To assess the influence of interleukin-8 (IL-8), epithelial cell-derived neutrophil-activating peptide (ENA-78), and regulated upon activation normal T cell expressed and secreted (RANTES) gene ...polymorphisms in the susceptibility and clinical expression of patients fulfilling classification criteria for Henoch-Schönlein purpura (HSP).
Fifty patients (25 men) from Northwest Spain with primary cutaneous vasculitis classified as HSP according to proposed criteria were studied. All patients were required to have had at least 2 years' followup. Patients and ethnically matched controls were genotyped for IL-8, ENA-78, and RANTES gene polymorphisms.
No allele or genotype differences between patients fulfilling HSP classification criteria and controls were observed for any of the chemokines. However, a significantly increased frequency of allele A of the IL-8 gene polymorphism was found in patients with HSP who developed renal manifestations compared with patients without renal involvement (p = 0.02; pcorr = 0.036). Moreover, the genotype distribution in HSP patients with and without renal involvement showed statistically significant differences (p = 0.02).
In unselected patients with cutaneous vasculitis, carriage of IL-8 allele A influences the susceptibility to renal involvement.
Cardiovascular disease in rheumatoid arthritis Gonzalez-Gay, Miguel A.; Gonzalez-Juanatey, Carlos; Miranda-Filloy, Jose A. ...
Biomedicine & pharmacotherapy,
12/2006, Letnik:
60, Številka:
10
Journal Article
Recenzirano
Epidemiological studies have disclosed an increased mortality due to cardiovascular (CV) complications in patients with rheumatoid arthritis (RA). Patients with this disease have an increased risk of ...left ventricular diastolic dysfunction and congestive heart failure that is unrelated to the presence of traditional atherosclerosis risk factors or ischemic heart disease. Endothelial dysfunction, an early step in the atherogenesis process, is observed in both early and long-standing actively treated patients with RA. High-resolution B-mode ultrasound studies of the common carotid artery have shown the presence of subclinical atherosclerosis, manifested by increased carotid intima-media thickness and carotid plaques, in patients with RA. Association between HLA-DRB1*04 shared epitope alleles, in particular with HLA-DRB1*0404, and endothelial dysfunction and CV mortality has also been observed in these patients. Chronic inflammation plays a pivotal role in the mechanisms associated with atherogenesis in RA. Tumor necrosis factor (TNF)-alpha is a potent proinflammatory cytokine implicated in the initiation and progression of inflammation as well as in the mechanisms associated with accelerated atherosclerosis in this disease. Anti-TNF-alpha therapy has proved to be clinically effective in patients with severe RA. Recent studies have also emphasized the positive effect of anti-TNF-alpha blockade in improving endothelial dysfunction in RA patients. However, this effect seems to be transient and in line with the persistence of chronic inflammation.
BACKGROUND: The TNFSF13B (TNF superfamily member 13b) gene encodes BAFF, a cytokine with a crucial role in the differentiation and activation of B cells. An insertion-deletion variant (GCTGT→A) of ...this gene, leading to increased levels of BAFF, has been recently implicated in the genetic predisposition to several autoimmune diseases, including multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis. Based on the elevated levels of this cytokine found in patients with giant cell arteritis (GCA) and systemic sclerosis (SSc), we aimed to assess whether this functional variant also represents a novel genetic risk factor for these two disorders. METHODS: A total of 1,728 biopsy-proven GCA patients from 4 European cohorts, 4,584 SSc patients from 3 European cohorts and 5,160 ethnically-matched healthy controls were included in the study. The single nucleotide polymorphism (SNP) rs374039502, which colocalizes with the genetic variant previously implicated in autoimmunity, was genotyped using a custom TaqMan assay. First, association analysis was conducted in each independent cohort using χ2 test in Plink (v1.9). Subsequently, different case/control sets were meta-analyzed by the inverse variance method. RESULTS: No statistically significant differences were found when allele distributions were compared between cases and controls for any of the analyzed cohorts. Similarly, combined analysis of the different sets evidenced a lack of association of the rs374039502 variant with GCA (P = 0.421; OR (95% CI) = 0.92 (0.75-1.13)) and SSc (P = 0.500; OR (95% CI) = 1.05 (0.91-1.22)). The stratified analysis considering the main clinical subphenotypes of these diseases yielded similar negative results. CONCLUSION: Our data suggest that the TNFSF13B functional variant does not contribute to the genetic network underlying GCA and SSc.
