Bahar Artim-Esen

Cluster Analysis of Autoantibodies in 852 Patients with Systemic Lupus Erythematosus from a Single Center

Objective. Associations between autoantibodies and clinical features have been described in systemic lupus erythematosus (SLE). Herein, we aimed to define autoantibody clusters and their clinical correlations in a large cohort of patients with SLE. Methods. We analyzed 852 patients with SLE who attended our clinic. Seven autoantibodies were selected for cluster analysis: anti-DNA, anti-Sm, anti-RNP, anticardiolipin (aCL) immunoglobulin (Ig)G or IgM, lupus anticoagulant (LAC), anti-Ro, and anti-La. Two-step clustering and Kaplan-Meier survival analyses were used. Results. Five clusters were identified. A cluster consisted of patients with only anti-dsDNA antibodies, a cluster of anti-Sm and anti-RNP, a cluster of aCL IgG/M and LAC, and a cluster of anti-Ro and anti-La antibodies. Analysis revealed 1 more cluster that consisted of patients who did not belong to any of the clusters formed by antibodies chosen for cluster analysis. Sm/RNP cluster had significantly higher incidence of pulmonary hypertension and Raynaud phenomenon. DsDNA cluster had the highest incidence of renal involvement. In the aCL/LAC cluster, there were significantly more patients with neuropsychiatric involvement, antiphospholipid syndrome, autoimmune hemolytic anemia, and thrombocytopenia. According to the Systemic Lupus International Collaborating Clinics damage index, the highest frequency of damage was in the aCL/LAC cluster. Comparison of 10 and 20 years survival showed reduced survival in the aCL/LAC cluster. Conclusion. This study supports the existence of autoantibody clusters with distinct clinical features in SLE and shows that forming clinical subsets according to autoantibody clusters may be useful in predicting the outcome of the disease. Autoantibody clusters in SLE may exhibit differences according to the clinical setting or population.

Metabolic syndrome is not only a risk factor for cardiovascular diseases in systemic lupus erythematosus but is also associated with cumulative organ damage: a cross-sectional analysis of 311 patients.

Background/Purpose Patients with systemic lupus erythematosus (SLE) have increased rates of cardiovascular disease (CVD) that are one of the major causes of mortality. The aim of this study was to determine the frequencies of metabolic syndrome (MetS) and CVD in SLE patients and investigate the link between these and clinical features of SLE. Methods A total of 311 SLE patients were consecutively assessed for cumulative organ damage (SDI/SLICC scores), history of CVD and MetS as defined by the National Cholesterol Educational Program Adult Treatment Panel III (NCEP ATP III). Clinical data of SLE patients were collected from the records. Results The mean age of the patients was 40.2 ± 13.4 years and 89% were female. The frequencies of CVD and MetS were 15.2% and 19%, respectively. In this SLE cohort increased age, cumulative damage, disease duration and CVD were associated with MetS. CVD was associated with disease duration, cumulative damage, pericarditis, hematologic involvement, lymphopenia, thrombocytopenia, neurological involvement and antiphospholipid antibody (aPL) positivity. Hydroxychloroquine (HCQ) use was found as a protective factor for CVD. Conclusion In SLE patients, MetS was associated with CVD and both increased with disease duration. Patients who developed MetS and/or CVD had increased cumulative organ damage. Certain clinical features of SLE and the presence of aPL were also associated with CVD. There was a significant protective effect of HCQ from CVD. The prevention of MetS and long-term use of HCQ may be beneficial in improving the prognosis of SLE.

Re-evaluation of 129 patients with systemic necrotizing vasculitides by using classification algorithm according to consensus methodology

