Is there an association between alopecia areata and systemic lupus erythematosus? A population-based study

Immunologic Research - The coexistence of alopecia areata (AA) and systemic lupus erythematosus (SLE) has been described, but the association between these conditions is yet to be firmly...     

The risk of systemic lupus erythematosus associated with Epstein–Barr virus infection: a systematic review and meta-analysis

Previous systematic reviews have found a higher sero-prevalence of EBV antibodies in SLE patients compared with controls. Because many studies have been published, there is a need to apply more precise systematic review methods. We examined the association between EBV and SLE patients by conducting a systematic review and meta-analysis of case–control studies that examined the prevalence of EBV antibodies and the DNA-positive rate. We searched the MEDLINE and EMBASE databases from 1966 to 2018 with no language restrictions. The Mantel–Haenszel odds ratios (OR) for EBV antibody sero-positivity were calculated, and meta-analyses were conducted. Quality assessment was performed using a modified version of the Newcastle–Ottawa scale, and 33 studies were included. Most studies found a higher sero-prevalence of VCA IgG and EA IgG in SLE patients compared with controls. Meta-analysis demonstrated a significantly higher OR for sero-positivity to VCA IgG and EA IgG for SLE cases (2.06 [95% confidence interval (CI) 1.30–3.26, p = 0.002] and 7.70, [95% CI 4.64–12.76, p < 0.001], respectively). The overall OR for the DNA-positive rate for SLE patients compared with controls was 3.86 (95% CI 1.52–9.83, p = 0.005). Other antibodies, i.e., VCA IgA/IgM, EBNA IgA, and EA IgA/IgM, also demonstrated a significant difference between SLE patients and controls. These findings support previous systematic reviews; however, publication bias cannot be excluded. The methodological conduct of studies could be improved, particularly when selecting controls and analyses of laboratory conduct.

     

Antral atrophy,intestinal metaplasia,and preneoplastic markers in Mexican children with Helicobacter pylori–positive and Helicobacter pylori–negative gastritis

Chronic inflammation and infection are major risk factors for gastric carcinogenesis in adults. As chronic gastritis is common in Mexican children, diagnosis of Helicobacter pylori and other causes of gastritis are critical for the identification of children who would benefit from closer surveillance. Antral biopsies from 82 Mexican children (mean age, 8.3 ± 4.8 years) with chronic gastritis (36 H pylori+, 46 H pylori−) were examined for gastritis activity, atrophy, intestinal metaplasia (IM), and immunohistochemical expression of gastric carcinogenesis biomarkers caudal type homeobox 2 (CDX2), ephrin type-B receptor 4 (EphB4), matrix metalloproteinase 3 (MMP3), macrophage migration inhibitory factor (MIF), p53, β-catenin, and E-cadherin. Atrophy was diagnosed in 7 (9%) of 82, and IM, in 5 (6%) of 82 by routine histology, whereas 6 additional children (7%) (3 H pylori+) exhibited aberrant CDX2 expression without IM. Significant positive correlations were seen between EphB4, MMP3, and MIF (P < .0001). Atrophy and follicular pathology were more frequent in H pylori+ biopsies (P < .0001), whereas IM and CDX2 expression showed no significant correlation with H pylori status. Antral biopsies demonstrating atrophy, IM, and/or aberrant CDX2 expression were seen in 21.95% (18/82) of the children, potentially identifying those who would benefit from closer surveillance and preventive dietary strategies. Biomarkers CDX2, EphB4, MMP3, and MIF may be useful in the workup of pediatric gastritis.     

