Systemic Lupus Erythromatosus Research Articles

Drug-Induced Lupus Associated with Rifabutin

Drug-induced lupus (DIL) is a rare adverse reaction to medications with features resembling idiopathic systemic lupus erythromatosis. Rifabutin/rifamycins have only rarely been reported as a cause of DIL, and no cases have been reported in blacks. A 55-year-old African American woman with HIV presented with severe generalized arthralgias and recurrent oral ulcers while receiving treatment for tuberculous meningitis. Arthralgias, which began in her knees after 5 weeks of antituberculous therapy, progressed to involve the joints in the ankles, wrists, and hands. She had no associated fever or rash. When she had these symptoms her antinuclear antibody (ANA) was 1:1280 homogenous pattern, antidouble stranded DNA was negative, antihistone antibody was strongly positive, anti-smith and antiribonucleoprotein (anti-RNP) were negative. Her symptoms resolved within 2 months of stopping rifabutin while continuing other antituberculous medications and her ANA titer started to decrease. We review the existing literature on this subject.

Evaluation of Serum Complement C3 and C4 Levels as biomarkers for Systemic Lupus Erythromatosus

Background: Systemic Lupus Erthematosis (SLE) is a chronic autoimmune disorder that affects multiple organ systems and also affects the skin and oral mucosa, with the exact cause is unknown. Many hypotheses try to explain the role of the complement C3, C4 in the pathogenesis of SLE. The aim of this study is to determine levels of serum complement C3 and C4 in patient with SLE, so that we may explain its role in diagnosis and pathogenesis of the disease. Methods: Twenty patients were informed from outcome patients of Dermatology Unit in El-Azhar University suffering from SLE. All the patients included in this study fulfilled 4 or more of the American Rheumatism Association classification Criteria for SLE. Blood samples from These 20 SLE patients (18 females and 2 males) aged from 20 to 45 years old were collected. Complement C3 and C4 were measured using radial immunodiffusion plates system technique. Clinical parameters such as Erythrocyte Sedimentation Rate (ESR), Total Protein (TPR), Serum Creatinine and Antinuclear Antibody (ANA) of those patients were considered in order to compare and explain the data obtained for the levels of C3 and C4. The data were collected and statistically analyzed. Results: Most of patients were female 90% and only 10% male. Of all patients, 60% have low level of serum C4, 40% have normal level of serum C4, 25% have abnormal level of serum C3, and 75% have normal level of serum C3.Statistical analysis of the data on the correlation between C4, and disease activity revealed significant (P> 0.05) correlation, however no significant correlation was found between C3 and disease activity. Analysis on the correlation between C3 and C4 with TPR, S. creatinne, and ESR, showed no significant correlation. No significant relationship was also found between C3 and C4.All patients have had high TPR, S. creatinne and ESR. All patients have had positive ANA which is an important marker of SLE as an auto immune disease. Conclusions: Patients showed different degrees of oral and systemic manifestations, which exacerbate and become acute with decreased level of complement C4 and instability of C3 level. Accordingly, the low level of C4 was associated with the development and exacerbation of SLE. Increased C3 levels is solely due to activity through the alternative pathway in SLE patients

Evaluation of Serum Complement C3 and C4 Levels as biomarkers for Systemic Lupus Erythromatosus

Evaluation of Serum Complement C3 and C4 Levels as biomarkers for Systemic Lupus Erythromatosus

The Changing Pattern of Renal Amyloidosis in Indian Subcontinent: Two Decades of Experience from a Single Center

