期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 128, 期 6, 页码 1295-U655出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2011.08.008
关键词
B lymphocytes; human; diabetes; antibodies; immunization; CD20
资金
- National Institutes of Health through the National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Allergy and Infectious Diseases
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- National Center for Research Resources
- Juvenile Diabetes Research Foundation International
- American Diabetes Association
- National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases
- National Institutes of Health/National Institute of Allergy and Infectious Diseases
- Bayhill Therapeutics
- Halozyme Inc
- Osiris Therapeutics
Background: B-lymphocyte depletion with rituximab has been shown to benefit patients with various autoimmune diseases. We have previously demonstrated that this benefit is also apparent in patients with newly diagnosed type 1 diabetes. Objectives: The effect of rituximab on in vivo antibody responses, particularly during the period of B-lymphocyte depletion, is incompletely determined. This study was designed to assess this knowledge void. Methods: In patients with recent-onset type 1 diabetes treated with rituximab (n = 46) or placebo (n = 29), antibody responses to neoantigen phiX174 during B-lymphocyte depletion and with hepatitis A (as a second neoantigen) and tetanus/diphtheria (as recall antigens) after B-lymphocyte recovery were studied. Anti-tetanus, diphtheria, mumps, measles, and rubella titers were measured before and after treatment by means of ELISA. Antibody titers and percentage IgM versus percentage IgG to phiX174 were measured by means of phage neutralization. B-lymphocyte subsets were determined by means of flow cytometry. Results: No change occurred in preexisting antibody titers. Tetanus/diphtheria and hepatitis A immunization responses were protective in the rituximab-treated subjects, although significantly blunted compared with those seen in the controls subjects, when immunized at the time of B-lymphocyte recovery. Anti-phiX174 responses were severely reduced during the period of B-lymphocyte depletion, but with B-lymphocyte recovery, anti-phiX174 responses were within the normal range. Conclusions: During the time of B-lymphocyte depletion, rituximab recipients had a decreased antibody response to neoantigens and significantly lower titers after recall immunization with diphtheria and tetanus toxoid. With recovery, immune responses return toward normal. Immunization during the time of B-lymphocyte depletion, although ineffective, does not preclude a subsequent response to the antigen. (J Allergy Clin Immunol 2011;128:1295-302.)
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