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This study aimed to examine the long-term efficacy, remission and survival of patients with severe systemic lupus erythematosus (SLE) after the combination treatment with high-dose immunosuppressive therapy (HDIT) and autologous peripheral blood stem cell transplantation (APBSCT).Chinese patients with severe SLE receiving combination therapy with HDIT and APBSCT in Peking Union Medical College Hospital were enrolled from July 1999 to October 2005. Disease activity, treatment, and adverse effects of these patients were evaluated. The 10-year overall survival and 10-year remission survival were also analysed.Among the 27 patients, one patient failed to collect enough CD34+ cells and data was missing for two patients. In the end, 24 patients were included in the final analysis. After APBSCT, one patient died, two patients achieved partial remission and 21 (87.5%) achieved remission at 6 months. The median follow-up duration of the 23 patients was 120 months. Fourteen patients had completed a ten-year follow-up. The median proteinuria level of the 14 patients with LN with ten years of follow-up significantly decreased from 4.00 g/24 hours at pre-treatment to 0.00g/24 hours at year 5 and 0.00 g/24 hours at year 10 (both p=0.001). The 10-year overall survival rate and 10-year remission survival rate were both 86.0% (95% CI: 71.1-100.9%). After a median follow-up for 120 months, 16 patients (66.7%) remained in remission, 4 patients were lost to follow-up, 2 patients died and 1 patient remained active.The combination of HDIT and APBSCT may be an option to improve the survival of severe lupus patients.

To explore the clinical features of immunoglobin (IgG4)-related Mikulicz's disease (MD).Since December 2010, a prospective cohort study of IgG4 related disease (IgG4RD) was performed our hospital. A total of 42 IgG4RD patients were recruited along with 18 MD patients. Their clinical, laboratory and histopathological features and response to treatment were analyzed.The 18 MD patients accounted for 42.9% of IgG4RD. There were 10 males and 8 females with a mean age of (48 ± 14) years. The mean follow-up period was 8.18 months. All of them had an involvement of salivary and lacrimal glands. Fifteen cases suffered other organs' damage, including autoimmune pancreatitis (n = 7), sclerosing cholangitis (n = 4) and lymph nodes (n = 6). And 10 patients complained of a history of allergies. All serum levels of IgG4 subclass significantly increased. Histological examinations in 16 patients revealed massive infiltration of lymphocytes and IgG4 positive plasma cells with obvious tissue fibrosis. Glucocorticoid and immunosuppressive therapies were effective for MD.As an IgG4-related systemic disease involving predominantly lacrimal and salivary glands without autoantibodies, MD is treated optimally with a combination therapy of glucocorticoid and immunosuppressive drugs.

We describe a case of systemic sclerosis (SSc) complicated with portal hypertensive ascites which did not improve with diuretics and ascitic drainage. When corticosteroid added, her ascites diminished dramatically. Though portal hypertension can be imputed to other causes, such as polycystic liver in this case, it can occur in limited SSc with positive anti-centromere antibody and respond to corticosteroid treatment.

To investigate clinical features of cutaneous sarcoidosis.A retrospective analysis was carried out based on the clinic data of 35 patients with cutaneous sarcoidosis who were hospitalized in Peking Union Medical College Hospital during 1980 - 2009. They were divided into two groups, the group without systemic involvement (skin group) and the group with systemic involvement (systemic group).(1) The ratio of men and women with cutaneous sarcoidosis was 1:3.38, and the average incident age was (47.5 ± 10.0) years old. The average incident age of skin group and systemic group were (41.8 ± 12.5) years old and (50.5 ± 7.1) years old, respectively. (2) The most common skin manifestation was subcutaneous nodule, followed by maculopapular and erythema nodosa. The most common involved sites were limbs. (3) The common involved systems extra-skin included the lung, joints and lymph nodes. The involvement rate of lung in cutaneous sarcoidosis of our present data was lower than those of foreign reports. However, the involvement rates of joints, lymph nodes, kidney, muscles and nervous system showed higher in our data. (4) The incidences of fatigue and weight loss in systemic group were higher than those in skin group (P0.05). The indexes of erythrocyte sedimentation rate, C-reactive protein and rheumatoid factor in systemic group were higher than those in skin group (P0.05). More patients in systemic group were treated with corticosteroid than that in skin group (95.7% vs 66.7%, P0.05).Subcutaneous nodules are the most common and the involvement rate of lung is lower in cutaneous sarcoidosis of our present data. Compared to the patients without systemic involvement, the average incident age of systemic ones is older, the indexes of inflammation markers and the usage of corticosteroid are higher.