Background: Renal amyloidosis is a major cause of morbidity and mortality among the patients of systemic amyloidosis. The causes of amyloidosis vary from country to country and from time to time at individual center. Aim: This study investigates the changes in epidemiological and clinical profile of renal amyloidosis in recent years. Method: Cases of biopsy-proven renal amyloidosis from January 1992 to December 2010 were studied retrospectively. They were divided into two groups: 1990s (between 1992 and 2002) and 2000s (between 2003 and 2010). The clinical characteristics of patients were studied and compared between the groups. Result: A total of 2498 (974 in 1990s and 1524 in 2000s) renal biopsies was done during the 19-year period. The incidence of amyloidosis in 1990s and 2000s was 1.74% (n = 17) and 1.9% (n = 29), respectively (p > 0.05). We noted that the incidence of renal amyloidosis increased significantly (p < 0.05) among the females in 2000s. The mean age of patients in 2000s and 1990s was 38 ± 17.9 and 39.2 ± 19 years, respectively (p = 0.83). Renal insufficiency in patients with renal amyloidosis significantly increased (p < 0.05) in 2000s (n = 14; 48.2%) in comparison to 1990s (n = 2; 12.8%). Subnephrotic proteinuria was observed in 12.8% (n = 2) and 48.82% (n = 14) of patients in 1990s and 2000s, respectively (p < 0.05). Infection (n = 10; 58.8%) was the most common cause of secondary amyloidosis during the 1990s, whereas chronic inflammation (n = 14; 48.2%) was the most common cause in 2000s. In 1990s, the incidence of ankylosing spondylitis (AS) and rheumatoid arthritis (RA) was 11.7% (n = 2) and 5.8% (n = 1), respectively, but in 2000s, their respective incidence was 17.2% (n = 5) each. Multiple myeloma (MM) was the most common cause of amyloid light chain protein (AL) amyloidosis in both the groups. We observed systemic lupus erythromatosus (SLE)-related renal amyloidosis in two cases and Hodgkin lymphoma-associated amyloidosis in one case in 2000s. Conclusion: The overall incidence of renal amyloidosis showed little change from 1990s to 2000s. Chronic inflammatory diseases were the most common cause of renal amyloidosis in 2000s in contrast to infections in 1990s. Female gender was more affected in 2000s than in 1990s. Renal insufficiency and subnephrotic-range proteinuria were more frequent clinical manifestations of renal amyloidosis in recent years (2000s) in comparison to the earlier decade (1990s).

Mesenchymal stem cells are a rescue approach for recovery of deteriorating kidney function

Stem cell (SC) therapy for chronic kidney disease (CKD) is urgently needed. The use of mesenchymal stem cells (MSC) is a possible new therapeutic modality. Our work aimed to isolate human MSC from adult bone marrow to improve kidney functions in CKD patients. In our study 30 patients with impaired kidney function were included, their ages ranged from 22 to 68 years. They included 10 inactive glomerulonephritis patients due to systemic lupus erythromatosus (SLE) (group I), 10 renal transplantation cases (group II) and 10 patients of other aetiologies as the control group. Fifty millilitres of bone marrow was aspirated from the iliac bone, for separation of MSC. There was a highly statistically significant difference between both CD271 and CD29 before and after culture with increase of both markers at end of culture, P < 0.01. Finally 50-70 million MSC in 10 mL saline (0.7-1.0 × 10(6) MSC/kg body weight) were infused intravenously in two divided doses one week apart. There was a highly statistically significant difference between each of serum creatinine and creatinine clearance levels before and after MSC injection at 1, 3 and 6 months post-infusion with SLE cases showing a greater decline of their serum creatinine and elevation of mean creatinine clearance levels after injection than transplantation and control groups, P < 0.05. Mesenchymal stem cells therapy is a potential therapeutic modality for early phases of CKD.

Systemic Autoantibodies in Neuromyelitis Optica: Is There Any Impact on Clinical Outcome? (P07.069)

