Medullary thymic epithelial cells (mTECs) help shape the thymic microenvironment for T cell development by expressing a variety of peripheral tissue-restricted antigens (TRAs). The self-tolerance of T cells is established by negative selection of autoreactive T cells that bind to TRAs. To increase the diversity of TRAs, a fraction of mTECs terminally differentiate into distinct subsets resembling atypical types of epithelial cells in specific peripheral tissues. As such, thymic tuft cells that express peripheral tuft cell genes have recently emerged. Here we show that the transcription factor Sox4 is highly expressed in mTECs and is essential for the development of thymic tuft cells. Mice lacking Sox4 specifically in TECs had a significantly reduced number of thymic tuft cells with no effect on the differentiation of other mTEC subsets, including Aire + and Ccl21a + mTECs. Furthermore, Sox4 expression was diminished in mice deficient in TEC-specific lymphotoxin β receptor (LTβR), indicating a role for the LTβR-Sox4 axis in the differentiation of thymic tuft cells. Given that Sox4 promotes differentiation of peripheral tuft cells, our findings suggest that mTECs employ the same transcriptional program as peripheral epithelial cells. This mechanism may explain how mTECs diversify peripheral antigen expression to project an immunological self within the thymic medulla.

A 59-year-old man presented with fever and lower extremity myalgia. Laboratory studies revealed elevated C-reactive protein. 18F-FDG PET/CT demonstrated FDG uptake not only in the brachial arteries, femoral arteries, and their main ramifications, which were equivalent to small- to medium-sized arteries but also in the kidneys. Angiography revealed a renal aneurysm, confirming the diagnosis of polyarteritis nodosa. The increased FDG uptake in the vessels and kidneys resolved after 6 months of glucocorticoid treatment.

BackgroundThe 2012 EULAR recommendations gave equal weight to intravenous cyclophosphamide (IVCY) and mycophenolate mofetil (MMF) as the induction therapy for class III/IV lupus nephritis (LN). However, there are no effective parameters that could inform the choice the induction therapy (IVCY or MMF) in individual cases.ObjectivesThis study examined the patient characteristics that determine the most appropriate treatment for LN: IVCY or MMF.MethodsWe retrospectively examined 29 patients with LN who received induction therapy with IVCY (n=16) or MMF (n=13) between January 1994 and December 2015. Their baseline characteristics and the complete response (CR) rate at week 24 were analysed. CR was defined as a urine protein:creatinine ratio <0.5 g/gCre with normal urine sediment.ResultsAt baseline, the time since diagnosis of systemic lupus erythematosus (SLE) was longer in the IVCY group than the MMF group (4.8±6.4 vs. 1.3±2.5 years, p=0.06) and the IVCY group had more frequent flares (1.9±2.4 vs. 0.7±1.1 times, p=0.08); however, the differences were not significant. Moreover, there was no difference in age, sex, complement levels, anti-dsDNA antibody titers, anti-Sm/RNP antibody positivity rates, proteinuria, or rate of abnormality in urine sediment at baseline between the two groups. CR was achieved at week 24 in 11/16 patients (69%) in the IVCY group and 9/13 patients (69%) in the MMF group. Considering the 20 patients who achieved CR at week 24, univariate analyses revealed that in addition to a longer time since diagnosis of SLE (4.5±6.6 vs. 1.0±1.7 years, p=0.12) and more frequent flares (1.9±2.8 vs. 0.6±1.0 times, p=0.16), the anti-RNP antibody positivity rate was higher (OR 8.15; p=0.07) in the IVCY group. Furthermore, the positivity rate of anti-RNP antibody differed significantly (OR 12.9; p=0.03) in the multivariate analysis.Abstract AB0525 – Table 1Univariate analyses of patients with CR at week 24 IVCY (n=11) MMF (n=9) p value age (years) 31.2±10.9 39.6±18.8 0.23 sex (male,%) 9.1 22.2 0.57, OR=2.71 time since diagnosis of SLE (years) 4.5±6.6 1.0±1.7 0.12 flares (times) 1.9±2.8 0.6±1.0 0.16 complement C3 level (mg/dL) 48.3±29.3 47.6±21.5 0.95 anti-dsDNA antibody (IU/mL) 161.2±187.4 128.8±154.2 0.68 anti-Sm antibody (%) 63.6 33.3 0.37, OR=3.27 anti-RNP antibody (%) 72.7 22.2 0.07, OR=8.15Abstract AB0525 – Table 2Multivariate analyses of patients with CR at week 24Model 1Model 2 OR (95% CI) p value OR (95% CI) p value age − − 0.9 (0.8–1.0) 0.15 sex (female) − − 1.2 (0.04–38.8) 0.92 time since diagnosis of SLE 1.1 (0.7–1.7) 0.77 1.0 (0.6–1.6) 0.91 flares 1.5 (0.5–4.2) 0.44 1.7 (0.6–4.4) 0.30 anti-RNP antibody 12.9 (1.3–132.3) 0.03* 31.8 (1.1–892.9) 0.04*Model 1 was adjusted by all of the characteristics which showed p<0.20 in the univariate analysis; model 2 was adjusted by age and sex in addition to model 1.dsDNA, double strand DNA; anti-Sm antibody, anti-smith antibody; anti-RNP antibody, anti-ribonucleoprotein antibody; OR, odds ratio; CI, confidence interval. (*p<0.05)ConclusionsAlthough IVCY and MMF ...

