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To understand the behavior and function of bone-marrow mesenchymal cells (BMMCs), we overviewed the morphological presentation of BMMCs in bone-marrow granules (b-BMMCs), isolated BMMCs (i-BMMCs), and BMMCs (c-BMMCs) cultured in H4434 methylcellulose semisolid and MEM media. All samples were derived from bone-marrow aspirates of 30 patients with hematocytopenia. Light microscopy exhibited b-BMMCs and i-BMMCs characterized by abundant cytoplasm and irregular shape in bone-marrow smears, as well as c-BMMCs in culture conditions. Scanning electron microscopy demonstrated cultured c-BMMCs with a sheet-like feature enveloping hematopoietic cells. Transmission electron microscopy revealed b-BMMCs constructing a honeycomb-like structure by thin bifurcate processes among hematopoietic cells. Furthermore, i-BMMCs had bifurcate parapodiums on the surface and prominent rough endoplasmic reticulum (rER) connected with the plasmalemma of the parapodiums. The detailed images suggested that rER may serve as a membrane resource for plasmalemmal expansion in BMMCs in bone marrow.

Objectives To assess the risk of developing cancer in patients with rheumatoid arthritis (RA) exposed to non-TNF inhibitors (TNFi) biologics or tofacitinib therapy. Methods Systematical search of PubMed, EMBASE and Cochrane Library plus a hand search of conference proceedings were performed. Observational studies that reported cancer incidence in patients with RA treated with biologics or tofacitinib with active comparator of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) or TNFi were eligible for inclusion. The pooled relative risk (RR) and 95% confidence interval (CI) were calculated with fix-effects or random-effects model. Results Of 2,819 identified articles, a total of 10 studies involving over 40,587 patients with more than 87,622 patient-years of exposure to non-TNF inhibitors (TNFi) biologics and 2,221 patients with more than 4,506 patient-years of exposure to tofacitinib were included. Pooled analysis showed there was no increased risk of developing cancer in general or specific cancer types in RA patients receiving treatment with rituximab (pooled RR 0.87, 95% CI 0.74-1.03), tocilizumab (pooled RR 0.92, 95% CI 0.79-1.06), or tofacitinib, compared with those receiving csDMARDs or TNFi. But abatacept was associated with a slightly increased overall cancer risk (pooled RR 1.13, 95% CI 1.02-1.24) and non-melanoma skin cancer (pooled RR 1.26, 95% CI 1.09-1.45), relative to csDMARDs or TNFi in RA patients. Conclusion Among RA patients, a small statistically significant increase in developing cancer was observed for abatacept exposure, while no increased cancer risk for rituximab, tocilizumab or tofacitinib, in comparison with csDMARDs or TNFi.

Objectives To evaluate the attainability of Lupus Low Disease Activity State (LLDAS) and definitions of remission in SLE (DORIS) in a treatment-naïve cohort of SLE. Methods LLDAS5 was defined as LLDAS with a prednisone dose ≤5 mg/day. There were four definitions in DORIS: clinical remission on treatment (RONT), complete RONT, clinical remission off treatment (ROFT) and complete ROFT. The treatment-naïve patients from Peking University First Hospital SLE cohort were enrolled. The time to each state and their annual cumulative probabilities were estimated. The frequencies of patients who achieved each component of LLDAS or DORIS during follow-up were determined. The predictors of time to each state were identified. Results A total of 218 patients were included, with a median follow-up of 4.48 years. Respectively, 190 (87.2%), 160 (73.4%), 148 (67.9%), 94 (43.1%), 23 (10.6%) and 18 (8.3%) patients achieved LLDAS, LLDAS5, clinical RONT, complete RONT, clinical ROFT and complete ROFT. The median time to LLDAS, LLDAS5, clinical RONT and complete RONT were 1.4, 2.3, 2.6 and 4.7 years, respectively. Positive anti-dsDNA, RP and anaemia were significantly associated with prolonged time to LLDAS, LLDAS5 or clinical RONT. Conclusion Our data confirmed that LLDAS is an attainable early treatment target for SLE. Though with more difficulty, RONT can be achieved in two-thirds of our patients. ROFT may not be an ideal treatment target at present as it is only attained in few patients.

