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ID PMID Title PublicationDate abstract
24287195 Salivary gland disease in Sjögren's syndrome: sialoadenitis to lymphoma. 2014 Feb Although the cause and molecular pathways of Sjögren's syndrome are still unknown, basic, clinical, and translational science have started to identify linkages to other known processes. With the advent of newer, more sensitive, and more accurate chemokine, cytokine, and genetic analysis, the molecular progression of the disease may be understood. The modern technology of sialoendoscopy to treat obstructive sialoadenitis from mucous plugging, and the addition of rituximab to current chemotherapy, have allowed patients with Sjögren's syndrome to have a better quality of life and, if they develop lymphomatous changes, a significant increase in their disease remission and survival rate.
23683373 Pulmonary manifestations of collagen diseases. 2013 Jun Collagen diseases are a large group of systemic inflammatory diseases of autoimmune etiology. The etiopathogenesis of collagen diseases is multifactorial. There is genetic susceptibility, as many connective tissue disorders show family history, and environmental factors may trigger the disease. Collagen diseases can affect almost all the organs of the body. The respiratory system is one of the most frequently affected, although the prevalence of pulmonary disease is not precisely known for the different collagen disorders. Any structure of the respiratory tract can be affected, but perhaps the most frequent is pulmonary parenchymal disease in the form of pneumonitis, which can be produced in any of the idiopathic interstitial pneumonitis patterns. The pleura, pulmonary vessels, airways and respiratory muscles may also be affected. The frequency of lung disease associated with collagen diseases is on the rise. This due in part to the better diagnostic methods that are available to us today (such as high-resolution computed tomography) and also to the appearance of new forms of pneumonitis associated with the new treatments that are currently used. The objective of this article is to offer a global vision of how collagen diseases can affect the lungs according to the latest scientific evidence.
25342375 Biologic treatment in Sjögren's syndrome. 2015 Feb SS is a chronic systemic autoimmune disease characterized by decreased exocrine gland function. A variety of other disease manifestations may also be present, including general constitutional symptoms and extraglandular features. A multidisciplinary approach focused on both local and systemic medical therapies is needed as the disease has a wide clinical spectrum. The current treatment for SS is mainly symptomatic. However, there is evidence that systemic drugs are effective in controlling extraglandular manifestations of the disease. Overall evidence for the role of conventional immunosuppressive therapy is limited. A number of attempts to use biologic therapies have led to variable results. Biologic agents targeting B cells, such as rituximab, epratuzumab and belimumab, have shown promising results, but further studies are needed to validate the findings. Early-phase studies with abatacept and alefacept proved that T cell stimulation inhibition is another potentially effective target for SS treatment. Modulation or inhibition of other targets such as IFN, IL-6 and Toll-like receptor are also currently being investigated. We have summarized the available evidence regarding the efficacy of biologic treatments and discuss other potential therapies targeting pathways or molecules recognized as being involved in the pathogenesis of SS.
24727841 Treatment of primary Sjögren syndrome with rituximab: a randomized trial. 2014 Feb 18 BACKGROUND: Primary Sjögren syndrome (pSS) is an autoimmune disorder characterized by ocular and oral dryness or systemic manifestations. OBJECTIVE: To evaluate efficacy and harms of rituximab in adults with recent-onset or systemic pSS. DESIGN: Randomized, placebo-controlled, parallel-group trial conducted between March 2008 and January 2011. Study personnel (except pharmacists), investigators, and patients were blinded to treatment group. (ClinicalTrials.gov: NCT00740948). SETTING: 14 university hospitals in France. PATIENTS: 120 patients with scores of 50 mm or greater on at least 2 of 4 visual analogue scales (VASs) (global disease, pain, fatigue, and dryness) and recent-onset (< 10 years) biologically active or systemic pSS. INTERVENTION: Randomization (1:1 ratio) to rituximab (1 g at weeks 0 and 2) or placebo. MEASUREMENTS: Primary end point was improvement of at least 30 mm in 2 of 4 VASs by week 24. RESULTS: No significant difference between groups in the primary end point was found (difference, 1.0% [95% CI, -16.7% to 18.7%]). The proportion of patients with at least 30-mm decreases in at least two of the four VAS scores was higher in the rituximab group at week 6 (22.4% vs. 9.1%; P = 0.036). An improvement of at least 30 mm in VAS fatigue score was more common with rituximab at weeks 6 (P < 0.001) and 16 (P = 0.012), and improvement in fatigue from baseline to week 24 was greater with rituximab. Adverse events were similar between groups except for a higher rate of infusion reactions with rituximab. LIMITATION: Low disease activity at baseline and a primary outcome that may have been insensitive to detect clinically important changes. CONCLUSION: Rituximab did not alleviate symptoms or disease activity in patients with pSS at week 24, although it alleviated some symptoms at earlier time points.
24038291 Toxic epitheliopathy from a single application of preservative free oxybuprocaine (0.4%) i 2013 Sep 13 Topical ocular anaesthetic agents are frequently used for ophthalmic diagnosis and surgery. While corneal complications following long-term use or misuse of local anaesthetic solutions have been described, toxic epitheliopathy after a single application of six drops of preservative free oxybuprocaine is rare. In order to increase the awareness of this ocular complication, we report such a case in a patient with Sjogren's syndrome who presented for elective cataract surgery. We outline the mechanisms proposed to explain the ocular toxic effects of oxybuprocaine and discuss the management principles in preventing this complication in the context of Sjogren's syndrome.
24656928 Early events in Sjögren's Syndrome pathogenesis: the importance of innate immunity in dis 2014 Jun Sjögren's Syndrome (SS) is a debilitating autoimmune disease that primarily affects women. Patients with SS experience dry eyes and dry mouth in addition to systemic disease manifestations, including arthritis, peripheral neuropathy and pulmonary fibrosis. As in many autoimmune diseases, the inciting factors that precipitate SS are poorly understood. Patients with SS have periductal and perivascular lymphocytic infiltration of salivary and lacrimal tissue, and this is a hallmark of disease. While this infiltration is well characterized, the pathologic events that precede and cause this inflammatory cell recruitment are unknown. Although few studies have examined SS salivary tissue prior to disease onset, there is strong evidence for innate immune hyperactivity. Accordingly, processes such as apoptosis of glandular tissue, heightened inflammatory cytokine and chemokine production, and toll-like receptor (TLR) activation are described in early disease and are each linked to innate immune activation in murine models of disease and SS patients. This review will explore the relationship between innate immunity and SS pathogenesis prior to overt disease onset and discuss therapeutic strategies to mitigate disease progression in SS patients.
24564052 Thymoma associated with myasthenia gravis and Sjögren syndrome. 2013 Mar Thymoma is the most common neoplasm of the anterior mediastinum but thymoma with Sjögren syndrome (SS) is rare. Sjögren syndrome is a systemic autoimmune inflammatory disorder. It is characterized by lymphocyte-mediated destruction of exocrine glands, which leads to absent glandular secretion. Here, we present the case of a 63-year-old man with thymoma and concurrent myasthenia gravis and SS, who achieved remission after thymectomy.
24443980 Dry eye management in a Sjögren's syndrome mouse model by inhibition of p38-MAPK pathway. 2014 Jan 20 BACKGROUND: To investigate the therapeutic effect of p38-MAPK inhibitor, SB203580, on dry eye in a mouse model of Sjögren's syndrome (MRL/lpr mice). METHODS: 18 female BALB/c mice and 44 female MRL/lpr mice were included. Mice were randomly assigned to the control or treatment group. The expression of phospho-p38 MAPK in lacrimal glands of BALB/c mice was determined by Western blot analysis following IL-1β treatment at various time points. Different doses of SB203580 were injected into lacrimal glands of MRL/lpr mice and phenol red thread test was performed seven days post-injection. Moreover, the levels of acetylcholine and norepinephrine expression in lacrimal glands of MRL/lpr mice were measured using spectrofluoremetric assay and the histopathology of lacrimal glands was also evaluated. RESULTS: The expression of p-p38 MAPK in lacrimal glands of BALB/c mice gradually increased following incubation with IL-1β ex vivo. Injection of SB203580 into lacrimal glands significantly improved the results of phenol red thread test in MRL/lpr mice. In addition, the secretions of acetylcholine and norepinephrine increased significantly compared to the control group. Less lymphocytes infiltration was observed in pathological section of lacrimal glands following SB203580 injection. CONCLUSIONS: Our results indicate that the activation of p38-MAPK pathway plays an important role in dry eye of a Sjögren's syndrome mouse model. Inhibition of p38-MAPK pathway by SB203580 might have potential therapeutic effect on Sjögren's syndrome associated dry eye. VIRTUAL SLIDES: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1256849631103092.
24552965 Imaging of fetal thymus in pregnant women with rheumatic diseases. 2014 Sep OBJECTIVE: To determine whether certain rheumatic diseases will affect the fetal thymus diameter when compared to uncomplicated singleton pregnancies. Additionally, we created a reference chart for fetal thymus size in healthy singleton pregnancies from 19 to 37 weeks of gestation. METHODS: Sonographic fetal thymus size was retrospectively evaluated in 190 healthy pregnant women, and 84 pregnancies of mothers suffering from systemic lupus erythematosus, antiphospholipid syndrome (APS), or Sjögren's syndrome between 19 and 37 weeks of gestation. These fetuses were matched one-to-one for gestational age with control fetuses. The thymic-thoracic ratio (TT-ratio) was defined as the quotient of the anteroposterior thymic and the intrathoracic mediastinal diameter. RESULTS: Rheumatic diseases often affect pregnancy outcome, especially in case of primary APS. The TT ratio of fetuses of mothers suffering from rheumatic disease was equal to controls (P=0.807). CONCLUSIONS: Ours is the first study to assess the correlation of fetal thymus size in high-risk pregnancies with rheumatic diseases in comparison to controls. Women with rheumatic diseases deal with pregnancy complications more frequently than controls. Our data suggest that maternal rheumatic diseases do not affect the fetal thymus size.
24436837 Can total wrist arthroplasty be an option in the treatment of the severely destroyed postt 2013 Nov Background Severely destroyed posttraumatic wrists are usually treated by partial or total wrist fusion or proximal row carpectomy. The indications for and longevity of total wrist arthroplasty (TWA) are still unclear. Case Description The aim of this study was to analyze a series in which one last-generation total wrist arthroplasty was used as a salvage procedure for wrists with severe arthritis due to traumatic causes. The data were prospectively recorded in a web-based registry. Seven centers participated. Thirty-five cases had a minimum follow-up time of 2 years. Average follow-up was 39 (24-96) months. Pain had improved significantly at follow-up, mobility remained unchanged. The total revision rate was 3.7%, and the implant survival was 92% at 4-8 years. Literature Review Very few studies have described specific results after TWA in posttraumatic cases and almost none using classical "third-generation" implants. The number of cases and the follow-up in the published series are small. Clinical Relevance Although painful posttraumatic wrists with severe joint destruction can be salvaged by partial or total fusion, we found that, evaluated at short- to midterm, total wrist arthroplasty can be an alternative procedure and gives results that are comparable to those obtained in rheumatoid cases. Level IV Case series.
24044031 The Relationship Between Function and Disease Activity as Measured by the HAQ and DAS28 Va 2013 OBJECTIVE: To investigate the relationship between function and disease activity in early inflammatory arthritis (EIA). METHODS: Canadian Early Arthritis Cohort (CATCH) (n=1143) is a multi-site EIA cohort. Correlations between the Health Assessment Questionnaire Disability Index (HAQ) and DAS28 were done at every 3 months for the first year and then at 18 and 24 months. We also investigated the relationship between HAQ and DAS28 by age (<65 versus ≥65) and RF (positive vs negative). RESULTS: Mean HAQ and DAS28 scores were highest at the initial visit with HAQ decreasing over 24 months from a baseline of 0.94 to 0.40 and DAS28 scores decreasing from 4.54 to 2.29. All correlations between HAQ and DAS28 were significant at all time points (p<0.01). The correlations between HAQ and DAS28 were variable over time. The strongest correlation between HAQ and DAS28 occurred at initial visit (most DMARD naive) (n=1,143) and 18 months (r=0.57, n=321) and 24 months (r=0.59, n=214). The baseline correlation between HAQ and DAS28 was significantly different than correlations obtained at 3, 6, and 12 months (p=0.02, 0.01, and 0.01, respectively). Age did not change the association between HAQ and DAS28 {<65 years old (r=0.50, n=868) versus ≥65 (r=0.48, n=254), p=0.49}. The correlation between HAQ and DAS28 was stronger with RF+ patients (r=0.63, n=636) vs RF negative (r=0.47, n=477), p=0.0043. CONCLUSION: Over 2 years in EIA, HAQ and DAS both improved; correlations at time points were different over 2 years and RF status affected the correlations.
24382722 Factors associated with longer length of hospital stay after primary elective ankle surger 2014 Jan 1 BACKGROUND: Longer length of stay in the hospital after elective surgery results in increased use of health-care resources and higher costs. Improved perioperative care permits many foot and ankle surgical procedures to be performed as day surgery. This study determined perioperative factors associated with a longer length of stay after elective total ankle replacement or ankle arthrodesis. METHODS: Data were prospectively collected on patients who underwent open or arthroscopic ankle fusion or total ankle replacement for end-stage ankle arthritis at our institution from 2003 to 2010. Univariate and multivariable generalized linear regression models with gamma distribution and log link function were conducted with use of the length of the hospital stay as the dependent variable and preselected risk factors of age, sex, physical and mental functional scores, comorbid factors, American Society of Anesthesiologists grade, body mass index, type of surgery, duration of surgery, and surgery day of the week as the independent variables. RESULTS: This study included 343 patients with a median length of stay of seventy-five hours (interquartile range, fifty-two to ninety-seven hours). With use of regression analyses, the variables of age, female sex, higher American Society of Anesthesiologists grade, multiple medical comorbidities, rheumatoid arthritis, lower Short Form-36 Physical Component Summary and General Health domain scores, and open surgery were significantly associated with increased length of stay. Conversely, the variables of obesity, Short Form-36 Mental Component Summary score, surgery day of the week, and surgical duration were not associated with length of stay. Two predictive models of the length of stay were developed: one included only patient-related factors, and the other included patient and surgery-related factors. CONCLUSIONS: The patients who are identified with a higher risk of a longer length of stay may warrant better education and more focused perioperative care when designing care pathways and allocating health-care resources.
25455683 Cardiovascular events in ankylosing spondylitis: an updated meta-analysis. 2015 Apr OBJECTIVES: Rheumatoid arthritis is associated with increased cardiovascular risk. In the guidelines, ankylosing spondylitis (AS) is considered to have an equally high cardiovascular risk. The literature findings remain controversial. This study aims to assess the risk of myocardial infarction (MI) and stroke in AS patients. METHODS: An updated meta-analysis with a new systematic literature review using PubMed was conducted up to January 2014. Incidence of MI or stroke was calculated by metaproportion. RESULTS: In addition to the 11 previously included studies, six new studies assessed the occurrence of MI or stroke in AS patients. (1) MI. A total of 2131 MI were reported in AS patients (n = 27,532) over a mean follow-up of 15 years: incidence 5.3% (1.6%-11.0%), i.e., 0.36/100 pyrs. Seven studies revealed 17,410 MI [2.5% (95% CI: 1.8%-3.4%)] in the control group (n = 1,349,964). Meta-analysis of the seven longitudinal studies showed a significant increase in MI [OR = 1.60 (95% CI: 1.32-1.93)] in AS patients. (2) Stroke. In 11 longitudinal studies (n = 51,990), 1807 strokes were reported in AS patients over 17.6 years of follow-up: incidence 3.6% (1.5%-6.5%), i.e., 0.24/100 pyrs. Three studies reported 22,899 strokes in controls (n = 1,239,041), giving an incidence of 1.78% (1.75%-1.80%). A significant increase in stroke [OR = 1.50 (95% CI: 1.39-1.62)] in AS patients was found. CONCLUSION: AS patients appear to have a higher risk of MI and stroke. Management of cardiovascular risk factors and control of systemic inflammation should be taken into account in AS to decrease this high cardiovascular risk.
25198901 Leptin induces oncostatin M production in osteoblasts by downregulating miR-93 through the 2014 Sep 5 Inflammatory response and articular destruction are common symptoms of osteoarthritis (OA) and rheumatoid arthritis (RA). Leptin, an adipocyte-secreted hormone that centrally regulates weight control, may exert proinflammatory effects in the joint, depending on the immune response. Yet, the mechanism of leptin interacting with the arthritic inflammatory response is unclear. This study finds that leptin increased expression of oncostatin M (OSM) in human osteoblasts in a concentration- and time-dependent manner. In addition, OBRl, but not OBRs receptor antisense oligonucleotide, abolished the leptin-mediated increase of OSM expression. On the other hand, leptin inhibited miR-93 expression; an miR-93 mimic reversed leptin-increased OSM expression. Stimulation of osteoblasts with leptin promoted Akt phosphorylation, while pretreatment of cells with Akt inhibitor or siRNA reversed leptin-inhibited miR-93 expression. Our results showed that leptin heightened OSM expression by downregulating miR-93 through the Akt signaling pathway in osteoblasts, suggesting leptin as a novel target in arthritis treatment.
25405141 Anti-cyclic citrullinated peptide antibodies in ulcerative colitis, and its relation with 2014 BACKGROUND: Ulcerative colitis an inflammatory bowel disease (IBD) and chronically idiopathic immune related that associates with extraintestinal manifestations such as arthritis. Despite of the highly specificity of anticyclic citrullinated peptide (CCP) antibodies for rheumatoid arthritis, their role in IBD remains unclear. There are only a few studies on the prevalence of anti-CCP antibodies in patients with IBD. This study aimed to assess the prevalence of anti- CCP antibodies in ulcerative colitis and to investigate possible associations with their clinical and laboratory characteristics Methods: In this cross-sectional study, 93 consecutive patients with ulcerative colitis referred to gastroenterology clinics in Razi referral hospital of Rasht, Iran, from September 2010 to September 2011. Rheumatologic examination, demographic data and clinical presentation of patients were recorded on specially prepared data sheets. Blood sample was collected for assessment of anti-CCP and other laboratory tests. Data were analyzed by the Chi square test, Fisher Exact test and student t test, using the SPSS 20 software for Windows, and P value less than 0.05 was considered significant. RESULTS: Of 93 patients, anti-CCP antibodies detected in 10.8% of cases (CI 95%: 4.5-17.1%). There were a significant relation between the prevalence of anti CCP positivity and aphthous ulcers and ocular manifestations whereas other parameters were not significantly related. CONCLUSION: Anti CCP may have a possible role in some ulcerative colitis manifestations but there was no association between the presence of these antibodies and activity or extension of inflammatory colitis. We suggest other studies especially molecular studies to investigate other aspects of these antibodies in IBD patients.
