Prevalence of anal high-risk human papillomavirus (HR-HPV) types in people living with HIV and a history of cancer.

This study aimed to describe the prevalence of high-risk human papillomavirus (HR-HPV) types in the anal canal in a cohort of people living with HIV (PLWHIV) with a history of malignancy. SETTING: Referral tertiary care hospital for adult patients with cancer. METHODS: We reviewed data of patients from the AIDS Cancer Clinic on antiretroviral therapy in chronic control who were consecutively referred for high-resolution anoscopy (HRA), where they underwent anal evaluation, collection of specimens for anal cytology and anal human papillomavirus (HPV) followed by HRA with directed biopsy if needed. RESULTS: A total of 155 patients were included; 149 (96.1%) were men, all of them men who have sex with men (MSM); the median age was 39 (IQR 32-47) years; 105 (67.7%) with Kaposi sarcoma, 40 (25.8%) with non-Hodgkin lymphoma and 10 (6.4%) with other neoplasms; only 7 (4.5%) had active cancer. The prevalence of HR-HPV infection was 89% (n=138) (95% CI 83-93) with at least one HR-HPV infection, and 62% (96) had coinfection with at least two types; the median HR-HPV types of coinfection were 3 (IQR 2-4). The number of patients infected with HPV 16 was 64 (41.3%, 95% CI 33.8-49.3), HPV 18 was 74 (47.7%, 95% CI 39.9-55.7) and with both 35 (22.6%). Some 59 patients (38%) had high-grade squamous intraepithelial lesions (HSIL) and 49 (31.6%) had low-grade squamous intraepithelial lesions (LSIL). The prevalence of HR-HPV and HSIL among patients aged ≤35 and >35 years was the same. CONCLUSIONS: In this cohort of PLWHIV with a history of malignancy we found a high prevalence of HR-HPV 16 and 18 and anal HSIL, even in persons aged ≤35 years. These data highlight the importance of anal cancer screening in PLWHIV and history of malignancy.

The rs1477196 SNP of the FTO Gene is Associated with Primary Knee Osteoarthritis in a Female Population from Northern Mexico.

Background: Osteoarthritis is a frequent rheumatic disease. Some single-nucleotide polymorphisms of the gene associated with fat mass and obesity are associated with increased body mass index and knee osteoarthritis. Objective: The objective of this study was to analyze the association of single nucleotide polymorphism rs1477196 of the fat mass and obesity gene with primary knee osteoarthritis. Methods: This observational and cross-sectional study included 347 Mexican participants. We performed the genotypification analysis with TaqMan® probe C_2031262_10 for rs1477196 (Thermo Fisher Scientific). Multivariate analysis included covariables such as age, type 2 diabetes, obesity, and postmenopause. Results: Type 2 diabetes, obesity, and postmenopause were associated with primary knee osteoarthritis in female participants. We did not find an association between rs1477196 and obesity. In the codominant and dominant genetic models, rs1477196 was significantly associated with primary knee osteoarthritis only in the female group, including in the model adjusted by other covariables (odds ratio = 2.517; 1.035-6.123; p = 0.042 and odds ratio = 2.387; 1.054-5.407; p = 0.037, respectively). The interaction between rs1477196 and obesity was significantly associated with primary knee osteoarthritis in female participants (p = 0.039 and p = 0.043). Conclusions: Our findings suggest that the rs1477196 variant of the fat and obesity mass gene may be associated with the risk of primary knee osteoarthritis in women.

In CKD, the Kidney Failure Risk Equation predicted 2-y risk for ESKD better than eGFR alone.

SOURCE CITATION: Bundy JD, Mills KT, Anderson AH, et al. Prediction of end-stage kidney disease using estimated glomerular filtration rate with and without race: a prospective cohort study. Ann Intern Med. 2022;175:305-13. 35007146.

A Spatial-Spectral Classification Method Based on Deep Learning for Controlling Pelagic Fish Landings in Chile.

