Histocompatibility antigens in systemic lupus erythematosus

Histocompatibility (HL-A) antigens were determined in 120 patients with systemic lupus erythematosus (SLE) and 120 matched controls. Increased frequencies of HL-A1 and HL-A8 were found. HL-A1 was more strongly associated with SLE in black patients (71 patients), whereas HL-A8 was more impressively associated with SLE in white patients (49 patients). In addition HL-A1 appeared more frequently in those with early onset of disease in both races; and HL-A1, HL-A8, and the HL-A1,8 phenotype seemed to be associated with severe SLE (renal and central nervous system involvement) in white patients. These data support the proposal that there are genetic influences in the pathogenesis and expression of SLE.     

Histocompatibility antigens in systemic lupus erythematosus.

Histocompatibility (HL-A) antigens were determined in 120 patients with systemic lupus erythematosus (SLE) and 120 matched controls. Increased frequencies of HL-A1 and HL-A8 were found. HL-A1 was more strongly associated with SLE in black patients (71 patients), whereas HL-A8 was more impressively associated with SLE in white patients (49 patients). In addition HL-A1 appeared more frequently in those with early onset of disease in both races; and HL-A1, HL-A8, and the HL-A1,8 phenotype seemed to be associated with severe SLE (renal and central nervous system involvement) in white patients. These data support the proposal that there are genetic influences in the pathogenesis and expression of SLE.     

HLA antigens in systemic lupus erythematosus.

Forty-five patients suffering from systemic lupus erythematosus were studied in respect of their serologically defined HLA antigens. HLA-B8 antigen was found in 37-8% of patients as compared to 22% of controls. Individuals carrying the HLA-B8 antigen have a 2-15 times greater risk of developing systemic lupus erythematosus than those not carrying this antigen.     

HLA antigens associated with systemic lupus erythematosus in Japan

We studied whether or not HLA-A,B,C and DR antigens were associated with clinical and immunological findings in 116 patients with systemic lupus erythematosus (SLE) in Japan. SLE patients tended to be associated with HLA-DR2, compared with 75 healthy individuals. Among the SLE patients, there was an association between HLA antigens and the presence or absence of certain clinical or immunological features. Different HLA antigens might have a predictive value for SLE and/or the same clinical and immunological abnormalities between Caucasian and Japanese SLE patients.     

Infection in patients with systemic lupus erythematosus

We have found subnormal amounts of chemotactic activity in zymosan-treated sera from 13 of 29 patients with systemic lupus erythematosus (SLE). As an explanation for this abnormality, the presence of a uniquely specific, heat-stable inhibitor of complement (C5)-derived chemotactic activity has been documented in sera from 11 of these patients. Sera from 2 other patients contained elevated levels of nonspecific, heat-labile chemotactic factor inactivator (CFI) activity. The serum from 1 patient contained the heat-stable inhibitor as well as elevated levels of CFI. Patients with SLE whose sera contained the heat-stable inhibitor had more active disease clinically, but otherwise they were indistinguishable from patients without the inhibitor. When patients with the heat-stable inhibitor improved clinically, this usually was accompanied by a decrease in serum inhibitory activity. Only one episode of bacterial infection was observed among 16 patients with SLE whose sera yielded normal amounts of chemotactic activity after treatment with zymosan. In contrast, 7 of 11 patients with SLE whose sera contained the heat-stable inhibitor suffered serious bacterial infections. The presence of this heat-stable inhibitor in sera from some patients with SLE may contribute, in part, to their increased susceptibility to infection.     

Hyperprolactinaemia in patients with systemic lupus erythematosus

OBJECTIVE: To verify the presence of hyper-PRL in SLE patients, its association with high disease activity, specific organ involvement or presence of anti-ds-DNA antibodies. METHODS: The group under study consisted of 80 patients with systemic lupus erythematosus (SLE), 28 patients with rheumatoid arthritis (RA) and 27 healthy controls. PRL serum levels were assayed using standard commercial kits (Immunotech Prague) with the radioimmunometric method for testing three samples of each of the subjects. The samples were taken in the morning hours (9-11 a.m.) of absolute rest 30 minutes after the introduction of the cannula at 30-minute intervals. RESULTS: A significantly higher rate of elevated PRL levels was found in SLE patients (40.0%) compared with the healthy controls (14.8%, p < 0.017). No proof was found of association with the presence of anti-ds-DNA or with specific organ involvement. Similarly, elevated PRL levels were found in RA patients (39.3%). The PRL elevation tended to decline from the 1st to the 3rd sample in the group of patients with SLE and RA but not in healthy controls. CONCLUSION: As follows from our measurements of prolactin serum values in SLE patients they are varriable by definition. According to our opinion further investigations are needed.     

