Long-term effects of anti-CD20 monoclonal antibody treatment of cryoglobulinaemic glomerulonephritis.
BACKGROUND
Type II mixed cryoglobulinaemia (MC) is a systemic vasculitis, associated in most cases with hepatitis C virus (HCV) infection, and sustained by proliferation of oligoclonal cells. Systemic B-cell depletion and clinical remission can be achieved in non-Hodgkin lymphoma by a human/mouse chimeric monoclonal antibody that specifically reacts with the CD20 antigen (Rituximab). Similar effects could be expected in type II MC.


METHODS
Six patients, mean age 64.2 years (range: 37-76 years), with HCV infection genotype 2a2c (three cases) or 1b (three cases) and symptomatic type-II MC with systemic manifestations, including renal involvement (five cases) and bone marrow clonal restriction (three cases), were considered eligible for Rituximab therapy. Rituximab was administered intravenously at a dose of 375 mg/m(2) on days 1, 8, 15 and 22. Two more doses were administered 1 and 2 months later. No other immunosuppressive drugs were added. Response was evaluated by assessing the changes in clinical signs, symptoms and laboratory parameters for < or = 18 months.


RESULTS
Levels of proteinuria, erythrocyte sedimentation rate and cryocrit significantly decreased at 2, 6 and 12 months. Rheumatoid factor and IgM significantly decreased at 6 months whereas C4 values significantly increased at 2 and 6 months. HCV viral load and immunoglobulin G remained stable. Bone marrow abnormalities were found to reverse to normal in all three positive cases. Constitutional symptoms (skin ulcers, purpura, arthralgia, weakness, paraesthesia and fever) disappeared or improved. No acute or delayed side effects were observed.


CONCLUSIONS
Rituximab appears to be a safe and effective therapeutic option in symptomatic patients with HCV-associated MC glomerulonephritis and signs of systemic vasculitis.
Roccatello
Dario
D
Centro Multidisciplinare di Ricerche di Immunopatologia e Documentazione su Malattie Rare, Struttura Complessa a Direzione Universitaria di Immunologia Clinica (CMID), P.zza del Donatore di Sangue 3, 10152 Torino, Italy. dario.roccatello@unito.it
Baldovino
Simone
S
Rossi
Daniela
D
Mansouri
Morteza
M
Naretto
Carla
C
Gennaro
Mariella
M
Cavallo
Roberto
R
Alpa
Mirella
M
Costanzo
Piera
P
Giachino
Osvaldo
O
Mazzucco
Gianna
G
Sena
Luigi Massimino
LM
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD / Q000276:immunology; D018951:Antigens, CD20 / Q000276:immunology*; D001799:Blood Sedimentation / Q000187:drug effects; D001853:Bone Marrow / Q000473:pathology; D003449:Cryoglobulinemia / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D005921:Glomerulonephritis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD; D018951:Antigens, CD20; D000069283:Rituximab