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J Allergy Clin Immunol. 2011 Dec;128(6):1295-1302.e5. doi: 10.1016/j.jaci.2011.08.008. Epub 2011 Sep 9.

Effect of rituximab on human in vivo antibody immune responses.

Collaborators (204)

Skyler JS, Anderson M, Becker D, Benoist C, Bingley P, Bosi E, Chase HP, Clare-Salzler M, Colman P, Eisenbarth GS, Fathman CG, Gitelman S, Goland R, Gottlieb P, Grave G, Greenbaum C, Harrison L, Herold K, Insel R, Kaufman F, Krischer JP, Leschek E, Mahon J, Marks J, Moran A, Nanto-Salonen K, Nepom G, Orban T, Palmer JP, Parkman R, Peakman M, Pescovitz M, Peyman J, Pugliese A, Raskin P, Rodriguez H, Schatz D, Sherwin R, Siegelman M, Simell O, Trucco M, Wagner J, Wherrett D, Wilson D, Winter W, Ziegler A, Fradkin J, Bluestone J, Brown D, Hering B, Jordan S, Lachin JM, Ridge J, Skyler JS, Greenbaum CJ, Krischer JP, Leschek E, Peyman J, Rafkin-Mervis L, Savage P, Spain L, Cowie C, Foulkes M, Krause-Steinrauf H, Lachin JM, Malozowski S, Ridge J, Zafonte SJ, Skyler JS, Greenbaum CJ, Kenyon NS, Sosenko JM, Lachin JM, Krause-Steinrauf H, McGee PF, Owens Hess K, Raiden E, Fradkin J, Leschek E, Savage P, Blumberg E, Braun J, Laffel L, Naji A, Nerup J, Orchard T, Tsiatis A, Veatch R, Wallace D, Lernmark A, Lo B, Mitchell H, Steffes M, Zinman B, Loechelt B, Baden L, Green M, Weinberg A, Eisenbarth GS, Marcovina S, Palmer JP, Weinberg A, Yu L, Ochs HD, Torgerson TR, Ocheltree E, Berger J, Koralnik I, Tyler K, Leschek RT, Pescovitz MD, Buckingham B, Gitelman S, Herold K, Kenyon N, Krause-Steinrauf H, Looney J, Lunney J, Ng D, Rodriguez H, Spain L, Greenbaum C, Lachin JM, Leschek E, Skyler JS, Owens Hess K, Greenbaum C, Bollyky J, Sanda S, McCulloch-Olson M, Hefty D, Webber C, Kuhns K, Murphy C, Goland R, Greenberg E, Gallagher MP, Trast J, Chan M, Rodriguez H, Pescovitz M, Christner L, Nicholson M, Mendez M, Wilson DM, Buckingham BA, Aye T, Esrey T, Soto A, Perry J, Baker B, Rigby A, Riley K, Chatav M, Berry B, Gitelman SE, Rosenthal SM, Anderson M, Adi S, Breen K, Hamilton C, Gottlieb P, Chase HP, Rawley-Payne M, George S, Weiner L, Schatz D, Haller M, Clare-Salzler M, Cook R, Mancini D, Abraham A, Hicks E, Cole G, Marks JB, Pugliese A, Matheson D, Blaschke C, Arazo L, Cisneros M, Moran A, Wagner J, Nathan B, Ann Boes M, Becker D, Toledo F, Riley K, Delallo K, Smith K, Raskin P, White P, Dickson B, Adhikari S, Siegelman M, Alford M, Torres N, Harden T, Pruneda L, Cordova E, Wherrett D, Eisel LA, Ahenkorah B, Razack N, Sriskandarajah M.

Author information

1
Department of Surgery, Indiana University, Indianapolis, IN, USA.

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.

PMID:
21908031
PMCID:
PMC3659395
DOI:
10.1016/j.jaci.2011.08.008
[Indexed for MEDLINE]
Free PMC Article

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