Fishing has provided mankind with a protein-rich source of food and labor, allowing for the development of an important industry, which has led to the overexploitation of most targeted fish species. The sustainable management of these natural resources requires effective control of fish landings and, therefore, an accurate calculation of fishing quotas. This work proposes a deep learning-based spatial-spectral method to classify five pelagic species of interest for the Chilean fishing industry, including the targeted Engraulis ringens, Merluccius gayi, and Strangomera bentincki and non-targeted Normanichthtys crockeri and Stromateus stellatus fish species. This proof-of-concept method is composed of two channels of a convolutional neural network (CNN) architecture that processes the Red-Green-Blue (RGB) images and the visible and near-infrared (VIS-NIR) reflectance spectra of each species. The classification results of the CNN model achieved over 94% in all performance metrics, outperforming other state-of-the-art techniques. These results support the potential use of the proposed method to automatically monitor fish landings and, therefore, ensure compliance with the established fishing quotas.

Predictive value of circulating NMR metabolic biomarkers for type 2 diabetes risk in the UK Biobank study.

BACKGROUND: Effective targeted prevention of type 2 diabetes (T2D) depends on accurate prediction of disease risk. We assessed the role of metabolomic profiling in improving T2D risk prediction beyond conventional risk factors. METHODS: Nuclear magnetic resonance (NMR) metabolomic profiling was undertaken on baseline plasma samples in 65,684 UK Biobank participants without diabetes and not taking lipid-lowering medication. Among a subset of 50,519 participants with data available on all relevant co-variates (sociodemographic characteristics, parental history of diabetes, lifestyle-including dietary-factors, anthropometric measures and fasting time), Cox regression yielded adjusted hazard ratios for the associations of 143 individual metabolic biomarkers (including lipids, lipoproteins, fatty acids, amino acids, ketone bodies and other low molecular weight metabolic biomarkers) and 11 metabolic biomarker principal components (PCs) (accounting for 90% of the total variance in individual biomarkers) with incident T2D. These 11 PCs were added to established models for T2D risk prediction among the full study population, and measures of risk discrimination (c-statistic) and reclassification (continuous net reclassification improvement [NRI], integrated discrimination index [IDI]) were assessed. RESULTS: During median 11.9 (IQR 11.1-12.6) years' follow-up, after accounting for multiple testing, 90 metabolic biomarkers showed independent associations with T2D risk among 50,519 participants (1211 incident T2D cases) and 76 showed associations after additional adjustment for HbA1c (false discovery rate controlled p < 0.01). Overall, 8 metabolic biomarker PCs were independently associated with T2D. Among the full study population of 65,684 participants, of whom 1719 developed T2D, addition of PCs to an established risk prediction model, including age, sex, parental history of diabetes, body mass index and HbA1c, improved T2D risk prediction as assessed by the c-statistic (increased from 0.802 [95% CI 0.791-0.812] to 0.830 [0.822-0.841]), continuous NRI (0.44 [0.38-0.49]) and relative (15.0% [10.5-20.4%]) and absolute (1.5 [1.0-1.9]) IDI. More modest improvements were observed when metabolic biomarker PCs were added to a more comprehensive established T2D risk prediction model additionally including waist circumference, blood pressure and plasma lipid concentrations (c-statistic, 0.829 [0.819-0.838] to 0.837 [0.831-0.848]; continuous NRI, 0.22 [0.17-0.28]; relative IDI, 6.3% [4.1-9.8%]; absolute IDI, 0.7 [0.4-1.1]). CONCLUSIONS: When added to conventional risk factors, circulating NMR-based metabolic biomarkers modestly enhanced T2D risk prediction.

Role of cathepsin B of Naegleria fowleri during primary amebic meningoencephalitis.

Naegleria fowleri causes primary amoebic meningoencephalitis in humans and experimental animals. It has been suggested that cysteine proteases of parasites play key roles in metabolism, nutrient uptake, host tissue invasion, and immune evasion. The aim of this work was to evaluate the presence, expression, and role of cathepsin B from N. fowleri in vitro and during PAM. Rabbit-specific polyclonal antibodies against cathepsin B were obtained from rabbit immunization with a synthetic peptide obtained by bioinformatic design. In addition, a probe was designed from mRNA for N. fowleri cathepsin B. Both protein and messenger were detected in fixed trophozoites, trophozoites interacted with polymorphonuclear and histological sections of infected mice. The main cathepsin B distribution was observed in cytoplasm or membrane mainly pseudopods and food-cups while messenger was in nucleus and cytoplasm. Surprisingly, both the messenger and enzyme were observed in extracellular medium. To determine cathepsin B release, we used trophozoites supernatant recovered from nasal passages or brain of infected mice. We observed the highest release in supernatant from recovered brain amoebae, and when we analyzed molecular weight of secreted proteins by immunoblot, we found 30 and 37 kDa bands which were highly immunogenic. Finally, role of cathepsin B during N. fowleri infection was determined; we preincubated trophozoites with E-64, pHMB or antibodies with which we obtained 60%, 100%, and 60% of survival, respectively, in infected mice. These results suggest that cathepsin B plays a role during pathogenesis caused by N. fowleri mainly in adhesion and contributes to nervous tissue damage.