Objective To clarify the frequency and outcome of patients with systemic lupus erythematosus (SLE) who achieved the clinical state as serologically active clinically quiescent (SACQ) and to identify factors associated with the flare of disease. Methods Clinical data of patients diagnosed as SLE and followed in Peking University First Hospital from 2009 to 2015 were retrospectively reviewed. Six hundred eighty-two patients who were followed up for more than 6 months were analyzed. SACQ was defined as an at least a 6-month period with persistent serologic activity and without clinical activity and daily dose of prednisone or equivalent were less than 7.5 mg. Serologically quiescent clinically quiescent (SQCQ) patients served as control groups. Data including demographics, initial symptoms, duration to SACQ, treatments before and after SACQ, and characteristics of the patients suffered from flare were analyzed. Results Among the 682 patients, 170 patients were SACQ (24.9%) and 187 patients were SQCQ. SQCQ patients (38.61 ± 15.08 years old) were older at baseline than SACQ patients (38.61 ± 15.08 years vs. 32.09 ± 14.35 years, p < 0.001). Of 170 SACQ patients, 32.9% experienced flare that was significantly higher than 15.5% of SQCQ patients (29/187). Corticosteroids (OR 1.323, 95% CI 1.129 to 1.550; p = 0.001) was an independent risk factor for flare, while antimalarials (OR 0.045, 95% CI 0.004 to 0.474; p = 0.010) and immunosuppressants (OR 0.332, 95% CI 0.156 to 0.706; p = 0.004) were protective factors in SACQ patients; however, only antimalarials was protective factors in SQCQ patients (OR 0.028, 95% CI 0.001 to 0.743; p = 0.033). Conclusion About one third of SLE patients with SACQ experience flare, significantly more frequent than that of patients with SQCQ. Thus, approach to prevent flare in SACQ patient is required. Maintenance therapy of hydroxychloroquine and immunosuppressant agents may be protective and beneficial treatment strategy in these patients.

COVID-19 vaccines are of great importance in reducing SARS-CoV-2 infection and severe cases. Patients with autoimmune inflammatory rheumatic diseases (AIIRDs) have been strongly recommended to be vaccinated according to the novel guidance because they are more vulnerable to SARS-CoV-2 infection.1 However, patients with AIIRDs were largely excluded from vaccine trials, leading to very limited data on the safety of COVID-19 vaccines. Notably, previous studies mainly focused on mRNA and adenovirus vector vaccines; however, little is known about inactivated COVID-19 vaccines that also have been authorised by WHO and widely used in several most populated countries, for instance, China, Brazil, Turkey and Indonesia.2 A large randomised clinical trial consisting of 40 382 participants has demonstrated two inactivated COVID-19 vaccines significantly reduced the risk of symptomatic COVID-19.3 We conducted a real-world survey to evaluate the safety profiles and disease flare in patients with AIIRDs who received any dose of inactivated COVID-19 vaccines in China. From 1 Aug 2021 to 15 Oct 2021, eligible participants completed a predefined 25-question-based questionnaire by invitation on social media or visiting the outpatient department. There was no restriction on the time interval from vaccination to completing the survey. In total, 1507 adults patients with AIIRDs who received inactivated COVID-19 vaccine participated in this study (flow diagram …

Objective To investigate the frequency and determinants of achieving the lupus low disease activity state (LLDAS), and the effect of LLDAS attainment on disease flare and damage accrual in a prospective, single-center cohort of Chinese lupus patients. Methods Baseline and follow-up data from consecutive patients at the Peking University First Hospital were collected from January 2017 to June 2020. Results A total of 185 patients were enrolled, with median (range) disease duration at enrolment of 2.3 (0.8–7.7) years, and median follow-up of 2.2 (1.0–2.9) years. By the end of the study, 139 (75.1%) patients had achieved LLDAS at least once; 82 (44.3%) patients achieved LLDAS for ≥ 50% of observations. Multivariable logistic regression analysis showed that 24-h urinary total protein (UTP; per g) (OR = 0.447, 95%CI [0.207–0.968], p = 0.041), serum creatinine (Scr; per 10 µmol/L) (OR = 0.72, 95%CI [0.52–0.99], p = 0.040), and C3 level (per 100 mg/L) (OR = 1.60, 95%CI [1.18–2.17], p = 0.003) at recruitment had independent negative associations with achieving LLDAS for ≥ 50% of observations. Kaplan–Meier analyses showed a significant reduction in flare rate with increased proportion of time in LLDAS. Attainment of LLDAS in at least 50% of observations was an independent protective factor for damage accrual (OR = 0.19, 95%CI [0.04–0.99], p = 0.049). Conclusions In this prospective Chinese cohort, LLDAS was an attainable goal in clinical practice. Nephritis-related markers (UTP and Scr) and C3 level at recruitment negatively influenced achievement of LLDAS. LLDAS achievement was significantly protective from flare and damage accrual. Key points • Low disease activity status (LLDAS) is an achievable target during SLE treatment in China. Urine protein, serum creatinine, and C3 level at recruitment independently affect LLDAS achievement in this group of Chinese lupus patients. • As a treatment target, LLDAS achievement has a highly protective effect for preventing flare and damage accrual, especially in case of achieving LLDAS for ≥ 50% of observations. • The present results further highlight the practical significance of treat-to-target principle in SLE management (T2T/SLE) and the needs for promoting the application of T2T/SLE in clinical practice as well as exploring the concrete implement strategy.

