Circulating autoantibodies to endogenous erythropoietin are associated with chronic hepatitis C virus infection-related anemia

BACKGROUND: Chronic hepatitis C virus(HCV) infection is associated with autoimmune phenomena and is often complicated by anemia. Circulating autoantibodies to endogenous erythropoietin(anti-EPO) have been detected in patients with chronic viral infections and were correlated to anemia. The present study aimed to determine anti-EPO prevalence in patients with chronic HCV infection and investigate its possible association with anemia.METHODS: Ninety-three consecutive patients(62 males and 31 females) with chronic HCV infection, who had never received antiviral therapy or recombinant EPO, were enrolled in the study. Circulating anti-EPO were detected in the serum by using an ELISA assay. Quantitative determination of serum EPO levels was done by radioimmunoassay. HCV RNA viral load measurement and genotype sequencing were also performed.RESULTS: Circulating anti-EPO were detected in 10.8% of HCV-infected patients and the prevalence of anti-EPO was significantly higher in patients with anemia(19.4% vs 5.3%, P=0.040) compared to that in those without anemia. Compared to anti-EPO negative cases, anti-EPO positive patients had higher frequency of anemia(70.0% vs 34.9%, P=0.030), lower EPO concentrations(median 16.35 vs 30.65 m U/m L, P=0.005), and higher HCV RNA viral load(median 891.5×103 vs 367.5×103 IU/m L, P=0.016). In multivariate regression analysis the presence of anti-EPO remained an independent predictor of anemia(adjusted OR: 14.303, 95% CI: 1.417-36.580, P=0.024). EPO response to anemia was less prominent among anti-EPO positive patients(P=0.001).CONCLUSIONS: Circulating anti-EPO are detected in a significant proportion of treatment-na?ve HCV-infected patients and are independently associated with anemia, suggesting a further implication of autoimmunity in the pathophysiology of HCV-related anemia.     

系统性红斑狼疮血液系统损害与疾病预后分析

目的 分析系统性红斑狼疮(SLE)血液系统损害与疾病活动情况、免疫学指标的异常及疾病预后相关性.方法 总结江苏省1999-2009年间首次住院SLE患者的临床及实验室资料,观察血液系统损害情况,并分析了血液系统损害与SLE疾病活动情况、免疫学指标及SLE患者病死率间的关系.统计学处理采用X2检验.结果 1958例SLE患者纳入研究范围,其中女性患者1836例,男性患者122 例.所有SLE患者中,1549例(79.1%)患者合并血液系统损害,其中贫血占62.3%,白细胞减少占45.5%,血小板减少占29.4%;轻、中、重度活动组患者血液学损害率均高于基本无活动组(P=0.01和P＜0.01);血液系统损害发生率在红细胞沉降率、补体C3、抗双链DNA(dsDNA)抗体阳性组高于阴性组(P＜0.01);有166例患者在随访中死亡,其中因重症感染死亡占38.6%,因肾功能衰竭死亡占22.9%,因神经系统损害死亡占15.1%,心血管疾病占10.2%,其他死因占13.3%.死亡病例中存在血液系统损害占91.6%,无血液系统损害占8.4%,血液系统损害率在死亡患者中明显增高(p＜0.01).结论 血液系统是SLE最常受累的系统之一,其中以贫血最为常见,血液系统损害与狼疮病情活动密切相关;免疫性指标异常的患者容易继发血液系统的损害;重症感染是SLE患者死亡的主要原因,存在血液系统损害的SLE患者病死率高于非血液系统损害的SLE患者.

Abstract：

Objective To explore the relationship between the impairment of hematological system and disease activity,immunological parameters,and the prognosis of systemic lupus erythematosus (SLE).Methods The clinical and laboratory data of in-patients with SLE in Jiangsu Province were investigated and all patients were hospitalized between 1999-2009.The impairment of hematological system was assessed and the relationship between hematological system damage and disease activity,immunological parameters,mortality rate of patients with SLE were analyzed.Statistic method used was X2 test.Results One thousand nine hundred and fifty eight cases of SLE were included in the study,in which,1836 were female and 122 were male.One thousand five hundred and forty nine (79.1%) patients complicated with hematological system damage,62.3% were anemia,45.5% with leucopenia and 29.4% with thrombocytopenia.There were significant differences in hematological system damage rate among patients with mild activity group,moderate activity group,severe activity group and almost no activity group,compared respectively with almost no activity group.The P values were P=0.01 and P＜0.01 respectively.The incidence of hematological system damage in elevated ESR,low complement C3 level,anti-dsDNA antibody group was higher than that in patients who had normal ESR,complement C3 level and anti-dsDNA group.(P＜0.01).During follow-up,166 patients died,of which the mortality rate(91.6%) in patients had hematological system damage,was obviously higher than those without hematological damage(8.4%)(P＜0.01 ).Among the 166 deceased patients,38.6% died of severe infection,22.9% died ofrenal failure,15.1% died ofnervous system damage,10.2% died of cadiovascular damage and 13.3% died from other causes.Conclusion Hematological system is one of the most commonly involved system in patients with SLE,of which anemia is the most common,and the incidence of leukopenia follows.The impairment of hematological system is closely related to lupus activity.Patients with abnormal immune parameters tend to have secondary hematological system damage.Severe infection is the main cause of death in patients with lupus,followed by nervous system damage and kidney damage.The mortality rate in patients with lupus that complicated hematological system damage is higher than patients who have no hematological system damage.     

