title: Differential inhibitory effects of intravenous immunoglobulin preparations on HLA-alloantibodies in vitro.
abstract: BACKGROUND
  Treatment of allosensitized patients with intravenously administered pooled immunoglobulin preparations (IVIG) may lead to a long-lasting reduction of anti-HLA alloantibody titers. An inhibitory response of IVIG preparations on lymphocytotoxicity is suggested to depend on IgG and to predict a successful reduction of anti-HLA alloantibodies upon the administration of high-dose IVIG in vivo.
  
  
  METHODS
  In this study, we evaluated different IVIG preparations for their in vitro inhibitory capacity on lymphocytotoxicity and binding of anti-HLA alloantibodies to purified HLA antigens. For that purpose sera from 24 highly sensitized patients awaiting kidney transplantation and serological HLA testing reagents were used. Panel-reactive antibody (PRA) determinations using standard complement-dependent cytotoxicity testing and anti-HLA alloantibody determination by ELISA were carried out in the presence and absence of 50% (v/v) IVIG.
  
  
  RESULTS
  The addition of IgG-containing IVIG preparations gave only a moderate inhibitory response judging from the average decrease of PRA levels (absolute DeltaPRA range: -2% to 16%), whereas the largest inhibition of lymphocytotoxicity was seen after the addition of IgM/IgA-containing IVIG preparations (absolute DeltaPRA range: 19% to 44%). For both IgG and IgM/IgA-containing IVIG preparations, the reduction of lymphocytotoxicity occurred in a dose-dependent fashion without a preference for particular anti-HLA class I antibody specificities. Significantly lower inhibitory effects on anti-HLA antibody reactivity were observed when the effects of IVIG preparations were monitored by ELISA (absolute DeltaPRA range: 7% to 22%).
  
  
  CONCLUSIONS
  Our data suggest that the immunomodulatory capacity is largely caused by the IgM/IgA fraction of IVIG when analyzed by lymphocytotoxicity. The different effect on ELISA versus complement-dependent cytotoxicity testing suggests that interactions of IVIG with complement rather than anti-idiotypic antibodies may contribute to the inhibitory effects of IVIG in vitro.
authors.affiliation: Department of Medicine III, University of Erlangen-Nürnberg, Erlangen, Germany. ralf.wassmuth@rzmail.uni-erlangen.de
authors.forename: R
authors.initials: R
authors.lastname: Wassmuth
authors.forename: I A
authors.initials: IA
authors.lastname: Hauser
authors.forename: K
authors.initials: K
authors.lastname: Schuler
authors.forename: H
authors.initials: H
authors.lastname: Erxleben
authors.forename: M L
authors.initials: ML
authors.lastname: Arnold
authors.forename: C A
authors.initials: CA
authors.lastname: Koelman
authors.forename: F H
authors.initials: FH
authors.lastname: Claas
authors.forename: J R
authors.initials: JR
authors.lastname: Kalden
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D003165:Complement System Proteins / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006680:HLA Antigens / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000494:pharmacology*; D007518:Isoantibodies / Q000032:analysis / Q000187:drug effects* / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D006680:HLA Antigens; D016756:Immunoglobulins, Intravenous; D007518:Isoantibodies; D003165:Complement System Proteins