Abstract
Patients who have TTP associated with acquired, severe ADAMTS13 deficiency have an autoimmune etiology and therefore may have increased risk for additional autoimmune disorders. The Oklahoma TTP-HUS Registry enrolled 247 consecutive patients with their first episode of clinically diagnosed TTP from 11-13-1995 (the date of our initial ADAMTS13 measurement) to 6-30-2006 for whom plasma exchange treatment was requested; ADAMTS13 activity was measured in 228 (92%) of patients immediately before their first plasma exchange treatment; 42 (18%) patients had ADAMTS13 activity <10%. Three patients were excluded from this analysis because of preexisting systemic rheumatic disease (systemic lupus erythematosus (SLE), 2, Sjogren’s syndrome, 1). To examine the potential risk for development of autoimmune disorders, we measured screening autoantibodies (ANA, dsDNA, Sm, nRNP, Ro, La, ribosomal P, Jo-1, anti-phospholipid (aPL) IgG and IgM) in 34 of the 39 (87%) remaining patients. The median age at initial presentation was 39 years (range 9–71 years); 27 (79%) patients were women; 13 (41%) patients were black. Autoantibodies were measured by indirect immunofluorescence, immunodiffusion, or ELISA. Measurements were performed only once in 16 patients; in 18 patients 2–3 measures were performed over a period of 13 to 126 months.
| Rheumatic disease autoantibodies . | TTP patients . |
|---|---|
| *1 patient had a maximum titer of >1:3240 in 2 samples; 1 patient developed overt SLE and his titer decreased with treatment. | |
| ANA ≥1:40 on at least one occasion | 33/34 (97%) |
| ANA ≥1:120 on at least one occasion | 29/34 (85%) |
| ANA measured ≥2 times, increasing titer | 14/16* (88%) |
| Anti-dsDNA ≥1:30 | 12/34 (35%) |
| Anti-Ro positive | 14/29 (48%) |
| Anti-Sm positive | 1/34 (3%) |
| Anti-nRNP positive | 1/34 (3%) |
| aPL IgG and/or IgM ≥moderate positive | 4/34 (12%) |
| Rheumatic disease autoantibodies . | TTP patients . |
|---|---|
| *1 patient had a maximum titer of >1:3240 in 2 samples; 1 patient developed overt SLE and his titer decreased with treatment. | |
| ANA ≥1:40 on at least one occasion | 33/34 (97%) |
| ANA ≥1:120 on at least one occasion | 29/34 (85%) |
| ANA measured ≥2 times, increasing titer | 14/16* (88%) |
| Anti-dsDNA ≥1:30 | 12/34 (35%) |
| Anti-Ro positive | 14/29 (48%) |
| Anti-Sm positive | 1/34 (3%) |
| Anti-nRNP positive | 1/34 (3%) |
| aPL IgG and/or IgM ≥moderate positive | 4/34 (12%) |
No patients had positive tests for anti-La, anti-Ribo-P, or anti-Jo-1. 23 (68%) of the 34 patients had a positive test for one or more rheumatic disease autoantibodies (dsDNA, nRNP, Ro, La, or moderately positive aPLs). 4 of the 34 patients died during their initial episode; the remaining 30 patients have been followed for a median of 6.4 years (range, 1–11.5 years). During this time only 1 patient has developed clinically evident SLE; no other patients have developed systemic rheumatic diseases.
Conclusions:
A high prevalence of rheumatic disease-associated autoantibodies were found in a cohort of consecutive patients with TTP associated with acquired severe ADAMTS13 deficiency.
The presence of dsDNA and Ro autoantibodies and increasing ANA titers suggest that patients with ADAMTS13-deficientTTP may have a potential risk for developing additional autoimmune disorders such as SLE or Sjogren’s syndromes.
[3] These serologic observations support clinical observations that presenting features of TTP and SLE may overlap.
Author notes
Disclosure: No relevant conflicts of interest to declare.