Chemokine tear levels in primary Sjögren's syndrome and their relationship with symptoms.

PURPOSE: To evaluate CCL2, CXCL8, and CXCL10 in the tears of patients with Primary Sjögren's syndrome (PSS) and correlate them with ocular symptoms/discomfort and objective ocular tests. METHODS: We studied 21 patients with PSS. A single ophthalmologist, expert in dry eye, examined the patients and assessed tear film breakup time, Schirmer I test, tear meniscus height, Van Bijsterveld staining score and SICCA Ocular Staining Score. We also assessed the ESSPRI and ocular dryness VAS and the Ocular Surface Disease Index (OSDI), a 12-item scale assessing symptoms associated with dry eye disease and their impact on vision (ocular symptoms/discomfort). Tear samples collected with sterile tear flow strips were frozen at -86 °C until testing. After thawing, tears were extracted from the strips. We tested CCL2, CXCL8, and CXCL10 by luminometry. We also included 21 healthy control subjects without a dry eye. RESULTS: CXCL8 levels were similar in patients and controls. PSS patients had lower levels of CXCL10 (472.8 vs. 1652 pg/µL, p = 0.009) and CCL2 (1.08 vs. 9 pg/µL, p = 0.0001) than controls. Patients with worse ocular sicca symptoms/discomfort had the lowest CXCL10 levels (239.3 vs. 646.2 pg/µL, p = 0.02). CCL2 correlated with tear meniscus height (τ = 0.37, p = 0.02) and with OSS (τ = -0.3, p = 0.05). CONCLUSIONS: We found lower levels of CXCL10 and CCL2 in the tears of patients with PSS, associating the former with worse ocular symptoms and the latter with positive ocular target tests.

Decreased kidney function and agricultural work: a cross-sectional study in middle-aged adults from Tierra Blanca, Mexico.

BACKGROUND: We aimed to determine the prevalence of decreased kidney function in a potential chronic kidney disease (KD) of unknown aetiology hotspot in Mexico, assess its distribution across occupations and examine the associated risk factors. METHODS: A cross-sectional study collected sociodemographic, occupational, medical and biometric data from 616 men and women aged 20-60 years who were residents of three communities within the Tierra Blanca region in Mexico. Kidney function was assessed by standardized serum creatinine and estimated glomerular filtration rate (eGFR) and semi-quantitative albumin-to-creatinine ratio (ACR). To examine the distribution of decreased kidney function within the population, age- and sex-adjusted prevalence of low eGFR (≤60 mL/min/1.73 m2) was estimated for all participants and across occupations. Multivariable logistic regression was used to assess the association of occupation with having low eGFR. RESULTS: Of the 579 participants analysed (37 excluded due to missing data), the age- and sex-adjusted prevalence of low eGFR was 3.5%. Agriculture was the occupation associated with the highest adjusted prevalence of low eGFR (8.8%), with 1 in every 11 agricultural workers having low eGFR. Working in agriculture was independently associated with more than a 5-fold risk of having low eGFR [odds ratio 5.2 (95% confidence interval 1.1-24.3), P = 0.032], after adjustment for age, sex, diabetes, hypertension, body mass index, ACR and family history of KD. Additionally, a quarter of the population (25%) had either low eGFR or an ACR >30 mg/g, mostly due to albuminuria. CONCLUSIONS: Our work suggests that there is a high prevalence of decreased kidney function in Tierra Blanca, particularly amongst agricultural workers.

A 250-kDa glycoprotein of Naegleria fowleri induces protection and modifies the expression of α4ß1 and LFA-1 on T and B lymphocytes in mouse meningitis model.

