Effect of rituximab on human in vivo antibody immune responses

Abstract

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.

Phage Neutralization by Sera of Patients Receiving Phage Therapy

“…The examinations performed on healthy volunteers and on patients with bacterial infections indicated that bacteriophages may have an influence on induction of antiphage antibody production (9,11). A safety test of PT performed by Bruttin and Brüssow (3) on 15 adult healthy volunteers using E. coli T4 phage orally indicated no increase in level of antiphage IgG, IgM, and IgA in the serum after 1 month of the study.…”

“…Kamme (8) also examined the level of antiphage antibodies in sera of 100 healthy volunteers, which showed a low level of antiphage antibodies for S. aureus phages mostly up to serum dilution 1:80. Pescovitz et al (11) performed a study of 52 healthy volunteers who received the E. coli uX174 phage intravenously. E. coli uX174 phage was in the body for 3-4 days after administration.…”

“…The neutralization of specific phage by patients' sera was estimated as the rate of phage inactivation (K; the formula for its calculation is shown below) during a 30 min reaction of the phage (50 lL) with diluted serum (450 lL) at 37°C according to the method described by Adams (2) and Pescovitz et al (11) with some modification. The sera were tested up to dilution 1:1,500.…”

Immune therapy in type 1 diabetes mellitus

“…The results underscore the need for further studies on the role of B lymphocytes in maintaining the chronic islet autoimmunity. In mice, it has been demonstrated that there is a significant crossspresentation of autoantigens to CD8+ T cells that precipitates diabetes (ref 47 . The observations on autoantibody and neoantigen responses is underscoring the importance of the B cell as an antigen-presenting cell that may not only interact with T helper cells but also directly with other antigen presenting cells such as dendritic cells to induce autoantibody formation ( Figure 6).…”

Meningococcal Sepsis Complicating Eculizumab Treatment Despite Prior Vaccination

“…Consequently, protection against meningococcal disease by antibody-mediated killing becomes essential. However, vaccination of patients using immunosuppressive drugs may be ineffective (3,4). Different immunosuppressive regimens vary in their effects on humoral responses after vaccination.…”