CLINICAL AND BIOLOGICAL FEATURES DISTINGUISH MYELOID DISEASES FROM MYELOID DISORDERS ASSOCIATED WITH AUTOIMMUNE DISEASES.

In a series of 11000 patients withmyeloproliferative neoplasms (MPN) and 43,000 matched controls, a Swedish group reported that a prior history of autoimmune diseases (ADs) was significantly associated with a higher risk of MPN. More recently, our group showed that in chronic myeloid leukemia (CML) some genes correlated with AD (GLYPR1, PCARD, S100) were highly expressed at diagnosis and that the treatment with Imatinib impacted on the “inflammatory” profile of CML patients. Aims To investigate the frequency of myeloid malignancies (i.e myelodysplastic syndrome (MDS) and chronic, either Philadelphia-positive or Philadelphia-negative, myeloproliferative disorders (MPNs)) in patients with ADs, their influence on the ADs clinical course and vice-versa, and to identify several distinctive clinical and biological features. Methods A retrospective systematic search through the electronic health records of the patients admitted at Rheumatology from 2009 and 2019 was performed to select those presenting with ADs and MDS or MPNs. Categorical variables were compared using chi square test and Fisher’s test; continuous variables were compared using Student’s t-test. A 2-tailed value of p <0.05 was taken to indicate statistical significance. Results Out of the medical records of 5040 patients, we identified 55 patients (33 F: 22 M, mean age: 61 years) with ADs and myeloid malignancies (1%): 20/55 with AD and MDS and 35/55 with AD and MPNs. No demographic differences were observed in the two subgroups. Regarding MDS, anemia was the most common hematologic presenting finding (16/20, 80%), with diagnosis of refractory anemia with excess of blasts (RAEB I/II) done in 25% of cases, followed by syderoblastic anemia in 12%. In the MPNs, 12/35 patients (34%) had a diagnosis of chronic myeloid leukemia (CML), 9/35 (26%) had MF 8/35 (23%) had an ET and 6/35 (17%) a PV. The JAK2 V617F mutation was detected in 100%, 57%, and 66% of PV, ET, and MF patients respectively. Regarding the temporal appearance of myeloid malignancy, MDS occurred concurrently (10/20) or followed (10/20) the diagnosis of Ads, whereas MPNs generally preceded the diagnosis of ADs (19/35). In MDS, the most commonly diagnosed ADs were seronegative arthritis (5/20, 25%), large and small vessel vasculitis (4/20, 20%), Systemic Lupus Erythematosus (3/20, 15%) and other ones in the remaining 8 cases. In patients with MPNs, the diagnosis of rheumatoid arthritis (2/9, 22%), and anti-phospholipid syndrome (3/9, 33%) were often associated with MF, whereas anti-Ro52 (TRIM21) positive systemic connective tissue disorders (4/8, 50%) were more frequently detected in ET. Cardiovascular events were observed in 14/55 (26%): 4/20 (20%) in MDS, 3/12 (25%) in CML and 7/23 (30%) in Philadelphia-negative MPNs. In this cohort, as expected, cardiovascular events were all observed in patients presenting JAK2V617F mutation. Conclusion Our study shows that the frequency of MDS and MPNs in ADs is not negligible and might be considered in the assessment of cardiovascular risk in systemic autoimmunity. It has been reported that, under viral infection, TRIM21 is up-regulated by activation of the IFN/JAK/STAT pathway; interestingly, anti-Ro52 (TRIM21) were over-represented in MPN, where the JAK/STAT signal is hyper activated. This could explain also our observation that frequently the onset of ADs follows the diagnosis of MPN. Ackowledges: this study received support from university of Pisa PRA 2018 PI Prof. Petrini