抗环瓜氨酸多肽抗体在类风湿关节炎诊断中的价值

目的 了解抗环瓜氨酸多肽(CCP)抗体在中国人群中诊断类风湿关节炎的敏感度、特异度及其对类风湿关节炎发病的预测价值.方法 收集2007年11月至2008年3月在上海长征医院进行健康体检的健康人群1018例,风湿科门诊及住院确诊类风湿关节炎患者212例,其他结缔组织病患者435例,应用酶联免疫吸附法检测其血清抗CCP抗体滴度,对健康人群及类风湿关节炎患者同时检测IgM型类风湿因子(IgM-RF).比较抗CCP抗体阳性率及滴度差异,并统计健康人群和类风湿关节炎患者中IgM-RF的阳性率,计算IgM-RF诊断类风湿关节炎的特异度.结果 (1)类风湿关节炎患者血清抗CCP抗体阳性率为48.1%(102例),明显高于健康人群(2.6%,26例)和其他结缔组织病患者(3.7%,16例),其诊断类风湿关节炎的特异度高达97.4%.(2)类风湿关节炎患者抗CCP抗体滴度为429.7 U,明显高于健康人群(29.3 U)和其他结缔组织病患者(36.5 U).(3)IgM-RF在类风湿关节炎患者中的阳性率为94.3%,而在健康人群中的阳性率为21.5%.抗CCP抗体的假阳性率(2%)显著低于IgM-RF(21.5%,P＜0.01).结论 抗CCP抗体在类风湿关节炎诊断中具有高度的特异度,且类风湿关节炎患者血清中抗CCP抗体滴度明显高于健康人群及其他结缔组织病患者.抗CCP抗体阳性对类风湿关节炎的诊断更具有价值.

Abstract：

Objective To determine the sensitivity and specificity of anti-cyclic citrullinated peptide antibodies (anti-CCP antibodies) in the diagnosis of rheumatoid arthritis. Method A total of 1018healthy donors, 212 patients with rheumatoid arthritis, 435 patients with other connective tissue disease were recruited to this study. Anti-CCP antibodies and IgM-rheumatoid factor (RF) were determined by ELISA according to manufacturer instructions, with a cut-off of 20U. Result The frequency of positive anti-CCP antibodies in patients with rheumatoid arthritis is 48.1% (n = 102 ), higher than healthy donors (2.6%,n = 26) and patients with other connective tissue diseases (3.7%, n = 16). The specificity of anti-CCP antibodies is 97.4%. The titer of anti-CCP antibodies in patients with rheumatoid arthritis (429. 7 U) is much higher than that in healthy donors (29. 3 U ) and patients with other connective tissue diseases (36. 5 U). The frequency of positive IgM-RF in patients with rheumatoid arthritis is 94. 3% whilst only21.5% in healthy donors. The false positivity rate of IgM-RF is higher than anti-CCP antibody. Conclusion Anti-CCP antibodies is a highly specific autoantibody in the diagnosis of rheumatoid arthritis.     

抗血小板抗体在系统性红斑狼疮血小板减少患者中临床意义的研究

目的 明确抗血小板抗体在系统性红斑狼疮(SLE)血小板减少患者中的临床意义.方法 采用改良抗原捕获酶联免疫吸附试验(ELISA)法检测抗血小板抗体(抗GPⅡb/Ⅲa、GPⅠb/Ⅸ、GPⅠa/Ⅱa、GPⅣ抗体),分别比较治疗前SLE血小板减少与SLE非血小板减少患者抗血小板抗体的阳性率、SLE血小板减少患者治疗前后抗血小板抗体的阳性率、SLE血小板减少治疗前患者病情与抗血小板抗体的关联性.统计方法采用秩和检验和x2检验.结果 治疗前SLE血小板减少组抗GPⅡb/Ⅲa抗体、抗GP Ⅰb,Ⅸ抗体阳性率分别为50%、67%.非血小板减少组阳性率分别为11%、28%,2组间阳性率差异有统计学意义(P＜0.05);治疗后SLE血小板减少组抗GPⅡb/Ⅲa抗体、抗GP Ⅰb/Ⅸ抗体阳性率分别为6%、28%,较治疗前显著降低(P＜0.05);SLE血小板减少组治疗前抗GPⅡb/Ⅲa抗体、抗GP Ⅰb/Ⅸ抗体之间显著关联,该2种抗体均与SLEDAI评分有显著关联性,与抗核抗体、抗双链DNA(dsDNA)抗体、抗中性粒细胞胞质抗体(ANCA)则无显著关联;各组间未检测出抗GPⅣ和GPⅠa/Ⅱa抗体.结论 抗GPⅡb/Ⅲa、GPⅠb/Ⅸ抗体在病情活动SLE血小板减少患者中表达显著升高,与SLE血小板减少病情发生发展和转归相关.

