mycophenolic-acid and Primary-Immunodeficiency-Diseases

Patients with immunocompromised disorders have mainly been excluded from clinical trials of vaccination against COVID-19. Thus, the aim of this prospective clinical trial was to investigate safety and efficacy of BNT162b2 mRNA vaccination in five selected groups of immunocompromised patients and healthy controls.. 539 study subjects (449 patients and 90 controls) were included. The patients had either primary (n=90), or secondary immunodeficiency disorders due to human immunodeficiency virus infection (n=90), allogeneic hematopoietic stem cell transplantation/CAR T cell therapy (n=90), solid organ transplantation (SOT) (n=89), or chronic lymphocytic leukemia (CLL) (n=90). The primary endpoint was seroconversion rate two weeks after the second dose. The secondary endpoints were safety and documented SARS-CoV-2 infection.. Adverse events were generally mild, but one case of fatal suspected unexpected serious adverse reaction occurred. 72.2% of the immunocompromised patients seroconverted compared to 100% of the controls (p=0.004). Lowest seroconversion rates were found in the SOT (43.4%) and CLL (63.3%) patient groups with observed negative impact of treatment with mycophenolate mofetil and ibrutinib, respectively.. The results showed that the mRNA BNT162b2 vaccine was safe in immunocompromised patients. Rate of seroconversion was substantially lower than in healthy controls, with a wide range of rates and antibody titres among predefined patient groups and subgroups. This clinical trial highlights the need for additional vaccine doses in certain immunocompromised patient groups to improve immunity.. Knut and Alice Wallenberg Foundation, the Swedish Research Council, Nordstjernan AB, Region Stockholm, Karolinska Institutet, and organizations for PID/CLL-patients in Sweden.

Topics: Adenine; Antibodies, Viral; BNT162 Vaccine; COVID-19; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Immunogenicity, Vaccine; Immunotherapy, Adoptive; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Mycophenolic Acid; Organ Transplantation; Piperidines; Primary Immunodeficiency Diseases; Prospective Studies; SARS-CoV-2; Seroconversion; Spike Glycoprotein, Coronavirus; Vaccination; Vaccine Efficacy

Gain of function (GOF) mutations in PIK3CD gene encoding PI3K p110δ were recently associated with a novel combined immune deficiency characterized by recurrent sinopulmonary infections, CD4 lymphopenia, reduced class-switched memory B cells, lymphadenopathy, cytomegalovirus and/or epstein-Barr virus (EBV) viremia, and EBV-related lymphoma. A subset of affected patients also had elevated serum IgM.. We report a patient who was diagnosed with systemic lupus erythematosus (SLE) at a young age and was recently found to carry heterozygous mutations in PIK3CD. The patient not only presented with recurrent sinopulmonary infections, CD4 lymphopenia, lymphadenopathy, EBV viremia, and elevated serum IgM, but also met classification criteria of SLE based on persistent proteinuria and hematuria, leukopenia and anemia, low level of serum complement, and positive autoantibody for antinuclear antibodies.. Activated PI3Kδ syndrome.. Oral prednisolone and hydroxychloroquine combined with mycophenolate mofetil was given to the patient. He was currently receiving intravenous immunoglobulin per month in association with hydroxychloroquine, low-dose prednisolone, and mycophenolate mofetil.. At present, the level of complement restored to normal, hematuria and proteinuria disappeared, and liver function returned to normal.. SLE may be a novel phenotype of GOF mutation in PI3CKD gene (GOF PIK3CD).

Topics: Adolescent; Antibodies, Antinuclear; Asian People; Class I Phosphatidylinositol 3-Kinases; Complement System Proteins; Enzyme Inhibitors; Epstein-Barr Virus Infections; Gain of Function Mutation; Glucocorticoids; Herpesvirus 4, Human; Humans; Hydroxychloroquine; Immunoglobulins, Intravenous; Immunologic Deficiency Syndromes; Lupus Erythematosus, Systemic; Male; Mycophenolic Acid; Phenotype; Prednisolone; Primary Immunodeficiency Diseases