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.
Abstract
BAFF, APRIL and BAFF-R are key proteins involved in the development of B-lymphocytes and autoimmunity. Additionally,
BAFF, APRIL
and
BAFFR
polymorphisms were associated with immune-mediated ...conditions, being
BAFF
GCTGT>A a shared insertion-deletion genetic variant for several autoimmune diseases. Accordingly, we assessed whether
BAFF, APRIL
and
BAFFR
represent novel genetic risk factors for Immunoglobulin-A vasculitis (IgAV), a predominantly B-lymphocyte inflammatory condition.
BAFF
rs374039502, which colocalizes with
BAFF
GCTGT>A, and two tag variants within
APRIL
(rs11552708 and rs6608) and
BAFFR
(rs7290134 and rs77874543) were genotyped in 386 Caucasian IgAV patients and 806 matched healthy controls. No genotypes or alleles differences were observed between IgAV patients and controls when
BAFF, APRIL
and
BAFFR
variants were analysed independently. Likewise, no statistically significant differences were found in the genotype and allele frequencies of
BAFF, APRIL
or
BAFFR
when IgAV patients were stratified according to the age at disease onset or to the presence/absence of gastrointestinal (GI) or renal manifestations. Similar results were disclosed when
APRIL
and
BAFFR
haplotypes were compared between IgAV patients and controls and between IgAV patients stratified according to the clinical characteristics mentioned above. Our results suggest that
BAFF, APRIL
and
BAFFR
do not contribute to the genetic network underlying IgAV.
To assess whether polymorphism of the macrophage migration inhibitory factor (MIF) gene at the position -173 is implicated in the development of sarcoidosis.
Twenty-eight patients with biopsy proven ...erythema nodosum (EN) associated with sarcoidosis, 70 patients with biopsy proven EN related to other etiologies, and 122 healthy matched controls from the Lugo region of Northwest Spain were studied. Patients and controls were genotyped for a single nucleotide polymorphism in the 5'-flanking region at position -173 of the MIF gene, using SNapshot ddNTP primer extension, followed by capillary electrophoresis (ABI 3100).
A significantly increased frequency of the C mutant allele was observed in patients with EN secondary to sarcoidosis compared to controls (p = 0.0016; p(corr) = 0.0032; OR 2.78, 95% CI 1.45, 5.35) and also compared to patients with EN unrelated to sarcoidosis (p = 0.0004; p(corr) = 0.0008; OR 3.72, 95% CI 1.75, 7.87). Patients with EN carrying an MIF 173 C allele were found to have an increased risk of sarcoidosis (57% in EN secondary to sarcoidosis vs 24% in patients with EN related to other etiologies; p = 0.002; p(corr) = 0.004; OR 4.16, 95% CI 1.64, 10.50).
This is the first attempt to assess the influence of MIF genetic polymorphism at position -173 in the development of sarcoidosis. The MIF 173 C allele is associated with a significantly increased risk of developing sarcoidosis in patients with EN.
Objective We assessed the contribution of clinical features, routine laboratory markers of inflammation, HLA-DRB1 alleles, and methotrexate therapy to cancer incidence and mortality in a cohort of ...rheumatoid arthritis (RA) patients prospectively followed at the single referral center for an area of Northwestern Spain. Methods Patients fulfilling the 1987 American College of Rheumatology classification criteria for RA seen at the rheumatology outpatient clinic of Hospital Xeral Calde, Lugo between March and September 1996 were included. HLA-DRB1 phenotype, epidemiological and clinical data from the time of RA diagnosis were assessed at that time. Afterward, patients were prospectively followed and clinical records were examined until the patient’s death or September 1, 2005. Presence of histologically confirmed diagnosis of cancer was assessed over the extended follow-up in all cases. Results One hundred eighty-two consecutive patients were assessed. Compared with the general Spanish population, the age- and gender-standardized mortality ratio for cancer was 1.01 (95% confidence interval: 0.49 to 1.75). Cancer mortality adjusted by age and sex was associated with chronic inflammation determined by C-reactive protein (CRP) (hazard ratio, HR, = 1.15; P < 0.001), and erythrocyte sedimentation rate (ESR) (HR = 1.05; P = 0.006). Increased risk of cancer was also associated with CRP (HR = 1.13; P = 0.001), ESR (HR = 1.04; P = 0.02), and the HLA-DRB1*0404 allele (HR = 3.24; P = 0.05). Conclusion This study does not support an increased mortality due to cancer in RA patients from Northwestern Spain. However, the present data indicate that high-grade inflammation contributes to both the risk and the mortality of cancer in RA.
Mucin 1/Krebs von den Lungen-6 (KL-6) is proposed as a serum biomarker of several interstitial lung diseases (ILDs), including connective tissue disorders associated with ILD. However, it has not ...been studied in a large cohort of Caucasian antisynthetase syndrome (ASSD) patients. Consequently, we assessed the role of MUC1 rs4072037 and serum KL-6 levels as a potential biomarker of ASSD susceptibility and for the differential diagnosis between patients with ILD associated with ASSD (ASSD-ILD +) and idiopathic pulmonary fibrosis (IPF). 168 ASSD patients (149 ASSD-ILD +), 174 IPF patients and 523 healthy controls were genotyped for MUC1 rs4072037 T > C. Serum KL-6 levels were determined in a subgroup of individuals. A significant increase of MUC1 rs4072037 CC genotype and C allele frequencies was observed in ASSD patients compared to healthy controls. Likewise, MUC1 rs4072037 TC and CC genotypes and C allele frequencies were significantly different between ASSD-ILD+ and IPF patients. Additionally, serum KL-6 levels were significantly higher in ASSD patients compared to healthy controls. Nevertheless, no differences in serum KL-6 levels were found between ASSD-ILD+ and IPF patients. Our results suggest that the presence of MUC1 rs4072037 C allele increases the risk of ASSD and it could be a useful genetic biomarker for the differential diagnosis between ASSD-ILD+ and IPF patients.
To determine whether disease activity, systemic inflammation and metabolic syndrome are potential determinants of circulating apelin in ankylosing spondylitis (AS) patients undergoing TNF-α ...antagonist-infliximab therapy.
We investigated apelin serum concentrations in a series of 30 non-diabetic AS patients without history of cardiovascular (CV) events that were treated with the TNF-α antagonist infliximab, immediately prior to an infliximab infusion. Correlations of apelin serum levels with disease activity, systemic inflammation and metabolic syndrome were assessed. Also, potential changes in apelin concentration following an infusion of the anti-TNF-α monoclonal antibody-infliximab were analysed.
No significant correlation between apelin concentration and demographic features, inflammation, adiposity and metabolic syndrome features was seen. Neither differences were seen in basal apelin in different categorical variables associated to AS. Following infliximab infusion, a reduction of apelin serum levels was observed. In this regard, the median (interquartile range) values of apelin decreased from 0.99 (0.74-1.25) ng/ml immediately prior to infliximab infusion to 0.92 (0.72-1.39) ng/ml at the end of the infusion (time 120 minutes). However, the reduction in apelin serum levels following administration of the drug did not achieve statistical significance.
The present study shows that in non-diabetic patients with AS on treatment with infliximab apelin serum levels do not correlate with disease activity or metabolic syndrome. A single infusion of infliximab does not yield a significant change of apelin serum levels in AS patients.
To investigate the potential implication of several polymorphisms of the C-reactive protein (CRP) gene in the predisposition to or clinical expression of giant cell arteritis (GCA).
A total of 125 ...patients diagnosed with biopsy-proven GCA and 234 ethnically matched controls from the Lugo region of Northwestern Spain were included in our study. Four functional gene polymorphisms for CRP rs1417938, rs1800947, rs1205, and rs3093059 variants were assessed using a polymerase chain reaction system with predeveloped TaqMan allelic discrimination assay.
Although we observed a significant increase in the frequency of heterozygotes for rs1417938 A/T odds ratio (OR) = 1.70; 95% confidence interval (CI) 1.04-2.80; p = 0.03 and rs1205 C/T (OR 1.73; 95% CI 1.07-2.78; p = 0.02) in patients with GCA, no statistically significant differences in the allelic frequencies of these 2 polymorphisms were found between patients with GCA and controls. A marginal significant increase in the frequency of rs3093059 allele T in patients with GCA compared to controls was observed (OR 1.81; 95% CI 0.97-3.39; p = 0.04). However, the increased frequency of patients with GCA homozygous for rs3093059 T/T in patients with GCA compared to controls was out of the range of significance (OR 1.77; 95% CI 0.92-3.40; p = 0.07). No significant differences were found when we stratified patients with GCA according to the presence of polymyalgia rheumatica or severe ischemic complications of the disease.
The functional CRP gene polymorphisms assessed in our study do not seem to play a major role in the pathogenesis of GCA in individuals from Northwestern Spain.
To assess the contribution of 2 polymorphisms within the inducible nitric oxide (NOS2A) promoter region to the susceptibility to Henoch-Schönlein purpura (HSP), and to determine if implications exist ...with severe systemic complications of HSP, in particular with severe renal involvement and permanent renal dysfunction (renal sequelae).
Fifty-eight patients from Northwest Spain with primary cutaneous vasculitis classified as HSP were studied. All patients were required to have had at least 2 years' followup. Patients and ethnically matched controls (n=251) were genotyped by PCR based techniques for a multiallelic (CCTTT)n and for the biallelic TAAA repeat in the promoter region of the NOS2A gene.
HSP patients exhibited a significantly increased frequency of the NOS2A short (8-11) CCTTTn alleles (OR 1.64, 95% CI 1.09-2.47, p=0.017) and genotypes (OR 3.59, 95% CI 1.79-7.20, p=0.0002) compared to controls, particularly when patients with nephritis were compared with controls. However, when the NOS2A TAAA repeat polymorphism was assessed, no differences were found.
Significant differences in the NOS2A promoter polymorphism allele and genotype frequency between HSP patients and controls suggest a potential role for this gene in the susceptibility to HSP and in the development of nephritis.
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