Abstract：

Objective To evaluate the clinical significance of antiplatelet antibody in patients with systemic lupus erythematosus complicated with thrombocytopenia.Methods Antiplatelet antibody (anti-GP Ⅱb/Ⅲa antibody, anti-GP Ⅰb/Ⅸ antibody, anti-GP Ⅰa/Ⅱ a antibody, anti-GP Ⅳ antibody) were detected by modified antigen capture ELISA. The positive rate of antiplatelet antibody between SLE complicated with thrombocytopenia group and without thrombocytopenia group before therapy were compared,and the positive rate of antiplatelet antibody before therapy and after therapy in SLE complicated with thrombocytopenia were compared,and the relevance between antiplatelet antibody and conditions in SLE complicated with thrombocytopenia were analyzed. Rank test and Chi square test were used for statistical analysis. Results The positive rate of anti-GP Ⅱb/Ⅲa antibody and anti-GP Ⅰb/Ⅸ antibody in SLE complicated with thrombocytopenia group before therapy was 50% and 67% respectively, however,the positive rate in SLE without thrombocytopenia group before therapy was 11% and 28% respectively,there was significant difference between the two groups (P＜0.05) and the positive rate of anti-GP Ⅱb/Ⅲa antibody and anti-GP Ⅰb/Ⅸ antibody in SLE complicated with thrombocytopenia group after therapy was 6% and 28% respectively, which was significantly lower than those before therapy (P＜0.05). In SLE complicated with thrombocytopenia group before therapy, there was significant relevance between anti-GP Ⅱb/Ⅲ a antibody and anti-GP[b/Ⅸ antibody, and there was significant relevance between these two antibodies and SLEDAI score,but no significant relevance between these two antibodies and ANA,dsDNA, ANCA. Neither anti-GPⅣ antibody nor anti-GP Ⅰ a/Ⅱ a antibody was detected in patients of this study. Conclusion The positive rate of antiplatelet antibody (anti-GP Ⅱb/Ⅲ a antibody, anti-GP Ⅰb/Ⅸ antibody) is significantly higher in patients with active systemic lupus erythematosus complicated with thrombocytopenia,and these two antibodies are significantly associated with clinical outcomes.     

抗血小板抗体在系统性红斑狼疮血小板减少患者中临床意义的研究

Objective To evaluate the clinical significance of antiplatelet antibody in patients with systemic lupus erythematosus complicated with thrombocytopenia.Methods Antiplatelet antibody (anti-GP Ⅱb/Ⅲa antibody, anti-GP Ⅰb/Ⅸ antibody, anti-GP Ⅰa/Ⅱ a antibody, anti-GP Ⅳ antibody) were detected by modified antigen capture ELISA. The positive rate of antiplatelet antibody between SLE complicated with thrombocytopenia group and without thrombocytopenia group before therapy were compared,and the positive rate of antiplatelet antibody before therapy and after therapy in SLE complicated with thrombocytopenia were compared,and the relevance between antiplatelet antibody and conditions in SLE complicated with thrombocytopenia were analyzed. Rank test and Chi square test were used for statistical analysis. Results The positive rate of anti-GP Ⅱb/Ⅲa antibody and anti-GP Ⅰb/Ⅸ antibody in SLE complicated with thrombocytopenia group before therapy was 50% and 67% respectively, however,the positive rate in SLE without thrombocytopenia group before therapy was 11% and 28% respectively,there was significant difference between the two groups (P＜0.05) and the positive rate of anti-GP Ⅱb/Ⅲa antibody and anti-GP Ⅰb/Ⅸ antibody in SLE complicated with thrombocytopenia group after therapy was 6% and 28% respectively, which was significantly lower than those before therapy (P＜0.05). In SLE complicated with thrombocytopenia group before therapy, there was significant relevance between anti-GP Ⅱb/Ⅲ a antibody and anti-GP[b/Ⅸ antibody, and there was significant relevance between these two antibodies and SLEDAI score,but no significant relevance between these two antibodies and ANA,dsDNA, ANCA. Neither anti-GPⅣ antibody nor anti-GP Ⅰ a/Ⅱ a antibody was detected in patients of this study. Conclusion The positive rate of antiplatelet antibody (anti-GP Ⅱb/Ⅲ a antibody, anti-GP Ⅰb/Ⅸ antibody) is significantly higher in patients with active systemic lupus erythematosus complicated with thrombocytopenia,and these two antibodies are significantly associated with clinical outcomes.     