Objective: To characterize the SS/SLE autoantibody profile and its impact on clinical features and disease severity of NMO/NMOSD patients. Background Neuromyelitis optica (NMO) and its spectrum disorders (NMOSD) have been associated with systemic inflammatory disorders, in particular Sjogren9s syndrome (SS) and systemic lupus erythromatosus (SLE). It is presently unknown if concomitant SS/SLE or systemic autoantibody seropositivity confers a worse prognosis in NMO/NMOSD patients. Design/Methods: We retrospectively reviewed patients who fulfilled diagnosis for NMO/NMOSD and underwent SS/SLE autoantibody evaluations, and compared autoantibody seropositivity to clinical characteristics and disease severity. Results: Twenty-nine patients (25 female, 4 male; 18 NMO, 11 NMOSD) were analysed. Mean disease duration was 84 months (range: 9 - 233 months). Overall systemic autoantibody seropositivity was high: anti-nuclear antibodies (48.3% [14/29]), anti-double stranded DNA (anti-dsDNA) (22.2% [6/27]) and anti-Ro and/or anti-La (21.4% [6/28]). Of those who tested for NMO-IgG, 83.3% (20/24) were positive; 55% (11/20) of these patients also had SS and/or SLE autoantibodies. All eleven patients with concomitant NMO-IgG and SS/SLE autoantibody seropositivity were female. Mean annualized relapse rate was not significantly different between systemic autoantibody-positive and autoantibody-negative patients (0.51 vs 0.91 relapse/year, p =0.089). Median Expanded Disability Status Scale (EDSS) score was similar in NMO/NMOSD patients with or without concomitant SS/SLE autoantibody positivity (3.0 vs 3.0, p=0.579). Similarly, there were no differences in ambulation (p=0.238), visual (p=0.702) and bladder/bowel dysfunction (p=0.192) scores in NMO/NMOSD patients with or without concomitant SS/SLE autoantibody positivity. Conclusions: Concomitant systemic inflammatory diseases such as SS and SLE and systemic autoantibody positivity in NMO/NMOSD are common and not mutually exclusive. Concomitant systemic autoantibody seropositivity does not translate to a worse clinical outcome in NMO/NMOSD patients, hence neurological prognosis appears to be exclusively mediated by NMO/NMOSD. Disclosure: Dr. See has nothing to disclose. Dr. Peh has nothing to disclose. Dr. Tan has received personal compensation for activities with Biogen Idec and Merck Serono as a consultant and/or speaker.

Pyoderma Gangrenosum and High Titer Serum Aanti-CCP2 Antibodies

Pyoderma gangrenosum is an uncommon ulcerative cutaneous neutrophilic dermatosis. In about 50 percent of cases, it is associated with systemic diseases like inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythromatosus, hematological diseases and various malignancies. There is no specific laboratory finding or histological features pathognomonic of pyoderma gangrenosum and it is often a diagnosis of exclusion. Here, we report an elderly female without history of any systemic disorders, presenting to us with extensive, bilaterally symmetrical, deep leg ulcers along with multiple superficial ulcers involving the right groin which was diagnosed as pyoderma gangrenosum. The only positive rheumatologic marker was serum anti-cyclic cittrulinated peptide2 antibody, which was found to be strongly positive. Dramatic response to systemic corticosteroid followed by successful split skin grafting was observed in our patient.

Immunologic response to influenza vaccine in at-risk children

Influenza infection can add particularly significant morbidity and mortality to children with chronic disease, especially those patients with compromised immune systems. In this issue of The Journal, Long et al evaluate the humoral and cell-mediated immune response to the H1N1/2009 monovalent vaccine in high-risk pediatric patients after solid organ transplantation (SOT), systemic lupus erythromatosus (SLE), asthma, and sickle cell disease. These data suggest that patients with SLE or SOT mount suboptimal responses, whereas children with asthma or sickle cell disease have a vigorous response to immunization, even in patients on oral steroids.

The Forgotten Guide Wire: A Rare Complication of Hemodialysis Catheter Insertion

A rare complication of a hemodialysis catheter insertion is the loss of the complete guide wire into the circulation. A complete guide wire in the circulation may not necessarily produce symptoms, and it may remain unnoticed for a significant period of time. We present a rare case where a complete guide wire was lost into the circulation during insertion of a hemodialysis catheter into the right femoral vein in a 19-year-old female with systemic lupus erythromatosis. The patient remained asymptomatic through two plasmapheresis treatments over a period of 2 days. The guide wire was eventually retrieved without complications. The factors leading to the wire being forgotten will be reviewed, and the measures initiated to prevent any future occurrence will be addressed.

