Background/Purpose: Patients with systemic lupus erythematosus (SLE) have a higher incidence of thrombotic thrombocytopenic purpura (TTP). Differentiating TTP from SLE activity may represent a challenge to clinicians, and there is no adequate biomarker to help distinguish between both entities. The aim of this study was to correlate different molecules associated with vascular and platelet regulation in patients with SLE-associated TTP at diagnosis (dx), after plasmapheresis (ap) and at remission (rem). 

Methods: We included 73 subjects (13 SLE/TTP patients, 14 SLE-remission, 13 active hematological SLE, 14 non-hematological active SLE and 19 healthy controls). Patients were diagnosed with TTP in the presence of the following parameters: microangiopathic hemolytic anemia, thrombocytopenia ≤100,000 cel/µl, high LDH levels and negative Coombs test. Patients with SLE were diagnosed with at least ≥ 4 ACR classification criteria. We obtained serum samples for each subject, including serial samples for SLE/TTP patients (dx, ap and rem). Serum sCD40L and VEGF were measured by ELISA, and different cytokine levels were measured by luminometry. 

Results: The main characteristics of each group are depicted in table 1. We found increased sCD40L levels in active hematological and non-hematological SLE in comparison to SLE/TTP^dx (p=0.039 and 0.001 respectively), but there were no differences between SLE/TTP^rem and active hematological SLE (3044±403 vs 3397±708 pg/ml, p=0.77). Interestingly, mean sCD40L levels progressively increased in treated SLE/TTP patients (see table) an also a positive correlation between sCD40L and VEGF levels was found (r=0.62, p=0.004), regardless of the improvement in platelet count. There were no significant differences in SLEDAI score among TTP and active SLE groups (p=0.54). Furthermore, CXCL1 levels were lower in SLE/TTP^dx vs active hematological SLE (22.5±5.7 vs 136.7±33.5 pg/ml, p=0.040). Other analyzed cytokines (IL2, 6, 8, 10, TNFα e IFNγ) were not different among groups. 

Conclusion: Our findings suggest that SLE/TTP patients have sCD40L depletion at baseline, which represents a differential serologic profile from active SLE. After the proper treatment is initiated, sCD40L levels increase progressively. It is possible that the depletion of this costimulatory molecule could be associated with recruitment at the vascular wall, denoting its potential pathogenic role in microangiopathy-associated endothelial dysfunction. Prospective studies, which ideally should include TTP patients without any autoimmune disease, are needed to confirm those findings.

Table 1. Clinical and serologic characteristics of the different groups

N/A= Not Applicable; N/D= Not Determined

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/depletion-of-serum-soluble-cd40l-characterizes-the-association-between-systemic-lupus-erythematosus-and-thrombotic-thrombocytopenic-purpura-longitudinal-single-center-study/