AI Article Synopsis
- Rheumatoid factors (RFs) are natural human antibodies that bind to other antibodies, particularly in the context of immune complexes, which can lead to misleading results in immunoassays for anti-human antibodies after monoclonal therapy.
- In patients with rheumatoid arthritis, there was a significantly higher baseline reactivity in blood samples compared to healthy individuals when tested with a sensitive electrochemiluminescent (ECL) assay.
- The presence of high molecular weight aggregates (as little as 0.55%) in therapeutic antibodies can increase false reactivity, but careful monitoring of storage conditions through size exclusion high-performance liquid chromatography (SE-HPLC) can help reduce this issue.
Article Abstract
Rheumatoid factors (RFs) are endogenous human antibodies that bind to human gamma globulins. RFs demonstrate preferential binding to aggregated gamma globulins and are involved in the clearing mechanism of immune complexes. Immunoassays designed to measure human anti-human antibodies (HAHA) after administration of monoclonal antibody therapeutics are thus vulnerable to interference from RFs. When using a sensitive electrochemiluminescent (ECL) bridging immunoassay, samples from subjects with rheumatoid arthritis demonstrated much higher baseline reactivity than healthy subjects. Interference was found to be dependent on the aggregation state of the therapeutic antibody that had been conjugated with the detection reagent (ruthenium). Size exclusion high performance liquid chromatography (SE-HPLC) demonstrated that of the total integrated peaks, as little as 0.55% high molecular weight aggregates (>600kDa) were sufficient to cause increased reactivity. Stability studies of the ruthenium and biotin conjugated therapeutic antibody indicated that storage time, temperature and buffer formulation were critical in maintaining the integrity of the reagents. Through careful SE-HPLC monitoring we were able to choose appropriate storage and buffer conditions which led to a reduction in the false reactivity rate in therapeutic-naïve serum from a rheumatoid arthritis population.
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| http://dx.doi.org/10.1016/j.jim.2010.03.012 | DOI Listing |
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