Objectives
To investigate the risk factors and clinical characteristics of lymphoproliferative disorder (LPD) in Japanese patients with rheumatoid arthritis (RA).
Methods
We enrolled patients with RA aged ≥20 years who visited the participating hospitals between April 2011 and July 2011. We investigated the risk factors for LPD using a Cox proportional hazard model and described pathological features and vital prognosis of LPD in patients with RA.
Results
We enrolled 9815 patients with the following characteristics at baseline: female 79.4%, median age 63 years; median disease duration 7 years; median DAS28-CRP (3) 3.1; prevalence of MTX use 60.0%. Sixty-eight patients (0.69%) developed LPD in 3-year observation period. Multivariable analysis showed that age by decade (hazard ratio [95% confidence interval], 1.47 [1.18–1.85]) and MTX use at baseline (2.35 [1.25–4.42] for ≤8 mg/week, 4.39 [2.07–9.32] for >8 mg/week versus non-use) were significant risk factors of LPD. Of 55 patients with pathological diagnosis, diffuse large B cell lymphoma was the most frequent (54%). The 5-year mortality of LPD was 24%. The major cause of death was lymphoma (81%).
Conclusion
This nationwide study revealed risk factors, clinical characteristics, and prognosis of LPD in the largest number of Japanese patients with RA.
We previously established a J774.1 monocyte/macrophage subline expressing a truncated EphA2 construct lacking the kinase domain. We demonstrated that following ephrin-A1 stimulation, endogenous EphA2 promotes cell adhesion through interaction with integrins and integrin ligands such as ICAM1 and that truncated EphA2 potentiates the adhesion and becomes associated with the integrin/integrin ligand complex. Based on these findings, we hypothesized that the EphA/ephrin-A system, particularly EphA2/ephrin-A1, regulates transendothelial migration/tissue infiltration of monocytes/macrophages, because ephrin-A1 is widely recognized to be upregulated in inflammatory vasculatures. To evaluate whether this hypothesis is applicable in the spleen, we screened for EphA2/ephrin-A1 expression and reexamined the cellular properties of the J774.1 subline. We found that ephrin-A1 was expressed in the vasculature of the marginal zone and the red pulp and that its expression was upregulated in response to phagocyte depletion; further, CD115, F4/80, and CXCR4 were expressed in J774.1 cells, which serve as a usable substitute for monocytes/macrophages. Moreover, following ephrin-A1 stimulation, truncated EphA2 did not detectably interfere with the phosphorylation of endogenous EphA2, and it potentiated cell adhesion possibly through modulation of integrin avidity. Accordingly, by intravenously injecting mice with equal numbers of J774.1 and the subline cells labeled with distinct fluorochromes, we determined that truncated EphA2 markedly potentiated preferential cell infiltration into the red pulp and the marginal zone. Thus, modulation of EphA2 signaling might contribute to effective transplantation of tissue-specific resident macrophages and/or monocytes.
Objective To compare the risk of hospitalized infection (HI) between users and non-users of hydroxychloroquine (HCQ) in systemic lupus erythematosus (SLE). Methods Using claims data, patients were defined as SLE cases by the following criteria: 1) they had at least one SLE diagnostic code; 2) they had a prescription for specific drugs, including corticosteroids, steroid pulse therapy, and immunosuppressive drugs; and 3) they were at least 16 years old between September 2015 and July 2017 (n = 17,483). The SLE cases with at least one prescription for HCQ were defined as the HCQ group (n = 1,431), while the others were defined as the non-HCQ group. Among the SLE cases, propensity score-matched cases were observed for 1 year (n = 1,095 in each group). Results The median age and proportion of female patients in both groups were about 42 years and 88%, respectively. The proportions of cases with HIs were similar (HCQ group, 4.5%; non-HCQ group, 5.6%; p = 0.240, McNemar test). The hazard ratio of the HCQ group for HIs after adjusting for patients’ characteristics was not significant at 0.9 (0.6–1.3). Conclusion The use of HCQ was not associated with a risk of HIs in patients with SLE.
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