Immunoglobulin G subclass distribution of anti-ADAMTS13 antibodies in a cohort of 47 patients with acquired thrombotic thrombocytopenic purpura

G. Sinkovits, M. Réti, Z. Prohászka (Budapest, Hungary)

Platelets - Physiology and Disorders of platelet number and function
Date: 17.02.2017,
Time: 17:15 - 18:15

Objective: The common, acquired form of thrombotic thrombocytopenic purpura (TTP) is an autoimmune disease, in which the underlying ADAMTS13 deficiency is caused by inhibitory autoantibodies, predominantly of the IgG isotype. As distinct IgG subclasses can have different immunological properties, the aim of our present study was to determine the subclass distribution of anti-ADAMTS13 autoantibodies in acquired TTP patients, and to investigate its associations with clinical parameters.

Methods: We determined the relative and absolute amount of anti-ADAMTS13 IgG subclasses with an in-house ELISA method based on a commercial ELISA kit. We analysed 52 ADAMTS13 deficient, anti-ADAMTS13 antibody positive samples of 47 acquired TTP patients (mean age 39 years, 38 women). Forty-four samples were drawn during the acute phase of the disease, and eight in remission; four patients had samples from both disease states.

Results: We found that the anti-ADAMTS13 antibodies were mostly of IgG1 and IgG4 subclasses. IgG4 was the most predominant subclass in 69.2% of the samples, and IgG1 in 28.8% of them. The mean proportion of IgG4 was 52.1%, that of IgG1 was 39.2%, followed by IgG3 with only 5.9%. The absolute amount of IgG3 inversely correlated with that of IgG4 (p=0.0001). The percentage of the IgG1 and IgG3 subclasses were lower in relapsing patients (medians: 24% vs. 43% and 0% vs. 5%, respectively), while that of IgG4 was higher (71% vs. 49%). Conversely, the relative amount of IgG3 was higher (14% vs. 1%), and that of IgG4 was lower (10% vs. 65%) in patients, who have deceased during the TTP episode.

Conclusion: Our results are in accord with those of previous studies, which also found that IgG4 and IgG1 are the most predominant subclasses, and that high IgG1 levels are associated with a higher risk of death during the episode. One of the previous studies also found that IgG4 levels are higher in relapsing TTP patients. However, whether the predominance of IgG4 is a risk factor of relapse or rather a consequence of the previous therapy needs to be clarified. Similarly, additional studies are necessary to investigate whether subclass distribution of anti-ADAMTS13 antibodies or its changes during immunosuppressive therapy provide clinically useful information.