Clinical Descriptors Research Articles

A clonal expression biomarker associates with lung cancer mortality.

An aim of molecular biomarkers is to stratify patients with cancer into disease subtypes predictive of outcome, improving diagnostic precision beyond clinical descriptors such as tumor stage1. Transcriptomic intratumor heterogeneity (RNA-ITH) has been shown to confound existing expression-based biomarkers across multiple cancer types2-6. Here, we analyze multi-region whole-exome and RNA sequencing data for 156 tumor regions from 48 patients enrolled in the TRACERx study to explore and control for RNA-ITH in non-small cell lung cancer. We find that chromosomal instability is a major driver of RNA-ITH, and existing prognostic gene expression signatures are vulnerable to tumor sampling bias. To address this, we identify genes expressed homogeneously within individual tumors that encode expression modules of cancer cell proliferation and are often driven by DNA copy-number gains selected early in tumor evolution. Clonal transcriptomic biomarkers overcome tumor sampling bias, associate with survival independent of clinicopathological risk factors, and may provide a general strategy to refine biomarker design across cancer types.

Comparison of Staging Systems to Assess Lymphedema Caused by Cancer Therapies, Lymphatic Filariasis, and Podoconiosis.

Background: Lymphedema is a disease of the skin and subcutaneous tissue resulting from a disturbance in lymph flow. Anyone can be affected, and causes include cancer therapy when lymph nodes are removed or irradiated, the parasitic disease lymphatic filariasis, and damage caused by exposure to irritant soils known as podoconiosis. Manifest lymphedema is progressive and a major contributor to disability, stigma, and social isolation for affected people. Although the pathogenesis of connective tissue changes in lymphedema will follow a similar course regardless of the disease of causation, several systems are used to stage progression. Disparity in these staging systems leads to inconsistency in reporting of the severity of lymphedema and prevents meta-analysis of research results. In the global health environment, integrated morbidity management for chronic illness is essential to meet the needs of affected people and to be sustainable for health care systems. Clinical descriptors for staging criteria within each system may assist clinicians in assessment and provide a format for consistency in reporting by lymphedema researchers.Methods and Results: Lymphedema staging systems used in oncology, filariasis, and podoconiosis settings were reviewed and the assessment techniques, diagnostic procedures, and clinical observations used by each system are described. The most commonly used staging systems are compared to identify similarities, and a matrix approach to lymphedema staging is proposed.Conclusion: A universal staging system would contribute to more consistent reporting of research on and clinical management of lymphedema arising from multiple causes.

334 GEMS: Geriatric Emergency Service - Rockwood’s Clinical Frailty Scale and Outcomes

Abstract Background Rockwood’s Clinical Frailty Scale (CFS), which uses clinical descriptors and pictographs, was developed to provide clinicians with an easily applicable tool to stratify older adults according to level of vulnerability. The CFS was validated in a sample of 2305 older participants from the Canadian Study of Health and Aging and was shown to be a strong predictor of institutionalisation and mortality (Rockwood K, 2005). Methods The aim of GEMS is to improve care, outcomes and the patient experience for older people living with Frailty. All people aged 75 years and older who attend as an emergency are screened on triage using the Variable Indicative of Placement Tool (VIP). The GEMS Acute Floor Team respond early to those who screen positive by starting a CGA. At the end of CGA all patients have a score 1 to 9 assigned from the Clinical Frailty Scale (CFS). Results 10,037 patients were triaged in the first two years of the service. 43% screened positive for Frailty. 66% had a CGA. 10% were vulnerable CFS 4, 32% mildly frail CFS 5, 32% moderately frail CFS 6 and 31% severely frail CFS 7. Increasing score on the CFS correlated with increased length of stay, death and institutionalisation. Conclusion The CFS correlates with Length of stay (LOS), mortality and institutionalisation in people aged 75 years and older who attend as an emegency and screen positive for Frailty.