Lack of specific association between gastric autoimmunity hallmarks and clinical presentations of atrophic body gastritis

AIM: To investigate the possible relationships between gastric autoimmune phenomena and clinical presentations of this disorder, in consecutive atrophic body gastritis patients. METHODS: A total of 140 atrophic body gastritis patients, diagnosed as consecutive outpatients presenting with macrocytic or iron deficiency anemia, or longstanding dyspepsia underwent gastroscopy with antral and body biopsies, assay of intrinsic factor, parietal cells and Helicobacter pylori (H pylori) antibodies. Gastritis was assessed according to Sydney System. RESULTS: Parietal cell antibodies were equally distributed in all clinical presentations, whereas the positivity of intrinsic factor antibodies (49/140, 35%) was significantly higher in pernicious anemia patients (49.2%) than in iron deficiency (21.1%) and dyspeptic patients (27.8%). No specific pattern of autoantibodies was related to the clinical presentations of atrophic body gastritis. A positive correlation was obtained between the body atrophy score and the intrinsic factor antibody levels (r=0.2216, P=0.0085). Associated autoimmune diseases were present in 25/140 (17.9%) patients, but the prevalence of autoimmune diseases was comparable, irrespective of the clinical presentations. CONCLUSION: The so-called hallmarks of gastric autoimmunity, particularly in intrinsic factor antibody cannot be usefully employed in defining an autoimmune pattern in the clinical presentations of ABG.     

抗磷脂综合征174例临床特点及与欧洲数据的比较分析

Objective To analyze the clinical characteristics of antiphospholipid syndrome (APS) in a cohort of Chinese patients. Methods From January 1996 to October 2009, 174 patients with defined APS were retrospectively studied,χ2 test was selected. Results The cohort consisted of 151(86.8%) female and 23 (13.2%) male. Mean age at study was (42±13) years (range: 14-75 years). Thirty-one (17.8%) patients had primary APS, 143 (82.2% ) patients had APS associated with other diseases, including 138 cases of systemic lupus erythematosus (SLE). One hundred and forty-one (81.0%) had thrombosis episodes, among which the most common presenting manifestations were stroke (27.6%), deep venous thrombosis (27.6%) and pulmonary embolism (6.3% ). Stroke was more prevalent in Chinese than European patients. Forty-five patients (31.9%) had thrombotic recurrences and 62 patients (44.0%) had more than two sites of thrombosis. Patients with primary APS had higher rates of rethrombosis than those with secondary APS (P<0.05). Fetal morbidity rate of 126 married women in our study was 50.0%. Seven of APS patients with APS nephropathy were characterized by thrombotic microangiopathy. The presence of anticardiolipin antibodies was detected in 112 patients (64.4% ), anti-beta-2 glycoprotein Ⅰ antibodies in 103 patients (59.1%) and lupus anticoagulant in 50 patients (28.7%). Conclusion APS is characterized by recurrent thrombosis, pregnancy morbidity and positive antiphospholipid antibodies tests. Stroke, deep venous thrombosis and pulmonary embolism are the most common manifestations both in Chinese and European patients. Rethrombosis is more prominent in primary APS. Thrombotic microangiopathy is one of the most common histological changes of APS nephropathy. Multiple tests for aPL are proposed.     

系统性红斑狼疮患儿外周血辅助性T17细胞表达的初步研究

Objective To investigate the Th17 cell expression in peripheral blood of childron with systemic lupus erythematosus (SLE) and explore the role of Th17 cells and the cytokines in the pathogenesis of SLE. Methods Twenty-five children with SLE were enrolled and 15 healthy children were controls. Flow cytometry (FCM) was employed to detect the expression of Th17 cells in peripheral blood of SLE children (SLE group, n=25), and IL-17, IL-21 levels in plasma were detected by ELISA. Two-independent sample t-test and Spearmen's test were used for correlation analysis. Results Compared with that of the control, the frequencies of CD3+CD8-IL-17+T[(1.24±0.64)% vs (0.59±0.21)%], CD3+CD8-IL-21+T cells[(1.5±0.6)%vs (0.8±0.4)% ] increased significantly in SLE patients (P＜0.01) and the plasma concentrations of IL-17, IL-21 were significantly higher (P＜0.01). The SLE activity was positively correlated with the frequencies of CD3+CD8-IL-17+T cells, but not with CD3+CD8-IL-21+T cells. Conclusion Th17 cells and the related cytokinesplay an important role in the pathogenesis of childhood SLE.     

Autoantibodies in Chinese patients with chronic hepatitis B:Prevalence and clinical associations

