IgA-producing plasma cells appear to be derived from GALT germinal centers in humans. B-cell receptor engagement promotes formation of germinal centers of GALT, with no more evidence for innate immune receptor activation in the mucosa than nonintestinal immune compartments. Germinal centers in GALT should be targets of mucosal vaccinations because they are the source of human intestinal IgA response.
Objectives
The association of B cell targeted therapies with development of hypogammaglobulinaemia and infection is increasingly recognized. Our aim was to develop consensus recommendations for immunoglobulin replacement therapy for management of hypogammaglobulinaemia following B cell targeted therapies in autoimmune rheumatic diseases.
Methods
A modified Delphi exercise involved a 17-member Taskforce committee, consisting of immunologists, rheumatologists, nephrologists, haematologists, a gastroenterologist, an immunology specialist nurse and a patient representative. The first round identified the most pertinent topics to address in the recommendations. A search string was agreed upon for the identification of publications in PubMed focusing on these areas, for a systematic literature review. Original data was presented from this review to the Taskforce committee. Recommendations from the British Society for Rheumatology, the UK Department of Health, EULAR, the ACR, and the American Academy of Allergy, Asthma, and Immunology were also reviewed. The evidence was discussed in a face-to-face meeting to formulate recommendation statements. The levels of evidence and statements were graded according to Scottish Intercollegiate Guidelines Network methodology.
Results
Three overarching principles, eight recommendation statements and a research agenda were formulated. The Taskforce committee voted on these statements, achieving 82–100% agreement for each recommendation. The strength of the recommendations was restricted by the low quality of the available evidence, with no randomized controlled trial data. The recommendations cover risk factors, monitoring, referral for hypogammaglobulinaemia; indications, dosage and discontinuation of immunoglobulin replacement therapy.
Conclusion
These are the first recommendations specifically formulated for B cell targeted therapies related to hypogammaglobulinaemia in autoimmune rheumatic diseases. The recommendations are to aid health-care professionals with clinical decision making for patients with hypogammaglobulinaemia.
The United Kingdom (UK) government set a target of offering all adults 2 doses of vaccination against the novel pandemic coronavirus (SARS-CoV-2, COVID-19) by 19th July 2021. The success of this national immunisation programme is dependent on both patient engagement and efficacy of the host immune response. Information on these factors remains limited in the setting of primary and secondary immunodeficiency [1,2]. Here we report on vaccine uptake and responses in adults under care of the Immunodeficiency Centre for Wales (ICW) revealing heterogenous anti-SARS-CoV-2 spike IgG responses across common diagnostic immunodeficiency sub-groups. With continued community circulation of SARS-CoV-2 and rising case rates, serosurveillance of vulnerable patient groups facilitates prompt and rational access to precision therapies such as monoclonal anti-SARS-CoV-2 antibodies.
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