The current role for clinical and renal histological findings as predictor for outcome in Australian patients with lupus nephritis.

Objectives To investigate the current demographic, clinical and histological characteristics of patients with lupus nephritis (LN) in Western Australia (WA) with regards to their predictive value for patient and renal outcome. Methods Retrospective study of adult systemic lupus erythematosus (SLE) patients with a first renal biopsy demonstrating LN between 1997 and 2017 at a metropolitan tertiary hospital in WA. Clinical data were collected at baseline and last follow-up with renal biopsy findings classified by International Society of Nephrology (ISN) criteria. Annual incidence rates (AIRs)/100,000, Kaplan-Meyer curves and Cox regression hazard ratio for independent predictors for patient and renal survival were applied. Results The AIR was 3.3, 3.1 and 0.4 for Asian ( n = 29), Indigenous Australian (IA) ( n = 11) and Caucasian ( n = 43) patients, respectively ( p < 0.01). There was no significant subgroup difference regarding ISN class (proliferative 66%, membranous 19%, mesangial 15%), levels of proteinuria (median PCR 300 mg/mmol) or frequency of raised creatinine (31%), anti-dsDNA antibody (89%) or hypocomplementaemia (88%). Treatment included corticosteroids (91%), cyclophosphamide (30%), mycophenolate (67%) and antihypertensive drugs (67%). Five- (81%) and 10-year (70%) survival was lower for IAs than for Caucasians and Asians (95% each at both time points) ( p = 0.016). Five- and 10-year renal survival (endpoint renal replacement therapy (RRT)) was 86% and 64% for IA vs 100% for Asian, 100% and 96% for Caucasian patients ( p = 0.02). IA background was the only independent predictor for poor patient survival and together with male gender also for renal survival. Only 25% of all patients remained free of any organ damage with non-renal damage observed in 53% of survivors. Conclusions LN incidence in WA was 0.75/100,000 with the lowest rate observed in Caucasians. While Asian patients have the same favourable outlook as Caucasians, the outcome is much bleaker for IA patients. Other clinical and histological findings did not predict outcomes, and importantly more than half of all surviving patients accrued non-renal damage.

Insulin-like growth factor-1 (IGF1) in systemic lupus erythematosus: relation to disease activity, organ damage and immunological findings.

Background Insulin growth factor-1 (IGF1) activates cell proliferation pathways and inhibits apoptosis. IGF1 is involved in tumour growth and required for T-cell independent activation of B cells. Activated B cells and autoantibody production are a hallmark of systemic lupus erythematosus (SLE). To investigate the possible role of IGF1 in SLE, we studied IGF1 across clinical characteristics, immunological biomarkers, disease activity and organ damage in SLE patients. Method In a cross-sectional study, we collected clinical characteristics, medication, disease activity (SLEDAI-2K) and organ damage (SDI) for 94 SLE patients. Autoantibodies and cytokines were measured by ELISA, and levels of IGF1 and IGF binding protein 3 (IGFBP3) by chemiluminescence. Free IGF1 was estimated by the IGF1:IGFBP3 ratio. Healthy controls served as a comparator group. Results There was a significant age-related decline in IGF1, IGFBP3 and free IGF1 (IGF1:IGFBP3 ratio) that was similar in SLE patients and controls with very few outliers. Free IGF1 was inversely related to blood pressure (Rs -0.327, p < 0.01) and HbA1c (Rs -0.31, p < 0.01). Free IGF1 was higher in disease-modifying antirheumatic drug-treated patients ( p < 0.01), but there was no significant association between the IGF1 axis and autoantibody profiles, cytokine levels or SLEDAI-2K or SDI categories. IGF1 correlated inversely with BAFF level and B, natural killer and CD8 + cell counts. Conclusion Free IGF1 levels in SLE patients declined appropriately with age. IGF1 levels were not associated with disease activity, severity or autoantibody levels in SLE. Free IGF1 had positive metabolic effects in SLE and may play an indirect role in dampening the cellular immune response by downregulating B- and T-cell activity.