AIM: To investigate the prevalence of autoantibodies and their associations with clinical features in Chinesepatients with chronic hepatitis B(CHB).METHODS: A total of 325 Chinese patients with CHB were enrolled in this retrospective,hospitalbased study.Patients with chronic hepatitis C(CHC),autoimmune hepatitis(AIH),or primary biliary cirrhosis(PBC) were included,with healthy donors acting as controls.A panel of autoantibodies that serologically define AIH and PBC was tested by indirect immunofluorescence assay and line immunoassay.The AIH-related autoantibody profile included homogeneous anti-nuclear antibodies(ANA-H),smooth-muscle antibodies,anti-liver kidney microsome type 1,antiliver cytosolic antigen type 1,and anti-soluble liver antigen/liver pancreas; the PBC-related antibodies were characterized by ANA-nuclear dots/membranous rimlike,anti-mitochondrial antibodies-M2(AMA-M2),antiBPO(recombinant antigen targeted by AMA-M2),antiSp100,anti-promyelocytic leukemia protein(anti-PML),and anti-gp210.The dichotomization of clustering was used to unequivocally designate the AIH or PBC profiles for each case.Anti-Ro52 antibodies were also tested.RESULTS: The prevalence of any autoantibody in CHB amounted to 58.2%,which was similar to the 66.2% prevalence in CHC,significantly higher than the 6.7% in the healthy controls(P < 0.001),and lower than the 100% found in AIH and PBC(P = 0.004 and P < 0.001,respectively).There were more anti-PML and anti-gp210 antibodies among the CHB patients than the CHC patients(11.1% vs 0%,P = 0.003; 12.6% vs 0%,P < 0.001,respectively).The prevalence and titer of AMA,anti-BPO,anti-PML,and anti-gp210 were higher in PBC than in those with CHB.Among the CHB patients,the prevalence of ANA,especially ANA-H,was significantly lower in patients with compensated and decompensated cirrhosis compared with patients without cirrhosis.Thirty-eight cases of hepatocellular carcinoma(HCC) in CHB showed a significant differencecompared with non-HCC patients in the prevalence of anti-PML(0% vs 12.5%,P = 0.013).Dichotomization of the autoantibodies revealed that the PBC profile was more prevalent in patients with CHB than in those with CHC,and that it was strongly correlated with both compensated and decompensated cirrhosis.In contrast,the prevalence of the AIH profile was significantly higher in non-cirrhosis patients with CHB than in those with compensated cirrhosis(18.5% vs 8.2%,P = 0.039).Moreover,the AIH profile was also closely associated with hepatitis B e-antigen positivity.CONCLUSION: ANA-H could be an indicator of earlystage CHB.Dichotomizing the autoantibody profiles revealed that the PBC profile is strongly associated with cirrhosis in CHB.     

Celiac disease in South-West of Iran

AIM: Celiac disease is characterized by life-long gluten intolerance. Clinical features of patients with celiac disease are variable. Studies about the prevalence of celiac disease in our country are scarce and there is no study on the prevalence of celiac disease in southern Iran. In the current study, clinical, laboratory and histological features of 52 patients with celiac disease were evaluated. METHODS: In a cross sectional study we retrospectively studied the characteristics of 52 celiac patients at Ahwaz JundiShapour University Hospitals (AJSUH) from November 1, 1999 to 1st Sep 2004. Intestinal biopsy and serum antigliadin and anti-endomysium antibodies were used for the diagnosis of patients. Mucosal lesions were classified according to the criteria of Marsh. Antigliadin antibodies were measured with a commercial enzyme-linked immunosorbent assay. Anti-endomysium antibodies were analyzed by indirect immunofluorescence with the use of a section of monkey esophagus. Routine hematological and biochemical analyses and measurement of immunoglobulin levels were undertaken. RESULTS: Male: female ratio was 1.08. The mean±SD patient age was 21±4.5 years (range 10-70 years) and the most common symptoms were diarrhea and weight loss (78.8%) followed by fatigue (73.1%), pallor (65.4%), anorexia (40.4%), abdominal distention (32.7%), and failure to thrive (23.1%). Diarrhea and weight loss and fatigue were the most common findings. Iron deficiency anemia was found in 63.2% of patients and this became normal after adoption of a gluten-free diet in all patients. Immunoglobulin A, IgG antigliadin antibodies and IgA anti-endomysium antibodies were found in 33 and 48 cases, 78.8% and 85.4% of patients, respectively. Biopsy of the small intestine revealed that 90.4% of patients had typical lesions according to the Marsh classification. CONCLUSION: Although classical presentation was seen in most of the patients, atypical clinical manifestations of celiac disease should be kept in mind. In particular, patients with uncommon findings, such as short stature, and iron-deficiency anemia, should be screened for celiac disease. Further epidemiological studies in our area in the general population and in high risk groups seem to be indicated.     

系统性红斑狼疮自身免疫性溶血性贫血的临床分析

目的 探讨系统性红斑狼疮(SLE)合并自身免疫性溶血性贫血(AIHA)患者的临床及血清学特点.方法 收集SLE患者222例,其中发生AIHA的患者17例,应用简单随机抽样法抽取未发生AIHA的34例SLE患者作为对照.回顾性分析患者的一般情况、临床表现、实验室及辅助检查等.计最资料采用t检验,计数资料采用x2检验.结果 SLE合并AIHA的发生率为7.6％.AIHA组抗心磷脂抗体IgG的阳性率(71％)与对照组(15％)相比明显升高(x2=15.366,P＜0.01),但2组抗磷脂抗体综合征的发生率差异无统计学意义(x2=0.000,P=1.000).AIHA组关节炎(12％,x2=4.554,P=0.033)、面部红斑(6％,x2=4.443,P=0.033)、白细胞减低(12％,x2=8.061,P=0.005)及淋巴细胞减低(41％,x2=5.075,P=0.024)的发生率较对照组低,差异有统计学意义.AIHA组有3例在病程中出现了肺泡出血,而对照组患者均未出现肺泡出血(x2=3.586,P=0.058).结论 SLE合并AIHA患者的抗心磷脂抗体IgG阳性率高,但抗磷脂抗体综合征的发生率无显著增加.SLE合并AIHA患者关节炎、面部红斑、白细胞减低及淋巴细胞减低的发生率低,但有发生肺泡出血的倾向.     

