Figure 2.
Examples of changes in ADAMTS13 conformation tested during longitudinal follow-up in 3 groups. (A) ADAMTS13 conformation at remission with no further relapse. Longitudinal follow-up of a patient from acute iTTP episode to remission reveals an open ADAMTS13 conformation consistent with severe ADAMTS13 deficiency. CIND decreases as ADAMTS13 activity recovers. The conformation remains open for some time despite the normalization of ADAMTS13 activity. A closed ADAMTS13 conformation is achieved at the peak ADAMTS13 activity. A normal anti-ADAMTS13 IgG antibody level is achieved by ADAMTS13 normalization and occurs before achieving a closed ADAMTS13 conformation. Increasing ADAMTS13 antigen levels correlate well with ADAMTS13 activity. To date, this patient has not had any further relapses. (B) Changes in ADAMTS13 conformation associated with clinical/ADAMTS13 relapse. (Bi) Longitudinal follow-up of a patient with multiple clinical relapses. ADAMTS13 conformation is open with peak ADAMTS13 activity before relapse, despite normal ADAMTS13 activity and negative anti-ADAMTS13 IgG antibody level at the same time point. At clinical relapse, there is a significant increase in CIND with severe ADAMTS13 deficiency. It took 3.9 months from peak ADAMTS13 activity to clinical relapse. With ADAMTS13 activity recovery, the CIND falls but remains open (CIND, 0.57) despite a peak ADAMTS13 activity of 103%. Over time, ADAMTS13 activity and antigen levels fall leading to another clinical relapse and is accompanied by a significant increase in CIND. The time from peak ADAMTS13 activity to clinical relapse was 9.6 months. The patient received ofatumumab instead of rituximab for this episode. With treatment, ADAMTS13 activity normalizes and ADAMTS13 conformation becomes closed at the peak ADAMTS13 activity. (Bii) This patient has an open ADAMTS13 conformation during clinical relapse. It remains borderline (CIND, 0.5) despite normalization of ADAMTS13 with treatment. This is followed by an ADAMTS13 relapse, which was treated at an ADAMTS13 activity of 28.3% due to severe symptoms in this patient. CIND increases further; however, the same is not seen with anti-ADAMTS13 IgG antibody. After first course of rituximab, ADAMTS13 activity improves but does not normalize, and the CIND improves but remains open (CIND, 1.5). This is followed by another ADAMTS13 relapse, accompanied by a further fall in ADAMTS13 activity and a rise in CIND value to 2.8. No significant rise in anti-ADAMTS13 IgG antibody is seen. With further elective rituximab, a closed ADAMTS13 conformation is achieved. However, it does not predict ADAMTS13 relapse within 2 years. (C) ADAMTS13 conformation in patient with low ADAMTS13 activity. This patient has persistent severe ADAMTS13 deficiency with a persistent open ADAMTS13 conformation. ADAMTS13 antigen levels remain adequate despite ADAMTS13 activity <10%, except for clinical relapse, when antigen levels fall significantly and are accompanied by a significant rise in CIND. Anti-ADAMTS13 IgG antibody levels are high, which explains the persistent severe ADAMTS13 deficiency and open ADAMTS13 conformation.

Examples of changes in ADAMTS13 conformation tested during longitudinal follow-up in 3 groups. (A) ADAMTS13 conformation at remission with no further relapse. Longitudinal follow-up of a patient from acute iTTP episode to remission reveals an open ADAMTS13 conformation consistent with severe ADAMTS13 deficiency. CIND decreases as ADAMTS13 activity recovers. The conformation remains open for some time despite the normalization of ADAMTS13 activity. A closed ADAMTS13 conformation is achieved at the peak ADAMTS13 activity. A normal anti-ADAMTS13 IgG antibody level is achieved by ADAMTS13 normalization and occurs before achieving a closed ADAMTS13 conformation. Increasing ADAMTS13 antigen levels correlate well with ADAMTS13 activity. To date, this patient has not had any further relapses. (B) Changes in ADAMTS13 conformation associated with clinical/ADAMTS13 relapse. (Bi) Longitudinal follow-up of a patient with multiple clinical relapses. ADAMTS13 conformation is open with peak ADAMTS13 activity before relapse, despite normal ADAMTS13 activity and negative anti-ADAMTS13 IgG antibody level at the same time point. At clinical relapse, there is a significant increase in CIND with severe ADAMTS13 deficiency. It took 3.9 months from peak ADAMTS13 activity to clinical relapse. With ADAMTS13 activity recovery, the CIND falls but remains open (CIND, 0.57) despite a peak ADAMTS13 activity of 103%. Over time, ADAMTS13 activity and antigen levels fall leading to another clinical relapse and is accompanied by a significant increase in CIND. The time from peak ADAMTS13 activity to clinical relapse was 9.6 months. The patient received ofatumumab instead of rituximab for this episode. With treatment, ADAMTS13 activity normalizes and ADAMTS13 conformation becomes closed at the peak ADAMTS13 activity. (Bii) This patient has an open ADAMTS13 conformation during clinical relapse. It remains borderline (CIND, 0.5) despite normalization of ADAMTS13 with treatment. This is followed by an ADAMTS13 relapse, which was treated at an ADAMTS13 activity of 28.3% due to severe symptoms in this patient. CIND increases further; however, the same is not seen with anti-ADAMTS13 IgG antibody. After first course of rituximab, ADAMTS13 activity improves but does not normalize, and the CIND improves but remains open (CIND, 1.5). This is followed by another ADAMTS13 relapse, accompanied by a further fall in ADAMTS13 activity and a rise in CIND value to 2.8. No significant rise in anti-ADAMTS13 IgG antibody is seen. With further elective rituximab, a closed ADAMTS13 conformation is achieved. However, it does not predict ADAMTS13 relapse within 2 years. (C) ADAMTS13 conformation in patient with low ADAMTS13 activity. This patient has persistent severe ADAMTS13 deficiency with a persistent open ADAMTS13 conformation. ADAMTS13 antigen levels remain adequate despite ADAMTS13 activity <10%, except for clinical relapse, when antigen levels fall significantly and are accompanied by a significant rise in CIND. Anti-ADAMTS13 IgG antibody levels are high, which explains the persistent severe ADAMTS13 deficiency and open ADAMTS13 conformation.

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