Trainee teachers’ knowledge of autism: implications for understanding and inclusive practice

ABSTRACTThis current study draws on data from a large sample of trainee teachers in England to provide a long overdue baseline assessment of the knowledge of autism. It has particular import given the recent research that shows that 60% of autistic young people identified ‘having a teacher who understands autism’ as the main thing that would make school better for them. We find that, based on the Autism Awareness Survey, levels of knowledge were comparatively high among our n = 326 respondents. However, whilst this is encouraging, our findings also point to an underestimation of knowledge, which indicates the need for additional resources and training to develop trainee teachers’ self-efficacy and confidence in their pedagogical practice. Finally, in order to understand more about the gap between autistic children’s experiences and teachers’ understanding, this study signals a need to review autism knowledge scales to better reflect an experiential knowledge that goes beyond the clinical descriptors.

Point Prevalence of Children Hospitalized With Chronic Critical Illness in the General Inpatient Units

Children with medical complexity (CMC) have high rates of mortality and morbidity, prolonged lengths of stay, and use a disproportionately high amount of health care expenditures. A subset of children with CMC have chronic critical illness requiring even higher levels of clinical support and resource use. We aimed to describe the point prevalence of children hospitalized in general inpatient care units with pediatric chronic critical illness (PCCI). Point prevalence analysis across 6 pediatric tertiary medical centers in the United States on a "snapshot day" (May 17, 2017). On the day of sampling, a number of demographic, historical, and clinical descriptors were collected. A previously published definition of PCCI was used to establish inclusion criteria. The point prevalence of patients with PCCI in general inpatient care units was 41% (232 out of 571). Of these, 91% (212 out of 232) had been admitted more than once in the previous 12 months, 50% (117 out of 232) had a readmission within 30 days of a previous admission, and 20% (46 out of 232) were oncology patients. Only 1 had a designated complex care team, and there were no attending physicians designated primarily for medically complex children. Children with chronic critical illness, a subset of CMC, may make up a substantial proportion of pediatric patients hospitalized in general inpatient care units. There is a critical need to understand how to better care for this medically fragile population. In our data, it is suggested that resources should be allocated for PCCI in nonintensive care clinical areas.

Tamoxifen side effects: pharmacogenetic and clinical approach in Mexican mestizos.

BackgroundTamoxifen metabolism is translated into four genetic phenotypes (GP): genetic poor metabolizer (gPM); genetic intermediate metabolizer (gIM); genetic normal metabolizer (gNM); and genetic ultra-rapid metabolizer (gUM). Although CYP2D6 is involved in tamoxifen biotransformation, its association with tamoxifen side effects (TSE) is limited. Therefore, we evaluated CYP2D6 GP and clinical variables as potential predictors of TSE in Mexican Mestizo patients.MethodsThis cross-sectional study evaluated CYP2D6 GP, clinical data, and self-reported TSE in 71 women. Potential predictors were tested in uni- and multivariable models.ResultsHot flashes (57.75%), arthralgia (45.07%), headache (43.66%), and cramps (39.44%) were the most frequent TSE. Three GP were identified: gPM (2.8%); gNM (93.0%); and gUM (4.2%). In the univariate analysis, none of the GP was predictive of TSE. However, the uni- and multivariable models showed contraceptive use and chemotherapy treatment prior to tamoxifen therapy to be predictive. Two alleles were identified for the first time at unusually high frequencies: CYP2D6*34 (13.2%); and *39 (14.7%).ConclusionsOur findings indicate that CYP2D6 GP were not significantly predictive of TSE, though two clinical descriptors were. The present results are a valuable contribution to pharmacogenetic characterization of Mexican Mestizo populations who, like other Latin-American groups, are poorly represented in the literature.