25351573 Patellar resurfacing in posterior cruciate ligament retaining total knee arthroplasty (PAT 2014 Oct 29 BACKGROUND: Anterior knee pain may occur after total knee arthroplasty (TKA). Patellar resurfacing, which is considered to lower the incidence of anterior knee pain after TKA, remains controversial. In the present study clinical and radiological outcomes after TKA performed on patients with clinical and radiological signs of femorotibial and patellofemoral osteoarthritis (OA) with and without patellar resurfacing will be compared. METHODS/DESIGN: Fifty patients will be included in a randomized controlled trial. Patients scheduled for TKA with clinical and radiological signs of femorotibial and patellofemoral OA will be included. Arthritis of the patellofemoral joint was determined based on the preoperative Baldini and Merchant X-ray views, which is assessed by the orthopaedic surgeon who treats the patient. Exclusion criteria are rheumatoid arthritis, history of patellar fracture, tuberosity transposition, high tibial osteotomy (HTO), hip arthroplasty and posterior cruciate ligament insufficiency. Patients will be randomized to undergo TKA either with or without patellar resurfacing. Outcomes will be assessed preoperatively, at 6 weeks and at 6, 12, 18 and 24 months postoperatively. Primary outcome measure is the patellofemoral scoring system according to Baldini. Secondary outcome measures are the Knee Society clinical rating system (KSS) and the Knee Osteoarthritis Outcome Scale (KOOS) scores. Conventional weight-bearing radiographs, and views according to Baldini will be used to asses component loosening, wear, and patellofemoral problems including fracture or loosening of resurfaced patellae, subluxation and wear of non-resurfaced patellae. DISCUSSION: There is no consensus regarding patellar resurfacing during primary TKA. Current prospective studies fail to determine any differences in clinical outcome among patients after TKA with or without patellar resurfacing. This randomized controlled trial has been designed to determine the effectiveness of patellar resurfacing during TKA in patients undergoing TKA who have clinical and radiological signs of tibiofemoral and patellofemoral OA, using a specific patellofemoral outcome measurement. TRIAL REGISTRATION: Netherlands Trial Registry NTR3108.
22935442 No detection of occult HBV-DNA in patients with various rheumatic diseases treated with an 2013 Jan OBJECTIVES: The widespread use of tumour necrosis factor (TNF)-targeted therapies in patients with rheumatic, digestive and dermatologic diseases has been associated with reports of reactivation of HBV replication and ensuing hepatitis flares both in asymptomatic HBsAg carriers and in subjects with occult HBV infection. The aim of our work was to investigate in a two-year prospective study the potential for HBV reactivation in patients with inflammatory joint diseases undergoing anti-TNF treatment from a southern Mediterranean area. METHODS: Fifty-seven consecutive outpatients attending the Academic Unit of Rheumatology at the University of Palermo (12 with rheumatoid arthritis, 17 with psoriatic arthritis and 28 with ankylosing spondylitis) were enrolled in the study. HBV-DNA was tested by a standard quantitative assay in HBsAg-positive subjects and by an ad hoc highly sensitive PCR in HBsAg-negative patients performed at baseline and then every six months on the anti-TNF agent. RESULTS: Occult HBV-DNA was never detected in the 54 HBsAg negative subjects, regardless of their anti HBs/HBc status. All HBsAg positive patients, who were started on prophylactic lamivudine, remained HBV-DNA undetectable throughout the anti-TNF treatment. CONCLUSIONS: Even in an area of previously high HBV endemicity, where occult HBV infection is likely to have a high prevalence, treatment of rheumatological patients with anti-TNF drugs is safe in terms of its potential to reactivate HBV. Prophylaxis with lamivudine is sufficient to prevent reactivation in HBsAg carriers.
24147732 The challenges, advantages and future of phenome-wide association studies. 2014 Feb Over the last decade, significant technological breakthroughs have revolutionized human genomic research in the form of genome-wide association studies (GWASs). GWASs have identified thousands of statistically significant genetic variants associated with hundreds of human conditions including many with immunological aetiologies (e.g. multiple sclerosis, ankylosing spondylitis and rheumatoid arthritis). Unfortunately, most GWASs fail to identify clinically significant associations. Identifying biologically significant variants by GWAS also presents a challenge. The GWAS is a phenotype-to-genotype approach. As a complementary/alternative approach to the GWAS, investigators have begun to exploit extensive electronic medical record systems to conduct a genotype-to-phenotype approach when studying human disease - specifically, the phenome-wide association study (PheWAS). Although the PheWAS approach is in its infancy, this method has already demonstrated its capacity to rediscover important genetic associations related to immunological diseases/conditions. Furthermore, PheWAS has the advantage of identifying genetic variants with pleiotropic properties. This is particularly relevant for HLA variants. For example, PheWAS results have demonstrated that the HLA-DRB1 variant associated with multiple sclerosis may also be associated with erythematous conditions including rosacea. Likewise, PheWAS has demonstrated that the HLA-B genotype is not only associated with spondylopathies, uveitis, and variability in platelet count, but may also play an important role in other conditions, such as mastoiditis. This review will discuss and compare general PheWAS methodologies, describe both the challenges and advantages of the PheWAS, and provide insight into the potential directions in which PheWAS may lead.
