Development of SLE among "potential SLE" patients seen in consultation: long-term follow-up.

OBJECTIVE: To identify factors associated with development of systemic lupus erythematosus (SLE) among patients evaluated at a tertiary care Lupus Center for potential SLE. METHODS: We identified patients first seen at the Brigham and Women's Hospital Lupus Center between 1 January 1992 and 31 December 2012 and thought to have potential SLE by a board-certified rheumatologist. All had 1-3 SLE ACR criteria at initial visit and > 2 follow-up visits ≥ 3 months apart. We reviewed medical records through 15 May 2013 for: SLE signs and symptoms, autoimmune serologies, prescriptions and diagnoses by board-certified rheumatologists. Bivariable analyses and multivariable logistic regression models were used to identify independent predictors of developing SLE. RESULTS: Two hundred and sixty four patients met inclusion criteria. At initial visit, mean age was 39.2 (SD 12.4) years, 94% were female and 67% white. Mean number of SLE ACR criteria was 2.7 (SD 1.0) and 88% were antinuclear antibody (ANA) positive at initial consultation. Mean follow-up time was 6.3 (SD 4.3) years and 67% were prescribed hydroxychloroquine in follow-up. At most recent visit, 56 (21%) had been diagnosed with SLE; 47 (18%) were thought not to have SLE and 161 (61%) were still considered to have potential SLE. In multivariable regression models, oral ulcers (OR 2.40, 95% CI 1.03-5.58), anti-dsDNA (OR 2.59, 95% CI 1.25-5.35) and baseline proteinuria or cellular casts (OR 16.20, 95% CI 1.63-161.02) were independent predictors of developing SLE. The most common other final diagnoses included fibromyalgia, Sjögren's syndrome, mixed connective tissue disease and cutaneous lupus. CONCLUSION: Among patients with potential SLE at initial consultation, 21% were diagnosed with definite SLE within 6.3 years. Oral ulcers, anti-dsDNA and proteinuria or cellular casts were independent predictors of developing definite SLE. A better means of accurately identifying those who will develop SLE among those presenting with potential disease is necessary.

Clinical manifestations and survival among adults with (SLE) according to age at diagnosis.

OBJECTIVES: The objective of this paper is to determine the effect of clinical and laboratory manifestations, and medication prescribing, on survival according to patient age at diagnosis in a large academic systemic lupus erythematosus (SLE) cohort. METHODS: We identified SLE patients with a diagnosis at age ≥18, seen between 1970 through 2011, and with more than two visits to our lupus center. Data collection included SLE manifestations, serologies, other laboratory tests, medications, dates, and causes of death. We examined characteristics of those diagnosed before age 50 (adult onset) compared to those diagnosed at or after age 50 (late onset) using descriptive statistics. We used Kaplan-Meier curves with log rank tests to estimate five- and 10-year survival in age-stratified cohorts. Predictors of 10-year survival were assessed using Cox regression models, adjusted for calendar year, race/ethnicity, sex, lupus nephritis, and medication use. RESULTS: Of 928 SLE patients, the mean age at diagnosis was 35. Among the adult-onset group, there was significantly higher prevalence of malar rashes and lupus nephritis. Glucocorticoids, azathioprine, mycophenolate, and cyclophosphamide use were also more frequent in the adult-onset group compared to the late-onset group. Five-year survival rates were 99.5% and 94.9% and 10-year survival rates were 97.8% and 89.5%, among those diagnosed before and at or after age 50. In the entire cohort, increasing age at diagnosis, male sex, and black race were statistically significant predictors of reduced 10-year survival. Compared to those diagnosed before age 50, the late-onset group had a multivariable-adjusted hazard ratio for 10-year risk of death of 4.96 (95% CI 1.75-14.08). The most frequent cause of known death was a lupus manifestation, followed by cardiovascular disease and infection. CONCLUSIONS: In our cohort, several demographic features, SLE manifestations, and medication prescribing differed between those with adult-onset and late-onset SLE. Ten-year survival rates were high for both groups, but relatively lower among late-onset patients. A lupus manifestation as the cause of death was more common among adult-onset compared with late-onset patients.

Quantifying anti-cyclic citrullinated peptide titres: clinical utility and association with tobacco exposure in patients with rheumatoid arthritis.