The influence of ERAP1 gene variants on clinical phenotype in ankylosing spondylitis.

OBJECTIVES: Endoplasmic reticulum aminopeptidase 1 (ERAP1) gene variants diminish the risk of developing ankylosing spondylitis (AS) through a reduction in ERAP1 activity. We investigated whether disease expression was altered in patients who developed AS despite the presence of two protective ERAP1 variants. METHOD: We conducted a cross-sectional and longitudinal cohort study of patients with established AS (n = 334, 90% B27+, mean age at study 45 years) for whom clinical data and biological samples were collected during a research visit. Genotyping for the single nucleotide polymorphisms (SNPs) rs27044 and rs30187 was performed on genomic DNA by reverse transcription polymerase chain reaction (RT-PCR) with interleukin (IL)-6 and tumour necrosis factor (TNF) levels determined by a sandwich enzyme-linked immunosorbent assay (ELISA). Associations between genotypes and haplotypes, clinical and serological findings were analysed using SNPstats. RESULTS: Both SNPs were in strong linkage disequilibrium and formed three common haplotypes (C/C 0.65, G/T 0.30, and C/T 0.04). Haplotype C/T carried a lower risk for uveitis [odds ratio (OR) 0.32, p = 0.03] and elevated C-reactive protein (CRP) levels (OR 0.26, p = 0.04). There was no effect of ERAP1 haplotypes on cytokine levels or major outcomes after 8 years of follow-up. CONCLUSIONS: The ERAP1 rs27044/rs30187 haplotype C/T is associated with lower risk of extraspinal disease and systemic inflammation in Nordic AS patients but has no impact on IL-6 or TNF levels.

Thrombopoietin levels in systemic lupus erythematosus are linked to inflammatory cytokines, but unrelated to thrombocytopenia or thrombosis.

BACKGROUND: Thrombopoietin (TPO) is a liver-produced protein that drives megakaryocyte maturation. TPO regulates platelet production and can increase platelet and endothelial reactivity. We investigated the relationship between TPO and the occurrence of thrombocytopenia and thrombosis in patients with systemic lupus erythematosus (SLE). METHODS: We undertook a cohort study of SLE patients (n = 98) with clinical data collected simultaneously with sampling for TPO, inflammatory cytokines and autoantibody detection. TPO levels were measured by sandwich ELISA with patients with rheumatoid arthritis (RA) (n = 100) and controls (n = 79) as comparators. Disease associations were evaluated using non-parametric methods. RESULTS: TPO levels in SLE (median 8 pg/ml, mean 326, range 8992) were moderately increased compared with RA (median 8 pg/ml, mean 100, range 1659, p = 0.07) and controls (median 8, mean 94, range 2088, p = 0.1). Among SLE patients, TPO levels did not correlate with platelet count or levels of antiphospholipid antibodies. The prevalence of thrombocytopenic episodes, thrombotic events or active disease was not increased in patients with high TPO levels. TPO levels correlated with MIP-1α (Rs 0.56, p < 0.001), IL6 (Rs 0.26, p = 0.02) and IL4 (Rs 0.29, p = 0.01), and inversely correlated to C4 (Rs -0.23, p = 0.04). MIP-1α was the strongest independent predictor of increased TPO levels. CONCLUSION: TPO levels are elevated in 20% of patients, but are not closely related to the occurrence of thrombocytopenia or thrombosis in SLE. MIP1-alpha is the main factor driving higher TPO levels among patients with SLE, likely through its inhibitory effect on megakaryocyte function.

APRIL levels strongly correlate with IL-17 in systemic lupus erythematosus.