The efficacy of low-dose mycophenolate mofetil for treatment of lupus nephritis in Taiwanese patients with systemic lupus erythematosus

Mycophenolate mofetil (MMF) has recently been introduced as an immunosuppressive agent for the treatment of glomerulonephritis with systemic lupus erythematosus (SLE) and the data have been encouraging. However, response to MMF treatment appears to differ ethnically. Therefore, we determined efficacy and safety of low-dose MMF for Taiwanese patients with lupus nephritis. We studied 36 lupus nephritis patients who were treated with MMF. The dose started at 0.5 g/day and we collected the data from patients who received up to 1 g/day MMF. Outcome measures were 24 h for proteinuria, serum creatinine, C3/C4 levels, and anti-dsDNA titers collected at the baseline and at 3-month treatment intervals. Daily urinary protein significantly decreased from 6.15 ± 4.28 g to 2.69 ± 2.36 g at the last visit (P < 0.01) in spite of the significant absence of changes in serum creatinine levels. The response rate was 65.7% including five (14.3%) cases of complete remission and 18 (51.4%) cases of partial remission. The concomitant oral prednisolone dose decreased significantly from 20.07 ± 11.78 mg/day to 13.93 ± 6.79 mg/day at 6 months (P < 0.01). The level of C3 increased significantly from 59.46 ± 32.73 to 71.99 ± 25.81 (P < 0.01) and the anti-dsDNA antibody titer decreased from 161.71 ± 221.42 to 46.57 ± 117.47 (P < 0.01). No severe adverse effects were observed in the study. Low-dose MMF (0.5 to 1 g/day) combined with glucocorticoids appears to be a safe and effective therapy for lupus nephritis in Taiwanese patients. Our results suggest that lupus nephritis in Oriental patients might respond to lower doses of MMF than Caucasians.     

Osteomyelitis in patients with systemic lupus erythematosus

OBJECTIVE: To investigate the clinical profile of and the risk factors for osteomyelitis in patients with systemic lupus erythematosus (SLE). METHODS: We reviewed 11 consecutive cases of patients with SLE who had also had osteomyelitis between 1981 and 2001 at a medical center in Taiwan, with special attention to predisposing factors, clinical features, laboratory values, and outcomes. RESULTS: The mean age at diagnosis of osteomyelitis was 34.5 +/- 22.0 years and the ratio of females to males was 9:2. The typical initial manifestations were nonspecific focal pain (82%) and fever (64%). The most commonly affected sites were the long bones (6 cases, 54%), followed by the vertebrae (4 cases, 36%). Salmonella (5 cases, 45%) and Staphylococcus aureus (4 cases, 36%) were the major causative organisms. Interestingly, once long bones had become involved, 5 of 6 (83%) isolates proved to be Salmonella, and for vertebral osteomyelitis, 3 of 4 (75%) isolates proved to be S. aureus. Predisposing factors include an active status of SLE (SLEDAI score >/= 4, 100%), coexistent underlying systemic disease (91%), chronic renal disease (82%), and intensified immunosuppressive agent usage (82%). Laboratory values either reflected an acute phase reaction that would be expected in an infection, such as a raised C-reactive protein (100%) and neutrophilia (55%), or reflected features consistent with active lupus disease. Four patients had longterm motor deficits and another patient died. Poor prognostic factors include delayed diagnosis, vertebral involvement, artificial implants in bones, and chronic carrier status. CONCLUSION: In patients with SLE who present with local osteoarticular pain, particularly those whose disease is active and who also have chronic renal disease and were taking intensified immunosuppressive agents, osteomyelitis must be considered seriously. Salmonella should be considered as a potential contributing pathogen for long bone osteomyelitis and S. aureus should be considered for cases of vertebral osteomyelitis when conducting empirical antimicrobial therapy. Early recognition and treatment is essential to avoid longterm sequelae or death.     

Infections in patients with systemic lupus erythematosus

Infection is a major contributor to morbidity and mortality in patients with systemic lupus erythematosus (SLE). In most clinical series, infection ranks first or second as the most common cause of death in SLE patients worldwide, including Hong Kong. In this article, the spectrum of infections and their protean manifestations in lupus patients will be reviewed with emphasis on clinical data from Hong Kong and other Asian countries. A high index of suspicion and dedicated work‐up to identify the causative pathogens is pivotal to the early diagnosis and effective management of infective complications in patients with SLE.     

儿童系统性红斑狼疮抗环瓜氨酸肽抗体检测及其临床意义

目的 检测儿童系统性红斑狼疮(JSLE)患者血清抗环瓜氨酸肽(CCP)抗体水平,了解抗CCP抗体在该病中的阳性检出率以及探讨其与关节炎表现相关性.方法 采用第3代抗CCP抗体酶联免疫吸附试验(ELISA)检测47例JSLE、54例幼年特发性关节炎(JIA)患者和40名年龄匹配的健康儿童血清中抗CCP抗体水平,并分析该抗体与JSLE实验室指标及临床特征,尤其是关节表现之间关系.正态分布的计量资料比较采用t检验,非正态资料比较采用Mann-Whitney U检验,率的比较采用χ2或Fisher精确检验.结果 47例JSLE患儿中6例为抗CCP抗体阳性,抗体阳性率明显高于健康对照组(13%与0,P＜0.05),与JIA组(26%)差异无统计学意义(P=0.098).抗CCP抗体阳性JSLE患儿中类风湿因子(RF)阳性率显著高于阴性患者(83%与15%,P＜0.01),在其他实验室指标和包含关节炎发生率等临床特征方面差异均无统计学意义(67%与51%,P＞0.05).47例JSLE患儿中以关节炎起病者25例,无一例出现关节畸形或影像学改变,关节受累与未受累者间抗CCP抗体水平及阳性率比较差异均无统计学意义(16%与9%,P＞0.05);3例在长达3年病程中始终伴有关节疼痛、活动受限患儿抗CCP抗体均呈阴性.结论 抗CCP抗体可在系统性红斑狼疮患儿血清中检出,在同JIA作鉴别诊断时应引起重视,但抗CCP抗体与JSLE关节炎发生、持续并无明显联系.     