To investigate the clinical features and treatment strategy for the thymoma-associated systemic lupus erythematosus (SLE) in a worldwide perspective.All articles between 1975 to 2008 were searched with the key words "SLE Thymoma" or "SLE thymectomy" in the database of PubmedMedline; the Chinese articles were searched with the same key words in the database of China Hospital Knowledge Database (CHKD). Data were extracted and analyzed.44 patients from 24 studies were available for this analysis with a male-to-female ratio of 1: 6. The mean age of SLE onset was 47.9 (21-76) while the mean age of discovery of thymoma was 48.5 (18-77). The clinical picture of SLE was classical with no statistical difference between genders. However, the thymoma-associated SLE occurs in patients older than the classical onset age of SLE (P0.01). As for treatment, the glucocorticoids-based immune-suppressive therapy still proves to be effective (P0.01). The thymoma could be benign or invasive which does not depend on gender or age. There is no statistical difference with regards to pathologic sub-types. As for the patients who already had SLE when discovering the thymoma, the clinical outcomes varied after the thymectomy (remission 27.8%, exacerbation 33.3%, no change 38.9%, P0.05).The possibility of thymoma should be considered among those late-onset SLE patients. The glucocorticoid-based immunosuppressive therapy is effective for thymoma-associated SLE. To treat SLE is not an indication for thymectomy.

To assess the safety and efficacy of high-dose immunosuppression and autologous peripheral blood cell transplantation (APBSCT) in severe and refractory primary Sjögren's syndrome (pSS) and to analyze immune reconstitution in pSS.Two patients with severe and refractory primary pSS were included in this study. They suffered still with active pSS despite the use of prednisone and immunosuppression agents. A regimen of high-dose immunosuppression and APBSCT was carried out for them. Dynamic T cell subgroup was tested with flow cytometry before and after PBSCT and the diversity of T cell receptor repertoire and CDR3 spectrum with RT-PCR and genescan.Both of the pSS cases underwent PBSCT smoothly. Clinical assessments showed improvement. Immune reconstruction lagged behind hematopoietic reconstitution. The skew of T cell receptor repertoire was somewhat corrected and CDR3 spectrum changed from oligoclonality to poly-clonality.High dose chemotherapy (HDC) and APBSCT are feasible and safe and can result in short-term or middle-term improvement of disease in patients with severe pSS which is refractory to conventional treatment. It is observed in this study that immune reconstruction recovered 3 moths after the treatment. Long-term efficacy of HDC + PBSCT in pSS should be studied in large number of cases with follow up of longer time.

To investigate the differences in immune reconstitution, hematopoietic reconstitution, efficacy, and complication between the two conditioning regimens with or without total body irradiation (TBI) in patients with refractory and severe autoimmune diseases (AID) who receiving autologous peripheral blood stem cell transplantation (APBSCT).Thirty-two AID patients, 5 males and 27 females, aged 29 (15 - 49), underwent APBSCT. The CD34(+) cells were mobilized with cytoxan (CTX) + granulocyte-colony stimulating factor (G-CSF) and selected by clinical magnetic activated cell sorting (CliniMACS). The conditioning regimen included CTX + antithymocyte globulin (ATG) in 11 patients and CTX + TBI in 21 patients. All the patients were followed up for more than 12 months.The median time of granulocyte recovery were 11 and 9 days in the CTX + TBI and CTX + ATG groups respectively (P = 0.003), the median time of platelet recovery were 13 and 8 days respectively (P = 0.001). In both groups, the lymphocyte subsets were recovered with the inverted CD4/CD8 ratio 12 months after transplantation. Relapse was seen in 3 cases of the CTX + TBI group (14.3%), and 2 cases of the CTX + ATG group (18.2%), and the rest of patients remained free of AID. During transplantation incidence of bacteria infection occurred in 5 of the 21 cases in the CTX + TBI group (23.8%) and in 2 of the 11 cases of the CTX + ATG group (18.2%) respectively; viral infection occurred in 1 of the 21 cases of the CTX + TBI group (4.8%) and in 2 of the 11 cases of the CTX + ATG group (18.2%) respectively. The number of radiated parotitis was 4 among the 21 patients of the CTX + TBI group (19%) and was 3 among the 12 patients of the CTX + ATG group (25%). Serum sickness reaction occurred in 3 of the 12 patients of the CTX + ATG group (25%). Bacterial and viral infections were cured soon after antibacterial or antiviral therapy, no fatal bleeding occurred due to thrombocytopenia in both groups.The conditioning regimen of TBI + CTX delays the hematopoietic reconstitution compared with the ATG + CTX regimen in treating AID. The regimen of CTX + TBI can be better tolerated, but there are no significant differences in efficacy and immune reconstitution among these two regimens.