BackgroundSeveral factors increasing the risk of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis have been reported. These include pulmonary and cardiovascular lesions, PR3-ANCA-positivity in patients with granulomatosis with polyangiitis, and persistent ANCA-positivity or an increase in the titer of such antibodies.ObjectivesWe aimed to identify potentially novel factors predicting relapse in patients with ANCA-associated vasculitis.MethodsWe reviewed data on 73 patients (61 with microscopic polyangiitis [MPA], 12 with granulomatosis with polyangiitis [GPA]; 46 females) treated in our centre from 1998 to 2017 for whom medical histories were available. All achieved at least one remission after induction therapy. Relapse was defined as novel organ involvement or a need for therapy intensification. Follow-up continued to the first relapse or for as long as possible if no relapse was noted.ResultsThe median age at disease onset (interquartile range) was 74 years (range: 67–80 years). The relapse rate was 42.5% (MPA 41%, GPA 50%), thus not significantly different between the two groups (p=0.75). The median follow-up duration was 23 months (range: 11–65 months) and the median time to relapse was 18 months (range: 10.5–54 months). Although pulmonary and cardiac lesions reportedly increase the relapse rate, neither contributed significantly to the rate in this study. Furthermore, ANCA-positivity after remission and increases in ANCA levels prior to relapse did not significantly increase the relapse risk. In terms of medical histories recorded at the time of first onset of disease, the frequency of diabetes, dyslipidemia, coronary artery disease, and cerebral infarction did not differ significantly between patients who did and did not relapse. However, in MPA patients, a history of hypertension was significantly less in those who relapsed (p=0.01). In a multiple logistic regression analysis adjusted for sex and age, history of hypertension was a significant predictor of fewer relapse (odds ratio: 0.23; 95% confidence interval 0.07–0.69, p=0.009).Abstract AB0682 – Table 1The clinical characteristics of two groupsRelapse, n=31Non-relapse, n=42pOR (95% CI) Age, yearsMean±SDMedian(interquartile range) 70.8±10.873 (65–79) 74.6±9.276 (68–82)0.10-Median follow up, month18 (11–54)*Time to 1st relapse30 (13–67)--Male/female10/2117/250.620.7 (0.23–2.05)ANCA phonotype, n (%)PR3-ANCAMPO-ANCA 4 (13.0%)27 (87.1%) 7 (16.7%)36 (85.7%) 0.75>0.99 0.74 (0.14–3.29)1.12 (0.24–5.97)Disease type, n (%)GPAMPA 6 (19.4%)25 (80.6%) 6 (14.3%)36 (85.7%)0.750.70 (0.17–2.94)Organ involvementPulmonaryCardiovascular 241 332 >0.99>0.99 0.94 (0.27–3.41)0.67 (0.01–13.44)Medical historiesDiabetes mellitusDyslipidemiaHypertension 7910 3728 0.090.260.005 3.70 (0.76–24.44)2.02 (0.58–7.43)0.24 (0.08–0.71)ANCA: antineutrophil cytoplasmic antibody; PR3: proteinase 3; MPO: myeloperoxidase; GPA: granulomatosis with polyangiitis; MPA: microscopic polyangiitis; OR: odds ratio; 95% CI: 95% confidence intervalConclusionsIn addition to known factors, a ...