抗β2糖蛋白I抗体在系统性红斑狼疮合并自身免疫性溶血性贫血中的意义

目的检测抗β2糖蛋白I抗体(β2 glycoprotein I,aβ2GPI)等多种自身抗体在系统性红斑狼疮(systemic lupus erythematous,SLE)并发自身免疫性溶血性贫血(autoimmune hemolytic anemia,AIHA)患者的阳性率,评估aβ2GPI在并发AIHA的SLE患者中的意义。方法收集2008年12月至2013年4月福建医科大学附属第一医院风湿科门诊和病房SLE患者资料,根据有无发生AIHA分为SLE-AIHA组和SLE-non-AIHA组。选取AIHA患者为AIHA组。检测IgM和IgG类的aβ2GPI、抗心磷脂抗体(anticardiolipin,ACL),以及抗Sm抗体、核小体抗体、组蛋白抗体、核糖体P蛋白抗体等多种自身抗体,采用SPSS11.5软件统计分析。结果共纳入SLE患者104例,SLE-AIHA组22例,SLE-non-AIHA组82例;AIHA组20例。SLE-AIHA组和SLE-non-AIHA组在年龄、性别、病程、受累器官等方面均无统计学差异;而SLE-AIHA组的IgG类aβ2GPI阳性率达45.5%,显著高于SLE-non-AIHA组的15.9%,差异有统计学意义(P0.01);两组患者的IgM类aβ2GPI、IgM和IgG类ACL、抗Sm抗体、核小体抗体、组蛋白抗体、核糖体P蛋白抗体阳性率比较差异均无统计学意义(均P0.05);SLE-AIHA组和AIHA组患者aβ2GPI和ACL阳性率比较差异均无统计学意义(均P0.05);SLE-AIHA组IgG类aβ2GPI阳性患者肾损害发生率高于该抗体阴性者,差异有统计学意义(P0.05)。结论 IgG类aβ2GPI在并发AIHA SLE患者和原发性AIHA患者中均表现较高阳性率,可能是SLE并发AIHA的重要血清学特征;同时该抗体可能是继溶血事件后加重狼疮患者肾损害的重要因素之一。     

Clinical analysis of primary Sjögren’s syndrome complicating anemia

This is a cross-sectional study to assess the prevalence and causes of anemia in the primary Sjögren’s syndrome (pSS). One hundred and thirty-two consecutive patients with pSS were enrolled into the study. Standard hematological and immunological tests and examination of bone marrow were performed. Anemia occurred in 45 (34.1%) patients. The causes of anemia included anemia of chronic disease (69%), autoimmune hemolytic anemia (AIHA, 18%), iron deficiency anemia (9%) and other causes (4%), of which AIHA caused the most severe anemia. The prevalence of ANA, anti-Ro/SSA, and anti-La/SSB was much higher in patients with anemia than those without anemia. Anticardiolipin antibodies were most commonly detected in AIHA; the prevalence of IgG and hypocomplementemia in AIHA was much higher in patients without anemia. Abnormal bone marrow changes were observed in two cases with anemia, one with morphological changes in the myeloid, megakaryocytic, and erythroid lineages and one with hypocellularity in the erythroid lineage. Therefore, pSS patients with anemia may be associated with destruction of peripheral mature blood cells, impaired red cells production, and hematopoietic abnormalities due to an immune mechanism, although the concrete pathogenesis is still unclear.     

Autoantibodies to erythropoietin receptor in patients with immune‐mediated diseases: relationship to anaemia with erythroid hypoplasia

The prevalence, clinical associations and pathogenic role of newly identified autoantibodies to the erythropoietin receptor (EPOR) in patients with anaemia were investigated. Sera from 203 patients with immune‐related or chronic kidney diseases were screened for anti‐EPOR antibodies by enzyme‐linked immunosorbent assay, and antibody specificity was evaluated by immunoprecipitating EPOR from AS‐E2 cells using purified immunoglobulin (Ig) fractions. In addition, the pathogenic role of anti‐EPOR antibodies was determined by examining their inhibitory effects on AS‐E2 cell proliferation. Clinical findings were compared between patients with and without anti‐EPOR antibodies, in all patients and those with systemic lupus erythematosus (SLE). Serum anti‐EPOR antibodies were detected in 52 patients. Purified IgG or IgM fractions from anti‐EPOR antibody‐positive sera immunoprecipitated EPOR and inhibited the EPO‐dependent proliferation of AS‐E2 cells in a dose‐dependent manner. Anti‐EPOR antibodies were associated with low haemoglobin concentrations and reticulocytopenia in all patients enrolled and those with SLE. Further, there was a negative correlation between the levels of anti‐EPOR antibodies and the number of bone marrow erythroblasts in patients who underwent bone marrow examinations. These findings suggest that EPOR autoantibodies are present in a subset of patients with anaemia and that impaired erythropoiesis can be mediated by anti‐EPOR antibodies, which functionally neutralize EPO activity.     