OBJECTIVE: To determine the significance of quantitative levels of antibodies to cyclic citrullinated peptides (anti-CCP) in a population of patients with rheumatoid arthritis (RA). METHODS: A total of 241 consecutive sera from patients with RA sent from a large rheumatology clinic for laboratory testing were selected for precisely quantifying anti-CCP antibody titres with the anti-CCP2 assay. Patient charts were reviewed for demographic information, smoking history, clinical diagnosis, rheumatoid factor (RF) titre, radiographic information and other laboratory information (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level). Correlations with anti-CCP titre and RF titre, disease parameters and smoking history were assessed. RESULTS: We confirm previous findings that anti-CCP seropositivity is associated with a higher incidence of erosions in patients with RA (56% vs 20% CCP+ vs CCP-, kappa = 0.297, p<0.001). We also found a moderate correlation between anti-CCP titre and RF titre. However, we failed to find an association between anti-CCP titre and presence of erosions, between anti-CCP titre and CRP or ESR level, or between anti-CCP titre and age or disease duration. Interestingly, we did find significantly higher anti-CCP titres in patients with a history of smoking (452 units/ml vs 229 units/ml, smokers vs non-smokers, respectively; p = 0.02). CONCLUSIONS: Although anti-CCP titres were not associated with clinical parameters of disease, they are increased in patients with RA with exposure to tobacco. By contrast, no elevation in RF was noted in patients with a history of smoking. These observations are consistent with a pathogenic contribution of smoking to RA and suggest the immune stimulus for anti-CCP is distinct from that for RF.

Anti-cyclic citrullinated peptide revised criteria for the classification of rheumatoid arthritis.

OBJECTIVE: The classification of rheumatoid arthritis (RA) is increasingly important as new therapies can halt the disease in its early stages. Antibodies to cyclic citrullinated peptides (anti-CCP) are widely used for RA diagnosis, but are not in the 1987 American College of Rheumatology (ACR) Criteria for RA Classification. We developed and tested the performance characteristics of new criteria for RA classification, incorporating anti-CCP. METHODS: We identified all subjects seen in our arthritis centre with rheumatoid factor (RF) and anti-CCP tested simultaneously between 1 January and 30 June 2004 and reviewed their medical records for the ACR criteria, rheumatologists' diagnoses, RF and anti-CCP. We revised the ACR criteria in two ways: (a) adding anti-CCP, and (b) replacing rheumatoid nodules and erosions with anti-CCP (CCP 6 criteria). We compared sensitivity and specificity of all criteria, in all subjects and in subjects with arthritis symptoms

Discordance between erythrocyte sedimentation rate and C-reactive protein measurements: clinical significance.

OBJECTIVE: C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are common measures of systemic inflammation. Our goal was to identify clinical factors associated with CRP/ESR discordance. METHODS: We identified patients with ESR and CRP results at our academic hospital over six months. We matched individuals with discordant results (one measure in highest tertile, other in lowest), by age and sex to those with non-discordant results, and reviewed medical records for laboratory and clinical factors. We employed analysis of variance (ANOVA) and Chi squared tests to compare these variables in discordant and non-discordant subjects. We used conditional logistic regression to estimate the relative risk of CRP/ESR discordance associated with each variable. RESULTS: 2,069 patients had CRP and ESR measured on the same day; 87 had discordant results, 55 (2.6%) with elevated ESR/low CRP, 32 (1.5%) with elevated CRP/ low ESR. Underlying infection was associated with > 14 fold risk of elevated ESR/low CRP discordance (p < 0.001). Renal insufficiency was associated with increased risk of elevated ESR/low CRP discordance, (p = 0.003). RA patients were slightly less likely to have elevated ESR/low CRP, (p = 0.008, NS after Bonferroni correction). Low serum albumin was associated with both kinds discordance. CONCLUSION: Infection, renal insufficiency, and low albumin were associated with having elevated ESR/low CRP; low albumin predicted elevated CRP/low ESR and elevated ESR/low CRP discordance. RA patients were less likely to have elevated ESR/depressed CRP. ESR as a measure inflammation in systemic rheumatic disease may be limited in settings of infection, renal insufficiency, and low albumin.

Antibodies to C reactive protein.