INTRODUCTION: Activated self-reactive B cells play an important part in systemic lupus erythematosus (SLE). A proliferation-inducing ligand (APRIL) and B cell-activating factor (BAFF) are B-cell specific stimulators, but activate B cells through different receptors. We investigated the reciprocal association between serum APRIL (s-APRIL), serum BAFF (s-BAFF) and immunological and clinical findings in SLE patients. METHODS: A cross-sectional case-control study was performed in 100 SLE patients (87% female, age 49 years, disease duration 12 years). APRIL and BAFF levels were measured by sandwich ELISA, compared with healthy controls and correlated with autoantibody, cytokine (IL-6 and IL-17) and clinical findings through nonparametric and multivariate regression analyses. RESULTS: Both median s-APRIL (478 vs. 0 pg/ml, p = 0.01) and s-BAFF (1720 vs. 0.9 pg/ml, p < 0.001) were higher in SLE patients than controls. Increased s-BAFF was observed in 86% of patients, while s-APRIL was increased only in 17% (p < 0.01). S-APRIL correlated with s-BAFF in controls (p = 0.04), but not in SLE (p = 0.8). Increased s-APRIL was strongly and independently associated with IL-17 activation (p < 0.001), while increased s-BAFF levels were associated with anti-nucleosome antibody presence (p = 0.001). Disease activity and organ damage were associated with s-BAFF but not s-APRIL. CONCLUSIONS: While both s-BAFF and s-APRIL levels are elevated in SLE patients, they reflect different immunologic and clinical pathways. The strong association between s-APRIL and IL-17 activation supports a role for Th17 helper cells in B cell activation in SLE.

The distribution of HLA-B27 subtype in patients with ankylosing spondylitis in Northern Norway.

BACKGROUND: Although the high prevalence of human leucocyte antigen (HLA)-B27 and ankylosing spondylitis (AS) in Northern Norway is now well documented, data on the distribution of HLA-B27 subtypes and their potential impact on disease presentation and course are lacking. METHOD: We conducted a cross-sectional study of patients (n = 124) with established (modified New York criteria) AS participating in a longitudinal disease registry. Clinical data at the time of sample collection were recorded and genotyping for HLA-B27 was performed by low-resolution polymerase chain reaction (PCR) screening. Subtyping was then performed with sequence-specific primers (PCR-SSP) and direct exon 2 and 3 sequencing. The results were analysed with SCORE and Seqscape software. RESULTS: Four patients (3%) were HLA-B27 negative in all genetic analyses. In the remaining 120 HLA-B27-positive patients, HLA-B27*05 was present in 117 (98%) and HLA-B27*02 in three patients (2%). There was complete concordance between the screening and subtyping results. The three patients with HLA-B27*02 had no distinguishing clinical characteristics. CONCLUSIONS: HLA-B27*05 is the predominant subtype of HLA-B27 in Northern Norway. This supports the concept of a North-South gradient for HLA-B27 subtypes with little regional drive to adapt to environmental challenges. Low-resolution HLA-B27 PCR screening captures all relevant subtypes in this region.

Low diagnostic and predictive value of anti-dsDNA antibodies in unselected patients with recent onset of rheumatic symptoms: results from a long-term follow-up Scandinavian multicentre study.

OBJECTIVES: To verify the diagnostic accuracy of anti-double-stranded DNA (anti-dsDNA) antibodies detected by the Crithidia luciliae immunofluorescence test (CLIFT) in a cohort of unselected patients, referred to a rheumatologist due to recent onset of rheumatic symptoms. METHOD: A total of 1073 consecutive patients were screened for anti-nuclear antibodies (ANAs). Serum samples from 292 ANA-positive and 292 matching ANA-negative patients were tested three times for anti-dsDNA antibodies, using two different CLIFT kits (ImmunoConcepts(®) and Euroimmun(®)). An initial clinical diagnosis was made by rheumatologists unaware of the results. The diagnoses were updated after a median follow-up of 4.8 years. RESULTS: CLIFT was positive at least once in 60 patients but only 23 patients were CLIFT positive in all of the assays. Diagnosis of systemic lupus erythematosus (SLE) was made initially in 65 patients, of whom 24 (37%) were CLIFT positive. Many other diagnoses were observed among the CLIFT-positive patients. Overall, 16 (5.5%) ANA-negative patients were CLIFT positive. After approximately 5 years, the diagnosis of SLE remained unchanged in 63 patients (23 CLIFT positive) and altered in only two (one CLIFT positive). Among the 36 CLIFT-positive patients who were not diagnosed with SLE at study entry, only one developed SLE during the follow-up period. CONCLUSIONS: CLIFT was not reliable as a diagnostic tool in unselected patients with rheumatic symptoms. ANAs were of little value as a screening test before the CLIFT analysis. CLIFT had surprisingly low positive predictive value (PPV) for the diagnosis of SLE despite its high specificity. For non-SLE patients, being CLIFT positive poses little risk of developing SLE within 5 years.

