The immune-modulator AS101 reduces anti-HLA antibodies in sera of sensitized patients: a structural approach.
BACKGROUND
Significant efforts are dedicated to identification of agents that eliminate anti-HLA antibodies (Ab) from sera of transplant candidates. Antibody titer following in vitro incubation of sera with desensitizing agents has shown to reflect the probability that a patient would benefit from clinical de-sensitization protocols. AS101 is a non-toxic, synthetic, organic tellurium compound. The aim of this research was to assess the ability of AS101 to reduce anti-HLA Abs and to identify patients likely to benefit from this effect.


METHODS
Sera of sensitized patients awaiting transplant were incubated in the presence of AS101. Measured mean fluorescence intensity (MFI) represents reactivity of anti HLA Abs in the serum, as detected by the Luminex platform. The repertoire of HLA antigen epitopes was recognized using HLA Matchmaker software.


RESULTS
AS101 Incubation caused a significant Ab titer decrease in approximately two thirds of the samples. The median Class I and II MFI decrease among the responding samples was 16.7% and 14%, respectively (p<0.05). HLA Matchmaker analysis of the patients' class I epitope sequences revealed apparent amino-acid differences between the patterns of the responding and non-responding patients.


CONCLUSIONS
In vitro incubation of sera in the presence of AS101 causes a decrease in the anti-HLA Ab's reactivity in several patient samples. Sera most likely to demonstrate this effect are characterized by a moderate MFI level and a distinct antibody reactivity pattern specific for defined HLA antigen epitopes. These results support further investigation of AS101 as a potential agent for desensitization of humoral reactivity prior to transplantation.
Tissue Typing Laboratory, Rabin Medical Center, Petach-Tikva, Israel. israelimoshe@yahoo.com
Moshe
M
Israeli
Benjamin
B
Sredni
Eitan
E
Mor
Chana
C
Zakai
Boaz
B
Tadmor
Tirza
T
Klein
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005030:Ethylenes / Q000008:administration & dosage*; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007518:Isoantibodies / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation; D010956:Plasmapheresis; D012984:Software; D013329:Structure-Activity Relationship; D019172:Transplantation Conditioning / Q000379:methods*; D014850:Waiting Lists; D055815:Young Adult
D005030:Ethylenes; D006680:HLA Antigens; D007518:Isoantibodies; C054105:ammonium trichloro(dioxoethylene-O,O'-)tellurate