Specific and durable elimination of antibody to donor HLA antigens in renal-transplant patients.
BACKGROUND
Donor-specific antibody (DSA) is the major barrier to success of kidney transplants. Attempts to deal with this problem have used plasmapheresis to remove antibodies or high-dose pooled immunoglobulin (IVIg) to down-regulate DSA. However, elimination of antibodies by these methods has been limited in duration or scope.


METHODS
We have confirmed the presence of immunoglobulin (Ig)G antibody to one or more donor HLA antigens in 49 patients treated with alternate-day, single-volume plasmapheresis followed by low-dose cytomegalovirus (CMV) hyperimmune globulin (CMV-Ig) combined with quadruple immunosuppression. We examined the effect of the treatment protocol on antibodies to donor HLA, third-party HLA, and nominal antigens.


RESULTS
At the end of treatment, 63% of patients had lost antibody to donor HLA, whereas only 27% had lost antibody to third-party HLA (P<0.001). More strikingly, loss of antibody to donor and third-party HLA antigens occurred in 89% and 19%, respectively, of patients followed for 2 or more months after end of treatment (P<0.0001). No elimination of antiviral antibodies tested was seen. With one exception, elimination of DSA appeared to be independent of antibody titer or specificity, the number of different antibody specificities, or whether or not the target antigen was a repeat mismatch. The effect appears to be long lasting, with no return of DSA observed in patients followed for an average of 13 months.


CONCLUSIONS
Plasmapheresis and low-dose CMV-Ig combined with traditional immunosuppression is effective in producing a specific and durable elimination of antibody to donor HLA.
Zachary
Andrea A
AA
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2222, USA. aaz@jhmi.edu
Montgomery
Robert A
RA
Ratner
Lloyd E
LE
Samaniego-Picota
Millie
M
Haas
Mark
M
Kopchaliiska
Dessislava
D
Leffell
Mary S
MS
D000917:Antibody Formation; D000918:Antibody Specificity; D003602:Cytotoxicity, Immunologic; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007518:Isoantibodies / Q000097:blood* / Q000302:isolation & purification*; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D008297:Male; D010956:Plasmapheresis / Q000379:methods
D006680:HLA Antigens; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D007518:Isoantibodies