Characteristics of late onset neutropenia in rheumatologic patients treated with rituximab: a case review analysis from a single center.

BACKGROUND: Late onset neutropenia (LON) secondary to rituximab has been reported as an adverse event in the treatment of hematological malignancies but reports on autoimmune diseases are scarce. AIM: To review the characteristics of LON in rheumatologic patients from a single center. DESIGN: Retrospective case record study. METHODS: Clinical and laboratory data since the introduction of rituximab in our clinic in 2006 were collected and analyzed retrospectively. LON was defined as an absolute neutrophil count <1.0 × 10(9)/l occurring 4 weeks after the last rituximab infusion. RESULTS: LON was identified in eight patients (6% of all patients receiving rituximab). All patients had complicated and refractory disease and had been treated with a median of 4.5 different immunosuppressive drugs prior to rituximab. LON appeared after a median interval of 23 weeks with recovery of LON after a median of 6.5 days. Four patients had concomitant infection at the onset of neutropenia, when six patients had both low immunoglobulin M and immunoglobulin G. Six patients were rechallenged with rituximab without recurrence of LON. CONCLUSION: The characteristics of LON after rituximab treatment in patients with autoimmune disease are comparable with experiences from hematological malignancies. LON seems to precede B-cell recovery implying a perturbation of the granulocyte homeostasis. LON with its rapid recovery does not seem to increase the risk for serious infection in contrast to the sustained hypogammaglobulinemia that may follow rituximab. The risk of LON recurrence after rechallenge is low.

Interleukin-6 promotes arthritis and joint deformation in patients with systemic lupus erythematosus.

The underlying mechanisms for the subsets of self-limiting, intermittent or chronic and deforming arthritis in systemic lupus erythematosus (SLE) are not well understood. We performed a cross-sectional analysis of pro-inflammatory cytokines (IL-1ß, IL-2, IL-6, IL-8 and TNF-α) and joint status in 47 SLE patients (79% females, age 42 years, disease duration 8.6 years). All cytokines levels were significantly elevated in SLE patients compared with controls, but only IL-2 and IL-8 levels were higher than in patients with rheumatoid arthritis. SLE patients with ongoing synovitis (19%) and joint deformities (11%) had increased erythrocyte sedimentation rate (ESR), IL-6 and anti-dsDNA Ab levels. IL-6 levels correlated with ESR, anti-dsDNA Ab and haemoglobin, but not with C-reactive protein levels. Arthritis constitutes a considerable burden of disease in SLE over time, and joint deformations are associated with longstanding disease and arthritis flare rates. IL-6 is a potential biomarker and therapeutic target in the prevention of joint damage in SLE arthritis.

Disease activity and damage accrual during the early disease course in a multinational inception cohort of patients with systemic lupus erythematosus.

