Background: Common variable immunodeficiency (CVID) is an inborn error of immunity characterized by disturbed immunoglobulin production. Despite of the terrain with severe antibody deficiency, autoantibody-mediated autoimmune phenomena belong to the most frequent autoimmune manifestation. However, many unresolved issues such as prevalence, clinical relevance and origin of autoantibodies detected in CVID patients receiving immunoglobulin replacement therapy (IRT) make the diagnostics of autoimmune complications difficult. Methods: A prospective observational study evaluating the spectrum of 38 different autoantibodies in 38 CVID patients receiving IRT, and in the immunoglobulin solutions used for IRT. Results: The study reveals a high prevalence of anti-GAD (55.3%) and anti-TPO (68.4%) autoantibodes in the cohort of 38 CVID patients on regular IRT. However, the titers of anti-GAD (3.22 vs. 22 kU/L, p≤0.0001) and anti-TPO (109.7 vs. 713 kU/L, p≤0.0001) were significantly lower compared to the newly diagnosed T1D and AIT patients. Moreover, none of the CVID patients with detectable antibodies manifested with T1D and only three patients became suspected of having AIT. A high quantity of anti-GAD (3.24-24.48 kU/L) and anti-TPO (123.6-156.55 kU/L) autoantibodies was found in immunoglobulin solutions for IRT. Conclusions: The study finds a very high prevalence of anti-GAD and anti-TPO autoantibodies in CVID patients receiving regular IRT. Nevertheless, the presence of anti-GAD and anti-TPO is not associated with the manifestation of the respective autoimmune disease. As the high titers of both anti-GAD and anti-TPO were also found in the therapeutics used for IRT, we suggest that the therapeutic immunoglobulins are the source of this false positivity.

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Background: Common variable immunodeficiency (CVID) is characterized by an impaired post-vaccination response, high susceptibility to respiratory tract infections, and a broad spectrum of non-infectious complications. Thus, patients with CVID are at high risk of coronavirus disease 2019 (COVID-19), and vaccination’s role in prevention is questionable. The main aim of this study was to evaluate the clinical outcomes, safety, and dynamics of humoral and T-cell immune responses induced by the mRNA vaccine BNT162b2 in CVID. Methods: This prospective observational cohort study focused on the clinical outcomes (proportion of infected patients, disease severity), safety (adverse-event incidence, laboratory-parameter changes), and dynamics of humoral (specific post-vaccination and virus-neutralizing-antibody assessment) and T-cell immune responses (anti-SARS-CoV-2 specific T-cell detection) in 21 patients with CVID after a two-dose administration of BNT162b2. The patients were followed for 6 months. Results: Humoral response was observed in 52% (11/21) of patients at month 1 post-vaccination but continuously decreased to 33.3% (5/15) at month 6. Nevertheless, they had a remarkably lower anti-SARS-CoV-2 neutralizing antibody titer than healthy controls. The T-cell response was measurable in 33% (6/17) of patients with CVID at month 1, and it persisted for the study period. Mild infection occurred in three patients (14.3%) within the follow-up period. The vaccine also exhibited a favorable safety profile. Conclusions: The BNT162b2 vaccine elicited a measurable antibody response in a high proportion of patients, but it was limited by low titer of the virus-neutralizing antibodies and rapid waning of anti-RBD SARS-CoV-2 specific antibodies. T-cell response was detected in one-third of the patients and remained stable within the follow-up period. Vaccination has favorable safety and clinical-related outcomes in preventing severe COVID-19.

Medical Algorithm: Diagnosis and Managemen of Humoral ImmunodeficienciesAnna Šedivá1, Tomáš Milota1, Jiří Litzman2, Isabella Quinti3, ESID Clinical Working Party, EAACI Primary Immunodeficiency Working Group, Stephen Jolles4Department of Immunology, 2nd Faculty of Medicine Charles University, V Uvalu, University Hospital in Motol, Prague, Czech RepublicFaculty of Medicine, Masaryk University Brno, Czech Republic; Department of Clinical Immunology and Allergology, St Anne´s University Hospital, Brno, Czech RepublicDepartment of Molecular Medicine, Sapienza University of Rome, Rome, ItalyImmunodeficiency Centre for Wales, University Hospital of Wales, Cardiff, UKFor ESID Clinical Working Party:Isabelle Meyts, Department of Pediatrics, Leuven University Hospitals, Leuven, BelgiumSiobhan Burns, Institute of Immunity and Transplantation, University College London, London, United Kingdom; Department of Immunology, Royal Free London NHS Foundation Trust, London, United KingdomAuthor´s contributions:AS prepared the concept and wrote the manuscript, TM edited Figures and wrote the manuscript, JL designed Figures and revised manuscript, IQ designed Figures and revised the manuscript, IM revised manuscript, SB revised manuscript, ST edited Figures and wrote the manuscript.

Adam Klocperk1, M.D., Ph.D., Zuzana Paračková1, MSc., Jitka Dissou2, M.D., Hana Malcová3, M.D., Ph.D., Petr Pavlíček4, M.D., Tomáš Vymazal4, M.D., As. Prof., Pavla Doležalová5, M.D., Prof., Anna Šedivá1, M.D., Prof.1Department of Immunology, 2ndFaculty of Medicine, Charles University in Prague and University Hospital in Motol, Prague, Czech Republic2Emergency Department for Children, University Hospital in Motol, Prague, Czech Republic3Department of Children and Adult Rheumatology, University Hospital in Motol , Prague, Czech Republic4Department of Anesthesiology and Intensive Care Medicine, 2nd Faculty of Medicine, Charles University in Prague and University Hospital in Motol, Prague, Czech Republic5Centre for Paediatric Rheumatology and Autoinflammatory Diseases, Department of Paediatrics and Adolescent Medicine, General University Hospital in Prague and 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic