The Frequency and Clinical Significance of IgA Anticardiolipin and Anti-β2-Glycoprotein-I Antibodies in Antiphospholipid Antibody Patients with and without Lupus

Background/Purpose: APS ACTION International Clinical Database and Repository was created to study the natural course of disease over 10 years in persistently antiphospholipid antibody (aPL)-positive patients with/without other systemic autoimmune diseases (SAIDx). Although, IgA aCL and IgA a\u3b22GPI were included in the new SLICC systemic lupus erythematosus (SLE) classification criteria, the prevalence and clinical significance of IgA isotype have been controversial. Thus our objective was to better define the prevalence and clinical significance of IgA aCL and a\u3b22GPI in aPL-positive patients with/without SLE. Methods: A web-based data capture system is used to store patient demographics, aPL-related history, and medications. The inclusion criteria are positive aPL based on the Updated Sapporo classification criteria at least twice within one year prior to enrolment. Patients are followed every 12\ub13 months with clinical data and blood collection. The baseline samples are analysed in the APS ACTION core laboratories to confirm aPL-positivity. For this cross sectional study, using chi square test, we compared the demographic and clinical characteristics of aPL-positive patients with/without SLE based on different aCL/a\u3b22GPI isotypes. Results: As of April 2016, 638 aPL-positive patients recruited from 24 centers; 489 (77%) had core laboratory assessments of IgG/M/A aCL/a\u3b22GPI. Forty-two patients were excluded due to the diagnosis of a SAIDx other than aPL/APS and/or SLE. Thus, 320 (72%) aPL-positive patients without SLE (258 [81%] with APS) and 127 (28%) with SLE (96 [76%] with APS) were analyzed. The frequency of aCL and a\u3b22GPI IgG/M/A positivity (defined as > 20U) was not different between the two groups except the IgG isotype, which was more common in aPL-positive patients without SLE (53% vs 42% [p: 0.03] for aCL and 38% vs 21% [p: 0.03] for a\u3b22GPI). However, the frequency of IgA a\u3b22GPI positivity was 3-fold higher than IgA aCL positivity (33% vs 11% [p<0.001] in those with SLE, and 32% vs 12% in those without SLE [p<0.001]). The demographics and aPL-related clinical manifestations were not different among aCL/a\u3b22GPI IgG, IgM, and IgA isotypes (Table). The results were similar when the aCL/a\u3b22GPI ELISA cut-off was set to 40U. Of note, the frequency (%) of isolated aCL IgG/M/A- and a\u3b22GPI IgG/M/A-positive patients (independent of the LA status) were 22/19/1 and 11/11/8, respectively (when the ELISA cut-off was set to 20U); isolated a\u3b22GPI IgA positivity was significantly higher in aPL-positive patients with SLE, compared to those without SLE (p: 0.006). Conclusion: Although IgA a\u3b22GPI positivity is more common than IgA aCL positivity, especially in SLE, the aCL/a\u3b22GPI IgA isotype does not distinguish between aPL-positive patients: a) with/without SLE; and b) with different aPL-related clinical events

Impact of discordance between patient's and evaluator's global assessment on treatment outcomes in 14 868 patients with spondyloarthritis

Funding: This work was supported by Novartis. Novartis had no influence on the data collection, statistical analyses, manuscript preparation or decision to submit.Peer reviewedPostprintPostprintPostprintPostprin

Genetic Association of a Gain-of-Function IFNGR1 Polymorphism and the Intergenic Region LNCAROD/DKK1 With Behcet's Disease

Objective. Behçet’s disease is a complex systemic inflammatory vasculitis of incompletely understood etiology. This study was undertaken to investigate genetic associations with Behçet’s disease in a diverse multiethnic population.Methods. A total of 9,444 patients and controls from 7 different populations were included in this study. Genotyping was performed using an Infinium ImmunoArray- 24 v.1.0 or v.2.0 BeadChip. Analysis of expression data from stimulated monocytes, and epigenetic and chromatin interaction analyses were performed.Results. We identified 2 novel genetic susceptibility loci for Behçet’s disease, including a risk locus in IFNGR1(rs4896243) (odds ratio [OR] 1.25; P = 2.42 × 10−9) and within the intergenic region LNCAROD/DKK1 (rs1660760) (OR 0.78; P = 2.75 × 10−8). The risk variants in IFNGR1 significantly increased IFNGR1 messenger RNA expression in lipopolysaccharide- stimulated monocytes. In addition, our results replicated the association (P 30 genetic susceptibility loci with a suggestive level of association (P < 5 × 10−5), which will require replication. Finally, functional annotation of genetic susceptibility loci in Behçet’s disease revealed their possible regulatory roles and suggested potential causal genes and molecular mechanisms that could be further investigated.Conclusion. We performed the largest genetic association study in Behçet’s disease to date. Our findings reveal novel putative functional variants associated with the disease and replicate and extend the genetic associations in other loci across multiple ancestries