BACKGROUND: C reactive protein (CRP) is a known indicator of inflammation. Serum CRP is often raised in patients with inflammatory conditions. OBJECTIVE: To determine whether individuals make antibodies to CRP and whether this might affect serum CRP concentrations. METHODS: An enzyme linked immunosorbent assay was developed for the detection of antibodies to CRP. Specificity of the reaction was determined by inhibition of the reaction. RESULTS: Sera from 413 patients were tested and 25 were found to be positive, particularly in patients with rheumatic diseases. Levels of anti-CRP did not correlate with serum CRP levels. CONCLUSIONS: The presence of low CRP levels may not reflect the presence of antibodies to CRP.

Lateralized cognitive dysfunction in patients with systemic lupus erythematosus.

This study was designed to determine whether there is a lateralized pattern of cognitive dysfunction in patients with systemic lupus erythematosus (SLE). Fifty right-handed patients with SLE, but no history of cerebrovascular disease participated in the study. Thirty right-handed healthy subjects matched for age and education served as controls. SLE and healthy control subjects underwent a three-hour neuropsychological evaluation designed to measure attention, memory, visual spatial skills, verbal skills reasoning, psychomotor speed, and motor function. A cognitive disability index was created to identify cognitive impairment. Percentile tables based on the performance of all subjects were constructed for 20 component scores. Any subject with five or more component scores below the 25th percentile was designated impaired. Using this criterion, cognitive impairment was identified in 50% of patients with SLE and 20% of healthy controls. Patients with SLE were impaired on measures of psychomotor speed/fluency, verbal speed/fluency and verbal memory. This pattern of performance on neuropsycholgical testing was consistent with left hemisphere brain dysfunction. The observed deficits were not clearly attributable to vascular lesions and suggest immune-mediated effects on specific brain regions in a subgroup of patients with SLE.

Clinical utility of the anti-CCP assay in patients with rheumatic diseases.

OBJECTIVES: To determine the frequency of antibodies to cyclic citrullinated peptides (CCP) in a group of patients with a diversity of rheumatic diseases. METHODS: 249 consecutive sera from an arthritis clinic sent for rheumatology testing were selected for testing with the anti-CCP2 assays and for the presence of rheumatoid factor (RF). Patient charts were reviewed for demographic information, clinical diagnosis, radiographic information, and other laboratory data. RESULTS: The sensitivity and specificity of anti-CCP reactivity for the diagnosis of rheumatoid arthritis (RA) were 66.0% and 90.4%, respectively. This compared with the sensitivity and specificity of RF for RA at 71.6% and 80.3%. Furthermore, 10/29 (34%) RF- patients with RA demonstrated reactivity to CCP. The presence of either anti-CCP or RF increased testing sensitivity for diagnosis of RA to 81.4%; the presence of both RF and anti-CCP demonstrated a testing specificity similar to that of anti-CCP reactivity alone for the diagnosis of RA (91.1%). CONCLUSIONS: The detection of anti-CCP is useful for the diagnosis of RA, in fact even more so than RF, because of its higher specificity.

Prevalence of migraine in patients with systemic lupus erythematosus.

OBJECTIVE: To determine the prevalence of migraine in patients with systemic lupus erythematosus (SLE), and to examine the relationships between headache type and other clinical, serologic, and treatment features of the disease. BACKGROUND: Headaches are common in SLE and are a significant source of patient disability. The exact prevalence of headaches in patients with SLE is unknown. The classification of headache syndromes in SLE is also unclear. Previous studies were based on small numbers of patients and the headache types and criteria to define headache types varied widely. METHODS: Four hundred fourteen patients meeting American College of Rheumatology criteria for the diagnosis of SLE were sent the University of California, San Diego Migraine Questionnaire. Patients who completed the questionnaire had their medical records reviewed for constitutional, respiratory, cardiac, vascular, skin, musculoskeletal, other neuropsychiatric, hematologic, renal, and immunologic manifestations of the disease. Recent corticosteroid, nonsteroidal anti-inflammatory drug, antimalarial, and immunosuppressive medications were also recorded. RESULTS: One hundred eighty-six patients completed the questionnaire. Sixty-two percent of patients reported headaches: 39% met diagnostic criteria for migraine and 23% met criteria for nonmigrainous headache. Of the patients with migraine, 56% met criteria for migraine without aura and 44% met criteria for migraine with aura. There were no significant associations between headache type and other clinical, serologic, or treatment features of the disease. CONCLUSIONS: There is a high prevalence of migraine in patients with SLE, and patients should be routinely evaluated for migraine symptoms.

Monoclonal gammopathy of undetermined significance and exposure to breast implants.