Pulmonary arterial hypertension (PAH) is a fatal disease characterized by vascular remodeling and chronic inflammation. Macrophages are the key orchestrators of inflammatory and repair responses, and have been demonstrated to be vital in the pathogenesis of PAH. However, specific phenotype of macrophage polarization (M1 & M2 macrophage) in the development of PAH and the underlying mechanisms how they work are still largely unclear. A rat model of monocrotaline (MCT) induced PAH was used. Hemodynamic analysis and histopathological experiments were conducted at day 3, 7, 14, 21 and 28, respectively. In PAH rat lung tissue, confocal microscopic images showed that CD68+NOS2+ M1-like macrophages were remarkably infiltrated on early stage, but dramatically decreased in mid-late stage. Meanwhile, CD68+CD206+ M2-like macrophages in lung tissue accumulated gradually since day 7 to day 28, and the relative ratio of M2/M1 macrophage increased over time. Results detected by western blot and immunohistochemistry were consistent. Further vitro functional studies revealed the possible mechanism involved in this pathophysiological process. By using Transwell co-culture system, it was found that M1 macrophages induced endothelial cell apoptosis, while M2 macrophages significantly promoted proliferation of both endothelial cell and smooth muscle cell. These data preliminarily demonstrated a temporal dynamic change of macrophage M1/M2 polarization status in the development of experimental PAH. M1 macrophages participated in the initial stage of inflammation by accelerating apoptosis of endothelial cell, while M2 macrophages predominated in the reparative stage of inflammation and the followed stage of aberrant tissue remodeling.

Background Psoriatic arthritis (PsA) is a progressive joint disease associated with psoriasis. Objectives To investigate the association of modifiable lifestyle and environmental factors with PsA risk among people with psoriasis. Methods We conducted a systematic search of PubMed, Embase, and Cochrane Library through May 2, 2020, for observational studies reporting lifestyle or environmental factors for PsA onset in patients with psoriasis. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were combined using a random-effects model. Results We included 16 studies comprising 322,967 individuals. Obesity and being overweight were associated with an increased PsA risk in patients with psoriasis (OR, 1.75 [95% CI, 1.42-2.16] and OR, 1.50 [95% CI, 1.08-2.09], respectively), with an increase of approximately 6% for each kg/m2 rise in body mass index (OR, 1.06; 95% CI, 1.03-1.10). The presence of PsA was associated with a history of physical trauma (OR, 1.33; 95% CI, 1.16-1.54) or fracture (OR, 1.46; 95% CI, 1.22-1.74). No significant associations were observed regarding alcohol consumption (OR, 0.99; 95% CI, 0.88-1.13), smoking (OR, 0.89; 95% CI, 0.75-1.06), female hormonal exposure (OR, 1.45; 95% CI, 0.95-2.20), and psychologically traumatic events. Limitations Inherent limitations in the included observational studies. Conclusions Several lifestyle and environmental factors are associated with PsA onset among patients with psoriasis. These findings indicate that such risk may be modified with lifestyle changes or avoidance of physical trauma in people with psoriasis.