Mannose-binding lectin gene: polymorphisms in Japanese patients with systemic lupus erythematosus, rheumatoid arthritis and Sjögren's syndrome

Mannose-binding lectin (MBL) is a key element of the innate immunity, with a structure similar to complement C1q. Serum MBL levels are greatly affected by the polymorphisms of the MBL gene. In particular, codon 54 mutation of the MBL gene results in a significant reduction of serum MBL. To determine whether polymorphism of the MBL gene is associated with occurrence of systemic lupus erythematosus (SLE), rheumatoid arthritis and Sj?gren's syndrome in the Japanese population, we analyzed the MBL gene polymophisms of these patients and controls, by polymerase chain reaction-restriction fragment length polymorphism methods. We found that patients studied had a significantly higher frequency of having homozygous codon 54 mutation compared to controls. In particular, patients with SLE or Sj?gren's syndrome showed higher probabilities of being homozygous for this mutation. Among subjects with the same genotype, SLE patients tended to have higher serum MBL concentration than controls. Analysis of the promotor region suggested that SLE patients heterozygous for the codon 54 mutation have a higher probability of having a low producing haplotype for the gene without the codon 54 mutation. We conclude that persons homozygous for codon 54 mutation of the MBL gene may be prone to occurrence of autoimmune disorders including SLE, in the Japanese. MBL may have protective effects on occurrence and progression of SLE.     

Is there an association between dipeptidyl peptidase-4 inhibitors and autoimmune disease? A population-based study

The association of dipeptidyl peptidase-4 inhibitors (DPP4is) with autoimmune diseases is controversial. While these agents were proposed as a novel therapeutic approach for several inflammatory diseases by blocking T cell proliferation and cytokine production, they were found to trigger inflammatroy bowel disease, inflammatory arthritis and bullous pemphigoid. Our objective is to examine the association between DPP4i and autoimmune diseases. This study was conducted as a cross-sectional study utilizing the database of Clalit Health Services. The prevalence of 15 autoimmune-/immune-mediated diseases was compared between patients on DPP4i treatment and age-, sex-, and ethnicity-matched controls. Univariate analysis was performed using chi-square and the Student t test and multivariate analysis was performed using a logistic regression model. The study included 283 patients treated with DPP4i agents and 5660 age-, sex-, and ethnicity-matched diabetic control subjects. The prevalence of Crohn’s disease (1.1 vs. 0.3%; odds ratios (OR), 3.56; 95% CI, 1.04–12.21, P?=?0.031), psoriasis (2.5 vs. 1.2%; OR, 2.12; 95% CI, 0.99–4.66; P?=?0.050), and Hashimoto’s thyroiditis (16.6 vs. 12.6%; OR, 1.38; 95% CI, 1.00–1.91; P?=?0.049) was significantly higher in patients on DPP4i treatment than in controls. The prevalence of the remaining autoimmune diseases did not differ significantly between DPP4i-treated patients and their matched control subjects. In conclusion, this population-based study demonstrates an association of DPP4i intake with three autoimmune and inflammatory diseases noted to be part of a distinct autoimmune cluster that includes multiple sclerosis, psoriasis, thyroiditis, bullous pemphigoid, and inflammatory bowel disease. Experimental studies are required to define the role of DPP4i in this autoimmune cluster.     

Are anti-nucleosome antibodies a better diagnostic marker than anti-dsDNA antibodies for systemic lupus erythematosus? A systematic review and a study of metanalysis