Hypocomplementemia in systemic lupus erythematosus and primary antiphospholipid syndrome: prevalence and clinical significance in 667 patients

The objective of the study was to analyse the prevalence and clinical significance of hypocomplementemia in a large series of patients diagnosed either with systemic lupus erythematosus (SLE) or with primary antiphospholipid syndrome (APS) and its association with the main clinical, hematological and immunological features of these diseases. Between 1992 and 2003, complement determinations (C3 and C4 levels, CH50 activity) were performed in 597 consecutive patients diagnosed with SLE (530 women and 67 men, mean age 32.6 years) and 70 with primary APS (57 women and 13 men, mean age 38.7) visited in our department. Complement determinations are routinely made at the first visit of patients and yearly during the follow-up. SLE and primary APS were diagnosed according to current classification criteria. Hypocomplementemia was detected in 371 (62%) of SLE patients. Compared with patients with normal complement values, those with hypocomplementemia showed a higher prevalence of female gender (P < 0.001), fever (P = 0.021), nephropathy (P < 0.001), cutaneous vasculitis (P = 0.023), positive anti-dsDNA antibodies (P = 0.012) and cryoglobulinemia (P < 0.001). In addition, patients with hypocomplementemia showed a higher prevalence of APS-related features such as hemolytic anemia (P = 0.001) and antiphospholipid antibodies (P < 0.001). Hypocomplementemia was prospectively related to accumulated hospitalization in SLE patients but not with the accumulated number of lupus flares or with the survival after follow-up of five years. In contrast, 33 (47%) patients with primary APS presented low complement values, which were associated with a higher prevalence of livedo reticularis (P = 0.022), thrombocytopenia (P = 0.004), lupus anticoagulant (P = 0.013), positive IgM-aCL (P = 0.039), positive ANA (P = 0.002) and anti-dsDNA (P = 0.046). The diagnostic value of hypocomplementemia in patients with SLE is based on the association with disease activity, immune-complex mediated manifestations (glomerulonephritis, cryoglobulinemia) and APS-related features (livedo reticularis, hemolytic anemia and aPL). Hypocomplementemia was found in nearly half of patients with primary APS, and was associated with some APS features (livedo reticularis, thrombocytopenia, aPL) but also with SLE-related immunological markers (ANA and anti-dsDNA), identifying a subset of patients with primary APS with a higher risk of evolving to SLE. These results clearly support the routine determination of complement factors in the clinical follow-up of patients with SLE and primary APS.     

四种常见贫血患者红细胞寿命的研究

目的:研究自身免疫性溶血性贫血(AIHA)患者的红细胞寿命,并与常见贫血患者的红细胞寿命比较。方法:回顾性分析AIHA、骨髓增生异常综合征(MDS)、重型再生障碍性贫血(SAA)和缺铁性贫血(IDA) 4组共55例患者的临床资料,以同期12例健康志愿者为正常对照组。采用一氧化碳(CO)呼气法测定红细胞寿命,比较4种贫血患者和健康志愿者红细胞寿命并作分析。结果:AIHA患者红细胞寿命为(30.41±31.12)d,比MDS(53.44±32.61)d、SAA(54.53±22.56)d和IDA(58.75±31.29)d患者的红细胞寿命均缩短(P0.05),4组患者红细胞寿命均较12例健康志愿者红细胞寿命(118.16±25.88)d显著缩短(P0.01)。结论:红细胞寿命缩短参与了AIHA、MDS、SAA和IDA患者贫血的发生,但在不同贫血疾病中所起作用程度不尽相同。     

Autoimmune hemolytic anemia following allogeneic hematopoietic stem cell transplantation in adult patients

Autoimmune hemolytic anemia (AIHA) after allogeneic hematopoietic stem cell transplantation (HSCT) is still not well characterized. The aim of this study was to analyze the incidence and risk factors for the development of AIHA, as well as its prognosis and response to treatment in a series of patients undergoing allogeneic HSCT at a single institution. Between 1996 and 2004, 272 adult patients with a variety of malignant hematopoietic disorders underwent allogeneic HSCT. Direct antiglobulin testing was performed in routine pretransfusion compatibility testing or after clinical suspicion of AIHA. Twelve patients developed AIHA after HSCT at a median time of 147 days (range, 41-170). The 3-year cumulative incidence of AIHA was 4.44%. Eight cold antibodies and four warm antibodies were detected. Multivariate analysis shows that HSCT from unrelated donors (P=0.02) and the development of chronic extensive graft-versus-host disease (GVHD) (P=0.0004) were the only independent factors associated with AIHA. Two patients are still alive. AIHA was never the primary cause of death but added morbidity in patients with other concomitant complications. Patients undergoing HSCT from unrelated donors and those who develop chronic extensive GVHD are especially predisposed for this complication.     