Background Overlapping Sjogren’s syndrome (SS) is not uncommon in rheumatoid arthritis (RA) and considered as a probable detrimental factor of RA. But data on the impact of overlapping SS on RA therapeutic response is limited. Our current study aimed to identify the effect in a real-world cohort from 2009 to 2019. Methods The medical records of RA patients who visited the rheumatology clinic of our medical center from 2009 to 2019 were reviewed. Their composite disease activity scores at each follow-up point were collected. The therapeutic response between RA patients with SS (RA-SS) and without (RA-noSS) was compared. To correct confounders which may affect the therapeutic response, both propensity score matched and unmatched cohorts were analyzed by using the Cox proportional hazards model. Results Among the 1099 RA patients, 129 (11.7%) overlapped with SS were validated by positive anti-SSA or a minor salivary gland biopsy with histological changes suggestive of SS. After propensity score matching based on their baseline characteristics, 126 of 129 RA-SS and 126 of 970 RA-noSS patients were statistically extracted. Overlapping SS was associated with a 29%, 26%, 18%, and 22% lower probability of reaching remission defined by DAS28-ESR, DAS28-CRP, SDAI, and CDAI in RA patients, respectively. Similar decreased probability of reaching low disease activity was also observed. Although ESR was most significantly affected (HR 0.69, 95% CI 0.61–0.79), other component of composite RA disease activity score was also affected by overlapping SS. Stratification by age, RF/ACPA status, or baseline DAS28-CRP was not associated with change of results. Conclusions Overlapping SS is associated with lower probability of reaching remission or low disease activity in RA patients and should be regarded as one of the poor prognostic factors.

Background:Treat-to-target in systemic lupus erythematosus (SLE) has been proposed for 7 years and several recommendations were developed [1]. In these recommendations, prevention of flares should be a realistic target. Meanwhile, ‘remission’ or ‘low disease activity’ was recommended as the treatment target and minimizing glucocorticoids (GC) dose or withdrawal if possible was suggested in the maintenance treatment. However, would target therapy and GC tapering/withdrawal influence disease flare?Objectives:To investigate the frequency and determinants of disease flare, especially the influence of target therapy as well as GC tapering on flare in Chinese lupus patients.Methods:The baseline and follow-up data of all consecutive patients in a prospective longitudinal lupus cohort from January 2017 to June 2020 were collected. The lupus low disease activity state (LLDAS) was defined as in Golder et al., 2019[2]. The criteria for remission were from DORIS definitions [3]. Flare was assessed using the SELENA-SLEDAI flare index [4].Results:We enrolled 185 patients with disease duration at recruitment of 2.3 (0.8–7.7) years. During the 26.2 (12.5-34.5) months of follow-up, 73 (39.5%) patients experienced 95 flares, including 70 mild/moderate and 25 severe flares. The incidence of flare per patient-year was 0.27. Kaplan-Meier analyses showed that compared with those who never achieved LLDAS or DORIS, the patients who achieved the target at least once had a higher flare free survival rate; meanwhile, the patients with prednisone withdrawn had significantly lower flare free rate compared with those with small dose of GC maintained (≤7.5mg/d) (Figure 1A), but among the patients with different prednisone maintain doses (7.5~5mg, 5~2.5mg, and ≤2.5mg) there was not significant difference (Figure 1B). Cox regression analysis showed that younger age at disease onset and lower Complement 3 (C3) level at recruitment were independent risk factors for flare and achieving LLDAS or DORIS ≥50% of visits was independent protective factor (Table 1).Conclusion:In this Chinese prospective SLE cohort, age at disease onset, C3 level at recruitment and therapeutic target achieving influenced disease flare independently and significantly. GC tapering in appropriate patients and with appropriate pace did not increase the flare rate, but prednisone withdrawal may induce more disease exacerbation, which needs to be confirmed by large prospective studies.References:[1]Van Vollenhoven R F, et al. Treat-to-target in systemic lupus erythematosus: recommendations from an international task force. Ann Rheum Dis, 2014. 73(6): 958-967[2]Golder, V., et al. Lupus low disease activity state as a treatment endpoint for systemic lupus erythematosus: a prospective validation study. The Lancet Rheumatology, 2019. 1(2): p. e95-e102.[3]van Vollenhoven R, et al. A framework for remission in SLE: consensus findings from a large international task force on definitions of remission in SLE (DORIS). Ann Rheum Dis. 2017. 76(3): 554–561.[4]Petri M, et al. Classification and definition of major flares in SLE clinical trials. Lupus. 1999. 8(8): 685-691.Table 1.Determinants of disease flare by multivariate Cox regression analysesModel 1(LLDAS) ΔModel 2(RONT) ΔModel 3(Complete RONT) ΔHR95%CIP valueHR95%CIP valueHR95%CIP valueAge at disease onset (years)†0.970.95-0.990.0040.970.95-0.990.0030.970.95-0.990.003Anti-dsDNA positive at recruitment1.340.82-2.180.2171.120.68-1.850.6491.190.73-1.960.486C3 (mg/L) at recruitment0.9980.997-0.9990.0040.9980.997-0.9990.0070.9980.997-1.0000.010Minimum prednisone dose during follow- up (mg/d)0.980.90-1.080.7161.010.94-1.080.7471.040.97-1.110.243Therapeutic target achieved≥50% of observationsΔ0.600.39-0.940.0010.540.34-0.870.0110.680.51-0.920.011Δ In the three hazard models, the different target achievement status were included respectively.RONT: Clinical remission on treatment; Complete RONT: Complete remission on treatment.Disclosure of Interests:None declared

