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橋本腦病臨床分析一例

Progression of CD20 monoclonal antibody in the treatment of autoimmune hemolytic anemia

Autoimmune hemolytic anemia (AIHA) is an autoimmune disease in which the life span of red blood cells is shortened by red blood cell autoantibodies. Due to immune intolerance and abnormal immune regulation, the hyperfunction of B lymphocytes produces too many red blood cell autoantibodies. Anti-CD20 monoclonal antibody is a second-line drug for warm antibody AIHA and first-line drug for cold antibody AIHA by reducing B lymphocytes. At present, the optimal dose of anti-CD20 monoclonal antibody in the treatment of AIHA has not been determined. There are no reports on the treatment of primary AIHA with second- or third-generation anti-CD20 monoclonal antibodies.

Effects of testosterone on optic nerve and retinal ganglion cells in experimenta l autoimmune encephalomyelitis

Objective:To observe the effects of testosterone on optic nerve an d retinal ganglion cells (RGC) in experimental autoimmune encephalomyelitis (EAE ). Methods:Fourty one female Wistar rats were randomly divide d into 3 groups: the normal group (10 rats), the untreated control group (15 rats) and the testos terone group (16 rats). The rats in the first two groups were fed with 1% ethano l every day, and the rats in the testosterone group were fed with methyltestoste rone (0.25 mg/kg) every day. On the 20th day, EAE model was induced in the untre ated control group and the testosterone group by injecting guinea pig spinal cor d homogenate in complete Freund's adjuvant and bordetella pertussis vaccine. RGC were labeled with flurogold (FG) by injecting it in superior colliculus and lat eral geniculate body 7 days before establishing EAE model. All rats were fed wit h drugs continuously, and after 1430 days, rats in normal group and rats in un t reated control and testosterone groups who had symptoms within 48～72 hours were observed by light microscopy and flash visual evoked potential (FVEP) to detect the functional and morphological changes of optic nerve. The number of RGC was counted by fluorescence microscopy，and apoptosis of RGC was observed by termina l deoxynucleotidyl transferasemediated biotinylated UTP nick end labeling (TUN E L) Results:EAE rats presented weakness or paralysis of tail a nd hind limbs 10 days after establishing EAE model. Compared with the rats in the untreated contr ol group, the rats in the testosterone group had longer disease delitescence and lower clinical score (P=0.042). Extensive demyelination of optic nerves wi th the circuitous configuration was found in the untreated control group; while mild demyelination of optic nerves with regular figure was found in the testosterone group. In the testosterone group, the latency of N1、P and N2 wave was shorter w hile the amplitude ofN1-P and P-N2was higher than that in the untreated cont rol group (Plt;0.05). The number of RGC was (2284plusmn;132), (934plusmn;78, and (1725 plusmn;95)cells/mm2 in the normal, untreated control and testosterone groups, respectively; w hich was higher in testosterone group than that in untreated control group (P=0.028). The number of TUNEL positive cells was (4.02plusmn;0.16), (24.44plusmn;2.22), and (9.84plusmn;2.36) cells per high power field (times;400) in the 3 grou ps, respectively; wh ich was less in testosterone group than that in untreated control group (P＝0.025). Conclusions:Testosterone may reduce the incidence and clinical score of EAE, inhibit the apoptosis of RGC, alleviate the demyelinatio n of optic nerves, and improved the conduction function of optic nerves.

MIDDLE- AND LONG-TERM EFFECTIVENESS OF PRIMARY TOTAL HIP ARTHROPLASTY FOR PATIENTS WITH CHRONIC AUTOIMMUNE INFLAMMATORY DISEASE

ObjectiveTo evaluate the middle- and long-term effectiveness of primary total hip arthroplasty (THA) in patients with chronic autoimmune inflammatory diseases. MethodsBetween January 1990 and June 2006, 42 patients (51 hips) with chronic autoimmune inflammatory diseases underwent THA. There were 15 males (18 hips) and 27 females (33 hips) with an average age of 36.9 years (range, 22-70 years). The locations were the left side in 29 hips and the right side in 22 hips. Of 42 cases, there were 11 cases of systemic lupus erythematosus (13 hips), 16 cases of rheumatoid arthritis (22 hips), and 15 cases of ankylosing spondylitis (16 hips). The causes of THA included avascular necrosis of the femoral head in 26 cases (34 hips), ankylosis of the hip in 15 cases (16 hips), and fracture of the femoral neck in 1 case (1 hip). The Harris score was 32.49 ± 9.50. The physical component summary (PCS) and mental component summary (MCS) of short form 36 health survey scale (SF-36) scores were 25.53 ± 4.46 and 42.28 ± 6.27, respectively. ResultsAll incisions healed primarily. All 42 patients were followed up 5-21 years (mean, 9.1 years). At last follow-up, the Harris score was 89.25 ± 8.47; PCS and MCS of the SF-36 were 51.35 ± 4.28 and 55.29 ± 8.31, respectively; and significant differences in the scores were found between pre- and post-operation (P lt; 0.05). Complications included limp (4 cases), prosthesis dislocation (2 cases, 2 hips), periprosthetic fracture (1 case, 1 hip), aseptic loosening (2 cases, 2 hips), and ectopic ossification (3 cases, 3 hips). ConclusionTHA seems to be a good choice for patients with chronic autoimmune inflammatory diseases.