MAJOR ADVERSE CARDIAC EVENTS IN LUPUS PATIENTS DURING PERIPARTUM: PP.22.413

Background: The purpose of this study was to determine the incidence of major adverse cardiac events (MACE) and mortality in lupus patients among peripartumin in Taiwan. Methods: A population-based cohort study was performed on 1,132,089 parturients during 1999 to 2003 using a dataset linking birth certificates and National Health Insurance hospital discharge data. Cumulated MACE-free rates, cumulated survival rate were estimated using the Kaplan-Meier method, and the log-rank test was used to examine the effect of systemic lupus erythromatosus (SLE) on the prevalence of MACE and mortality. Sociodemographic factors and obstetric complications were used in multivariate logistic regression models to determine the adjusted hazard ratios of SLE on the risk of MACE and mortality during pregnancy and at least within the first postpartum year. Results: Single independent variables that were statistically and clinically significant, including age, years of education, marital status, multiple gestation, birth-weight, parity, anemia, SLE, cesarean delivery, diabetes, chronic hypertension, pregnancy-related hypertension, antepartum hemorrhage, and postpartum hemorrhage were entered into a multivariable logistic regression mode. The incidence of any MACE and mortality in lupus group among peripartum was 0.88% and 1.98% respectively. The pregnant women with SLE have higher MACE including myocardial infarction, (Hazard ratio 56.4), heart failure (Hazard ratio 11.2), stroke (Hazard ratio 8.2), any MACE (Hazard ratio 10.2), maternal death (Hazard ratio 11.9) than those without SLE. Their risk remains significant at least 12 months postpartum. Conclusions: Although MACE and mortality are a rare events in women of reproductive age, pregnant women with SLE increases the risk 10 fold. Clinicians would be well advised to pay more attention to MACE in lupus patients even one year after delivery.

Hormonal therapy in a patient with ovarian agenesis and possible SLE: a choice to be made

Systemic lupus erythromatosus (SLE) is an autoimmune disease, which affects mainly women in the reproductive age and is influenced by hormonal changes. Therefore, hormone supplementation for patients with SLE either as contraceptives or as postmenopausal supplementation remains a controversial issue. Herein, we report a case of a 22-year-old woman with a history of ovarian agenesis, treated for several years with hormone therapy in order to reduce the risk of osteoporosis and other estrogen-deficient disorders. At the current evaluation, she met 3 of 11 diagnostic criteria for SLE along with a strong familial autoimmune predisposition. Precipitation of SLE in patients treated with hormonal therapy has been previously described. This prompted us to seek alternative drug therapies that prevent both the onset of overt SLE as well as the progression of estrogen-deficient phenomena. This unique case illustrates the dilemma of using hormone therapy in patients at risk to develop SLE and the current therapeutic alternatives.

Sex hormone-independent capacities of female hematopoietic cells from lupus-prone mice (83.23)

Abstract Many systemic autoimmune diseases are more commonly found in females than in males. This is evident in Systemic Lupus Erythromatosis (SLE), a prototypic systemic autoimmune disorder, where the ratio of females to males is 9:1. Our current understanding of the etiology of SLE implies important roles for genes and environmental factors such as sex hormones. Analyses of mouse models of SLE have proven good models for both; however, the relative importance of genes versus sex hormones is still largely unresolved. Using the (NZB x NZW)F1 mouse model system of SLE we have created a system in which we can segregate the effects of genes and hormones on the immune system in vivo. Briefly, male or female (NZB x NZW)F1 mice were lethally irradiated and reconstituted by age-matched male or female bone marrow (BM) or fetal liver (FL) cells. The resulting chimera mice were followed for the development of lupus-like disease. We found that female BM and FL cells express an intrinsic capacity to drive accelerated lupus-like disease development even in the presence of male pubertal sex hormones. Interestingly, chimera mice receiving female cells also presented with increased serum cytokine and immunoglobulin levels, suggesting that activation of both T and B cells happened more easily in female than male cells. These data represent a new system in which to investigate intrinsic differences between male and female immune mechanisms during the development of systemic autoimmunity.