To evaluate the feasibility and safety of peripheral CD34+ cell mobilization in patients with severe autoimmune disease.Forty-two patients underwent a total of 46 mobilizations by the regimen of cyclophosphamide 2-3 g/m2+ recombinant human granulocyte colony stimulating factor (rhG-CSF) 5 microg x kg(-1) x d(-1). The positive selection of CD34+ cell was performed through the CliniMACS.In 8.1 +/- 2. 3 days after administration of cyclophosphamide, the peripheral white blood cell and mononuclear cell (MNC) decreased to the lowest level. In 3.7 +/- 1.6 days after injection of rhG-CSF, the peripheral absolute MNC and CD34+ cell counts were 0.95 x 10(9)/L and 0.035 x 10(9)/L, respectively. After 2.4 +/- 0.6 times of leukapheresis, there gained 4.46 x 10(8)/kg of MNC and 5.26 x 10(6)/kg of CD34+, respectively. After mobilization, the underlying diseases were ameliorated more or less. In systemic lupus erythematosus (SLE) patients, SLE Disease Activity Index (SLEDAI) decreased from a median of 17 to 3 (P0.01). In rheumatic arthritis patients, an American College of Rheumatology criteria for 20% (ACR20) response was achieved in all five patients. Totally, 17.4% of patients whose absolute neutrophil count0.5 x 10(9)/L suffered infection, and 31.0% of patients had bone pain after the injection of rhG-CSF. Two patients suffered severe complications, one with acute renal failure and recovered by hemodialysis, the other died of thrombotic thrombocytopenic purpura. Failed mobilization occurred in three patients.Sufficient CD34+ cells can be mobilized by low dose of cyclophosphamide and rhG-CSF. CD34+ cell mobilization for treatment of severe autoimmune disease not only is appropriate in both effectiveness and safety but ameliorates disease also.

To study the neuropsychiatric (NP) manifestations of systemic lupus erythematosus (SLE) and evaluate treatment with intrathecal (IT) methotrexate (MTX) and dexamethasone (DXM).240 patients with NP syndromes of SLE (NPSLE) from 1990 to 2004 were retrospectively reviewed and IT injection group and non-IT injection group were compared. The side effects of IT injection were also discussed. 130 patients were followed up after discharge.Fifteen of the 19 ACR NP syndromes were identified. 86 (35.8%) patients presented one NP syndrome and 154 (64.2%) presented with more than one. The most frequent manifestations were headache and seizure disorder. 109 patients received IT injections. After IT injection, the CSF index had significantly improved. The mean SLEDAI score, mean duration of hospitalization and mortality rate of patients with IT injection were lower than those patients without IT injection (P0.05 - 0.001). The side effects of IT injection were found in 11.0% patients. 23 of 130 patients had recurrent NP events during follow up.There was heterogeneity of NPSLE in our study group. The most common NP features were headache and seizure. IT injection of MTX and DXM is an effective and safe alternative to traditional treatment of NPSLE.