IgG4 Related Lung Disease: Two Cases Report and Literature Review

ObjectiveTo summarize the clinical characteristic of IgG4 related lung disease. MethodsThe clinical manifestation,laboratory examination,imaging,diagnosis and treatment data of 2 patients with IgG4 related lung disease admitted in the PLA General Hospital from January 2000 to January 2014 were collected and analyzed retrospectively.Related literatures were also reviewed. ResultsThe serum IgG level of IgG4 related lung disease might be normal and the levels of IgG1,2,3 and 4 might increase.Some autoantibodies were positive.IgG4 related lung disease could be easily misdiagnosed as Sjogren's syndrome associated with interstitial pneumonia when the lacrimal gland and salivary gland were involved,and the chest CT occasionally showed multiple vesicles.The immunochemical staining of lung tissues revealed the increase of IgG4/IgG and the number of IgG4 positive lymphatic plasma cells >10/HP.The combination of clinical manifestation,laboratory examination,imaging and pathology results was more conducive for the diagnosis of IgG4 related lung disease.After the treatment of glucocorticoid,the clinical symptoms were relieved and the serum IgG4 level obviously decreased. ConclusionIgG4 related lung disease is rare in clinic,which can involve the lung alone or multiple organs.The increase of IgG4/IgG indicated by the immunochemical staining of lung tissues is the gold standard for diagnosis.Glucocorticoid has good treatment effect in IgG4 related lung disease.

Value of Superparamagnetic Iron Oxide in the Experimental Autoimmnune Encephalomyelitis Model

【摘要】 目的 在實驗性自身免疫性腦脊髓炎(experimental autoimmune encephalomyelitis,EAE)模型中,比較常規T2加權成像(T2weighted imaging,T2WI)、釓二乙三胺五醋酸(gadoliniumdiethylenetriamine pentaacetic acid,GdDTPA)和超順磁性氧化鐵(superparamagnetic iron oxide,SPIO)增強圖像之間的差異,探討巨噬細胞在多發性硬化(multiple sclerosis,MS)炎性活動病灶中的細胞學標志。方法 在EAE模型臨床癥狀的亞臨床期、初發期、高峰期,13只復發緩解(relapsingremitting,RR)EAE大鼠模型組和13只正常對照組大鼠在注入對比劑之前均行常規T2WI掃描,接著分別在其尾靜脈注入GdDTPA后5 min行T1加權成像(T1weighted imaging,T1WI),再注入SPIO,24 h后行T2WI掃描。掃描完畢后立即處死大鼠取腦,行腦組織切片的ED1免疫組織化學染色和Prussian blue染色。結果 EAE模型組大鼠在第11天出現臨床癥狀(初發期),第14天達到高峰期;MRI檢查:SPIO增強圖像對EAE病灶的顯示較常規T2WI和GdDTPA增強圖像好。病理學檢查:ED1染色,在SPIO顯示為低信號的區域內出現了炎癥細胞(以巨噬細胞為主)浸潤;Prussian blue染色示病灶內巨噬細胞胞質內出現了藍染顆粒,沉積部位與T2WI上低信號區對應。對照組大鼠均無異常。結論 SPIO較GdDTPA更好地顯示EAE模型中炎性活動性病灶內血管周圍以巨噬細胞為主的浸潤。

EXPERIENCE IN DIAGNOSIS AND TREATMENT FOR HASHIMOTO′S DISEASE (REPORT OF 78 CASE)

Objective To sum up experiences in diagnosis and treatment for Hashimoto′s disease (HD). Methods Clinical records of 78 patients who underwent operations and were diagnosed as Hashimoto′s disease by histologic examination in our hospital from Jan. 1988 to Dec. 1998 were analyzed. Results Seventy females and 8 males, aged 9 to 70 years (average of 41.6 years). HD was coexistent with 10.3% of thyroid gland malignant tumor, 23.1% of adenoma and 30.8% of other thhroid gland diseases. The misdiagnosis rate was 35.9% and missed diagnosis rate was 46.2%. The clinical feature of HD and most common cause of misdiagnosis and missed diagnosis have been discussed. Conclusion It is emphasized that patients with diffuse goiter, palpable nodules, lighty color on scintillation scintigraphy, elevation of antimicosomiaux and antithyroglobuline but no finding on Bus should be highly suspected of having Hashimoto′s disease.