PPARγ-2andBMPR2Genes Were Differentially Expressed in Peripheral Blood of SLE Patients with Osteonecrosis

Most researchers believe that the peroxisome proliferative activated receptor gamma (PPARgamma-2) and bone morphogenetic protein receptor type II (BMPR2) play important roles in steroid-induced osteonecrosis (ON). However, the molecular mechanism of this process is still unclear. Recent studies indicate that steroid treatments cause adipocyte formation due to differentiation of mesenchymal stem cells, which then prevents osteoblast formation. This study examined PPARgamma-2, bone morphogenetic protein 2 (BMP2), and BMPR2 in patients with systemic lupus erythromatosus (SLE) who eventually developed ON after prolonged steroid treatment. The subjects of this experiment included 220 SLE patients who had undergone steroid treatment for at least 2 years. Fifty-five of the 220 patients were ON patients, and 165 were non-ON patients. Real-time PCR was performed to analyze the expression of the PPARgamma-2, BMP2, and BMPR2 mRNA in the peripheral blood of these patients. The results indicated that the expression of PPARgamma-2 mRNA increased 37% in the ON patients' peripheral blood, but the expression of BMPR2 mRNA decreased 57%. The average expression of the PPARgamma-2 mRNA in the ON patients was significantly higher than that in the non-ON patients (p = 0.044). Conversely, the expression of BMPR2 mRNA was significantly lower than that in non-ON patients (p = 0.036), but the expression of BMP2 mRNA did not significantly differ. This study demonstrated that the PPARgamma-2 and BMPR2 have important roles in the ON process after prolonged steroid administration in SLE patients; however, the detailed molecular mechanisms of this process require further study.

Decreased DNA Methyltransferase 3A and 3B mRNA Expression in Peripheral Blood Mononuclear Cells and Increased Plasma SAH Concentration in Adult Patients with Idiopathic Thrombocytopenic Purpura

DNA methylation is known to play an important role in gene transcription and alterations of methylation contribute to the development of certain disorders such as cancer and immunodeficiency. Recent years have found an increasing interest in the role of epigenetic modifications in the etiology of human autoimmune diseases, such as systemic lupus erythromatosus (SLE) and rheumatoid arthritis (RA). DNA methyltransferases (DNMTs) are involved in the epigenetic control of DNA methylation processes. S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), as the substrate and product of essential cellular methyltransferase reactions, have important indicator action of cellular methylation status. The aim of this study is to explore if DNA methylation plays a role in the pathogenesis of idiopathic thrombocytopenic purpura (ITP). DNMT1, DNMT3A, and DNMT3B mRNA expression in peripheral blood mononuclear cells (PBMCs) of adult ITP patients were analyzed by real-time quantitative polymerase chain reaction. Plasma SAM and SAH levels were assayed with reversed-phase high performance liquid chromatography (HPLC). DNMT3A and DNMT3B mRNA expressions were significantly lower in ITP patients than in healthy controls (p < 0.001), while DNMT1 mRNA expression was not significantly different between the two groups (p = 0.774). Plasma SAH concentration was significantly elevated in ITP patients than in healthy controls (p < 0.05), while the plasma SAM and SAM/SAH were not significantly different between the two groups (p = 0.133, p = 0.624 respectively). Our observations suggest that aberrant DNA methylation status reflected by increased plasma SAH concentration and decreased mRNA expression levels of DNMT3A and 3B are possibly involved in the pathogenesis of ITP although the precise mechanisms need further study.