The aims of this work were to evaluate the protective role of the 250-kDa polypeptide band of Naegleria fowleri. We designed an immunization strategy in Balb/c mice which were inoculated by i.n. route with an electrocuted 250-kDa polypeptide band of N. fowleri. We observed that the 250-kDa band induced 80% of protection, whereas the coadministration with Cholera Toxin induced 100% of protection. Moreover, high levels of IgA- and IgG-specific antibodies were detected by ELISA assay. We also analysed migration molecules (α4ß1 and LFA-1) on T and B lymphocytes in nose-associated lymphoid tissue (NALT), cervical lymph nodes (CN) and nasal passages (NP) by flow cytometry. We observed that the percentage of B cells (B220/α4ß1) and T cells (CD4/α4ß1) in NP were higher in all immunized groups compared with the other compartments analysed. Finally, we detected by immunohistochemistry ICAM-1 and V-CAM-1 in the nasal cavity. The immunization with the 250-kDa polypeptide band, protect mice against N. fowleri challenge and modifies migration molecules and their ligands.

Reduction in new cardiac electronic device implantations in Catalonia during COVID-19.

AIMS: During the COVID-19 pandemic, concern regarding its effect on the management of non-communicable diseases has been raised. However, there are no data on the impact on cardiac implantable electronic devices (CIED) implantation rates. We aimed to determine the impact of SARS-CoV2 on the monthly incidence rates and type of pacemaker (PM) and implantable cardiac defibrillator (ICD) implantations in Catalonia before and after the declaration of the state of alarm in Spain on 14 March 2020. METHODS AND RESULTS: Data on new CIED implantations for 2017-20 were prospectively collected by nine hospitals in Catalonia. A mixed model with random intercepts corrected for time was used to estimate the change in monthly CIED implantations. Compared to the pre-COVID-19 period, an absolute decrease of 56.5% was observed (54.7% in PM and 63.7% in ICD) in CIED implantation rates. Total CIED implantations for 2017-19 and January and February 2020 was 250/month (>195 PM and >55 ICD), decreasing to 207 (161 PM and 46 ICD) in March and 131 (108 PM and 23 ICD) in April 2020. In April 2020, there was a significant fall of 185.25 CIED implantations compared to 2018 [95% confidence interval (CI) 129.6-240.9; P < 0.001] and of 188 CIED compared to 2019 (95% CI 132.3-243.7; P < 0.001). No significant differences in the type of PM or ICD were observed, nor in the indication for primary or secondary prevention. CONCLUSIONS: During the first wave of the COVID-19 pandemic, a substantial decrease in CIED implantations was observed in Catalonia. Our findings call for measures to avoid long-term social impact.

[Bilateral adrenal hemorrhage after severe COVID-19 infection. Report of one case]. / Hemorragia adrenal bilateral en paciente recuperado de neumonía COVID-19 Grave. Caso Radiológico.

We report a 47-year-old male with a severe disease caused by COVID-19, who required mechanical ventilation for 18 ays. During the hospital stay he received dexamethasone and anticoagulation with heparin. After discharge a new chest CT scan showed homogeneous hypo vascular enlargement of both adrenal glands, not present in the initial imaging studies. It was interpreted as a subacute bilateral adrenal hemorrhage. The patient remained stable and without any complaint.

Immunosenescence profile and expression of the aging biomarker (p16INK4a) in testicular cancer survivors treated with chemotherapy.

BACKGROUND: Cytotoxic chemotherapy can cure advanced germ cell tumors. Nevertheless, cancer treatment may induce cellular senescence and accelerate molecular aging. The aging process implies an increase of cells expressing p16INK4a and changes in lymphocyte subpopulations. Our aim was to study the potential induction of premature immunosenescence in testicular cancer survivors (TCS) exposed to chemotherapy. METHODS: Case-control exploratory study of TCS treated with chemotherapy (≥3 BEP cycles, disease-free ≥3 months) compared with age matched healthy controls. Peripheral blood mononuclear cells were isolated, and lymphocyte subpopulations were analyzed by flow cytometry. CDKN2A/p16INK4a expression in T cells was measured using qPCR. The percentage of lymphocyte subpopulations and the CDKN2A/p16INK4a expression in TCS were compared with the control group using the Wilcoxon signed-rank test. RESULTS: We included 16 cases and 16 controls. The median age was 27 years (minimum 24, maximum 54) and the median time on surveillance was 26.5 months (minimum 3, maximum192). TCS had a lower percentage of total T cells and CD4+ T cells in total lymphocytes. Among the CD4+ T lymphocytes, TCS had less naïve CD4+ and increased memory CD4+ cells. Within the CD8+ T lymphocytes, TCS exhibited a decrease in the percentage of naïve cells and an increase in CD8 + CD45RA + CD57+ cells. TCS also exhibited decreased memory CD19+ B cells compared to the controls. The relative expression of CDKN2A/p16INK4a in T cells was increased in TCS (mean 1.54; 95% CI of the mean: 1.074-2.005; p = 0.048). CONCLUSION: In this exploratory study, TCS showed increased expression of CDKN2A/p16INK4a and a lymphocyte phenotype that has been associated with immunosenescence. Further studies are warranted to define the clinical implications of these alterations in TCS.