Recently, a new classification algorithm (CA) for systemic necrotizing vasculitides was proposed by Watts et al. (Annals Rheum Dis 66:222–227, 2007) by using the American College of Rheumatology (ACR), Chapel Hill Consensus Criteria (CHCC) and Sorensen surrogate markers (So). We aimed to validate CA in our patients. One hundred twenty-nine patients followed up in our vasculitis clinic were reclassified according to CA in different categories (ACR or Lanham criteria in “1” for Churg–Strauss Syndrome (CSS); ACR in “2a”; CHCC-Wegeners granulomatosis (WG) in “2b”; CHCC-microscopic polyangiitis (MPA), So-WG in “2c”; So-WG, proteinase 3 (PR3) or myeloperoxidase antineutrophil cytoplasmic antibody (MPO ANCA) serology in “2d” for WG; clinical features and histology compatible with small vessel vasculitis without So-WG in “3a”; So-MPA, PR3 or MPO ANCA serology in “3b” for MPA; CHCC-classic-polyarteritis nodosa (c-PAN) or typical angiographic features in “4” for c-PAN; unclassifiable in “5”). Kappa statistic was used to analyse the agreement of the criteria that formed the algorithm. All of 12 CSS, 91% of 69 WG, 78% of 18 MPA and 93% of 26 c-PAN patients remained in their previous diagnosis. WG patients were placed in 2a (83%), 2c (3%), 2d (14%) categories. Four WG (6%) and four MPA (22%) patients were categorized as MPA (in 3a (75%), 3b (25%)) and WG (in 2c (75%), 2d (25%)), respectively. Three of four unclassified patients could be classified as c-PAN (two) and MPA (one). Significant agreement was demonstrated only for ACR and So criteria in WG (κ = 0.62, p < 0.001). The majority of our patients stayed on their previous diagnosis in “CA”. Our findings suggest that this algorithm is helpful and practical for epidemiological studies. Poor correlation of defined criteria was thought to be related to the fact that each criteria mainly consist of different characteristics of vasculitides such as clinical, histopathological and serological features.

Amyloid arthropathy mimicking seronegative rheumatoid arthritis in multiple myeloma: case reports and review of the literature

We report two patients who suffered from symmetrical polyarthritis simulating rheumatoid arthritis. Acute phase response was almost within normal limits, and autoantibodies including rheumatoid factor were negative. Both of them were diagnosed as having amyloid arthropathy (AmyA) secondary to kappa multiple myeloma based on deposition of κ-light chain-immunoreactive amyloid in biopsied tissue and Bence Jones protein in urine. Systemic AL amyloidosis may be important in the differential diagnosis of chronic polyarthralgia.

The impact of platelet membrane glycoprotein Ib alpha and Ia/IIa polymorphisms on the risk of thrombosis in the antiphospholipid syndrome.

BACKGROUND Pathogenesis of thrombus formation in antiphospholipid syndrome (APS) is not clear. Platelet membrane glycoprotein (GP) receptors play important roles in development of thrombosis. OBJECTIVES We investigated the association between development of thrombosis in APS and polymorphisms of GPIb alpha variable number of tandem repeats (VNTR), Kozak, and GPIa C807T. Patients/Methods Sixty patients with APS (30 with proven thrombosis and 30 without thrombosis) and 63 controls were included. Presence of GPIa C807T polymorphism was determined with real-time PCR and GPIb alpha Kozak and VNTR polymorphisms by conventional PCR. RESULTS Frequency of C807T TT genotype was significantly higher in APS with thrombosis than APS without thrombosis (p=0.023) and also in APS with multiple thrombi compared to APS without thrombi (p=0.023). Frequency of Kozak TC genotype was higher in APS with arterial thrombosis compared to APS with venous thrombosis, controls, and APS without thrombosis (p=0.03, p=0.0007, and p=0.0024 respectively). D allele frequency and D allele carrier state for VNTR were significantly less in APS than controls (p=0.0018 and p=0.0046 respectively). CONCLUSIONS C807T TT genotype may confer a risk for thrombosis and Kozak TC genotype for arterial thrombosis. D allele of VNTR may protect from APS. No patients with C807T TT or Kozak TC genotypes carried the protective DD genotype of VNTR. These polymorphisms may increase risk for both arterial and venous thrombosis. The utility of prophylaxis with anti-platelet drugs in at least a subgroup of APS patients should be investigated with clinical trials.

Comparison of Disease Characteristics, Organ Damage, and Survival in Patients with Juvenile-onset and Adult-onset Systemic Lupus Erythematosus in a Combined Cohort from 2 Tertiary Centers in Turkey

Objective. Age at onset has been shown to affect the clinical course and outcome of systemic lupus erythematosus (SLE). Herein, we aimed to define the differences in clinical characteristics, organ damage, and survival between patients with juvenile-onset (jSLE) and adult-onset SLE (aSLE). Methods. For the study, 719 patients (76.9%) with aSLE and 216 (23.1%) with jSLE were examined. Comparisons between the groups were made for demographic characteristics, clinical features, auto-antibody profiles, damage, and survival rates. Results. These results were significantly more frequent in jSLE: photosensitivity, malar rash, oral ulcers, renal involvement, neuropsychiatric (NP) manifestations, and autoimmune hemolytic anemia (AIHA). Of the autoantibodies, a higher frequency of anti-dsDNA and anticardiolipin IgG and IgM were observed in the jSLE group. A significant proportion of patients with aSLE had anti-Sm positivity and pleuritis. The proportion of patients with jSLE who developed organ damage was comparable to that of patients with aSLE (53% vs 47%) and the mean damage scores were similar in both groups. Renal damage was significantly more frequent in jSLE while musculoskeletal and cardiovascular system damage and diabetes mellitus were more prominent in aSLE. Comparison of survival rates of the 2 groups did not reveal any significant differences. Conclusion. We report a higher frequency in the jSLE group of renal involvement, cutaneous symptoms, oral ulcers, NP manifestations, AIHA, and anti-dsDNA positivity. A significant proportion of patients in the jSLE group had damage, most prominently in the renal domain. Our findings might support different genetic/environmental backgrounds for these 2 subgroups.