Method of determining disease severity in women with pelvic varicose veins

Using assessment scales in clinical and research practice is one of fundamental reference methods of evaluation in human pathological states. Pelvic vein varicosity is an independent nosological entity within the framework of chronic vein diseases. Currently, the clinical methods of assessment in the aspect of a patient-oriented approach in this type of disease are largely understudied and still not duly defined. The study was aimed at analyzing clinical outcomes of surgical treatment in the form of resection of the ovarian vein in female patients with pelvic varicose veins, based on the developed specialized scale of clinical assessment of disease severity. We carried out an open prospective study of efficacy of resection of the ovarian vein in 37 women with pelvic varicose veins. The main criterion for assessment was a clinical method of determining manifestations of the disease by means of the Pelvic Venous Clinical Severity Score. According to the Pelvic Venous Clinical Severity Score, improvement of the condition was observed in 36 (97.3%) operated female patients and 1 (2.7%) woman turned out to have negative dynamics. The median of the composite score of the severity scale decreased form 11.78±5.06 points to 5.22±3.19 (p<0.05). The total positive gradient of the score amounted to 6.57±3 .65 points. A significant decrease in manifestations of severity was observed for 9 of the 10 clinical descriptors of the disease. The use of the suggested scale in practical assessment of the results made it possible to prove high efficacy of resection of the ovarian vein in women with pelvic varicose veins in the form of decreased intensity of the disease's symptomatology. The VCSS is an easy-to-fill-in tool, taking up little time, ensuring no influence of the physician's personality on the answers, presenting quantitative expression of therapeutic results.

Survival after Aortic Valve Replacement for Aortic Regurgitation: Prediction from Preoperative Contractility Measurement

Background: Noninvasive measurement of myocardial contractility (end-systolic wall stress-adjusted change in left ventricular ejection fraction from rest to exercise [ΔLVEF – ΔESS]) predicts heart failure, subnormal LVEF_rest, and sudden death in asymptomatic patients with chronic severe aortic regurgitation (AR). Here we assess the relation of preoperative ΔLVEF – ΔESS to survival after aortic valve replacement (AVR). Methods: Patients who underwent AVR for chronic, isolated, pure severe AR (n = 66) were followed for 13.0 ± 6.4 event-free years. Preoperative ΔLVEF – ΔESS (from combined echocardiographic and radionuclide cineangiographic data) enabled cohort stratification into 3 terciles (–1 to –11% [normal or mild] contractility deficit, –12 to –16% [moderate], and ≤–17% [severe], identical with segregation in our earlier study) to relate preoperative contractility to postoperative survival and to age- and gender-matched US census data. Results: Since AVR, 22 patients died (average annual risk [AAR] for all-cause mortality for the entire co hort = 3.15%). Preoperative ΔLVEF – ΔESS predicted postoperative survival (p = 0.009, log rank test). By contractility terciles, all-cause AARs were 1.44, 2.58, and 6.40%. Survival was lower than among US census comparators (p < 0.02), but the “mild” tercile was indistinguishable from census data (p = ns). By multivariable Cox regression, survival prediction by pre-AVR ΔLVEF – ΔESS was independent of, and superior to, prediction by age at surgery, gender, preoperative functional class, LVEF_rest, LVEF_exercise, change in LVEF_{rest to exercise}, and LV diastolic or systolic dimensions (p ≤ 0.01, pre-AVR ΔLVEF – ΔESS vs. other covariates). Conclusion: In severe AR, preoperative contractility predicts post-AVR survival and may be prognostically superior to clinical, geometric and performance descriptors, potentially impacting on patient selection for surgery.

Clinical Manifestation of Acute, Subacute, and Chronic Low Back Pain in Different Age Groups: Low Back Pain in 35,446 Patients.