BackgroundMethods to detect anti-nucleosome antibodies (ANuA) have been available for more than 10 years and the test has demonstrated its good sensitivity and high specificity in diagnosing systemic lupus erythematosus (SLE). Despite these data produced through clinical and laboratory research, the test is little used.ObjectiveTo verify the diagnostic performance of methods for measuring ANuA and to compare them with those for anti-dsDNA antibodies.Data sourcesA systematic review of English and non-English articles using MEDLINE and EMBASE with the search terms “nucleosome”, “chromatin”, “anti-nucleosome antibodies” and “anti-chromatin antibodies”. Additional studies were identified checking reference lists in the selected articles.Study selectionWe selected studies reporting on anti-nucleosome tests performed by quantitative immunoassays, on patients with SLE as the index disease (sensitivity) and a control group (specificity).A total of 610 titles were initially identified with the search strategy described. 548 publications were subsequently excluded based on abstract and title. Full-text review was undertaken as the next step on 62 publications providing data on anti-nucleosome testing; 25 articles were then excluded because they did not include either SLE patients or a control group, and 37 articles were selected for the metanalysis. Finally, a sub-metanalysis study was conducted on the 26 articles providing data on both ANuA and anti-dsDNA antibody assays in the same series of patients.Data extractionExtraction of data from selected articles was performed by two authors independently, using predefined criteria: the number of patients with SLE as the index case, and the number of healthy or diseased controls; specification of the analytical method used to detect anti-nucleosome and anti-dsDNA antibodies; the cut-off used in the study; and the sensitivity and specificity of the assay. Demographic and clinical data on the population investigated (adults or children; lupus patients with or without nephritis; patients with active or inactive disease) were also recorded and analyzed in a separate evaluation.ResultsThe systematic review and metanalysis showed that the overall sensitivity of the ANuA assay is 61% (confidence interval-CI, 60–62) and the specificity 94% (CI, 94–95). The overall positive likelihood ratio is 13.81 (CI, 9.05–21.09) and the negative likelihood ratio 0.38 (CI, 0.33–0.44). The odds ratio for having SLE in ANuA-positive patients is 40.7.The comparative analysis on anti-dsDNA antibodies conducted on the 26 studies which provided data for both antibodies showed that ANuA have greater diagnostic sensitivity (59.9% vs 52.4%) and a specificity rating only slightly higher (94.9% vs 94.2%). The probability that a subject with positive ANuA have SLE is 41 times greater than a subject with negative ANuA, while for anti-dsDNA the probability is 28 times greater.These figures are even more impressive in children, in whom ANuA have an odds ratio for the diagnosis of SLE of 146, compared to 51 for anti-dsDNA antibodies.In selected studies, ANuA (p < 0.0001) but not anti-dsDNA antibodies (p = 0.256) were significantly associated with disease activity measured by the international score systems. However, neither antibody appears to correlate with kidney involvement.ConclusionsData from the metanalysis have shown that ANuA have equal specificity but higher sensitivity and prognostic value than anti-dsDNA antibodies in the diagnosis of SLE. Despite a certain heterogeneity among the various studies, the use of ANuA appears more efficacious than anti-dsDNA.     

Interleukin-6-174G > C (rs1800795) polymorphism distribution and its association with rheumatoid arthritis: A case-control study and meta-analysis

The association of interleukin-6 (IL-6)-174G?>?C (rs1800795) single nucleotide polymorphism (SNP) with the risk of acquiring rheumatoid arthritis (RA) is a relevant issue because of conflicting and consensus lacking reports published in literature. We investigated IL-6-174G?>?C promoter polymorphism in 34 RA patients, attending a tertiary care hospital in north India. We also performed a meta-analysis, of the previously published studies reporting this genetic relationship, in overall population, and independently in Asian and Caucasian ethnicities to further elucidate this association. A total of 13 studies, including the current one, involving 3291 RA cases and 3812 controls were analyzed. Out of the 13 studies, 6 were from Asian, 6 from Caucasian and 1 from a mixed population. Our case-control study showed significant association of IL-6-174G?>?C SNP with increased RA risk: allelic (OR?=?3.750, 95% CI?=?1.800–7.813, p?<?0.001); dominant (OR?=?2.800, 95% CI?=?1.167–6.721, p?=?0.021); and recessive (OR?=?36.72, 95% CI?=?2.004–672.7, p?=?0.015). The meta-analysis revealed the increased RA risk associated with IL-6-174G?>?C SNP in overall population: allelic (OR?=?1.650, 95% CI?=?1.169–2.329, p?=?0.004); homozygous (OR?=?1.380, 95% CI?=?0.906–2.101, p?=?0.133); heterozygous (OR?=?1.559, 95% CI?=?1.001–2.428, p?=?0.049); dominant (OR?=?1.663, 95% CI?=?1.078–2.567, p?=?0.022); and recessive (OR?=?1.366, 95% CI?=?0.964–1.935, p?=?0.079). Subgroup analysis also showed this polymorphism to be associated with increased RA risk in Asian population: allelic (OR?=?3.724, 95% CI?=?1.361–10.190, p?=?0.010); dominant (OR?=?3.823, 95% CI?=?1.320–11.074, p?=?0.013); and recessive (OR?=?4.357, 95% CI?=?1.634–11.623, p?=?0.003), but not in Caucasian population. This meta-analysis shows that IL-6-174G?>?C SNP is significantly associated with increased RA risk in overall, and specifically in Asian population.     