"Candidatus Borrelia ibitipoquensis," a Borrelia valaisiana-Related Genospecies Characterized from Ixodes paranaensis in Brazil.

Borrelia burgdorferi sensu lato (Bbsl) spirochetes include the agents of Lyme borreliosis in temperate regions of the Northern Hemisphere, and merge their transmission cycles mainly with ticks of the Ixodes ricinus complex. Twenty genospecies compose Bbsl currently, and with the exception of Borrelia chilensis, and Borrelia garinii, all have been described only for North America, Europe, North Africa, and Asia. Here, we collected specimens of Ixodes paranaensis, a tick associated with swifts in a Brazilian natural park from the state of Minas Gerais, and performed a molecular characterization of 11 borrelial genes. Based on comparisons of inter and intraspecific genetic divergences, and Bayesian phylogenetic trees inferred for 16S rRNA, flaB, p66, and concatenated clpA, clpX, pepX, pyrG, recG, nifS rlpB, and uvrA genes, we demonstrate the occurrence of a new genospecies of Bbsl. "Candidatus Borrelia ibitipoquensis" Ip37 is closely related to Borrelia sp. Am501, and Borrelia valaisiana, a spirochete transmitted by ticks of the I. ricinus complex in Eurasia that uses birds as reservoirs. In a similar ecological scenario involving ticks and avian hosts, the migratory swift Streptoprocne biscutata is the sole-documented bird associated with I. paranaensis, and, although not assessed in this study, could correspond to the vertebrate reservoir of this newly described genospecies in Brazil. Pathogenic roles of "Ca. B. ibitipoquensis" are still unknown. However, its possible vector I. paranaensis is not an anthropophilic tick, so human infections would be unlikely to occur. Our finding enhances the knowledge on Bbsl in South America, highlights the occurrence of ecologically and genetically related genospecies with vastly separated geographical distributions, and calls for the attention to explore a barely known diversity of spirochetes of this group in the region.

Omega-3 and omega-6 fatty acids in primary Sjögren's syndrome: clinical meaning and association with inflammation.

OBJECTIVES: Lipid mediators derived from polyunsaturated fatty acids (FA), have been related to inflammation and immune response regulation. Herein we evaluated the intake and serum levels of ω-3 and ω-6 FA among patients with primary Sjögren's syndrome (pSS), and correlated with ocular/oral sicca symptoms, disease activity and a panel of chemokines/cytokines. METHODS: We included 108 patients and 100 controls. Dietary information was obtained from a food questionnaire of one-day reminder and processed using a nutritional software. Among the SS group, we measured serum ω-3 (α-linolenic acid [α-LN], eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA]) and ω-6 (linoleic acid [LA], arachidonic acid [AA]) by gas chromatography flame ionization. We scored the ESSDAI, ESPRI, Schirmer-I test and NSWSF. In a subsample, we assessed the OSDI, ophthalmologic staining scores and measured CXCL8, CXCL10, CCL2, IL-22 and IL-21 in saliva, and CXCL8, CXCL10, CCL2 and CXCL9 in tears by Luminometry. RESULTS: ω-3 and ω-6 intake was lower in SS patients than controls, and did not correlate with serum levels. We found a negative correlation between α-LN and the OSDI and ESSDAI, as well as DHA and ESSDAI. In tears, AA positively correlated with CXCL9, whereas in saliva, α-LN, DHA and the ω3 sum negatively correlated with CCL2. We observed a negative correlation between the ω6 sum and IL-21. CONCLUSIONS: pSS patients had deficient omega intake. Lower ocular symptoms, ESSDAI scores and salivary CCL2 correlated with higher ω-3 levels, possible suggesting a role in chronic inflammation. Further studies are warranted to deepen in the knowledge of this association.

The Transcription Factor SCX is a Potential Serum Biomarker of Fibrotic Diseases.