Assessment of damage in juvenile-onset systemic lupus erythematosus: a multicenter cohort study

OBJECTIVE: To investigate the prevalence of cumulative organ damage in patients with juvenile-onset systemic lupus erythematosus (SLE) and its association with demographic and clinical variables, medication use, and quality of life. METHODS: The occurrence of organ system damage, as measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), was determined for 387 patients consecutively enrolled in pediatric rheumatology centers from Europe, the US, Mexico, and Japan. Risk factors for damage included demographic variables; clinical manifestations at diagnosis; previous corticosteroid, immunosuppressive, and antimalarial therapies; disease activity; and quality of life. RESULTS: Overall, 195 (50.5%) patients had damage within a mean of 5.7 years after disease onset. Renal (21.8%) and neuropsychiatric (15.8%) system involvement were observed most frequently, followed by musculoskeletal (11.7%), ocular (10.9%) and skin (9.6%) system involvement, with a mean SDI score of 1.1. In multivariate models, the occurrence of neuropsychiatric manifestations at diagnosis, a longer disease duration, and a greater number of intravenous cyclophosphamide pulses showed the strongest association with the presence of damage. CONCLUSION: We found evidence of cumulative organ damage, as measured by the SDI, in half of the patients with juvenile-onset SLE. Damage was significantly more likely in patients who had experienced neuropsychiatric manifestations at diagnosis, had a longer disease duration, and had received more intravenous pulses of cyclophosphamide.     

HLA-DRB1 and -DQB1 alleles and gene polymorphisms of selected cytokines in systemic lupus erythematosus

Objective The objective of this study was to evaluate the genetic profiles of selected cytokines (transforming growth factor beta 1, tumor necrosis factor alpha, interleukin-6, interferon gamma, and interleukin-10) in systemic lupus erythematosus and the contributions of human leukocyte antigen (HLA)-DRB1 and -DQB1 alleles to susceptibility for this disease.Patients and methods The study was carried out in 24 SLE patients and 36 healthy controls (from Upper Silesia) using polymerase chain reaction methods. All persons were of Caucasoid origin. Standard association analysis was used to compare the HLA alleles and frequency of cytokine gene polymorphisms between these groups.Results Only the frequency of HLA-DRB1*07 allele was higher in SLE patients than controls (odds ratio 2.92, 95% confidence interval 1.16–7.33), but the difference did not reach statistical significance when Bonferronis adjustment procedure was performed. No other significant associations were noted between class II alleles (DR1-DR6, DR8-DR10, DQ1-DQ4) and SLE. The frequency of the interleukin-6 GG and GC genotypes was significantly higher in SLE patients than in controls, and a significantly higher percentage of the G vs C alleles between patients and controls was revealed (odds ratio 2.53, 95% confidence interval 1.37–4.65, chi-squared test 8.16, P<0.05). The most significant association of increased frequency of the G allele with SLE was more commonly noted in HLA-DRB1*07-positive patients (odds ratio 10.29, 95% confidence interval 5.34–19.83, P<0.001). These data indicate that this combination could contribute toward determining the susceptibility to SLE, but its possible significance will require confirmation by further studies.     

HLA-DR antigens and anticardiolipin antibodies in northern Italian systemic lupus erythematosus patients

Eighty systemic lupus erythematosus (SLE) patients attending 3 clinical centers were evaluated immunologically and immunogenetically. No HLA class II antigens were found to be significantly associated with SLE in these patients. A highly significant (P = 6.17 x 10(-7) association was observed between anticardiolipin antibodies and DR7. A lesser association (P less than 0.025) was also observed between DR2 and/or DR3 and anti-Ro (SS-A) antibodies. No relationship was found between any DR antigen and anti-Sm/RNP, anti-double-stranded DNA, or anti-La (SS-B) antibodies.     

Lymphocyte response to virus antigens in systemic lupus erythematosus

The cell-mediated immune response of lymphocytes to rubella, measles, parainfluenza types 1, 2, and 3, varicella-zoster, and herpes virus type 1 virus antigens was evaluated in 15 SLE patients and 15 matched controls by incorporating ³H-thymidine in whole blood cultures as a measure of blastic transformation. SLE patients were less responsive than normal individuals to six of eight virus antigens tested. Culture of washed SLE cells in AB plasma did not reverse the hyporesponsiveness. The results indicated that a functional impairment of the circulating lymphocytes appeared to be responsible for the in vitro hyporesponsiveness of SLE patients to virus antigens.