BACKGROUND: Animal studies and uncontrolled case series in humans have suggested a possible association between breast implant exposure and monoclonal gammopathy. OBJECTIVE: To assess whether there is an increased risk of monoclonal gammopathy in women with silicone breast implants, we conducted a retrospective study of women exposed to breast implants and matched nonexposed women nested within a prospective cohort study (the Nurses' Health Study). METHODS: We used serum protein electrophoresis and immunoglobulin subtype by immunofixation to test 288 women exposed to breast implants and 288 age-matched, nonexposed women who previously had provided a blood sample (1989-1990) for monoclonal proteins. RESULTS: Among the women exposed to breast implants, 5 had monoclonal gammopathy of undetermined significance (MGUS) compared with 4 women among those not exposed (odds ratio, 1.25; 95% confidence interval, 0.27-6.39). The distribution of isotypes was similar across exposure groups. The exposed women with MGUS tended to be older than the nonexposed women (mean age, 60.4 years vs 52.5 years, respectively; P =.03). None of the 9 women with MGUS had reported multiple myeloma or other hematologic malignancies up through 1996. CONCLUSIONS: We find little evidence to support a substantial increased risk of MGUS in women exposed to breast implants. Larger studies are needed to determine if a more modest relationship exists.

Abdominal thrombotic and ischemic manifestations of the antiphospholipid antibody syndrome: CT findings in 42 patients.

PURPOSE: To determine the abdominal computed tomographic (CT) findings in patients with antiphospholipid antibody syndrome (APS). MATERIALS AND METHODS: Retrospective review of medical records from two university medical centers from 1994 through 1997 revealed 215 patients who had a hypercoagulable state attributed to primary or secondary APS. Abdominal CT findings in these patients were reviewed for evidence of large-vessel occlusion or visceral ischemia. RESULTS: In 42 (19.5%) of 215 patients with APS (age range, 32-65 years; mean age, 42 years), abdominal thromboses or ischemic events were detected at CT. Twenty-two (52%) had major vascular thromboses, including those in the inferior vena cava (n = 10), portal and superior mesenteric veins (n = 7), splenic vein (n = 4), and aorta (n = 1). Thirty-six (86%) patients had abdominal visceral ischemia resulting in renal infarction (n = 22), bowel ischemia (n = 13), splenic infarction (n = 6), pancreatitis (n = 3), hepatic infarction (n = 1), and/or hepatic dysfunction with portal hypertension (n = 1). In some patients, more than one abdominal organ and/or vessel was involved. CONCLUSION: Patients who have circulating antiphospholipid antibodies are at risk for major abdominal vascular thromboses and organ infarction. Radiologists must be familiar with this syndrome; they may be the first physicians to suggest the diagnosis on the basis of findings of unusual or recurrent sites of thrombosis, especially in young patients.

Lateralized EEG findings in patients with neuropsychiatric manifestations of systemic lupus erythematosus.

Routine and quantitative EEG were used to determine whether there is a lateralized pattern of electrophysiologic dysfunction in patients with diverse neuropsychiatric manifestations of SLE. Twenty consecutive patients with neuropsychiatric symptoms of SLE underwent 20-minute EEG recordings with an 18-channel polygraph. Ten 1-second intervals were randomly selected for each patient. Once selected, the intervals were analyzed for the presence of theta and delta slow activity. Mapping was done by four-point interpolation around the 18 acquired data points. On routine EEG, abnormalities were identified in 14/20 patients with SLE. In 12/14 patients, the abnormalities were localized to the left temporal region. Quantitative EEG analyses revealed theta and delta slow activity predominantly affecting the left hemisphere in 16/19 patients with SLE. Taken together, these findings suggest selective involvement of the left hemisphere in patients with diverse neuropsychiatric manifestations of SLE.

Prospective analysis suggests susceptibility genes for deficiencies of IgA and several other immunoglobulins on the [HLA-B8, SC01, DR3] conserved extended haplotype.

