High risk of systemic lupus erythematosus and antiphospholipic syndrome in patients with idiopathic thrombocytopenic purpura: Genetic aspects

Sir,

In the post-genomic era, the genomic revolution in translational medicine has not escaped attention of clinician and researchers focusing on the medical management of idiopathic thrombocytopenic purpura (ITP). ITP is a hematologic disorder diagnosed clinically upon onset of thrombocytopenia in the absence of other hematologic abnormalities. It is defined by low platelet counts, thus presenting with an increased bleeding risk. ¹ No extended data related to the co-morbidities of other autoimmune diseases with ITP had been presented thus far. Recently, Zhu et al., ² conducted a very interesting 14 years’ population-based study and demonstrated that patients with new diagnosed ITP are at a higher risk of subsequent new-onset systemic lupus erythematosus (SLE), a chronic inflammatory autoimmune disease that involves multiple systems and appears a remitting or relapsing course. ³ Thus, it was demonstrated that the patients with ITP had a 26 times higher risk of new-onset SLE compared with the control population analysed. ² Moreover, Inanc et al. ⁴ pointed out that in some patients initially diagnosed with ITP, features of antiphospholipid syndrome (APS) may be developed, given that patients with ITP and positive antiphospholipid autoantibodies (aPL) had developed APS during long-term follow-up. This data was consistent with a recent study by Zhu et al. ² that had also provided important data on the association of APS with ITP, by identifying a percentage of 2.77% cases of APS in the ITP group. APS is a rare, heterogeneous, multisystemic disorder associated with recurrent arterial and/or venous thrombosis, recurrent fetal loss and immune thrombocytopenia in the presence of aPL. ⁵

Together, the aforementioned studies posed the intriguing question concerning the putative role of a shared genetic background as regards with the concurrence of ITP and SLE and/or ITP and APS. In this framework, various studies have pointed to potential genetic factors for developing both ITP and SLE or ITP and APS, thus suggesting a shared genetic predisposition in some cases. As summarized recently by Goulielmos and Zervou, ⁶ forty-one pathways, 27 genes and various gene polymorphisms, i.e. IL-10 -592 C/A, IL-4 VNTR, IL-17F rs763780 etc, are shared by ITP and SLE. In our attempt to provide a comprehensive update on the current understanding of the potential shared genetic component of ITP and APS, we found that the human leukocyte antigen (HLA) DQB1*03, PTPN22, LTA, IRF5, FcγRIIA, IL-6 and STAT1 genes had been reported to be associated with both diseases.^7–10

In conclusion, despite our present effort, we did not manage to identify genetic factors involved in the development of all three diseases examined, due probably to the complicated and confusing data that are available so far for these conditions. The further identification of either shared or disease-specific genetic loci associated with both the development of ITP, SLE and APS as well as their specific clinical features may help to better delineate the mechanisms for these diseases and improve diseases’ classification and management.