Could TH1 and TH2 diseases coexist? Evaluation of asthma incidence in children with coeliac disease, type 1 diabetes, or rheumatoid arthritis: a register study.

BACKGROUND: Asthma is generally regarded as a disease with strong T(H)2-type cytokine expression, whereas in autoimmune disorders, such as coeliac disease (CD), insulin-dependent diabetes mellitus (IDDM), and rheumatoid arthritis (RA), T(H)1-type expression is seen. According to the cross-regulatory properties of T(H)1 and T(H)2 cells, one would assume that these diseases exist in different patient populations. OBJECTIVE: We sought to test the hypothesis that asthma could exist in children with T(H)1-type diseases, such as CD, IDDM, and RA. METHODS: Comparison was made of the cumulative incidence of asthma in children with CD, IDDM, or RA by linking Finnish Medical Birth Register data on the whole 1987 birth cohort (n = 60,254 births) with the data of several national health registers to obtain information on the incidences of these diseases during the first 7 years of life. RESULTS: The cumulative incidence of asthma in children with CD (24.6%) or RA (10.0%) was significantly higher than in children without CD (3.4%) or RA (3.4%; P < .001 and P = .016, respectively). Asthma tended to be more common in children with IDDM than in children without IDDM. CONCLUSION: These data indicate that the T(H)1 and T(H)2 diseases can coexist, indicating a common environmental denominator behind the disease processes.     

The <Emphasis Type="Italic">PTPN22</Emphasis> R263Q polymorphism confers protection against systemic lupus erythematosus and rheumatoid arthritis,while <Emphasis Type="Italic">PTPN22</Emphasis> R620W confers susceptibility to Graves’ disease in a Mexican population

Objective

The functional PTPN22 R620W polymorphism (rs2476601) is clearly associated with susceptibility to several autoimmune diseases (ADs). However, the PTPN22 R263Q polymorphism (rs33996649) has been scarcely explored in different ADs. Here we aimed to examine the associations of the PTPN22 R620W and R263Q polymorphisms with susceptibility to or protection against rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Graves’ disease (GD) among Mexican patients.

Methods

We conducted a case–control study including 876 patients (405 with SLE, 388 with RA, and 83 with GD) and 336 healthy control individuals. PTPN22 genotypes were determined using the TaqMan 5′ allele discrimination assay.

Results

PTPN22 R620W was associated with GD susceptibility (OR 4.3, p = 0.004), but was not associated with SLE (OR 1.8, p = 0.19). We previously demonstrated that this polymorphism is associated with RA susceptibility (OR 4.17, p = 0.00036). Moreover, PTPN22 R263Q was associated with protection against SLE (OR 0.09, p = 004) and RA (OR 0.28, p = 0.045), but was not associated with GD.

Conclusions

Our data provide the first demonstration that PTPN22 R620W confers GD susceptibility among Latin-American patients. Moreover, this is the second report documenting the association of PTPN22 R263Q with protection against SLE and RA.

     

A systematic review of existing peripheral biomarkers of cognitive aging: Is there enough evidence for biomarker proxies in behavioral modification interventions?: An initiative in association with the nutrition,exercise and lifestyle team of the Canadian Consortium on Neurodegeneration in Aging

Peripheral biomarkers have shown significant value in predicting brain health and may serve as a useful proxy measurement in the assessment of evidence-based lifestyle behavior modification programs, including physical activity and nutrition programs, that aim to maintain cognitive function in late life. The aim of this systematic review was to elucidate which peripheral biomarkers are robustly associated with cognitive function among relatively healthy non-demented older adults. Following the standards for systematic reviews (PICO, PRIMSA), and employing MEDLINE and Scopus search engines, 222 articles were included in the review. Based on the review of biomarker proxies of cognitive health, it is recommended that a comprehensive biomarker panel, or biomarker signature, be developed as a clinical end point for behavior modification trials aimed at enhancing cognitive function in late life. The biomarker signature should take a multisystemic approach, including lipid, immune/inflammatory, and metabolic biomarkers in the biological signature index of cognitive health.