Low back pain (LBP) is a major healthcare problem causing tremendous economic costs. Clinical manifestation of LBP was characterized in 35,446 patients. We focused on the comparison of the acute, subacute, and chronic LBP stage with regard to patients' ages, based on epidemiologic and clinical questionnaires (eg, painDETECT Questionnaire, Pain Disability Index), pain intensity, pain descriptors, and functional impairment. We found that neuropathic components were most frequent in chronic LBP patients at the ages of 51 to 60 years. Elderly LBP patients showed a decrease in neuropathic and an increase in nociceptive pain. The most frequently reported pain descriptors were "pressure pain" and "pain attacks" through all stages of LBP, whereas "burning" and "prickling" were most frequent in the chronic stage. Patients after back surgery presented neuropathic pain symptoms most frequently and had the highest amount of pain medication intake. Burning and prickling were revealed as possible indicators for LBP chronicity. Combined with pain attacks and pressure pain, these 4 pain descriptors might be a promising adjunct to pain intensity in terms of outcome parameters for future LBP studies. The decrease of neuropathic pain syndromes in the elderly might be explained by degenerative processes. The presented work provides important insights on LBP management in the acute, subacute, and chronic stages.

Systems Immunology: Learning the Rules of the Immune System.

Given the many cell types and molecular components of the human immune system, along with vast variations across individuals, how should we go about developing causal and predictive explanations of immunity? A central strategy in human studies is to leverage natural variation to find relationships among variables, including DNA variants, epigenetic states, immune phenotypes, clinical descriptors, and others. Here, we focus on how natural variation is used to find patterns, infer principles, and develop predictive models for two areas: (a) immune cell activation-how single-cell profiling boosts our ability to discover immune cell types and states-and (b) antigen presentation and recognition-how models can be generated to predict presentation of antigens on MHC molecules and their detection by T cell receptors. These are two examples of a shift in how we find the drivers and targets of immunity, especially in the human system in the context of health and disease.

Uteroglobin and FLRG concentrations in aqueous humor are associated with age in primary open angle glaucoma patients

BackgroundThe pathophysiological changes occurring in the trabecular meshwork in primary open angle glaucoma are poorly understood, but are thought to include increased extracellular matrix deposition, trabecular meshwork cell apoptosis, inflammation, trabecular meshwork calcification and altered protein composition of the aqueous humor. Although many proteins are present in aqueous humor, relatively few have been studied extensively, and their potential roles in primary open angle glaucoma are unknown.MethodsAnalyte concentrations in aqueous humor from 19 primary open angle glaucoma and 18 cataract patients were measured using a multiplex immunoassay. Fisher’s exact test was used to assess statistical significance between groups, and correlations of analyte concentrations with age, intraocular pressure, pattern standard deviation, mean deviation, cup-to-disc ratio and disease duration since commencing treatment were tested by Spearman’s method.ResultsCHI3L1, FLRG, HGF, MIF, P-selectin and Uteroglobin were detected in more than 50% of samples of one or both patient groups, some of which have not previously been quantified in aqueous humor. In the glaucoma but not the cataract group, significant correlations were determined with age for Uteroglobin/SCGB1A1 (rs = 0.805, p < 0.0001) and FLRG (rs = 0.706, p = 0.0007). Furthermore, HGF correlated significantly with disease duration (rs = − 0.723, p = 0.0007). There were no differences in analyte concentrations between groups, and no other significant associations with clinical descriptors that passed correction for multiple testing.ConclusionsThe correlations of uteroglobin and FLRG with age in primary open angle glaucoma but not cataract may suggest a heightened requirement for anti-inflammatory (uteroglobin) or anti-calcification (FLRG) activity in the ageing glaucomatous trabecular meshwork.

Pulmonary quantitative CT imaging in focal and diffuse disease: current research and clinical applications.