Role of gonadotropin releasing hormone analogues for ovarian protection in systemic lupus erythematosus patients treated with cyclophosphamide

To evaluate the effectiveness of gonadotropin releasing hormone analogues (GnRH-a) in protection against premature ovarian failure during cyclophosphamide (CTX) therapy for systemic lupus erythematosus (SLE). 28 female patients with SLE, aged 35.3 +/- 2.4 (30-39) were treated with prednisone orally 1 mg/kg daily for 8 weeks, and then the dose was decreased by 10% every 10 days. CTX 200 mg with normal saline 200 ml was intravenously injection every other day for 4 months. Peripheral white blood cell (WBC) count was made every week. If the WBC count was less than 3.5 x 10(9)/L, the use of CTX should be stopped temporarily until the WBC count became normal. And then, the CTX administration should be adjusted to 400 mg intravenously every week. All patients were offered treatment with Hypodermic injection of GnRH-a 3.75 mg was given monthly just at the beginning of the standard CTX regimen for 3 months. Follow-up was conducted for 6 months after the last prescription of GnRH-a. All patients developed amenorrhea after treated by GnRH-a. Menstruation recovered 73 days (69-82 days) after the last subcutaneous injection in 25 patients. Among these 25 patients, one developed amenorrhea again after two normal menses periods. The other 3 patients were in persistent amenorrhea during the following 6 months after the GnRH-a treatment. The levels of plasma estradiol (E2) was 998 +/- 308 pmol/L before GnRH-a treatment, and decreased significantly 1, 2, and 3 months after the last injection of GnRH-a (132 +/- 44 pmol/L, 88 +/- 37 pmol/L and 81 +/- 29 pmol/L respectively, all P < 0.05). The level of plasma E2 increased 2 months after the last injection of GnRH-a in the 25 patients with return of menses, and the level of plasma E2 returned to the normal baseline level after 6 months in 24 patients. Treatment with GnRH-a during CTX therapy is associated with a significant reduction of premature ovarian failure in most women with SLE.

Antiphospholipid syndrome patients display reduced titers of soluble CD21 in their sera irrespective of circulating anti-β2-glycoprotein-I autoantibodies

A soluble form of the complement receptor CD21 (sCD21) is shed from the lymphocyte surface. The sCD21 is able to bind all known ligands such as CD23, sCD23, Epstein-Barr virus and C3d in immune complexes. Here, we show the serum levels of sCD21 in sera the of antiphospholipid syndrome (APS) patients. Antiphospholipid syndrome is an autoimmune disorder in which autoantibodies cause heart attack, stroke and miscarriage. Antiphospholipid syndrome may appear as primary or in association with systemic lupus erythromatosus (SLE) and other autoimmune diseases. Here, we ask whether APS patients have different sCD21 titers compared to healthy persons and whether sCD21 levels correlate with the presence of anti-beta2-GPI autoantibodies. We show that autoimmune APS patients have significantly reduced amounts of sCD21 in their sera, irrespective of the presence of anti-beta2-GPI autoantibodies. In our APS patients cohort additional SLE, vasculities, DVT (deep vein thrombosis), fetal loss or thrombosis did not correlate to the reduced level of sCD21.

Primary Total Hip Arthroplasty in Systemic Lupus Erythromatosus

Objective: The purpose of this study is to evaluate the short term results of total hip arthroplasty (THA) for avascular necrosis in patients with systemic lupus erythematosus (SLE). Methods: This is a retrospective case control, matched pair study. Ten patients (15 hips) with SLE and avascular necrosis of the femoral head (AVNFH) underwent THA. Eight patients (12hips) with a minimum follow up of 2 years were reviewed. To determine whether these patients had results similar to those of patients with other diagnosis, we formed a control group of 12 patients who had 12 THA. They were matched for age, sex, BMI, activity, follow-up period, and type of implant with SLE group. The clinical and radiographic results were evaluated by Harris hip score (HSS) and serial radiographic findings, respectively. Results: There was no complication during the perioperative period. In the SLE group, HHS was from 67.3 preoperatively to 97.7 at last follow-up. In the control group, HHS was from 70.1 preoperatively to 97.8 at last follow-up. On the last roentgenograms, none of acetabular components demonstrated any evidence of migration, tilt, rotation or shedding of metal particles in both groups. All femoral components demonstrated no evidence of subsidence, pedestal, or shedding of metal particles in both groups. Conclusion: Patients with SLE and AVNFH had excellent results after THA. Results were not different from that of patients who had hip replacement for other diagnoses. Therefore, it is considered that uncemented THA was useful treatment method for the patient who had SLE and AVNFH.

