (HR: 2.05; 95% CI: 1.45-2.88), or any of the endpoints of interest (HR: 2.06; 95% CI: 1.45-2.93). Healthcare utilisation was highest in cluster 3. Conclusions: Novel model-based clusters identify patients with IBD at higher risk of adverse disease outcomes who are high-volume users of healthcare.
MeSH term(s)	Adult ; Humans ; Follow-Up Studies ; Syndrome ; Prospective Studies ; Inflammatory Bowel Diseases/diagnosis ; Inflammatory Bowel Diseases/drug therapy ; Patient Acceptance of Health Care
Language	English
Publishing date	2023-10-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639012-2
ISSN	1365-2036 ; 0269-2813 ; 0953-0673
ISSN (online)	1365-2036
ISSN	0269-2813 ; 0953-0673
DOI	10.1111/apt.17735
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Article ; Online: Health-seeking behaviour and beliefs around sore throat in The Gambia: A qualitative study.

Suau Sans, Maria / Manneh, Muhammed / Ceesay, Isatou / Bittaye, Amat / de Crombrugghe, Gabrielle / Keeley, Alexander J / de Silva, Thushan I / Palmer, Jennifer / Armitage, Edwin P / Marks, Michael

PLOS global public health

2024 Volume 4, Issue 3, Page(s) e0002257

Abstract: Group A Streptococcus (Strep A) bacteria causes a broad spectrum of diseases. The most common manifestations of Strep A infection are sore throat and pus-producing skin infections such as impetigo. Complications of Strep A infection can lead to ... ...

Abstract	Group A Streptococcus (Strep A) bacteria causes a broad spectrum of diseases. The most common manifestations of Strep A infection are sore throat and pus-producing skin infections such as impetigo. Complications of Strep A infection can lead to inflammation in the bones, muscles, joints, and internal organs causing acute rheumatic fever and rheumatic heart disease (RHD). In The Gambia, the RHD burden is thought to be very high. However, epidemiological data is minimal, and Strep A control programmes do not exist. This study aimed to explore common beliefs and practices related to sore throats among primary caregivers of children, and healthcare providers in a community with a high Strep A disease burden. Four informal conversations with providers and fifteen semi-structured interviews with caregivers were conducted in the peri-urban area of Sukuta, The Gambia. Sampling was purposive and gradual, beginning from households identified to have recently experienced sore throat through a parallel cohort study. Themes explored in qualitative analysis included: sore throat causal attributions and diagnoses, care practises, health-seeking behaviour, and perceived barriers to using the biomedical sector. We found that sore throats were typically perceived to affect one child in a family, disproportionately or exclusively. Sore throats were rarely perceived as life-threatening, and awareness of links between sore throat and ARF or RHD was not reported among caregivers or providers in this study population. Most cases of sore throat were initially managed at home using traditional medicine which delayed resort to antibiotics, though in two instances of severe pain with the presence of exudate, fear that the child's life was at risk prompted care-seeking through the formal health system. Our findings can inform the development of tailored strategies to increase community knowledge of the potential long-term consequences of sore throats and appropriate care-seeking, alongside improvements in the health system, to prevent Strep A sequelae effectively.
Language	English
Publishing date	2024-03-25
Publishing country	United States
Document type	Journal Article
ISSN	2767-3375
ISSN (online)	2767-3375
DOI	10.1371/journal.pgph.0002257
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Article ; Online: Impact of Opioid Use on the Natural History of Inflammatory Bowel Disease: Prospective Longitudinal Follow-up Study.

Riggott, Christy / Fairbrass, Keeley M / Selinger, Christian P / Gracie, David J / Ford, Alexander C

Inflammatory bowel diseases

2023

Abstract: Background: Opioid use is increasingly prevalent amongst patients with inflammatory bowel disease (IBD), but whether opioids have deleterious effects, or their use is merely linked with more severe disease, is unclear. We conducted a longitudinal follow- ...

Abstract	Background: Opioid use is increasingly prevalent amongst patients with inflammatory bowel disease (IBD), but whether opioids have deleterious effects, or their use is merely linked with more severe disease, is unclear. We conducted a longitudinal follow-up study examining this issue. Methods: Data on demographics, gastrointestinal and psychological symptoms, quality of life, and opioid use were recorded at baseline. Data on healthcare use and adverse disease outcomes were obtained from a review of electronic medical records at 12 months. Characteristics at baseline of those using opioids and those who were not were compared, in addition to occurrence of flare, prescription of glucocorticosteroids, treatment escalation, hospitalization, or intestinal resection during the 12 months of follow-up. Results: Of 1029 eligible participants, 116 (11.3%) were taking opioids at baseline. Medium (odds ratio [OR], 4.67; 95% confidence interval [CI], 1.61-13.6) or high (OR, 8.03; 95% CI, 2.21-29.2) levels of somatoform symptom-reporting and use of antidepressants (OR, 2.54; 95% CI, 1.34-4.84) or glucocorticosteroids (OR, 6.63; 95% CI, 2.26-19.5; P < .01 for all analyses) were independently associated with opioid use. Following multivariate analysis, opioid users were significantly more likely to undergo intestinal resection (hazard ratio, 7.09; 95% CI, 1.63 to 30.9; P = .009), particularly when codeine or dihydrocodeine were excluded (hazard ratio, 42.9; 95% CI, 3.36 to 548; P = .004). Conclusions: Opioid use in IBD is associated with psychological comorbidity and increased risk of intestinal resection, particularly in stronger formulations. Future studies should stratify the risk of individual opioids, so that robust prescribing algorithms can be developed and assess whether addressing psychological factors in routine IBD care could be an effective opioid avoidance strategy.
Language	English
Publishing date	2023-10-31
Publishing country	England
Document type	Journal Article
ZDB-ID	1340971-2
ISSN	1536-4844 ; 1078-0998
ISSN (online)	1536-4844
ISSN	1078-0998
DOI	10.1093/ibd/izad256
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