Increased serum leptin levels are associated with metabolic syndrome and carotid intima media thickness in premenopausal systemic lupus erythematosus patients without clinical atherosclerotic vascular events

Aim To assess subclinical atherosclerosis and the role of inflammatory mediators, vascular endothelial cell activation markers and adipocytokines in systemic lupus erythematosus (SLE) in the presence or absence of metabolic syndrome (MetS). Methods We studied 66 premenopausal female SLE patients (20 with MetS) and 28 female healthy controls (HCs) without history of cardiovascular disease (CVD). Subclinical atherosclerosis was screened by measuring carotid intima media thickness (CIMT). Serum levels of high sensitivity C-reactive protein (hs-CRP), tumour necrosis factor α (TNFα), interleukin 6 (IL-6), soluble intercellular adhesion molecule 1 (sICAM-1), soluble E-selectin, leptin and visfatin were measured. Results The mean age of MetS+SLE, MetS- and HC were 38.3 ± 6.7, 32.7 ± 9.3 and 29.9 ± 5.6 years, respectively. The mean disease duration, SLICC (Systemic Lupus International Collaborating Clinics damage index) and Systemic Lupus Erythematosus Disease Activity Index scores were 74.8 ± 54.9 months, 0.16 ± 0.48 and 1.18 ± 1.5, respectively, and were similar between MetS+and MetS- SLE patients. CIMT values were higher in both MetS+ and MetS- SLE patients than HCs (p < 0.001). sICAM-1 and erythrocyte sedimentation rate levels were higher in both MetS+ and MetS- SLE patients than HCs (p < 0.001; p = 0.002, p = 0.001). The SLE MetS+ group had higher CIMT values than SLE MetS- (right: p = 0.003; left: p = 0.025). Leptin levels and homeostatic model assessment (HOMA) scores were significantly higher in SLE MetS+ than SLE MetS- (p = 0.018; p = 0.04). Leptin and CRP levels and body mass index, SLICC and HOMA scores were correlated with CIMT values (right: p = 0.03, p < 0.001, p < 0.001, p = 0.026 and p < 0.001, and left: p = 0.028, p = 0.03, p = 0.003, p = 0.002 and p = 0.025). Conclusions In premenopausal women with SLE without a history of CVD, CIMT values were increased and related to MetS. Leptin was increased in patients with MetS and correlated with CIMT values.

358 A single centrecenter experience of rituximab treatment in 79 patients with systemic lupus erythematosus

Background and aims B-cell-targeted therapies have been promising new treatments for SLE. Herein, we aimed to analyse the effects of Rituximab in lupus patients with involvement of different domains. Methods This is an analysis of 79 lupus patients treated with rituximab at the rheumatology outpatient clinic. Patient features, previous and concomitant treatments, baseline clinical and serological characteristics, treatment response at 3 and 6 months, number of cycles, flares, infections and infusion reactions were analysed. Disease activity was assessed using SLE disease activity index (SLEDAI) and treatment response was defined according to the system involved. Results 37 patients received Rituximab for lupus nephritis (LN), 15 for thrombocytopenia and/or autoimmune hemolytic anaemia (AIHA), 12 for arthritis, 7 for vasculitis and 8 for general activity. Majority of the patients received one or two cycles of Rituximab. The reason of further cycles was maintenance in 40.5% of patients, non-remission in 50% and flare in 9.5%. Highest complete response (CR) rate at the 6th month was within the general disease activity group followed by the arthritis group. Comparison of treatment response between classIV and V LN revealed a a significantly higher number of CR in class IV at the 6th month of treatment. Comparison of SLEDAI score, steroid dose, anti-dsDNA positivity and complement levels between baseline and at the 6th month favoured treatment. There were 9 infusion reactions and 12 infections. Conclusions Rituximab remains as a therapeutic option, especially in severe and refractory cases. Safety profile is good but infusion reactions may represent a problem.