Objectives To explore the risk of new and recurrent cancer in adult RA patients with prior malignancy and subsequently exposed to biologic therapies. Methods Separate searches were performed of PubMed, EMBASE and Cochrane Library and conference proceedings for observational studies reporting cancer incidence or recurrence in patients with RA and prior malignancy treated with biologics and conventional synthetic DMARDs (csDMARDs). Mantel-Haenszel fixed-effects method was conducted to calculate relative risk and 95% CI. Results A total of 12 studies involving 13 598 patients and 32 473 patient-years of follow-up were included (10, 3 and 1 studies for TNF inhibitors [TNFi], rituximab and anakinra, respectively). The crude incidence of new and recurrent cancer per 1000 patient-years were 34.4 for TNFi, 32.3 for rituximab, 32.3 for anakinra and 31.8 for csDMARDs. In the quantitative meta-analysis, biologics were not associated with an increased risk of new or recurrent cancer compared with csDMARDs in patients with RA and prior cancer (TNFi: relative risk = 0.95, 95% CI = 0.83, 1.09; rituximab: relative risk = 0.89, 95% CI = 0.52, 1.53). Secondary analyses of stratification of cancer types, the interval between initiation of TNFi and prior cancer diagnosis, and duration of TNFi exposure, found similar results. Conclusion Compared with csDMARDs, there is no increased risk of developing cancer overall or some specific subtypes in RA patients with a prior cancer receiving biologics. More investigations are warranted to explore the risk of cancer development in individual cancer as well as to determine optimal time to initiate biologic therapy after the diagnosis of cancer or completion of cancer treatment.

Background:After the introduction of treat-to-target strategy in systemic lupus erythematosus (SLE), Lupus Low Disease Activity State (LLDAS) and definitions of remission in SLE (DORIS) were developed and validated. Several studies had demonstrated that the achievement and maintenance of LLDAS or DORIS was associated with good prognosis.Objectives:To evaluate the attainability of LLDAS and DORIS in a treatment-naïve cohort of SLE.Methods:LDAS5 was defined as LLDAS with a prednisone dose ≤5 mg/d. There were 4 definitions in DORIS: clinical remission on treatment (RONT), complete RONT, clinical remission off treatment (ROFT) and complete ROFT. The treatment-naïve patients from Peking University First Hospital SLE cohort were enrolled. The time to each state and their annual cumulative probabilities were estimated by Kaplan-Meier approach. The frequencies of patients who achieved each component of LLDAS or DORIS during follow-up were determined.Results:A total of 218 treatment-naïve patients were included, with a median follow-up of 4.48 years. Respectively, 190 (87.2%), 160 (73.4%), 148 (67.9%), 94 (43.1%), 23 (10.6%) and 18 (8.3%) patients achieved LLDAS, LLDAS5, clinical RONT, complete RONT, clinical ROFT and complete ROFT at least once during the follow-up time. The median time to LLDAS, LLDAS5, clinical RONT and complete RONT were 1.4, 2.3, 2.6 and 4.7 years, respectively.Table 1.Frequencies, time to achieve and annual cumulative probabilities of each state by Kaplan-Meier approachStatesAchieved patientsNumber (%)Time to achieve(years)Cumulative probabilities of achievement (%)Year 1Year 2Year 3Year 4Year 5LLDAS190 (87.2)1.418.869.786.789.192.6LLDAS5160 (73.4)2.36.940.763.376.082.3Clinical RONT148 (67.9)2.65.536.156.168.876.6Complete RONT94 (43.1)4.74.122.637.545.350.4Clinical ROFT23 (10.6)NA1.42.95.46.710.6Complete ROFT18 (8.3)NA0.92.54.84.88.8Table 2.Patients who achieved each component of LLDAS or DORIS during follow-upComponentsNumber (%)SLEDAI-2K ≤4, with no activity in major organ systems (renal, central nervous system, cardiopulmonary, vasculitis, fever), and no haemolytic anaemia or gastrointestinal active213 (97.7)Clinical SLEDAI-2K =0210 (96.3)PGA ≤1217 (99.5)PGA 199 (91.3)Serology (anti-dsDNA and complement) negative148 (67.9)Prednisone dose ≤7.5 mg/day201 (92.2)Prednisone dose ≤5 mg/day171 (78.4)No prednisone dose40 (18.3)No prednisone dose and Immunosuppressants32 (14.7)Conclusion:Our data confirmed that LLDAS is an attainable early treatment target for SLE. Though with more difficulty, RONT can be achieved in two-thirds of our patients. ROFT may not be an ideal treatment target at present as it is only attained in few patients.References:[1]Franklyn, K. et al. Ann Rheum Dis. 2016 Sep;75(9):1615-21.[2]van Vollenhoven, R. et al. Ann Rheum Dis. 2017 Mar;76(3):554-561.Disclosure of Interests:None declared