An inception cohort of patients with systemic lupus erythematosus from 14 European centres was followed for up to 5 years in order to describe the current early disease course. At inclusion patients (n = 200, 89% female, mean age 35 years, 97% Caucasian, mean SLEDAI 12.2) fulfilled a mean of 6.5 ACR classification criteria. The most prevalent criteria were antinuclear Ab presence (97%) followed by anti-dsDNA Ab (74%), arthritis (69%), leukocytopenia (54%) and malar rash (53%), antiphospholipid Ab (48%) and anti-synovial membrane Ab (21.6%). Clinical signs of lupus nephritis (LN) were present in 39% with biopsy-confirmed LN seen in 25%. Frequent additional findings were hypocomplementaemia (54%), anti-SSA Ab (49%), alopecia (26%) and Raynaud's phenomenon (31%). There were few regional differences in disease presentation and management. One and 5-year survival rates were 99% and 97% respectively. During the mean follow-up of 4.1 years 25% entered a state of early disease quiescence by global physician assessment, but the overall risk of subsequent flare was 60%. Maximum SLEDAI scores decreased over time, but 45% of patients accrued damage (SDI >or=1) for which baseline presence of proteinuria and persistent disease activity were independent predictors. The results indicate minor differences in SLE presentation and treatment within various regions of Europe and a high diagnostic reliance on anti-dsDNA Ab. Despite early reductions in disease activity and improved mortality, the risk for disease flare and damage development is, however, still substantial, especially in patients not entering an early remission.

Contemporary use of disease-modifying drugs in the management of patients with early rheumatoid arthritis in Norway.

OBJECTIVE: As treatment options for rheumatoid arthritis (RA) are rapidly expanding, we evaluated the current use of disease-modifying anti-rheumatic drugs (DMARDs) in the management of patients with early RA in Norway with particular attention to the influence of risk factors for a poor disease outcome on DMARD selection. METHODS: An observational multicentre study registering the type of therapy initiated in 820 DMARD-naive patients with early active RA [67% female, mean age 51 years, disease duration 4 months, 57% rheumatoid factor (RF) positive]. The impact of baseline risk factors associated with poor prognosis (disease activity parameters and biomarkers of inflammation) on DMARD selection was analysed through odds ratios (ORs) by multivariate logistic regression. RESULTS: Methotrexate (MTX) monotherapy was selected for 78% of patients. MTX was preferred over sulfasalazine (SSZ) monotherapy (19%), leflunomide monotherapy (2%), and combination therapy (2%) in female patients [OR 1.6, 95% confidence interval (CI) 1.1-2.5], age >50 years (OR 2.5, 95% CI 1.6-3.8), short disease duration (OR 2.7, 95% CI 1.4-5.0), 10 swollen joints (OR 2.2, 95% CI 1.2-4.0), and erosive disease (OR 1.8, 95% CI 1.1-3.2). Concurrent steroid therapy was started in 73% of patients, regardless of the type of DMARD therapy initiated. CONCLUSION: Monotherapy with MTX is currently the DMARD treatment of choice for early RA in Norway. Disease duration, age, swollen joint count, and erosive disease have considerable impact on DMARD selection in contrast to the presence of biomarkers. Few patients with early RA in Norway receive combination DMARD therapy, while the majority of patients receive corticosteroid bridging therapy.

Epidemiological and clinical characteristics of psoriatic arthritis in northern Norway.

BACKGROUND: To determine the characteristics of psoriatic arthritis (PsA) in northern Norway, where the human leucocyte antigen HLA-B27 is prevalent. METHODS: An observational study of patients with ICD-9 CR codes for psoriatic arthropathy (696.0 and 713.3) and spondylarthritis (720) seen during a 19-year period at a single regional rheumatology department. In patients with confirmed PsA demographics, date of onset of arthritis and psoriasis, clinical presentation and subsequent disease course (including therapeutic measures) were recorded during a mean follow-up of 11.1 years. RESULTS: Arthritis was documented in 329/657 (50%) of patients with a diagnostic code for PsA. The mean annual incidence rate for PsA was 6.9/100 000 and the point prevalence was 130/100 000 (0.13%) adults. The male to female ratio was 1.4 and the mean age at onset of psoriasis was 27.8 years (SD 14.1), and 35 years (SD 11.8) at onset of arthritis. Arthritis preceded psoriasis in 13.8% of cases. Oligoarthritis was the most frequent subtype (48%), followed by polyarthritis (32%), spondylitis (9%), monoarthritis (7%), and classic distal interphalangeal (DIP) arthritis (2%). Erosive disease (56% of cases) occurred mainly with polyarthritis; arthritis mutilans occurred in six patients (2%). Surgical interventions were performed in 22% of patients. Disease activity fluctuated considerably over time. Mortality (4.3%) was increased in PsA patients with polyarthritis and secondary amyloidosis (n = 5). CONCLUSION: The prevalence of PsA and related spondylitis is not increased in northern Norway. PsA does, however, lead to a considerable burden of disease due to erosive disease development and surgical intervention.

