Rituximab treatment in a patient with severe thyroid-associated ophthalmopathy: effects on orbital lymphocytic infiltrates.
Rituximab (RTX) has been shown in previous work to improve thyroid-associated ophthalmopathy (TAO), but very little data is available on the effects of RTX in the target tissues. We studied the effects of RTX on peripheral lymphocytes and on the intra-orbital infiltrates in one patient with severe TAO who was treated with two cycles of therapy. Intra-orbital tissues derived at decompression from 3 patients with moderate-severe and 1 with severe TAO, treated with standard immunosuppression, were studied as controls. Peripheral blood lymphocytes were analyzed throughout the study period, while intra-orbital tissue lymphocytes at decompression. In the patient treated with RTX visual field and acuity improved in response to peripheral CD 20+ cell depletion, although there was a proportion of persisting CD 19+ cells. After RTX re-treatment the patient's optic nerve function improved only transiently. The number of CD 20+ cells was lower in orbital tissues (0-1%) than in the peripheral blood (3%). A greater percentage of CD 19+ was observed in the orbits compared to the periphery, most of which were CD 19+5+ (80%). By immunohistochemistry, orbital tissues from all control patients showed CD 20+ and CD 3+ cells, independently of the duration of TAO and of the treatment with either steroids or radiotherapy. This is the first report on the therapeutic effect of RTX in active, severe TAO associated to the depletion of intra-orbital CD 20+ lymphocytes. After RTX, CD 19+5+ lymphocytes were shown to be 2-3 times more prevalent in the orbital infiltrates, compared to CD 20+ cells. Persistence of autoreactive cells is believed to be related to TAO relapse.
Salvi
Mario
M
Department of Medical Sciences (Padiglione Granelli), University of Milan, Fondazione Ospedale Maggiore, IRCCS Via Sforza, Milan, Italy. mario.salvi@bergamoscienza.it
Vannucchi
Guia
G
Campi
Irene
I
Currò
Nicola
N
Simonetta
Simona
S
Covelli
Danila
D
Pignataro
Lorenzo
L
Guastella
Claudio
C
Rossi
Stefania
S
Bonara
Paola
P
Dazzi
Davide
D
Ratiglia
Roberto
R
Beck-Peccoz
Paolo
P
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D002478:Cells, Cultured; D005260:Female; D049970:Graves Ophthalmopathy / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009915:Orbit / Q000187:drug effects / Q000276:immunology*; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D000069283:Rituximab