Effect of interleukin-23R overexpression on Th17/Treg balance in experimental autoimmune uveitis mice

ObjectiveTo investigate the effect of interleukin (IL)-23 receptor (IL-23R) overexpression on the balance of T helper 17 (Th17 cells)/regulatory T cells (Treg cells) in experimental autoimmune uveitis (EAU) mice. MethodsTwelve 8-week-old female C57BL/6J mice were randomly divided into LV-Ctrl group and LV-IL-23R group, with 6 mice in each group. Two groups of mice were injected with LV-Ctrl and LV-IL-23Rlentiviruses through the tail vein, respectively; 7 days after injection, the EAU mouse model was established by active immunization with vitamin A-binding protein 1-20 between photoreceptors. Starting from 13 days after immunization, the fundus of the mice was observed by indirect ophthalmoscopy every 2 days and clinical scores were performed; 30 days after immunization, hematoxylin-eosin staining was used to observe the histopathological changes of mouse retina. The levels of IL-17 in serum of the two groups of mice were detected by enzyme-linked immunosorbent assay; the proportion of Th17 cells and Treg cells was detected by flow cytometry. The relative mRNA expression of IL-23R, IL-17, retinoic acid-related orphan receptor γt (RORγt), IL-10 and forkhead transcripyion factor p3 (Foxp3) were detected by real-time quantitative polymerase chain reaction. Comparisons between groups were performed using repeated measures analysis of variance, independent samples Mann-Whitney U test, and independent samples t test. ResultsCompared with the LV-Ctrlgroup, the retinal inflammatory reaction of the LV-IL-23R group was more severe. At 13 days after immunization, there was no significant difference in fundus inflammation scores between LV-IL-23R group and LV-Ctrl group (t=－2.001, P=0.058); 15-29 days after immunization. The fundus inflammation scores of LV-IL-23Rgroup were higher than those of LV-Ctrl group, and the difference was statistically significant (t=－4.429, －6.578, －7.768, －10.183, －6.325, －7.304, －4.841, －6.872; P＜0.001). Histopathological examination showed that the infiltration of inflammatory cells in the fundus increased, the retinal structure was damaged more seriously, and the histopathological score was significantly increased, and the difference was statistically significant (t=－4.339, P=0.001). Compared with the LV-Ctrl group, the relative expression of IL-23RmRNA in the spleen of the LV-IL-23R group was significantly increased, and the difference was statistically significant (Z=2.087, P=0.037). The relative expression of IL-17 and RORγt mRNA increased, while the relative expression of IL-10 and Foxp3 mRNA decreased, and the differences were statistically significant (t=－6.313,－5.922, 4.844, 7.572; P=0.003, 0.004, 0.008, 0.002). Compared with the LV-Ctrl group, the level of IL-17 in the serum of the mice in the LV-IL-23R group was significantly increased, and the difference was statistically significant (t=－5.423, P=0.002); the proportion of Th17 cells in the spleen and lymph nodes was significantly increased, whereas, the proportion of Treg cells was significantly reduced, and the difference was statistically significant (t=－4.290, 3.700; P=0.002, 0.006). ConclusionIL-23R overexpression can promote Th17/Treg imbalance in EAU mice, and aggravate the clinical and pathological manifestations of EAU.

自身免疫起源的遲發性癲癇流行率和臨床結局：一項前瞻性觀察性人群隊列研究

眾所周知，隨著年齡增長新發癲癇的發病率增加。通常，這些患者的病因難以明確。研究調查了有非誘導性遲發性癲癇發作且不合并腫瘤（可能患有副腫瘤性腦炎）患者的潛在自身免疫反應情況。在 4.75 年內前瞻性連續納入了 66 例患者（至少有一次癲癇或癲癇發作，病程≤6 個月，36 例女性，年齡≥55 歲）。檢測所有患者的血清、腦脊液抗體和神經細胞表面、細胞內抗原。45 例患者（68%）進行了核磁共振（MRI）檢查。對于抗體陽性的患者隨訪時間至少 6 個月。2 例患者血清、腦脊液中抗接觸蛋白相關性蛋白樣-2（Contactin associated protein-like 2, CASPR2）抗體滴度高，符合明確邊緣性腦炎的診斷標準。另外 2 例患者 MRI 顯示雙側腦顳區炎性異常，盡管血清、腦脊液抗體陰性，也符合明確邊緣性腦炎的診斷標準。這 4 例患者年齡 55～70 歲之間，均接受了抗免疫治療和（或）抗癲癇治療之后變成癲癇再無發作。該研究發現提示自身免疫應該被認為是遲發型癲癇患者的一個重要病因。對于這些患者，神經元抗體檢測和大腦 MRI 可能是有價值的檢查手段。

抗體介導的自身免疫性腦炎患者的癲癇特點

越來越多的自身免疫性腦炎（Autoimmune encephalitis，AE）患者的資料顯示，其臨床表現和結局的特異性依賴于患者腦脊液、血清中特定抗原的抗體。這些特異性包括了癲癇相關的臨床表現及對抗癲癇藥物的反應。雖然學者們對這一類疾病的研究熱情不斷增加，且發現了新的抗體和相關的臨床綜合征，但仍有一些問題需要進一步解答。首先，鑒于每一種自身免疫性抗體介導的綜合征的嚴重程度、患者特點、治療時間不盡相同，治療需要個體化；其次，缺乏隨機對照試驗是形成適當的免疫治療策略的重大障礙。文章就一些已闡明的 AE 患者的癲癇診斷和治療方面的新進展和挑戰作一綜述，并闡述在這一新興領域中合理應用精確藥物的原則。