Background:As a consensus-based definition of minimally acceptable disease activity in systemic lupus erythematosus (SLE), Lupus Low Disease Activity State (LLDAS) has been well-validated and widely accepted. However, no data about the time to LLDAS in Asian ethnicity has been reported so far.Objectives:To estimate the time to LLDAS and the predictors of time to LLDAS in our prospective observational cohort of Chinese patients with SLE.Methods:Patients were from Peking University First Hospital SLE cohort and those having not fulfilled LLDAS at enrolment were included in this study. The time to LLDAS and annual cumulative probabilities of LLDAS achievement were estimated by the Kaplan-Meier approach. The predictors of time to LLDAS were identified by univariate and multivariable Cox proportional hazards.Results:A total of 574 patients with SLE were included and 435 (75.8%) of them achieved LLDAS during a median 4.2 years of follow-up. The median time to LLDAS was 19.0 months and the cumulative probabilities at 1, 2, 3, 5 and 10 years were 19.8%, 57.6%, 72.0%, 85.1% and 98.0%, respectively. In multivariable Cox models, older age at disease onset, treatment-naïve and hydroxychloroquine prescription were found to be independent predictors of shorter time to LLDAS, after adjusted by daily prednisone dose, SLE Disease Activity Index 2000 and physician’s global assessment. Finally, we developed a matrix model based on the identified independent predictors to present the time to LLDAS in patients with respective characteristics.Conclusion:Our study proved that LLDAS is attainable as an early treatment target for SLE in Chinese patients. The older age at disease onset, treatment-naïve and hydroxychloroquine prescription were independent predictors of shorter time to LLDAS.References:[1]Franklyn K, Lau CS, Navarra SV, Louthrenoo W, Lateef A, Hamijoyo L, Wahono CS, Chen SL, Jin O, Morton S, Hoi A, Huq M, Nikpour M, Morand EF; Asia-Pacific Lupus Collaboration. Ann Rheum Dis. 2016 Sep;75(9):1615-21.Table 1Baseline variables associated with LLDAS achievement based on multivariable Cox modelsCharacteristicsModel 1Model 2Model 3HR (95% CI)pvalueHR (95% CI)pvalueHR (95% CI)pvalueAge at disease onset, years1.010 (1.003-1.016)0.0051.009 (1.002-1.016)0.0101.010 (1.003-1.017)0.004Treatment-naïve1.346 (1.105-1.641)0.0031.425 (1.161-1.749)0.0011.484 (1.204-1.830)Nephritis0.776 (0.641-0.939)0.0091.066 (0.820-1.385)0.6340.925 (0.737-1.160)0.498SLEDAI0.968 (0.950-0.987)0.001PGA0.685 (0.551-0.853)0.001Daily prednisone (or equivalent) dose, mg/d1.003 (0.998-1.007)0.2661.005 (0.999-1.010)0.093HCQ1.638 (1.263-2.123)1.713 (1.318-2.225)1.664 (1.284-2.157)Disclosure of Interests:None declared

Paracoccus denitrificans degraded poly(3-hydroxybutyrate) (PHB) in the cells under carbon source starvation. Intracellular poly(3-hydroxyalkanoate) (PHA) depolymerase gene ( phaZ ) was identified near the PHA synthase gene ( phaC ) of P. denitrificans . Cell extract of Escherichia coli carrying lacZ–phaZ fusion gene degraded protease-treated PHB granules. Reaction products were thought to be mainly D (−)-3-hydroxybutyrate (3HB) dimer and 3HB oligomer. Diisopropylfluorophosphonate and Triton X-100 exhibited an inhibitory effect on the degradation of PHB granules. When cell extract of the recombinant E. coli was used, Mg 2+ ion inhibited PHB degradation. However, the inhibitory effect by Mg 2+ ion was not observed using the cell extract of P. denitrificans .