The frenetic development of imaging technology-both hardware and software-provides exceptional potential for investigation of the lung. In the last two decades, CT was exploited for detailed characterization of pulmonary structures and description of respiratory disease. The introduction of volumetric acquisition allowed increasingly sophisticated analysis of CT data by means of computerized algorithm, namely quantitative CT (QCT). Hundreds of thousands of CTs have been analysed for characterization of focal and diffuse disease of the lung. Several QCT metrics were developed and tested against clinical, functional and prognostic descriptors. Computer-aided detection of nodules, textural analysis of focal lesions, densitometric analysis and airway segmentation in obstructive pulmonary disease and textural analysis in interstitial lung disease are the major chapters of this discipline. The validation of QCT metrics for specific clinical and investigational needs prompted the translation of such metrics from research field to patient care. The present review summarizes the state of the art of QCT in both focal and diffuse lung disease, including a dedicated discussion about application of QCT metrics as parameters for clinical care and outcomes in clinical trials.

Development of a novel observer reported outcome tool as the primary efficacy outcome measure for a rare disease randomized controlled trial

We developed an Observer-Reported Outcome (ObsRO) survey instrument to be applied in a multicenter, placebo-controlled, crossover randomized controlled trial of dichloroacetate in children with pyruvate dehydrogenase complex deficiency. The instrument quantifies a subject's at-home level of functionality, as reported by a parent/caregiver, who were instrumental in providing the clinical descriptors and domains that formed the instrument's content. Feasibility testing of the ObsRO tool showed it to be easy to use and comprehensive in capturing the major clinical functional limitations of affected children and requires less than 5min for a parent/caregiver to complete daily.

Head Impact Locations in U.S. High School Boys' and Girls' Soccer Concussions, 2012/13-2015/16.

This study describes concussions and concussion-related outcomes sustained by high school soccer players by head impact location, sex, and injury mechanism. Data were obtained for the 2012/13-2015/16 school years from the National High School Sports-Related Injury Surveillance System, High School RIO™. This Internet-based sports injury surveillance system captures data reported by athletic trainers from an annual average of 162 U.S. high schools. Data were analyzed to describe circumstances of soccer concussion (e.g., symptomology, symptom resolution, and return-to-play time) by impact location (i.e., front- [face included], back-, side-, and top-of-the-head) and sex. Most concussions were from front-of-the-head impacts (boys, 30.5%; girls, 34.0%). Overall, 4.1 ± 2.2 and 4.6 ± 2.3 symptoms were reported in boys and girls, respectively. In boys, symptom frequency was not associated with head impact location (p = 0.66); an association was found in girls (p = 0.02), with the highest symptom frequency reported in top-of-the-head impacts (5.4 ± 2.2). Head impact location was not associated with symptom resolution time (boys, p = 0.21; girls, p = 0.19) or return-to-play time (boys, p = 0.18; girls, p = 0.07). Heading was associated with 28.0% and 26.5% of concussions in boys and girls, respectively. Most player-player contact concussions during heading occurred from side-of-the-head impacts (boys, 49.4%; girls, 43.2%); most heading-related ball contact concussions occurred from front-of-the-head (boys, 41.4%; girls, 42.6%) and top-of-the-head (boys, 34.5%; girls, 36.9%) impacts. Head impact location was generally independent of symptom resolution time, return-to-play time, and recurrence among high school soccer concussions. However, impact location may be associated with reported symptom frequency. Further, many of these clinical concussion descriptors were associated with sex.

Traumatic Brain Injury Severity, Neuropathophysiology, and Clinical Outcome: Insights from Multimodal Neuroimaging.