Analysis of the common genetic component of large-vessel vasculitides through a meta- Immunochip strategy

Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P?=?7.54E-07; ORGCA?=?1.19, ORTAK?=?1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (PGCA?=?5.52E-04, ORGCA?=?1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus

Bupropion Hydrochloride Induced Serum Sickness-Like Reaction

Sustained-release bupropion is commonly used for the symptomatic relief of depressive disorders and as an adjuvant in smoking cessation therapy. The frequency of adverse reactions with bupropion has been estimated to be more than 1%. Hypersensitivity reactions to bupropion are fairly common and include rare cases of serum sickness-like reaction. Here we report a case of bupropion hydrochloride induced serum sickness-like reaction. Complete resolution of symptoms was achieved on discontinuing bupropion and instituting therapy with glucocorticoid and a non-steroidal antiinflammatory drug.We report this case to notify clinicians of potential serious multisystem complications that can occur with sustained-release bupropion therapy

An in vitro evaluation of the interactions of Legionella pneumophila serogroups 2 to 14 strains with other bacteria in the same habitat

The aim of the present study is to determine in vitro inhibitory and/or stimulatory effects of different bacteria on concomitant Legionella pneumophila. The interactions between Legionella and other bacteria were investigated by using bacteria culture and cell-free supernatants (CFSs) on Buffered Charcoal Yeast Extract agar (BCYEA) and/or in BCYEA lacking L-cysteine. Additionally, CFSs of non-Legionella bacteria that possess inhibitory effect on L. pneumophila were characterised using enzyme and heat treatments. The inhibition ratio of the CFSs and the cultures of Gram-negative rod bacteria (GNRB) and Gram-positive rod bacteria (GPRB) on the growth of L. pneumophila strains were 26-47% and 33-67%, respectively, on BCYEA. It was detected that the cultures of Aeromonas hydrophila, Aeromonas spp. strain and Bacillus pumilus stimulated the growth of one of the investigated L. pneumophila strains, but their CFSs did not show any stimulatory effect. The results indicated that growth and multiplication of legionellae could be affected by different bacteria sharing the same habitat and the level of this effect varies among the species. To our knowledge, this is the first study which determined the inhibitory effects of B. pumilus and Brevibacillus brevis against Legionella. The biologically active substances produced by the bacteria could play an important role in the control of L. pneumophila. This phenomenon may be used an alternative approach for controlling legionellae in man-made environments

The effect of parental consanguinity on the clinical and laboratory findings of rheumatoid arthritis

Aims: We aimed to evaluate the frequency of consanguinity among the parents of patients with rheumatoid arthritis (RA) and the influence of parental consanguinity on several clinical and laboratory parameters which reflect the severity of the disease. Methods and patients: The study population consisted of 265 patients with RA which were divided into two groups with respect to the presence or absence of consanguinity between their parents. The frequency of parental consanguinity was compared with the general population. The two groups were compared with respect to family history of RA, the age of onset, the age at which RA was diagnosed, duration of the disease, the presence of rheumatoid nodules, vasculitis, serositis and the need for orthopaedic surgery, amyloidosis, the presence and level of rheumatoid factor and anti-cyclic citrullinated peptide antibodies, erosive changes on radiographs, and the need for anti-tumour necrosis factor therapy. Results: Twenty-one patients (8%) had parents who were consanguineous, which was not more frequent compared with the general population (14%). The mean age of disease onset and the mean age at which RA was diagnosed were lower in patients with parental consanguinity, although the difference was not statistically significant. The other clinical and laboratory parameters were also not different between the two groups. Conclusion: The present data suggests that parental consanguinity has no effect on disease severity, and the frequency of consanguinity is not increased among the parents of patients with RA. A possible exception is the earlier disease onset and age at diagnosis which needs to be confirmed by larger studies