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1. Clinical and laboratory characteristics of patients with symptomatic secondary immunodeficiency following the treatment of haematological malignancies

Author

Adrian M. Shields, Sian E. Faustini, Siobhan Young, Sarah Terjesen, Nicholas I. McCarthy, Rachel L. Anderson, Mark T. Drayson, and Alex G. Richter

Subjects
haematological malignancy, immunoglobulin replacement, secondary immunodeficiency, vaccination, Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Abstract Secondary immunodeficiency (SID), manifesting as increased susceptibility to infection, is an emergent clinical problem in haematoncology. Management of SID includes vaccination, prophylactic antibiotics (pAbx) and immunoglobulin replacement therapy (IgRT). We report clinical and laboratory parameters of 75 individuals, treated for haematological malignancy, who were referred for immunological assessment due to recurrent infections. Forty‐five were managed with pAbx while thirty required IgRT after failing to improve on pAbx. Individuals requiring IgRT had significantly more bacterial, viral and fungal infections resulting in hospitalization at least 5 years after their original haemato‐oncological diagnosis. Following immunological assessment and intervention, a 4.39‐fold reduction in the frequency of hospital admissions to treat infection was observed in the IgRT cohort and a 2.30‐fold reduction in the pAbx cohort. Significant reductions in outpatient antibiotic use were also observed in both cohorts following immunology input. Patients requiring IgRT were more hypogammaglobulinaemic and had lower titres of pathogen‐specific antibodies and smaller memory B cell populations than those requiring pAbx. Test vaccination with pneumococcal conjugate vaccine discriminated poorly between the two groups. Patients requiring IgRT could be distinguished by combining wider pathogen‐specific serology with a frequency of hospital admissions for infection. If validated in larger cohorts, this approach may circumvent the need for test vaccination and enhance patient selection for IgRT.

Published
2023
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2. Antibodies to gp210 and understanding risk in patients with primary biliary cholangitis

Author

Hannah Norman, Kenneth Chung, Bettina E. Hansen, Emily Russell, Olivia Serevina, Bridget Gunson, Palak J. Trivedi, Matthew Davidson, Alex G. Richter, Debashis Haldar, Ashnila Janmohamed, Gideon M. Hirschfield, Kashif Qamar, and Tim Plant

Subjects
medicine.medical_specialty, Cirrhosis, Anti-nuclear antibody, medicine.medical_treatment, Liver transplantation, Gastroenterology, Serology, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Cholestasis, Internal medicine, medicine, Humans, Autoantibodies, Glycoproteins, Retrospective Studies, Hepatology, Liver Cirrhosis, Biliary, business.industry, Ursodeoxycholic Acid, medicine.disease, Ursodeoxycholic acid, Transplantation, Antibodies, Antinuclear, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, business, medicine.drug
Abstract

BACKGROUND AND AIMS A variety of auto-antibody assays are available as part of the clinical care of patients with liver disease. We sought to better understand the clinical utility of immune serological testing in patients with primary biliary cholangitis (PBC). METHODS We retrospectively analysed data from 2846 patients investigated for liver disease at a UK liver centre between 2001 and 2017. A total of 499 patients with PBC were identified. Immune serology results were examined for their diagnostic utility and prognostic significance to predict transplant-free survival. RESULTS Antimitochondrial antibodies (AMAs) were specific (94.5%) and sensitive (85.6%) for PBC; antinuclear antibodies (ANAs) against glycoprotein 210 (gp210) and sp100 were specific (>98%) but not sensitive (

Published
2021

3. The prevalence and significance of monoclonal gammopathy of undetermined significance in acute medical admissions

Author

Alex G. Richter, Vinay Reddy-Kolanu, Elizabeth Sapey, Catherine Atkin, and Mark T. Drayson

Subjects
Adult, Male, Immunofixation, Emergency Medical Services, medicine.medical_specialty, Adolescent, Population, Monoclonal Gammopathy of Undetermined Significance, 03 medical and health sciences, Patient Admission, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, Internal medicine, Prevalence, medicine, Humans, education, Multiple myeloma, Aged, Aged, 80 and over, education.field_of_study, biology, medicine.diagnostic_test, business.industry, Age Factors, Hematology, Middle Aged, medicine.disease, United Kingdom, 030220 oncology & carcinogenesis, Heart failure, Serum protein electrophoresis, biology.protein, Female, Abnormal results, Multiple Myeloma, business, Monoclonal gammopathy of undetermined significance, 030215 immunology, Kidney disease
Abstract

Monoclonal gammopathy of undetermined significance (MGUS) affects 3·2% of adults aged >50 years. MGUS carries a life-long risk of progression to multiple myeloma and causes complications including infection and renal impairment; common causes of hospital admission. This study aimed to assess MGUS prevalence in emergency medical hospital admissions. Patients were recruited from unselected emergency medical admissions in a hospital in the United Kingdom. Serum protein electrophoresis was performed, with immunofixation of abnormal results. Reason for admission and routine test results were recorded. After education about MGUS and myeloma, patients chose whether they wished to be informed of new diagnoses. A total of 660 patients were tested and 35 had a paraprotein suggestive of MGUS. The overall rate of MGUS was 5·3%. MGUS prevalence in those aged >50 years was 6·94%, higher than the previously published rate of 3·2% (P < 0·0005). There were higher rates in those with chronic kidney disease (13·75% vs. 4·14%, P = 0·002), heart failure (14% vs. 4·59%, P = 0·012), anaemia (8·96% vs. 3·41%, P = 0·003) or leucocytosis (9·33% vs. 3·04%, P = 0·002). In all, 96% of patients wished to be informed of their screening results. The prevalence of MGUS in emergency hospital admissions is higher than expected based on previous population-based rates. This may suggest a selected population for screening.