23951169 Anti-dsDNA antibody isotypes in systemic lupus erythematosus: IgA in addition to IgG anti- 2013 OBJECTIVES: To evaluate the role of serum IgG, IgM and IgA anti-dsDNA antibody isotypes in the diagnosis of systemic lupus erythematosus (SLE), and their association with clinical features and disease activity, in a large cohort of SLE patients. METHODS: Sera of 200 SLE patients (mean age 34±10.3 years; 26 male and 174 female; median duration of disease 115 months, range 7-378), and of 206 controls, including 19 Sjögren's syndrome, 27 rheumatoid arthritis, 26 psoriatic arthritis, 15 idiopathic inflammatory myopathies (IIM), 13 systemic sclerosis, 49 infectious diseases and 57 healthy subjects, were tested for anti-dsDNA IgG, IgM and IgA isotypes. RESULTS: Selecting a cutoff corresponding to 95% specificity, the sensitivity of IgG, IgM and IgA anti-dsDNA antibodies in SLE was 55%, 30% and 49%, respectively; 12.5%, 1% and 7.5% of SLE patients had positive IgG, IgM or IgA isotype alone, respectively. SLE patients with glomerulonephritis showed higher levels of IgA anti-dsDNA (p = 0.0002), anti-dsDNA IgG/IgM (p = 0.001) and IgA/IgM (p<0.0001) ratios than patients without renal disease. No significant associations have been found between anti-dsDNA isotypes and other clinical features. IgA anti-dsDNA (p = 0.01) (but not IgG or IgM) and IgG/IgM ratio (p = 0.005) were significantly higher in patients with more active disease (ECLAM score >4). CONCLUSIONS: The detection of IgA anti-dsDNA autoantibodies seems to improve our ability to diagnose SLE and to define lupus nephritis phenotype and active disease. By contrast, IgM anti-dsDNA antibodies might be protective for renal involvement. These data support the hypothesis that anti-dsDNA antibody class clustering may help to refine SLE diagnosis and prognosis.
23890223 The immunogenicity to the first anti-TNF therapy determines the outcome of switching to a 2013 Jul 26 INTRODUCTION: Anti-TNF drugs have proven to be effective against spondyloarthritis (SpA), although 30% of patients fail to respond or experience adverse events leading to treatment discontinuation. In rheumatoid arthritis, the presence of anti-drug antibodies (ADA) against the first TNF inhibitor influences the outcome after switching. Our aim was to assess whether the response to a second anti-TNF drug is related to the previous development of ADA to the first anti-TNF drug SpA patients. METHODS: Forty-two SpA patients began a second anti-TNF drug after failing to respond to the first anti-TNF therapy. Clinical activity was assessed by the Ankylosing Spondylitis Disease Activity Score (ASDAS) at baseline (at the beginning of the first and second anti-TNF therapy) and at 6 months after switching. The drug and ADA levels were measured by ELISA before each administration. RESULTS: All patients were treated with anti-TNF drugs and mainly due to inefficacy were switched to a second anti-TNF drug. Eleven of 42 (26.2%) developed ADA during the first biologic treatment. At baseline, no differences in ASDAS were found in patients with or without ADA to the first anti-TNF drug (3.52 ± 1.03 without ADA vs. 3.14 ± 0.95 with ADA, p = 0.399) and to the second anti-TNF drug (3.36 ± 0.94 without ADA vs. 3.09 ± 0.91 with ADA, p = 0.466). At 6 months after switching, patients with previous ADA had lower disease activity (1.62 ± 0.93 with ADA vs. 2.79 ± 1.01 without ADA, p = 0.002) and most patients without ADA had high disease activity state by the ASDAS (25 out of 31 (80.6%) without ADA vs. 3 out of 11 (27.3%) with ADA, p = 0.002). CONCLUSIONS: In SpA the failure to respond to the first anti-TNF drug due to the presence of ADA predicts a better clinical response to a second anti-TNF drug.