BackgroundGiant cell arteritis (GCA) can be refractory to corticosteroid therapy. Tocilizumab (TCZ) has been approved in the treatment of GCA. There are no studies comparing the efficacy and safety ...when using TCZ as monotherapy or in combination with conventional immunosuppressive drugs in GCA.ObjectivesOur aim was to compare efficacy and safety of TCZ combined or in monotherapy in GCA.MethodsMulticenter study on 134 patients with refractory GCA who received TCZ therapy as monotherapy or combined with conventional immunosuppressants. Prolonged remission, absence of clinical symptoms and signs and normalization of the acute phase reactants for at least 6 months. Relapse, recurrence of signs or symptoms of GCA and/or ESR >20 mm/h in men or >25 mm/h in women, and/or serum CRP >0.5 mg/dL related to GCA, both before and after starting TCZ therapy.ResultsWe evaluated 134 patients (101 w/33 m) with a mean age of 73.0±8.8 years. TCZ was prescribed as monotherapy in 82 (62.2%) cases and combined with conventional immunosuppressants in 52 (38.8%) patients: MTX (n=48), AZA (n=3), and LFN (n=1). A comparative study between both groups is summarized in TABLE. Patients who received combined TCZ were younger and had a higher C-reactive protein (CRP) and a higher presence of aortitis in imaging techniques. After TCZ was started, prolonged remission was reached with combined therapy (statistical significance at 12 and 24 months). The corticosteroids sparing effect was similar in both groups. And in terms of side effects no significant difference was seen between TCZ as monotherapy or combined with conventional immunosuppressants.ConclusionPatients receiving combined conventional immunosuppressants with TCZ in the clinical practice study showed a higher prolonged remission. The incidence of serious infections and/or relevant adverse events was not affected according to the treatment. As well as the corticoid-sparing effect was achieved in the same way in both groups.References1 Goercke .Calderón-M. Tocilizumab in giant cell arteritis. Observational, open-label multicenter study of 134 patients in clinical practice. Semin Arthritis Rheum. 2019 Jan 5. pii: S0049-0172(18)30571-7. doi: 10.1016/j.semarthrit.2019.01.003. Epub ahead of print2 Loricera J et al. Semin Arthritis Rheum.2015;44:717-723
Data from a small series suggested that the Interleukin 1 beta (IL1ß) rs16944 polymorphism may be associated with severe renal involvement and persistent renal damage (renal sequelae) in ...Henoch-Schönlein purpura (HSP). To confirm this association, we assessed the largest cohort of Caucasian HSP patients ever considered for genetic studies.
338 Spanish HSP patients and 635 sex and ethnically matched controls were recruited in this study. All patients were required to have had at least 6 months' follow-up. Patients and controls were genotyped for IL1β rs16944 by TaqMan genotyping assay.
No differences between IL1β rs16944 genotype or allele frequencies were found either in the case/control study or when HSP patients were stratified according to the age at disease onset, presence of nephritis or gastrointestinal manifestations. Nevertheless, 4 (25%) of the 16 HSP patients who developed severe renal manifestations carried the TT genotype versus 29 (9%) of 322 who did not develop this complication (p=0.01, OR=5.48, 95% CI: 1.01-28.10). Accordingly, patients carrying the mutant T allele had an increased risk of developing severe nephropathy (p=0.016, OR=2.35, 95% CI: 1.09-5.07). Additionally, a significant increase of the TT genotype was observed in patients with persistent renal damage when compared with those patients without this complication (25% versus 8.6%, respectively; p=0.0035, OR=4.90, 95% CI: 1.26- 18.51). Moreover, renal sequelae were more common in patients carrying the mutant T allele (p=0.0076, OR=2.20, 95% CI: 1.17-4.14).
Our results support that the IL1ß rs16944 polymorphism may be a potential marker of severe renal manifestations and renal sequelae in HSP.
To investigate the possible role of FCGR2A 519A>G and FCGR3A 559A>C functional polymorphisms in the genetic predisposition to susceptibility to systemic sclerosis (SSc) or clinical phenotype.
A total ...of 1566 patients with SSc and 2271 geographically matched controls were included in our study. We analyzed the genotype and allele frequencies of the FCGR2A 519A>G and FCGR3A 559A>C functional variants in 6 independent European cohorts of white patients with SSc, and white controls. The cohorts comprised 165 Dutch patients with SSc and 1326 controls, 236 Spanish patients with SSc and 257 controls, 267 German patients with SSc and 270 controls, 202 Swedish patients with SSc and 261 controls, 416 Italian patients with SSc and 157 controls, and additionally 280 English patients with SSc. Genotyping was performed using Taqman 5' allelic discrimination assay. The study reached a 99% power to detect the effect of a polymorphism at an OR of 1.3.
Neither FCGR2A 519A>G nor FCGR3A 559A>C was significantly associated with susceptibility to SSc. We did not find an association with specific disease phenotypes, limited or diffuse cutaneous involvement, autoantibody profiles, or pulmonary involvement.
Our study strongly suggests the lack of a role for the FCGR2A 519A>G and FCGR3A 559A>C polymorphisms in SSc susceptibility or clinical phenotype in 6 independent European cohorts.
Granulomatosis with polyangiitis (GPA), previously called Wegener's granulomatosis, is a small vessel vasculitis often associated with clinical head and neck manifestations, which are sometimes the ...presenting symptoms of the disease. The aim of our study was to identify ear, nose and throat (ENT) manifestations associated with GPA and propose a work-up for the management and diagnosis for patients with suspicion or confirmed diagnosis of this ENT pathology.
Retrospective review of the medical records of all patients diagnosed with GPA who were seen at the Department of Otolaryngology from a tertiary public hospital in Cantabria (Spain) over a 20-year period. Clinical and laboratory data, in particular those concerning ENT manifestations, were retrieved from the patients' medical records.
Twenty-five patients (age range: 30-81 years) were included in the study. Of these, 88% had ENT manifestations at some point in the course of the disease. In 28% of the cases, ENT features were the presenting manifestations. The most frequent ENT manifestations were sinonasal symptoms (52%), followed by otological manifestations (32%).
Patients with GPA often present with clinical ENT manifestations. Consequently, routine ENT physical examination must be performed in patients with suspected vasculitis to establish a diagnosis of GPA or to better determine the degree of organ system involvement in patients with GPA.
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