Fibrosing diseases are causes of morbidity and mortality around the world, and they are characterized by excessive extracellular matrix (ECM) accumulation. The bHLH transcription factor scleraxis (SCX) regulates the synthesis of ECM proteins in heart fibrosis. SCX expression was evaluated in lung fibroblasts and tissue derived from fibrotic disease patients and healthy controls. We also measured SCX in sera from 57 healthy controls, and 56 Idiopathic Pulmonary Fibrosis (IPF), 40 Hypersensitivity Pneumonitis (HP), and 100 Systemic Sclerosis (SSc) patients. We report high SCX expression in fibroblasts and tissue from IPF patients versus controls. High SCX-serum levels were observed in IPF (0.663 ± 0.559 ng/mL, p < 0.01) and SSc (0.611 ± 0.296 ng/mL, p < 0.001), versus controls (0.351 ± 0.207 ng/mL) and HP (0.323 ± 0.323 ng/mL). Serum levels of the SCX heterodimerization partner, TCF3, did not associate with fibrotic illness. IPF patients with severely affected respiratory capacities and late-stage SSc patients presenting anti-topoisomerase I antibodies and interstitial lung disease showed the highest SCX-serum levels. SCX gain-of-function induced the expression of alpha-smooth muscle actin (α-SMA/ACTA2) in fibroblasts when co-overexpressed with TCF3. As late and severe stages of the fibrotic processes correlated with high circulating SCX, we postulate it as a candidate biomarker of fibrosis and a potential therapeutic target.

Immature ticks on wild birds and the molecular detection of a novel Rickettsia strain in the Ibitipoca State Park, southeastern Brazil.

Birds are recognized hosts of ticks, especially for the immature stages which may harbor various species and strains of Rickettsia. To explore landscapes inhabited by birds and their ticks would expand the knowledge on host-parasite relationships and the rickettsiae. The aim of this paper was to record the diversity of ticks collected on wild birds and assess the phylogenetic position of a novel Rickettsia strain detected in immature ticks. Birds were captured in the Ibitipoca State Park, located in the Minas Gerais state, southeastern Brazil, as part of a long-term research project on the ecology of ticks, birds and Rickettsia. We found three tick species parasitizing birds: Amblyomma aureolatum (63 larvae, 10 nymphs), Haemaphysalis leporispalustris (28 larvae, seven nymphs) and Amblyomma romarioi (27 larvae). Among these, A. aureolatum was the most abundant species including 54% (73/135) of the collected ticks. New tick-host records were: A. romarioi on Turdus amaurochalinus and H. leporispalustris on Thamnophilus caerulescens, Saltator similis and Zonotrichia capensis. Of the 82 ticks tested for Rickettsia spp. by PCR, two larvae (2.5%) of A. romarioi were infected with 'Candidatus Rickettsia paranaensis', a novel putative Rickettsia species closely related to Rickettsia africae, Rickettsia sibirica and Rickettsia parkeri, as corroborated by our phylogenetic analysis. Finally, we present a list of all records of immature stages of H. leporispalustris on passerine birds in Brazil.

Antioxidant effect of resveratrol in single red blood cells measured by thermal fluctuation spectroscopy.

The human red blood cell (RBC) membrane has significant elastic capabilities which can be described measuring typical membrane edge fluctuations and mechanical properties by optical techniques. The RBC elastic properties can be affected by changes in the surrounding media. In an attempt to elucidate the molecular mechanisms of the interaction of resveratrol with the red cell membrane and of its antioxidant capacity the changes in mechanical properties of the RBC membrane were analyzed. These studies were carried out through measurements of RBC membrane fluctuations in the presence of the oxidant agent HClO using thermal fluctuation spectroscopy (TFS). The observed results showed that the elastic capabilities of RBC changed with low concentration of hypochlorous acid but without morphological changes. However, in the presence of resveratrol the deformation and decrease of elastic capabilities induced by HClO on RBC decreased. These in vitro results demonstrated the protective effect of RV against the detrimental effects triggered by HClO upon human erythrocytes.

α-enolase is an antigenic target in primary Sjögren's syndrome.