Simultaneous Heart and Kidney Transplantation for Combined Cardiac and Renal Failure

Simultaneous heart and kidney transplantation (SHKT) is feasible for combined cardiac and renal failure. Herein we reviewed our 10-year experience in SHKT. Six patients underwent SHKT from June 1995 to December 2004. Their ages ranged from 13 to 63 years old with a mean of 45.5 ± 15.8 years. They were all men except one girl, who was the youngest (aged 13) who suffered from dilated cardiomyopathy with congestive heart failure and chronic renal failure due to systemic lupus erythromatosus. Because of aggravating heart failure, she changed from hemodialysis to peritoneal dialysis. Because of intractable heart failure, she underwent SHKT from a 24-year-old female donor. All received hemodialysis before SHKT. The indications for heart transplantation included dilated cardiomyopathy ( n = 3), ischemic cardiomyopathy ( n = 1), cardiac allograft vasculopathy ( n = 1), and cardiac allograft failure ( n = 1). The immunosuppressive protocol and rejection surveillance were these employed for heart transplantation. No operative mortality was noted in this study. The 1-year and 5-year survival rates were the same, 83%. The 10-year survival rate was 55%. No cardiac or renal allograft rejection was noted. No renal allograft loss was noted. There were two late mortalities: the one, who underwent redo heart transplantation for coronary artery vasculopathy died of cardiac allograft failure 1 year after SHKT. The other patient died of massive ischemic necrosis of the intestine at 6 years after SHKT. Our experience showed that SHKT had good short- and long-term results without increasing immunosuppressive doses. End-stage failure of either the heart or the kidney did not preclude heart plus kidney transplantation.

Variations within OLF1/EBF-associated zinc finger protein gene confer susceptibility to lupus nephritis in Chinese population

To observe whether single nucleotide polymorphisms (SNPs) within the OLF1/EBF-associated zinc finger protein (OAZ) gene are associated with lupus nephritis (LN) susceptibility in Chinese population. Eight SNPs located around the positive microsatellite marker D16S517 within OAZ gene with relatively high heterozygosity were chosen for genotyping on 184 systemic lupus erythromatosus (SLE) patients, including 101 non-LN patients and 83 LN patients, and 286 normal controls using TaqMan MGB allelic discrimination method. Data were collected by SDS 2.0 software. Haplotypes and their frequencies were constructed and estimated, and linkage disequilibrium analysis between pairs of SNPs was evaluated by calculating the D Prime using Helixtree program. Case-control study was performed between the SLE, LN, and non-LN groups and normal control group. (1) The frequency of SNP rs1344531 T allele was 47.0% in the SLE patients, significantly higher than that in the controls [38.1%,; chi(2) = 7.300, P = 0.008, OR (95% CI) = 1.441 (1.105 - 1.878)], which showed that the frequency of SNP rs1344531 T allele is associated with SLE susceptibility. The genotypic distribution of SNP rs1344531(CC/CT/TT) differed significantly between the SLE patients (25.5%/54.9%/19.6%) and normal controls (38.1%/47.6%/14.3%) (chi(2) = 8.394, P = 0.015). The CC genotype frequency of the SLE patients was 25.5%, significantly lower than that of the normal controls [38.1%; chi(2) = 7.976, P = 0.005, OR (95% CI) = 0.557 (0.370 - 0.838)] (2) The SNP rs1344531 T allele frequency of the SLE patients was 53.0%, significantly higher than that of the normal controls [38.1%; chi(2) = 11.769, P = 0.001, OR (95% CI) = 1.832 (1.293 - 2.596)], which showed an associated between SNP rs1344531 T allele frequency and LN susceptibility. The genotypic distribution of SNP rs1344531 (CC/CT/TT) differed significantly between the LN patients (22.9%/48.2%/28.9%) and the normal controls (38.1%/47.6%/14.3%) (chi(2) = 12.065, P = 0.002). The CC genotype frequency of the LN patients was 22.9%, significantly lower than that of the normal controls (38.1%) [chi(2) = 6.578, P = 0.013, OR (95% CI) = 0.481 (0.274 - 0.848)]. The TT genotype frequency of the LN patients was 28.9%, significantly higher than that of the normal controls (14.3%) [chi(2) = 9.423, P = 0.003, OR (95% CI) = 2.431 (1.363 - 4.334)]. No statistical significance was observed between the non-LN patients and normal controls in TT genotype frequency. (3) The frequencies of haplotypes containing rs1344531:rs1420676-rs1344531(C-T) [chi(2) = 11.731, P = 0.001, OR (95% CI) = 1.867 (1.302 - 2.676)], rs3803665-rs1420676-rs1344531(C-C-T) [chi(2) = 8.876, P = 0.004, OR (95% CI) = 1.772 (1.213 - 2.589)], and rs2292155-rs3803665-rs1420676-rs1344531(C-C-C-T) [chi(2) = 9.962, P = 0.002, OR (95% CI) = 1.915 (1.274 - 2.880)] were all significantly higher in the LN patients in comparison with the normal control group (41.0% versus 27.1%; 33.3% versus 21.8%; and 27.0% versus 16.2%); while the frequencies of other haplotypes: rs1344531-rs2080353(C-A) [chi(2) = 8.06, P = 0.005, OR (95% CI) = 0.603 (0.424 - 0.856)], rs1344531-rs2080353-rs933564 (C-A-G) [chi(2) = 7.929, P = 0.006, OR (95% CI) = 0.602 (0.422 - 0.859)] were significantly lower than those of the normal control group (39.5% versus 52.2%, and 36.6% versus 49.2%), which produced additional support for such association. SNP rs1344531 and some haplotypes containing SNP rs1344531 within OAZ are significantly associated with LN susceptibility. Genetic variants of the OAZ gene are involved in the pathogenesis of LN.

