Protracted remission of proteinuria after combined therapy with plasmapheresis and anti-CD20 antibodies/cyclophosphamide in a child with oligoclonal IgM and glomerulosclerosis.
We describe a child presenting with oligoclonal plasma IgM (1.2 g%) and nephrotic syndrome with focal segmental glomerulosclerosis. Oligoclonality was demonstrated by the analysis of the complementary determining region 3 (CDR 3) on immunoglobulin heavy chains and by two dimensional electrophoresis and Western blot analysis that showed the bulk of isoforms having a cationic muU chain compared with the normal homologue (pI 7.5 vs 6.5). Urinary light chains were absent, and bone marrow aspirate was normal. Usual therapies for nephrotic syndrome with steroids and cyclosporin were useless. At the age of 9 years the patient was treated with plasmapheresis plus cyclophosphamide (2 mg/kg per day for 60 days), which temporarily reduced plasma IgM, and proteinuria was normal for 3 years. After this period, due to new recurrence of nephrotic syndrome, the patient received a cycle with anti-CD20 antibodies (500 mg/m(2) every week for a month) associated with a cycle of plasmapheresis that normalized proteinuria again, and, after 3 years, the proteinuria is still in remission. This is the first case of nephrotic syndrome associated with oligoclonal plasma IgM and mesangial IgM deposits. Both cyclophosphamide and anti-CD20 antibodies associated with plasmapheresis induced, at different stages, stable and protracted remission of proteinuria without evident side effects. Long term efficacy and safety of the association are still to be determined.
Department of Nephrology, G. Gaslini Children's Hospital, Genoa, Italy. labnefro@ospedale-gaslini.ge.it
Gian Marco
GM
Ghiggeri
Luca
L
Musante
Giovanni
G
Candiano
Maurizio
M
Bruschi
Laura
L
Santucci
Giancarlo
G
Barbano
Antonella
A
Trivelli
Lucia
L
Rivabella
Rosanna
R
Gusmano
Francesco
F
Perfumo
D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D002648:Child; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage*; D005921:Glomerulonephritis / Q000188:drug therapy / Q000276:immunology; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D009404:Nephrotic Syndrome / Q000188:drug therapy / Q000276:immunology; D043025:Oligoclonal Bands / Q000097:blood*; D010956:Plasmapheresis; D011507:Proteinuria / Q000188:drug therapy* / Q000276:immunology; D012074:Remission Induction; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D043025:Oligoclonal Bands; D000069283:Rituximab; D003520:Cyclophosphamide