OBJECTIVES: Although anti-cyclic citrullinated peptides antibodies are specific markers for rheumatoid arthritis (RA), they might be present in other diseases. Our aim was to assess the native or citrullinated antigens recognised by patients with primary Sjögren's syndrome (pSS) and to evaluate their association with clinical and serological features. METHODS: In an initial screening, we assessed the serum reactivity of 12 patients with pSS against native or in vitro citrullinated antigens of HEp-2 cells by immunoblotting. We identified a 47kDa band, which was preferentially recognised and corresponded to α-enolase. Thus, levels of IgA and IgG anti-native and citrullinated α-enolase antibodies were measured in 50 pSS patients, 20 RA patients and 20 healthy subjects (HS) by ELISA. RESULTS: We identified α-enolase as a predominant antigen recognised in pSS. These patients had higher levels of anti-citrullinated α-enolase IgG antibodies compared with RA or HS (p=0.003 and p<0.0001, respectively). Furthermore, there was an increase of IgG anti-citrullinated α-enolase vs IgG anti-non-citrullinated α-enolase antibodies in pSS patients (p=0.001), by contrast no difference was found in RA. The presence of IgA and IgG anti-non-citrullinated and anti-citrullinated α-enolase antibodies were not associated with any clinical manifestation whatsoever, including non-erosive arthritis among pSS, but an association of IgA anti-citrullinated α-enolase with anti-Ro/SSA antibodies was found. CONCLUSIONS: We characterised α-enolase as a dominant antigen in lysates of HEp- 2 cells in pSS. Nevertheless, their precise role in pSS remains to be elucidated.

Autoimmune comorbidity in achalasia patients.

BACKGROUND AND AIM: Idiopathic achalasia is a rare esophageal motor disorder. The disease state manifests local and systemic inflammation, and it appears that an autoimmune component and specific autoantibodies participate in the pathogenesis. The study aims to determine the prevalence of autoimmune and chronic inflammatory diseases in patients with achalasia and compare the results with those from patients with gastroesophageal reflux disease (GERD). METHODS: It was a cross-sectional and included 114 patients with idiopathic achalasia and 114 age-matched and sex-matched control patients with GERD. Data on the presence of autoimmune and inflammatory diseases, the time of presentation, and any family history of autoimmune disease were obtained from the hospital's medical records. RESULTS: Seventy three (64%) were female patients (mean age: 42.3 ± 15.5; median disease duration: 12 months). We identified the presence of autoimmune disease in 19 patients with achalasia (16.7%), hypothyroidism was the main diagnosis, and it was present in 52.6% of patients compared with 4.2% in controls. Thirteen of the 19 achalasia patients (68.4%) with autoimmune disease had history of familial autoimmunity. We identified 11 achalasia (9.6%) and 5 GERD patients (4.16%) with an inflammatory condition. Compared with the GERD, the achalasia group was 3.8 times more likely to have an autoimmune disease (95% CI: 1.47-9.83), 3.0 times more likely to have thyroidopathies (95% CI: 1.00-9.03), and 3.02 times more likely to suffer from any chronic inflammatory disease (95% CI: 1.65-6.20). CONCLUSIONS: The non-negligible number of patients with autoimmune diseases identified among the patients with idiopathic achalasia supports the hypothesis that achalasia has an autoimmune component.

Endothelial progenitor dysfunction associates with a type I interferon signature in primary antiphospholipid syndrome.

OBJECTIVES: Patients with antiphospholipid syndrome (APS) are at risk for subclinical endothelial injury, as well as accelerated atherosclerosis. In the related disease systemic lupus erythematosus, there is a well-established defect in circulating endothelial progenitors, which leads to an accrual of endothelial damage over time. This defect has been at least partially attributed to exaggerated expression of type I interferons (IFNs). We sought to determine whether these pathways are important in APS. METHODS: We studied 68 patients with primary APS. Endothelial progenitors were assessed by flow cytometry and functional assay. Type I IFN activity was determined by a well-accepted bioassay, while peripheral blood mononuclear cells were scored for expression of IFN-responsive genes. RESULTS: Endothelial progenitors from patients with APS demonstrated a marked defect in the ability to differentiate into endothelial cells, a phenotype which could be mimicked by treating control progenitors with APS sera. Elevated type I IFN activity was detected in the circulation of patients with APS (a finding that was then replicated in an independent cohort). While IgG depletion from APS sera did not rescue endothelial progenitor function, the dysfunction was successfully reversed by a type I IFN receptor-neutralising antibody. CONCLUSIONS: We describe, for the first time to our knowledge, an IFN signature in primary APS and show that this promotes impaired endothelial progenitor function. This work opens the door to novel approaches that may mitigate vascular damage in APS, such as anti-IFN drugs.