To evaluate the feasibility, efficacy, and safety of high dose immunosuppressive therapy (HDIT) and autologous hemopoietic stem cell transplantation (HSCT) with CD34+ cell selection in patients with severe, refractory autoimmune diseases.Twenty-six patients with persistent systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), primary Sjögren's syndrome (pSS), or systemic sclerosis (SSc) who had been treated unsuccessfully with conventional treatment were enrolled in the trial in Peking Union Medical College Hospital from September 1999 to June 2004. The patients received HDIT with 200 mg/kg cyclophosphamide followed by an infusion of autologous stem cells that were CD34 selected. Disease activity, adverse effect, hemopoietic and immune reconstitution, and time to recurrence of disease were monitored.Overall treatment related mortality was 7.7% (2/26) with 1 patient died of cytomegalovirus infection and another of severe pneumonia. Relapse occurred in 3 SLE patients (17.6%) in 37, 26, and 19 months posttransplantation respectively, and 1 RA patient in 15 months posttransplantation. SLE Disease Activity Index (SLEDAI) scores of SLE survivors decreased significantly (P0.01). RA patients recorded a drop of Disease Activity Score 28 (DAS 28). The pSS patient remained symptoms free up to now, more than 50 months after the transplantation.HSCT can be performed relative safely in patients with severe autoimmune disease. Short-term effect of HSCT is promising. However treatment related mortality and relapse were observed in a subset of patients.

To investigate the feasibility, efficacy and safety of high dose immunosuppressive therapy (HDIT) and autologous peripheral blood stem cell transplantation (PBSCT) with CD(34)(+) cell selection in patients with refractory and severe autoimmune diseases.Twenty-one patients with SLE, RA, pSS, SSc or MCTD were enrolled in the study from 1999. Autologous haemopoietic stem cells were mobilized with CTX 3 approximately 4 g/m(2) and granulocyte colony stimulating factor (G-CSF). CD(34)(+) cells were selected by CliniMACS. After conditioning with CTX (200 mg/kg) and pig antithymocyte globulin (ATG, 90 mg/kg) or CTX (150 mg/kg) and total body irradiation (TBI, 4 approximately 6 Gy), the enriched CD(34)(+) cells were reinfused.All patients completed the mobilization and leukapheresis procedures successfully, and proceeded to receive conditioning and transplantation. Two patients died of complication related to transplantation, one is CMV infection, the other is severe pneumonia during the course of granulocyte deficiency. A MCTD patient completed the stem cell mobilization and died of severe pulmonary hypertension and heart failure before CD(34)(+) cells reinfusing. Two SLE patients relapsed in 26, 37 months respectively and a RA patient relapsed in 15 months after transplantation. Other patients got improved, with SLE-DAI score decreasing from 17 to 4 score and proteinuria decreasing from 6.7 g to 2.3 g in SLE patients; DAS28 score from 7.9 to 2.1 in RA patient; Symptom improved and lab results recovered in SS.High dose immunosuppressive therapy followed by autologous peripheral blood stem cell transplantation with CD(34)(+) cell selection is feasible and relative safe. Patients remain free from disease active and improved continuously. Some patients could relapse after transplantation. Long-term effect need to be further observed.

To investigate the clinical manifestations, diagnosis and treatment of anti-phospholipid syndrome (APS).61 patients with defined APS admitted from Jan 1986 to Dec 2002 were analyzed retrospectively.10 patients with primary APS and 51 patients with secondary APS were analyzed. Women were affected 3.1 times as that of men. 48 of the 51 (94.1%) patients with secondary APS were complicated with other autoimmune diseases, including 33 cases (64.7%) of systemic lupus erythematosus. Vascular thrombosis was presented in around 80.3% of the patients in this study. Thrombosis frequently involved the gastrointestinal system (21 cases, 22.6%), pulmonary system (19 cases, 20.4%), the cerebral vascular system (17 cases, 18.3%), lower limb deep venous system (16 cases, 17.2%), and infrequently coronary arteries or adrenal glands. The abnormal pregnancy rate in the 37 married women was 45.9%. The prevalence of anticardiolipin antibody (ACL) and lupus anticoagulant (LA) was 77.0% and 62.3% respectively. LA was associated with ACL.APS occurs most commonly among young women, is a disorder characterized by recurrent venous or arterial thrombosis and/or fetal losses associated with positive ACL or LA. Thrombosis frequently occurs in gastrointestinal system, pulmonary system, cerebral vascular system and deep venous system. The association between clinical features of APS and antiphospholipid antibody is significant. LA is a stronger risk factor for thrombosis and abnormal pregnancy than ACL. Antiplatelet with low-dosage aspirin and long-term anticoagulation are main therapeutics.