Polymorphism in the 5' regulatory region of the B-lymphocyte activating factor gene is associated with the Ro/La autoantibody response and serum BAFF levels in primary Sjogren's syndrome.

OBJECTIVE: To investigate the association between haplotypes in the 5' regulatory region of the B-lymphocyte activating factor (BAFF) gene, disease susceptibility and serum BAFF (s-BAFF) levels in Caucasian primary SS (pSS) patients. METHODS: Case-control study in an established pSS cohort with PCR-RFLP genotyping for four SNPs (-2841 T-->C, -2704 T-->C, -2701 T-->A, -871 C-->T), which tag a haplotype block in the 5' regulatory region of the BAFF gene and s-BAFF determination by ELISA. RESULTS: s-BAFF levels were elevated in Ro/La-positive pSS patients (n = 85, 1770 pg/ml) compared with both Ro/La-negative pSS patients (n = 27, 1193 pg/ml) and controls (n = 59, 1171 pg/ml), P < 0.001. s-BAFF increased with diversification of the anti-Ro/La antibody response, but was not correlated with age, RF or immunoglobulin G levels. There were four common BAFF haplotypes. While the CTAT haplotype was associated with Ro/La-positive pSS [odds ratio (OR) 2.6; 95% CI 1.7, 4.1; P = 0.00004], the TTTT haplotype was associated with elevated s-BAFF in autoantibody-positive pSS (n = 85; 88% females; P = 0.008). The shared -871 T allele had no independent contribution to disease susceptibility or s-BAFF. CONCLUSIONS: Disease susceptibility for Ro/La-positive pSS is increased with the CTAT haplotype, but not associated with high s-BAFF levels. Elevated s-BAFF levels in pSS are associated with the TTTT haplotype and may be a secondary phenomenon in Ro/La-positive pSS. While both haplotypes carry the -871 T allele, this allele is not independently associated with disease susceptibility.

Current causes of death in systemic lupus erythematosus in Europe, 2000--2004: relation to disease activity and damage accrual.

Current therapeutic and diagnostic resources have turned systemic lupus erythematosus (SLE) into a chronic disease by reducing mortality rates. The exact contribution of disease activity and disease related damage to mortality is not well studied. The aim of this study was to describe the current causes of death (COD) in a multinational European cohort of patients with SLE in relation to quantified measures of disease activity and damage. Prospective five-year observational study of case fatalities in SLE patients at 12 European centres was performed. Demographics, disease manifestations, interventions and quantified disease activity (by ECLAM and SLEDAI) and damage (by SLICC-DI) at the time of death were related to the various COD. Ninety-one case fatalities (89% females) occurred after median disease duration of 10.2 years (range 0.2-40) corresponding to a annual case fatality of one for each of the participating cohorts. Cumulative mortality correlated linearly with disease duration with nearly 10% of fatalities occurring in the first year and 40% after more than 10 years of disease. Death occurred during SLE remission in one third of cases. In the remaining cases a mixture of disease activity (median ECLAM 5.5, median SLEDAI 15) and accrued damage (median SLICC-DI 5.0) with opposing relationships to disease duration contributed to death. Infections and cardiovascular events were the most frequent COD in both early and late fatalities with no gender differences for type of COD, disease activity, damage or comorbidity. In Europe, case fatalities have become uncommon events in dedicated SLE cohorts. The bimodal mortality curve has flattened out and deaths now occur evenly throughout the disease course with infectious and cardiovascular complications as the main direct COD in both early and late fatalities. Accrued damage supplants disease activity over time as the main SLE specific contributor to death over time.

