[Nonspecific reacting materials that interferes tacrolimus assay by ACMIA].
We report two cases of falsely elevated levels of Tacrolimus (TAC) measured by affinity column mediated immunoassay (ACMIA). Potential reasons for this are herein explored. Patient 1, a post-renal transplantation patient, was treated by TAC, while patient 2, a patient with rheumatoid arthritis, was not. TAC levels measured by ACMIA of patients 1 and 2 were greater than 40 and 20 ng/ml, respectively. In patient 2, rheumatoid factor (RF) levels were constantly higher than 1,000 IU/ml, and levels of TAC were shown to be correlated with RF. Results of immunoglobulin adsorption tests and gel filtration suggested that the false positivities for TCA were induced by IgG of patient 1 and IgM of patient 2. After the addition of anti-TAC antibody, levels of TAC decreased to an undetectable range in both cases. TAC levels also became undetectable after the addition of MAK33-Framework IEP in patient 1 and IIR in patient 2. In patient 2, the addition of HBR-1 and MAK absorbent prevented the false positive phenomenon. In both cases, human anti mouse antibodies (HAMAs) reacted to anti-TAC mouse monoclonal antibodies within the reagent and produced falsely elevated results. These results were inhibited by MAK33-Framework IEP binding to the hyper-variable region of immunoglobulin; therefore, the causative agent of this phenomenon in patient 1 was likely an anti-idiotype antibody against the mouse monoclonal anti-TAC antibody used in the assay. Furthermore, a close relationship between measured levels of TAC and RF, along with the finding that the addition of HBR-1 and IRR prevents false positive results, suggests that RF produced false positive results through IgM-HAMA activity in patient 2. These data indicate that false positive results of TAC can be due to the presence of HAMAs with different specificities.
Central Clinical Laboratory, The Jikei University Katsushika Medical Center, Katsushika-ku, Tokyo 125-8506, Japan. ma_abe@jikei.ac.jp
Masaki
M
Abei
Central Clinical Laboratory, The Jikei University Katsushika Medical Center, Katsushika-ku, Tokyo 125-8506, Japan.
Michitaka
M
Yagi
Central Clinical Laboratory, The Jikei University Katsushika Medical Center, Katsushika-ku, Tokyo 125-8506, Japan.
Takako
T
Watanabe
Central Clinical Laboratory, The Jikei University Katsushika Medical Center, Katsushika-ku, Tokyo 125-8506, Japan.
Ken-ichi
K
Sugimoto
Central Clinical Laboratory, The Jikei University Katsushika Medical Center, Katsushika-ku, Tokyo 125-8506, Japan.
Yudou
Y
Tanno
Central Clinical Laboratory, The Jikei University Katsushika Medical Center, Katsushika-ku, Tokyo 125-8506, Japan.
Ken
K
Kaito
D000888:Antibodies, Anti-Idiotypic; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D002846:Chromatography, Affinity; D002850:Chromatography, Gel; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D007075:Immunoglobulin M / Q000097:blood* / Q000276:immunology; D008875:Middle Aged; D016559:Tacrolimus / Q000097:blood*
D000888:Antibodies, Anti-Idiotypic; D007075:Immunoglobulin M; D016559:Tacrolimus