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Arthritis Rheumatol ; 2021 Dec 28.
Article in English | MEDLINE | ID: covidwho-1589171


OBJECTIVES: Patients with autoimmune inflammatory rheumatic diseases receiving rituximab (RTX) therapy are at higher risk for poor COVID-19 outcomes and show substantially impaired humoral anti-SARS-CoV-2 vaccine responses. However, the complex relationship between antigen-specific B and T cells and the level of B cell repopulation necessary to achieve anti-vaccine responses remain largely unknown. METHODS: Antibody responses to SARS-CoV-2 vaccines and induction of antigen-specific B and CD4/CD8 T cell subsets were studied in 19 rheumatoid arthritis (RA) and ANCA-associated vasculitis (AAV) patients receiving RTX, 12 RA patients on other therapies and 30 healthy controls after SARS-CoV-2 vaccination with either mRNA or vector based vaccines. RESULTS: A minimum of 10 B cells/µL (0,4% of lymphocytes) in the peripheral circulation appeared to be required in RTX patients to mount seroconversion to anti-S1 IgG upon SARS-CoV-2 vaccination. RTX patients lacking IgG seroconversion showed reduced RBD+ B cells, lower frequency of TfH-like cells as well as less activated CD4 and CD8 T cells compared to IgG seroconverted RTX patients. Functionally relevant B cell depletion resulted in impaired IFNγ secretion by spike-specific CD4 T cells. In contrast, antigen-specific CD8 T cells were reduced in patients, independently of IgG formation. CONCLUSIONS: In patients receiving RTX, a minimum of 10 B cells/µl in the peripheral circulation candidates as biomarker for a high likelihood of an appropriate cellular and humoral response after SARS-CoV-2 vaccination. Mechanistically, the data emphasize the crucial role of co-stimulatory B cell functions for the proper induction of CD4 responses propagating vaccine-specific B and plasma cell differentiation.

Sci Immunol ; 6(60)2021 06 15.
Article in English | MEDLINE | ID: covidwho-1369380


Patients with kidney failure are at increased risk for SARS-CoV-2 infection making effective vaccinations a critical need. It is not known how well mRNA vaccines induce B and plasma cell responses in dialysis patients (DP) or kidney transplant recipients (KTR) compared to healthy controls (HC). We studied humoral and B cell responses of 35 HC, 44 DP and 40 KTR. Markedly impaired anti-BNT162b2 responses were identified among KTR and DP compared to HC. In DP, the response was delayed (3-4 weeks after boost) and reduced with anti-S1 IgG and IgA positivity in 70.5% and 68.2%, respectively. In contrast, KTR did not develop IgG responses except one patient who had a prior unrecognized infection and developed anti-S1 IgG. The majority of antigen-specific B cells (RBD+) were identified in the plasmablast or post-switch memory B cell compartments in HC, whereas RBD+ B cells were enriched among pre-switch and naïve B cells from DP and KTR. The frequency and absolute number of antigen-specific circulating plasmablasts in the cohort correlated with the Ig response, a characteristic not reported for other vaccinations. In conclusion, these data indicated that immunosuppression resulted in impaired protective immunity after mRNA vaccination, including Ig induction with corresponding generation of plasmablasts and memory B cells. Thus, there is an urgent need to improve vaccination protocols in patients after kidney transplantation or on chronic dialysis.

Antibodies, Viral/blood , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunocompromised Host , Kidney Transplantation , Adult , Aged , Aged, 80 and over , Antibodies, Viral/immunology , COVID-19/immunology , Female , Humans , Immunity, Humoral/drug effects , Immunity, Humoral/immunology , Male , Middle Aged , Renal Dialysis , SARS-CoV-2 , Transplant Recipients
Front Med (Lausanne) ; 8: 618599, 2021.
Article in English | MEDLINE | ID: covidwho-1247873