Risk of venous thromboembolism among hospitalizations of adults with selected autoimmune diseases

Previous research has suggested autoimmune diseases are risk factors for developing venous thromboembolism (VTE). We assessed whether having diagnoses of selected autoimmune diseases associated with antiphospholipid antibodies—autoimmune hemolytic anemia (AIHA), immune thrombocytopenic purpura (ITP), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE)—were associated with having a VTE diagnosis among US adult hospitalizations. A cross-sectional study was conducted using the 2010 Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality. VTE and autoimmune diseases were identified using International Classification of Diseases, Ninth Revision, Clinical Modification coded diagnoses information. The percentages of hospitalizations with a VTE diagnosis among all non-maternal adult hospitalizations without any of the four autoimmune diseases of interest and among those with AIHA, ITP, RA, and SLE diagnoses were 2.28, 4.46, 3.35, 2.65 and 2.77 %, respectively. The adjusted odds ratios (OR) for having a diagnosis of VTE among non-maternal adult hospitalizations with diagnoses of AIHA, ITP, RA, and SLE were 1.25 [95 % confidence interval (CI) 1.05–1.49], 1.20 (95 % CI 1.07–1.34), 1.17 (95 % CI 1.13–1.21), and 1.23 (95 % CI 1.15–1.32), respectively, when compared to those without the corresponding conditions. The adjusted OR for a diagnosis of VTE associated with a diagnosis of any of the four autoimmune diseases was 1.20 (95 % CI 1.16–1.24). The presence of a diagnosis of AIHA, ITP, RA, and SLE was associated with an increased likelihood of having a VTE diagnosis among the group of all non-maternal adult hospitalizations.     

Anaemia in systemic lupus erythematosus: aetiological profile and the role of erythropoietin

OBJECTIVE: To study the prevalence of different causes of anaemia in patients with systemic lupus erythematosus (SLE) and their associations with immunological and clinical parameters and to evaluate the contribution of erythropoietin (Epo) and anti-erythropoietin (anti-Epo) autoantibodies to the development of SLE anaemia. METHODS: 132 SLE patients with anaemia (defined as haemoglobin of 12 g/dl or less for women and 13.5 g/dl or less for men) from among a total of 345 consecutive SLE patients were prospectively enrolled into the study. Standard haematological and immunological tests were performed and serum Epo and anti-Epo antibodies were assayed. RESULTS: The identified causes were anaemia of chronic disease (ACD) n=49 (37.1%), iron deficiency anaemia (IDA) n = 47 (35.6%), autoimmune haemolytic anaemia (AHA) n = 19 (14.4%) and other causes n = 17 (12.9%). There was significant heterogeneity in the severity of anaemia between the four groups (p<0.01) with AHA cases being on average more severe. The proportion of patients with anticardiolipin antibodies, low complement levels and anti-dsDNA differed significantly among the four groups; these markers were particularly common in patients with AHA, and uncommon in patients with IDA. Twenty one of 100 tested patients had anti-Epo antibodies. Such antibodies were seen practically only in patients with ACD (odds ratio 3.1, p = 0.041) and in patients with high lupus activity (ECLAM) scores (odds ratio 1.27 per point, p = 0.055). Epo response was inadequate in 42.4% and 41.2% of patients with ACD and AHA, respectively. CONCLUSIONS: Anaemia in SLE usually takes the form of ACD and IDA, however autoimmune haemolysis is not uncommon. SLE patients with different causes of anaemia differ in regard to several immunological parameters. Epo response is blunted in anaemic SLE patients, particularly those with ACD and AHA.     

Autoimmune hemolytic anaemia in the antiphospholipid syndrome

Antiphospholipid syndrome (APS) is a multisystem disease with recurrent thrombosis in the presence of antiphosphlipid antibodies, which may include cardiac, neurological, gastrointestinal, hematologic or cutaneous manifestations. The occurrence of autoimmune hemolytic anaemia (AIHA) in APS has not been well established. The purpose of this study was to review the occurrence of AIHA in patients with APS and its relation to other disease manifestations. Three-hundred and eight patients with APS from seven medical centers in Israel, Serbia and the Slovac Republic were included and evaluated for associations between AIHA and various manifestations of APS. AIHA was documented in 32 patients (10.4%). The odds ration for AIHA was increased in the presence of anticardiolipin antibodies and livedo reticularis (5.4 and 7.8, respectively). There was a highly significant association between AIHA and cardiac valvular vegetations and thickening (P < 0.0001), arterial thrombosis (P < 0.02), livedo reticularis (P < 0.0001) and CNS signs of epilepsy or chorea (P < 0.02 and P < 0.03, respectively). Thus, APS patients with AIHA are at risk of developing these manifestations, and should therefore be investigated for them. In addition, the occurrence of AIHA may define a subgroup of patients with a significant risk for subsequent development of SLE.