狼疮性肾炎并发社区获得性肺炎患者的抗感染用药监护

目的:分析临床药师参与狼疮性肾炎并发社区获得性肺炎患者抗感染用药监护。方法:对1例狼疮性肾炎并发社区获得性肺炎(重症)患者进行全程药学监护,协助医师制定抗感染药物治疗方案,并随病情变化作修正或调整。结果:莫西沙星和哌拉西林钠/他唑巴坦钠的联合用药,使患者的肺部感染得到及时有效控制,避免了潜在狼疮性肾炎复发或加重的危险。结论:特殊人群抗菌药物的选择,不仅要考虑抗菌谱、抗菌活性,还应结合患者的个体特征和药动学特性来做综合选择,可提高患者用药的安全性和有效性。     

Apport de la détection des anticorps antiphosphatidylsérine/prothrombine (aPS/PT) dans le diagnostic et la prise en charge du syndrome des antiphospholipides (SAPL)

Antiphospholipid syndrome (APS) is an autoimmune disease and one of the most common causes of acquired thrombophilia. It is characterised by the occurrence of thrombotic or obstetric events associated with the presence of persistent antiphospholipid antibodies. The diagnosis can be challenging, particularly because some biological tests can be disturbed by anticoagulant treatment or inflammation.In the recent years, new antiphospholipid antibodies, including anti-phosphatidylserine/prothrombin antibodies (anti-PS/PT), have emerged but their clinical significance and causality remain uncertain.Biologically, several studies have found a strong correlation between the presence of lupus anticoagulant (LA) and anti-PS/PT antibodies. Clinically, the presence of anti-PS/PT antibodies is associated with an increased risk of thrombosis and obstetric complications. There is also an association with thrombocytopenia, suggesting that the presence of anti-PS/PT antibodies may be associated with more severe clinical APS. Among seronegative APS patients, 6–17% of patients are positive for anti-PS/PT antibodies. This might influence the therapeutic management of patients.This article aims to provide an update on contribution of anti-PS/PT antibodies detection for the diagnosis and management of APS.     

Anti-alpha-actinin antibodies are part of the anti-cell membrane antibody spectrum that characterize patients with lupus nephritis

Anti-membrane autoantibodies (MbA) have been reported in sera from patients with lupus nephritis (LN) but the targets of the MbA remain to be explored, which is the aim of the current study. Sera were collected from 40 patients with LN determined by renal biopsy, and from 30 systemic lupus erythematosus (SLE) patients without clinical evidence of LN. Thirty autoimmune disease control patients (rheumatoid arthritis, Sjögren's syndrome and systemic sclerosis), and 30 healthy controls were also included. Using flow cytometry, the presence of anti-MbA was explored revealing that IgG anti-MbA positivity was associated with LN (62.5% vs 13.3%) when compared to non-LN SLE patients, autoimmune disease patients (6.7%) and healthy controls (0%). Next, using purified plasma membrane fractions from human embryonic kidney (HEK) cells, the more prominent targets and their occurrence rates were located at 50 kDa, 60/65 kDa, 90 kDa, 110 kDa, 180 kDa and 220 kDa. Alpha-actinin (110 kDa) autoAb was characterized as a major target in LN patients positive for anti-MbA, and anti-MbA binding activity was reduced (36.9 ± 13.7%) in the presence of α-actinin. Laminin (200 kDa) was also characterized as a minor target, which was not the case for annexin A2 (36 kDa). Finally, anti-MbA IgG subclass analysis indicated a predominance of IgG2. In conclusion, IgG anti-MbA were detected at high levels in LN patients supporting a primary pathogenic role for anti-MbA and anti-MbA/α-actinin+ in LN that needs further research.     

Deleting the BAFF receptor TACI protects against systemic lupus erythematosus without extensive reduction of B cell numbers

B cell-activating factor of the TNF family (BAFF) is an essential B cell survival factor. However, high levels of BAFF promote systemic lupus erythematosus (SLE) in mice and humans. Belimumab (anti-human BAFF) limits B cell survival and is approved for use in patients with SLE. Surprisingly, the efficacy of rituximab (anti-human CD20) in SLE remains controversial, despite depleting B cells more potently than belimumab. This raises the question of whether B cell depletion is really the mechanism of action of belimumab. In BAFF transgenic mice, SLE development is T cell-independent but relies on innate activation of B cells via TLRs, and TLR expression is modulated by the BAFF receptor TACI. Here, we show that loss of TACI on B cells protected against BAFF-mediated autoimmune manifestations while preserving B cells, suggesting that loss of BAFF signaling through TACI rather than loss of B cells may underpin the effect of belimumab in the clinic. Therefore, B cell-sparing blockade of TACI may offer a more specific and safer therapeutic alternative to broad B cell depletion in SLE.     