Extracorporeal photopheresis and multimodality immunomodulatory therapy in the treatment of cutaneous T-cell lymphoma.

The use of photochemotherapy for the treatment of cutaneous T-cell lymphoma (CTCL) was first reported by Gilchrest et al. in 1976. Oral 8-methoxypsoralen (8MOP) was administered to patients with early-stage disease, followed by photoactivation with ultraviolet-A irradiation to the skin. This technique, referred to as PUVA, has since become a mainstay of therapy for CTCL and other inflammatory skin conditions. In the early 1980s PUVA was modified for the treatment of CTCL patients with more advanced disease. Subsequent to oral 8MOP administration, whole blood was collected and enriched for white blood cells. The leukocyte-enriched population was then irradiated with UVA and returned to the patient intravenously. This technique was referred to as extracorporeal photopheresis (ECP) and represented the first ‘‘systemic’’ form of PUVA therapy. In 1987 Edelson published the first report documenting the use of ECP in the treatment of patients with erythrodermic CTCL. A 73% overall clinical response rate was reported, with a median survival time of 62 months from the onset of erythroderma. In comparison to historical controls, ECP was associated with improved survival and decreased morbidity among patients with similar clinical characteristics. In 1988, ECP was approved by the U.S. Food and Drug Administration (FDA) for the treatment of CTCL. Aside from its proven effectiveness in the management of CTCL, ECP has been shown to be of clinical benefit in the treatment of systemic sclerosis, cutaneous graft-versus-host disease, systemic lupus erythromatosis (SLE), allograft rejection, and potentially other autoimmune conditions. Numerous studies have addressed the utility of ECP for CTCL both as a monotherapy and in combination with other biologic response modifying agents. Over the past decade, we have observed higher clinical response rates among patients treated with a multimodality approach consisting of one or more biologic response modifying agents in combination with ECP. The biologic response modifiers utilized have been shown to exert potent immunomodulatory effects with the ability to enhance cell-mediated antitumor immunity. Since the year 2000, with the use of novel combinations of therapy, including interferon gamma, bexarotene, and skin-directed PUVA, along with ECP, we have achieved a greater than 90% clinical response rate among patients treated with this approach.