Increased ferritin response in adult Still's disease: specificity and relationship to outcome.

BACKGROUND: The disproportionate ferritin response encountered in some patients with adult Still's disease (ASD) may reflect a fundamental aspect in the pathophysiology of ASD. METHODS: An observational case-control study of 22 ASD patients followed for 63 months. Baseline laboratory data were compared with age- and gender-matched controls with new-onset rheumatoid arthritis (RA). Serum levels of ferritin and C-reactive protein (CRP) and the ferritin/CRP ratio were related to clinical outcome in ASD through nonparametric statistical analyses. RESULTS: Compared to RA patients, haemoglobin levels were lower (11.8 vs. 13.5 g/dL; p = 0.009) and leucocyte counts (17.1 vs. 8.6 10(9)/mL; p<0.001), erythrocyte sedimentation rate (ESR) (84 vs. 38 mm; p = 0.001), CRP (154 vs. 27 mg/L; p<0.001), aspartate aminotransferase (ASAT) (52 vs. 23 U/l; p = 0.004), serum ferritin (8750 vs. 62 microg/L; p<0.001) and ferritin/CRP ratios (9.7 vs. 1.7; p<0.001) were higher in ASD patients at baseline. Six patients (27%) achieved sustained remission (monocyclic disease), while 16 patients (73%) developed chronic disease (progressive in 27%, relapsing/remitting in 46%). The levels of ESR and CRP or other baseline variables were not associated with outcome. However, baseline serum ferritin was significantly higher in ASD patients with chronic disease (p = 0.04), while a cut-off of five times the normal upper level (NUL) was 100% sensitive and 60% specific for predicting chronic disease. CONCLUSION: An exaggerated ferritin response with levels>5 times the NUL and high ferritin/CRP ratios is useful for distinguishing between ASD and RA patients. Ferritin levels>5 times the NUL are also associated with a chronic disease course.

Anti-dsDNA antibodies and disease classification in antinuclear antibody positive patients: the role of analytical diversity.

BACKGROUND: The presence of "anti-DNA antibodies in abnormal titres" is a well established criterion for SLE classification, but there is no agreement on the performance of this test. OBJECTIVE: To study the correlation between clinical findings and five different solid and solution phase anti-DNA antibody assays. METHODS: 158 consecutively collected ANA positive sera were studied in a double blind fashion. Anti-DNA antibodies were determined by different solid phase assays (ssDNA-, dsDNA- specific ELISA, EliA anti-dsDNA assay, Crithidia luciliae assay), and by an experimental solution phase anti-DNA assay using biotinylated pUC18 plasmid, human, calf thymus, and E coli DNA. Antibody affinity was determined by surface plasmon resonance. Clinical data were obtained independently of the laboratory analyses and later related to the anti-dsDNA findings. RESULTS: Anti-dsDNA antibodies were most frequently detected by ELISA, but were not specific for SLE as they were present in up to 30% of other disease groups. Those detected by the Crithidia luciliae assay were predictive for SLE, while antibodies binding in solution phase ELISA using the pUC18 correlated strongly with the Crithidia luciliae assay. Surface plasmon resonance analysis showed that antibody binding to pUC18 was not due to higher relative affinity for dsDNA in general, but apparently to specificity for that plasmid DNA. Serum samples from three patients with lupus nephritis were positive in both pUC18 solution phase and Crithidia luciliae assays. CONCLUSIONS: Assay principle selection is decisive for the detection of clinically significant anti-DNA antibodies. Revision of the anti-DNA antibody criterion in the SLE classification may be needed.