Published
2020

4. Author response for 'SARS‐CoV‐2‐specific IgG1/IgG3 but not IgM in children with Pediatric Inflammatory Multi‐System Syndrome'

Author

Eslam Al-Abadi, Deepthi Jyothish, Sian E Faustini, Eleni Syrimi, Joel D. Allen, Mahboob Salim, Marisol Perez-Toledo, Alex G. Richter, Steven B. Welch, Scott Hackett, Benjamin E. Willcox, Ashish Chikermane, Hari Krishnan Kanthimathinathan, Mark T. Drayson, Kavitha Masilamani, Tonny Veenith, Barnaby R. Scholefield, Max Crispinl, Margaret Goodall, Edith Marcial-Juarez, Carrie R. Willcox, Yasunori Watanabe, Adrian M Shields, David C. Wraith, Sian E Jossi, and Adam F. Cunningham

Subjects
business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology, Medicine, business
Published
2021

5. The United Kingdom Primary Immune Deficiency (UKPID) registry 2012 to 2017

Author

C. Bangs, Smita Y. Patel, Austen Worth, V. Pavaladurai, Alex G. Richter, Matthew Buckland, Aarnoud Huissoon, H. Alachkar, David Sanchez-Migallon Guzman, Grant Hayman, C. Waruiru, Hilary Longhurst, Andrew R. Gennery, Cathal Laurence Steele, J. Bernatonienne, H. Bourne, Patrick F.K. Yong, M. Thomas, Sinisa Savic, Peter D. Arkwright, Mark Gompels, B. Shillitoe, Dinakantha S. Kumararatne, Malini Bhole, Tomaz Garcez, Stephen Jolles, Helen Baxendale, Sadia Noorani, Richard Herriot, C. Chopra, D. M. Edgar, Peter Kelleher, and Mary Slatter

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Immunology, Prevalence, CLINICAL-DIAGNOSIS, 03 medical and health sciences, autoinflammatory disease, Humans, Immunology and Allergy, Medicine, Registries, Autoinflammatory disease, human, Science & Technology, business.industry, Incidence (epidemiology), PRIMARY IMMUNODEFICIENCIES, autoimmunity, Immunologic Deficiency Syndromes, RECOGNITION, RESEARCH DATABASE, Original Articles, medicine.disease, United Kingdom, Transplantation, immunodeficiency diseases, 030104 developmental biology, Treatment modality, 1107 Immunology, Clinical diagnosis, Family medicine, Epidemiological Monitoring, PRIMARY ANTIBODY DEFICIENCIES, Primary immunodeficiency, Female, Database research, business, Life Sciences & Biomedicine, INTERNET-BASED PATIENT, transplantation
Abstract

Summary This is the second report of the United Kingdom Primary Immunodeficiency (UKPID) registry. The registry will be a decade old in 2018 and, as of August 2017, had recruited 4758 patients encompassing 97% of immunology centres within the United Kingdom. This represents a doubling of recruitment into the registry since we reported on 2229 patients included in our first report of 2013. Minimum PID prevalence in the United Kingdom is currently 5·90/100 000 and an average incidence of PID between 1980 and 2000 of 7·6 cases per 100 000 UK live births. Data are presented on the frequency of diseases recorded, disease prevalence, diagnostic delay and treatment modality, including haematopoietic stem cell transplantation (HSCT) and gene therapy. The registry provides valuable information to clinicians, researchers, service commissioners and industry alike on PID within the United Kingdom, which may not otherwise be available without the existence of a well-established registry.

Published
2018

6. Poor functional antibody responses are present in nearly all patients with chronic lymphocytic leukaemia, irrespective of total IgG concentration, and are associated with increased risk of infection

Author

Mark T. Drayson, Guy Pratt, Peter Hazlewood, James A. H. Murray, Helen Parry, Jane Birtwistle, Nyasha Mudongo, Tina McSkeane, Alison Whitelegg, Paul Moss, Chris Hudson, and Alex G. Richter

Subjects
Male, Infections, Antibodies, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Medicine, Humans, 030212 general & internal medicine, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Immunodeficiency, Aged, Aged, 80 and over, Lymphocytic leukaemia, business.industry, Hematology, medicine.disease, Virology, Leukemia, Lymphocytic, Chronic, B-Cell, infection, Increased risk, Antibody response, Cross-Sectional Studies, 030220 oncology & carcinogenesis, Immunoglobulin G, Immunology, Antibody Formation, Female, business, immunodeficiency, chronic lymphocytic leukaemia

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