The relationship between the acute clinical presentation of patients with traumatic brain injury (TBI), long-term changes in brain structure prompted by injury and chronic functional outcome is insufficiently understood. In this preliminary study, we investigate how acute Glasgow coma score (GCS) and epileptic seizure occurrence after TBIs are statistically related to functional outcome (as quantified using the Glasgow Outcome Score) and to the extent of cortical thinning observed 6 months after the traumatic event. Using multivariate linear regression, the extent to which the acute GCS and epileptic seizure occurrence (predictor variables) correlate with structural brain changes (relative cortical atrophy) was examined in a group of 33 TBI patients. The statistical significance of the correlation between relative cortical atrophy and the Glasgow Outcome Score was also investigated. A statistically significant correlative relationship between cortical thinning and the predictor variables (acute GCS and seizure occurrence) was identified in the study sample. Regions where the statistical model was found to have highest statistical reliability in predicting both gray matter atrophy and neurological outcome include the frontopolar, middle frontal, postcentral, paracentral, middle temporal, angular, and lingual gyri. In addition, relative atrophy and GOS were also found to be significantly correlated over large portions of the cortex. This study contributes to our understanding of the relationship between clinical descriptors of acute TBI, the extent of injury-related chronic brain changes and neurological outcome. This is partly because the brain areas where cortical thinning was found to be correlated with GCS and with seizure occurrence are implicated in executive control, sensory function, motor acuity, memory, and language, all of which may be affected by TBI. Thus, our quantification suggests the existence of a statistical relationship between acute clinical presentation, on the one hand, and structural/functional brain features which are particularly susceptible to post-injury degradation, on the other hand.

An Examination of PAI Clinical Descriptors and Correlates in an Outpatient Sample: Tailoring of Interpretive Statements

The Personality Assessment Inventory (PAI; Morey 1991, 2007) was designed to evaluate patterns of psychopathology utilizing validity, clinical, treatment, and interpersonal scales. Its psychometric strengths include easily read items, gradations of responses, and extensive validation. The primary focus of the current study is to examine item-level clinical correlates to inform interpretation. For external validity, the Psychiatric Diagnostic Screening Questionnaire (PDSQ; Zimmerman 2002) was utilized by examining individual items and subscales. The investigation used archival data from 192 outpatients. The most specific and detailed clinical correlates were found for PAI mood disorder scales. Several other clinical scales, such as Schizophrenia (SCZ), had comparatively few clinical correlates. The current findings underscore the need to further validate PAI external correlates in order to augment PAI statements.

Alcohol-related presentations to the Royal Perth Hospital Emergency Department: A prospective study.

To quantify and describe alcohol-related presentations to our ED, as part of the binational Alcohol Harm in Emergency Departments study. A prospective observational study at Royal Perth Hospital of every patient attending ED for the 168-h period commencing 08.00 hours Monday 1 December 2014. Patient presentations were classified as alcohol-related (alcohol-positive) using predefined criteria. These patients were compared to alcohol-negative patients on a range of demographic and clinical descriptors. Two hundred and thirteen (15.2%) of 1403 patients screened were alcohol-positive. Compared with alcohol-negative patients, alcohol-positive patients were more likely to be male (148/213, 69.5% vs 636/1190, 53.4%, P < 0.001) and younger (mean 38 years vs 48 years, P < 0.001). They were more likely to arrive in police custody (OR 3.7, 95% CI 1.3-9.5, P = 0.005), and be admitted to the State Adult Major Trauma Unit (OR 4.2, 95% CI 2.1-8.3, P < 0.001). Forty-two (19.7%) of 213 patients had injuries suspected to be caused by an alcohol-affected third party. The ED length of stay and admission rate were not significantly different between the groups. 15.2% of patient presentations over the study week were alcohol-related. These patients were more likely to present with injury; one in five having injuries suspected to be caused by a third party affected by alcohol. This is a significant public health problem.

Clinical descriptors for the recognition of central sensitization pain in patients with knee osteoarthritis