The extended major histocompatibility complex (MHC) haplotype [HLA-B8, SC01, DR3] is increased in frequency among patients with immunoglobulin (Ig)A deficiency and common variable immunodeficiency. Because the genomic region from HLA-B to HLA-DR/DQ is virtually the same on all instances of the haplotype in the general population, we reasoned that all independent instances of [HLA-B8, SC01, DR3] carry MHC susceptibility genes for these disorders. To define immunoglobulin deficiencies determined by genes on this haplotype and their mode of expression and penetrance, serum immunoglobulin class and IgG subclass concentrations were determined prospectively in homozygotes and heterozygotes of this haplotype and in Caucasian controls. Prevalence of individual immunoglobulin deficiencies in persons with [HLA-B8, SC01, DR3] ranged from 13% to 37%, significantly higher than rates in non-carriers or general controls. We found significantly increased frequencies of IgA and IgG4 deficiency only in homozygotes (13.3% and 30%, respectively) compared with heterozygotes (1.7% and 3.4%) or non-carriers (1.6% each), suggesting recessive expression. In contrast, IgD and IgG3 deficiencies were significantly more common in both homozygotes (36.7% and 30%) and heterozygotes (20.3% and 17.5%) compared with controls (4.9% and 3.4%), suggesting dominant inheritance. These results indicate multiple distinct susceptibility genes, some recessive and others dominant, for deficiency of IgA, IgD, IgG3 or IgG4 (but not for IgE, IgG1, IgG2 or IgM) on [HLA-B8, SC01, DR3]. These observations may also help to explain the observed associations of [HLA-B8, SC01, DR3] with both IgA deficiency and common variable immunodeficiency and the common occurrence of IgG subclass deficiencies in some patients with IgA deficiency.

A computer based intervention to reduce unnecessary serologic testing.

OBJECTIVE: Laboratory testing is important in the evaluation of patients with possible systemic rheumatic disease, but uncritical use of any test may result in misleading information and unnecessary costs. We attempted to reduce the number of unnecessary antinuclear antibody, rheumatoid factor, and complement level tests ordered by house officers at a large teaching hospital, where inpatient orders are written through a computer based order entry system. METHODS: We conducted a prospective cohort study of an interactive test ordering program. The intervention consisted of displaying post-test probability estimates during the usual physician order entry session. These estimates were based on pretest probabilities entered by the ordering physician and sensitivities and specificities derived from a literature review. Another group of test orders did not prompt the intervention and were considered controls. The outcome of interest was the percentage of tests canceled in the intervention group versus the control group. RESULTS: Eleven percent (11/99) of intervention orders were canceled, versus only one order among 236 controls (p = 0.001). However, there was no association between the physicians' pretest probability estimates and whether test orders were canceled (p = 0.59). Additionally, 43 of the 335 orders (13%) yielded positive tests, but only 4 patients (1%) were given new diagnoses of rheumatic disease. CONCLUSION: The computer based intervention significantly reduced orders for antinuclear antibody and rheumatoid factor levels by 10%. Further reductions without clinical harm are probably possible, since the yield of testing for new rheumatic diseases was low.

CD4 TCRBV CDR3 analysis in prevalent SLE cases from two ethnic groups.

We examined CD4+ T cell TCRBV-CDR3 transcripts from 19 lupus patients and 16 controls to test the hypothesis that CD4+ TCRBV-CDR3 expression in SLE differs from normals. Within the disease group we also performed exploratory analyses to determine the association between risk of oligoclonality and HLA-DRB specificities and the duration of the CDR3 patterns. Oligoclonal patterns consistent with CDR3 restriction were three times more likely in SLE than in controls (OR = 3.7). TCRBV1, BV4, BV5.1, BV7, BV9, BV18 and BV22 gene segment CDR3 patterns of oligoclonality were seen exclusively among lupus patients. HLA-DRB3 increased the risk of oligoclonal expression in SLE. In four patients studied over time, the pattern of TCRBV-CDR3 expression was stable in a second sample obtained 6-14 months later. The increased frequency of CD4+ T cell TCRBV-CDR3 oligoclonal expression in SLE when compared to controls and the persistence of these patterns are consistent with an expanded pool of autoreactive CD4 T cells in SLE which recognize peptides derived from autoantigens. The association of HLA-DRB3 genes with increased risk of CDR3 oligoclonality among the SLE subjects is compatible with the hypothesis that molecules encoded by HLA-DRB3 may facilitate autoantigen recognition by CD4 T cells.

Association of silicone breast implants with immunologic abnormalities: a prospective study.

