Impact of rituximab on immunoglobulin concentrations and B cell numbers after cyclophosphamide treatment in patients with ANCA-associated vasculitides.
OBJECTIVE
To assess the impact of immunosuppressive therapy with cyclophosphamide (CYC) and rituximab (RTX) on serum immunoglobulin (Ig) concentrations and B lymphocyte counts in patients with ANCA-associated vasculitides (AAVs).


METHODS
Retrospective analysis of Ig concentrations and peripheral B cell counts in 55 AAV patients.


RESULTS
CYC treatment resulted in a decrease in Ig levels (median; interquartile range IQR) from IgG 12.8 g/L (8.15-15.45) to 9.17 g/L (8.04-9.90) (p = 0.002), IgM 1.05 g/L (0.70-1.41) to 0.83 g/L (0.60-1.17) (p = 0.046) and IgA 2.58 g/L (1.71-3.48) to 1.58 g/L (1-31-2.39) (p = 0.056) at a median follow-up time of 4 months. IgG remained significantly below the initial value at 14.5 months and 30 months analyses. Subsequent RTX treatment in patients that had previously received CYC resulted in a further decline in Ig levels from pre RTX IgG 9.84 g/L (8.71-11.60) to 7.11 g/L (5.75-8.77; p = 0.007), from pre RTX IgM 0.84 g/L (0.63-1.18) to 0.35 g/L (0.23-0.48; p<0.001) and from pre RTX IgA 2.03 g/L (1.37-2.50) to IgA 1.62 g/L (IQR 0.84-2.43; p = 0.365) 14 months after RTX. Treatment with RTX induced a complete depletion of B cells in all patients. After a median observation time of 20 months median B lymphocyte counts remained severely suppressed (4 B-cells/µl, 1.25-9.5, p<0.001). Seven patients (21%) that had been treated with CYC followed by RTX were started on Ig replacement because of severe bronchopulmonary infections and serum IgG concentrations below 5 g/L.


CONCLUSIONS
In patients with AAVs, treatment with CYC leads to a decline in immunoglobulin concentrations. A subsequent RTX therapy aggravates the decline in serum immunoglobulin concentrations and results in a profoundly delayed B cell repopulation. Surveying patients with AAVs post CYC and RTX treatment for serum immunoglobulin concentrations and persisting hypogammaglobulinemia is warranted.
Department of Rheumatology and Clinical Immunology, University Hospital Freiburg, Freiburg, Germany.
Nils
N
Venhoff
Nora M
NM
Effelsberg
Ulrich
U
Salzer
Klaus
K
Warnatz
Hans Hartmut
HH
Peter
Dirk
D
Lebrecht
Michael
M
Schlesier
Reinhard E
RE
Voll
Jens
J
Thiel
D000328:Adult; D000368:Aged; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000188:drug therapy* / Q000276:immunology*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D003520:Cyclophosphamide / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000097:blood*; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D000069283:Rituximab
D058846:Antibodies, Monoclonal, Murine-Derived; D007136:Immunoglobulins; D007155:Immunologic Factors; D000069283:Rituximab; D003520:Cyclophosphamide