Background: Despite growing awareness of the contribution of central pain mechanisms to knee osteoarthritis pain in a subgroup of patients, routine evaluation of central sensitization is yet to be incorporated into clinical practice.Aim: The objective of this perspective is to design a set of clinical descriptors for the recognition of central sensitization in patients with knee osteoarthritis that can be implemented in clinical practice.Methods: A narrative review of original research papers was conducted by nine clinicians and researchers from seven different countries to reach agreement on clinically relevant descriptors.Results: It is proposed that identification of a dominance of central sensitization pain is based on descriptors derived from the subjective assessment and the physical examination. In the former, clinicians are recommended to inquire about intensity and duration of pain and its association with structural joint changes, pain distribution, behavior of knee pain, presence of neuropathic-like or centrally mediated symptoms and responsiveness to previous treatment. The latter includes assessment of response to clinical test, mechanical hyperalgesia and allodynia, thermal hyperalgesia, hypoesthesia and reduced vibration sense.Conclusions: This article describes a set of clinically relevant descriptors that might indicate the presence of central sensitization in patients with knee osteoarthritis in clinical practice. Although based on research data, the descriptors proposed in this review require experimental testing in future studies.Implications for RehabilitationLaboratory evaluation of central sensitization for people with knee osteoarthritis is yet to be incorporated into clinical practice.A set of clinical indicators for the recognition of central sensitization in patients with knee osteoarthritis is proposed.Although based on research data, the clinical indicators proposed require further experimental testing of psychometric properties.

Modulation of the Muscle Activity During Sleep in Cervical Dystonia.

Impaired sleep has been reported as an important nonmotor feature in dystonia, but so far, self-reported complaints have never been compared with nocturnal video-polysomnographic (PSG) recording, which is the gold standard to assess sleep-related disorders. Twenty patients with idiopathic isolated cervical dystonia and 22 healthy controls (HC) underwent extensive clinical investigations, neurological examination, and questionnaire screening for excessive daytime sleepiness and sleep-related disorders. A full-night video PSG was performed in both patients and HC. An ad hoc montage, adding electromyographic leads over the muscle affected with dystonia, was used. When compared to controls, patients showed significantly increased pathological values on the scale assessing self-reported complaints of impaired nocturnal sleep. Higher scores of impaired nocturnal sleep did not correlate with any clinical descriptors but for a weak correlation with higher scores on the scale for depression. On video-PSG, patients had significantly affected sleep architecture (with decreased sleep efficiency and increased sleep latency). Activity over cervical muscles disappears during all the sleep stages, reaching significantly decreased values when compared to controls both in nonrapid eye movements and rapid eye movements sleep. Patients with cervical dystonia reported poor sleep quality and showed impaired sleep architecture. These features however cannot be related to the persistence of muscle activity over the cervical muscles, which disappears in all the sleep stages, reaching significantly decreased values when compared to HC.

Identification of a HERV-K env surface peptide highly recognized in Rheumatoid Arthritis (RA) patients: a cross-sectional case–control study

Endogenous retroviruses (HERV) are believed to be pathogenic in several autoimmune diseases. Among them, HERV-K viruses have been reported recently to be involved in the pathogenesis of rheumatoid arthritis (RA). In this study we have explored the role of humoral immune response against HERV-K as a potential pathogenetic mechanism in RA. Four different peptides from the extracellular portion of the env protein of HERV-K (env-su19-37 , env-su109-126 , env-su164-186 , env-su209-226 ) were selected by bioinformatic analysis on the basis of their putative immunogenicity. Indirect enzyme-linked immunosorbent assay (ELISA) was then carried out to quantify antibodies against those peptides on blood samples of 70 consecutive RA patients and 71 healthy controls (HC). Differences between the two groups were analysed using the Mann-Whitney test. Potential correlations between RA laboratory, clinical descriptors and immunoglobulin (Ig)G levels were explored by bivariate regression analysis. Serum autoantibodies against one of four tested peptides of HERV-K (env-su19-37 ) were significantly higher in RA than in HC (19 versus 3%, P = 0·0025). Subgroup analysis showed no association between anti-HERV-K peptide humoral response and clinical, serological and clinimetric RA disease descriptors. Serum from RA patients in our series reacted significantly against HERV-K env-su19-37 peptide in comparison to the general population suggesting a role for the HERV-K- related, secondary antigenic-driven immune response in the pathogenesis of RA. Further studies are needed to confirm these results and to explore the role of this HERV-K surface peptide as a potential therapeutic target.