Lupus arthropathy: historical evolution from deforming arthritis to rhupus

Systemic lupus erythematosus is an autoimmune and inflammatory disease with multiple clinical manifestations, including arthropathy. The clinical presentation of articular involvement is variable, ranging from arthralgia without erosions or deformity to an erosive arthropathy and severe functional disability. A subset of patients with this articular involvement have Jaccouds arthropathy, and others have an arthropathy with clinical findings similar to rheumatoid arthritis that has been called rhupus. In this paper we review the historical evolution of concepts of lupus arthropathy, from deforming arthritis to rhupus, and conclude that rhupus is not a combination of rheumatoid arthritis and lupus. Instead, rhupus arthropathy should be regarded as a variant of the arthropathy of systemic lupus erythematosus.     

Clinical utility of urinary soluble CD163 in evaluation of lupus nephritis patients

Aim of the workTo assess urinary soluble CD163 (sCD136) in systemic lupus erythematosus (SLE) patients compared to healthy controls. In addition to determine its association with different SLE clinical features, laboratory investigations and pathological indices focusing on those suggest renal disease activity.Patients and methodsThe study included 58 SLE patients and 30 controls. SLE disease activity index (SLEDAI) was assessed and patients subdivided into active lupus nephritis (ALN) (renal SLEDAI ≥ 4) and no-renal activity (NRA) SLE patients (renal SLEDAI = 0). Urinary sCD163 was measured by Enzyme-Linked Immunosorbent Assay (ELISA). Urine values were normalized to urinary creatinine excretion. Renal biopsies were performed in 21 ALN patients.ResultsThey were 54 females and 4 males with a mean age 31.8 ± 9.1 years and disease duration 6.2 ± 4.8 years. They were 31 with ALN and 27 NRA SLE patients. Urinary sCD163 level was significantly higher in SLE patients (1.85 ± 0.3) than controls (0.5 ± 0.36, p < 0.001). In ALN, it was significantly higher (2.91 ± 2.52) compared to NRA SLE patients (0.64 ± 0.38) and controls (p < 0.001 in both). The optimum cut-off value above which normalized urinary sCD136 can predict renal activity was > 0.82 with sensitivity of 90.3%, specificity of 88.89%, p < 0.001. Urinary sCD163 significantly correlated with renal (r = 0.75, p < 0.001) but not with extra-renal SLEDAI. It correlated with activity index of renal biopsy (r = 0.46, p = 0.038).ConclusionUrinary sCD163 is a potential biomarker for LN activity. Its level is associated with clinical features, laboratory investigations and pathological indices that indicate renal disease activity.     

血清B淋巴细胞刺激因子在系统性红斑狼疮中的意义

目的 研究血清B淋巴细胞刺激因子（Blys）在系统性红斑狼疮（SEE）中的意义。方法 酶联免疫吸附试验（ELISA）法检测125例SLE患者血清Blys水平，并与狼疮活动程度和临床表现进行相关性分析。结果 125例SLE患者血清平均Blys水平显著高于正常对照组[（0．72±0．18）ng／ml vs（0．34±0．10）ng／ml，P=0．0031]；SLE患者血清平均Blys水平与SLE疾病活动指数（SLEDAI）积分呈一定程度相关性（r=0．73，P=0．018）；SLE患者血清Blys水平与抗dsDNA抗体滴度呈正相关，而与血清IgG、补体、蛋白尿、白细胞、血小板计数，以及皮疹、关节痛、口腔溃疡、脱发、发热等临床表现等均无显著相关性（P〉0．05）。结论 SLE患者血清Blys水平升高，与狼疮活动呈一定相关性，但不能准确反映病变部位及严重程度。     

Drug-related lupus in a patient with rheumatoid arthritis under sulfasalazine treatment

Summary The induction of lupus-like syndromes with the appearance of single-stranded DNA antibodies is a well-known complication of drug therapy. In this report we present a patient with an erosive seropositive rheumatoid arthritis developing the clinical and serological features of systemic lupus erythematosus including the occurrence of double-stranded DNA antibodies under sulfasalazine treatment.     

狼疮肾炎泼尼松治疗后骨密度及骨代谢指标的变化

目的 观察狼疮肾炎（LN）长期泼尼松治疗后骨矿含量及骨代谢生化指标的变化。方法 研究对象为女性，健康对照A组20例，患者组25例（肾功能正常），于泼尼松治疗前（B），治疗后2个月，4个月分别用双能X线骨密度仪测定相关部位骨密度，同时测定空腹血钙，磷，碱性磷酸酶，甲状旁腺激素（PTH－M），骨钙素（BGP）及其他生化指标。结果：（1）LN治疗前组除腰2外各部分骨密度与对照组差异无显著性（P＞0．05）。泼尼松治疗后2个月骨密度无明显变化，治疗4个月时桡骨骨密度较治疗前下降（P＜0．01）。（2）患者治疗后2个月，4个月血钙，磷，碱性磷酸酶无明显变化，血PTH均较治疗前上升（P＜0．01），血BGP均较治疗前下降（P＜0．01）。结论 （1）狼疮肾炎长期泼尼松治疗后各部位骨密度逐渐下降，桡骨骨密度较早发生改变。（2）泼尼松治疗后血BGP下降，PTH上升，血BGP和PTH是反映继发性骨量减少的 敏感性生化指标，较骨形态学改变早。