PURPOSE: To study the possible association of silicone-breast-implant exposure and immunologic abnormalities within the Nurses' Health Study, an ongoing prospective cohort study of women. SUBJECTS AND METHODS: From this cohort, we randomly selected 200 women who had been exposed to silicone breast implants and who had never reported connective tissue diseases during 14 years of follow-up, and 500 age-matched, nonexposed women, including 100 with definite connective tissue diseases validated by medical record review, 100 with at least one symptom of a connective tissue disease, 100 with diabetes, and 200 healthy controls. Assays for antinuclear antibodies (ANA), including anti-dsDNA, anti-ssDNA, anti-Sm/RNP/Ro/La, and anti-Scl-70, rheumatoid factor, immunoglobulins, serum complement, and C-reactive protein level, and anticardiolipin, antithyroglobulin, antithyroid microsomal, and antisilicone antibodies were performed by standard techniques in blood samples collected in 1989 or 1990 before collection of silicone-breast-implant exposure data in 1992. RESULTS: ANA was positive (> or = 1:40) in 14% of women with silicone breast implants compared with 20% of healthy women (P = 0.11). Rheumatoid factor was positive (> or = 1:40) in 5% of women with silicone breast implants and 2% of healthy women (P = 0.16). Women with silicone breast implants had a significantly higher frequency of anti-ssDNA antibodies than healthy women (41% and 29%, P = 0.012). Duration of implant was associated with a higher frequency of anti-ssDNA antibodies (P = 0.03) but not with ANA or rheumatoid factor. No other significant differences in the frequencies of autoantibodies were observed in silicone breast implant-exposed women. Antisilicone antibodies were not found in any sample. CONCLUSION: We found no increased frequency of any immunologic abnormalities in women exposed to silicone breast implants, except for anti-ssDNA, which has unknown clinical relevance.

EEG abnormalities in systemic lupus erythematosus.

The medical records of 478 SLE patients were reviewed. Ninety-five patients (19.9%) with a history of seizures were identified. EEG reports were available on 62. EEGs were interpreted as normal in 8 (12.9%) and abnormal in 54 (87.1%). Abnormal EEGs were reviewed for the presence of unilateral and bilateral abnormalities. Left hemisphere abnormalities were identified in 43 (79.6%), right hemisphere abnormalities in 4 (7.4%), and bilateral abnormalities in 7 (13.0%) patients with SLE. Abnormalities included theta and delta slowing and sharp wave activity. In 32 of the 43 (74.4%) patients with left hemisphere abnormalities, the abnormalities were localized to the left temporal leads. These findings suggest selective damage to the left temporolimbic region in patients with SLE.

It is lupus?

It has been said that the essence of medicine is the reduction of uncertainty for patients and physicians (Ludo Baghius). Confronting patients who have some symptoms suggesting lupus but who do not meet criteria for classic SLE is challenging. Evaluating and caring for these patients, when not making a diagnosis of SLE, demands clinical acumen, confidence, and effective communication skills.

Molecular analysis of major histocompatibility complex allelic associations with systemic lupus erythematosus in Taiwan.

OBJECTIVE: To investigate the association of HLA class II alleles/haplotypes, type I C2 deficiency gene, and tumor necrosis factor a gene promoter allele (TNF2) with systemic lupus erythematosus (SLE) in the Chinese population in Taiwan. METHODS: The HLA-DRB1 and DQB1 alleles were studied in 105 SLE patients and 115 controls by the polymerase chain reaction (PCR)/sequence-specific oligonucleotide probe method, the subtyping of DRB1*15/16 and DRB5 by PCR with sequence-specific primers, type I C2 deficiency gene by PCR, and TNF2 by PCR-Nco I restriction fragment length polymorphism. RESULTS: The frequencies of the HLA class II alleles DRB1*02, DRB1*1502, DRB5*0102, DQB1*0501, and DQB1*0602 and DR2-associated haplotypes DRB1* 1501,DRB5*0101,DQB1*0602 and DRB1*1502,DRB5* 0102,DQB1*0501 were higher among SLE patients than among controls; however, only DQB1*0501 was statistically significantly associated with SLE. No specific allele/haplotype was significantly associated with lupus nephritis. No subject had type I C2 deficiency. SLE patients had a marginally higher percentage of TNF2, which was in linkage disequilibrium with DR3. Since DR3 was not associated with SLE in this Taiwanese Chinese population, TNF2 might play a role in the immunopathogenesis of SLE. CONCLUSION: Although no HLA-DRB1 allele was found to be significantly associated with SLE, the associations with DQB1*0501 and TNF2 suggest that DQB1 and tumor necrosis factor a may be important genetic factors in SLE susceptibility in the Chinese population in Taiwan.