Publications by authors named "Robert Colbert"
Background: The Paediatric Rheumatology International Trials Organisation (PRINTO) recently undertook an effort to better harmonize the pediatric and adult arthritis criteria. These provisional criteria are being refined for optimal performance. We aimed to investigate differences between patients who did and did not fulfill these PRINTO criteria amongst youth diagnosed with juvenile spondyloarthritis (SpA) that met axial juvenile SpA (axJSpA) classification criteria.
View Article and Find Full Text PDFHLA-B27 and spondyloarthritis: at the crossroads of innate and adaptive immunity.
Nat Rev Rheumatol
December 2024
Article Synopsis
- HLA-B*27 significantly increases the risk of developing spondyloarthritis (SpA), which encompasses various forms including axial SpA, peripheral arthritis, and inflammation in several areas of the body.
- The exact mechanism by which HLA-B*27 contributes to SpA is unclear, but three major hypotheses suggest it may promote autoimmune responses, activate harmful immune pathways, and lead to misfolding issues that enhance inflammation and bone formation.
- This review highlights current theories about HLA-B*27's role in SpA, notes recent advancements in research, identifies knowledge gaps, and suggests areas for future investigation.
The Spondylitis Association of America (SAA) and the National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS) convened a conference on the campus of the National Institutes of Health (NIH) on September 28 and 29, 2023, to identify unmet needs in spondyloarthritis (SpA) research. The conference featured presentations by experts in areas of disease endotypes, pain, innovative imaging in SpA, health disparities in rheumatic diseases, and therapeutics. Members of the conference planning committee moderated the sessions and led the development of manuscripts summarizing recommendations to address unmet research needs.
View Article and Find Full Text PDFObjective: The goal was to develop and validate classification criteria for axial juvenile spondyloarthritis (SpA; AxJSpA).
Methods: This international initiative consisted of four phases: (1) item generation, (2) item reduction, (3) criteria development, and (4) validation of the AxJSpA criteria by an independent team of experts in an internationally representative validation cohort.
Results: These criteria are intended to be used on youth with a physician diagnosis of juvenile SpA and for whom axial disease is suspected.
Article Synopsis
- HLA-B27, a significant risk factor for spondyloarthritis (SpA), may involve impaired protein folding and subsequent inflammation pathways, particularly IL-23 induced by endoplasmic reticulum (ER) stress.
- Researchers studied the effect of deleting the CHOP transcription factor, which influences ER stress-related IL-23 production, on gut inflammation in genetically modified rats (HLA-B27-Tg).
- Findings revealed that removing CHOP did not reduce gut inflammation; instead, it increased other pro-inflammatory markers, suggesting that CHOP might actually help mitigate severe gut inflammation linked to HLA-B27.
Inter-reader reliability of a new scoring system for evaluating joint inflammation and enthesitis in whole body MRI (WBMRI) in juvenile idiopathic arthritis was tested. The scoring system grades 732 item-region combinations of bone marrow and soft tissue changes for commonly involved joints and entheseal sites. Five radiologists rated 17 WBMRI scans through an online rating platform.
View Article and Find Full Text PDFPatients with classical melorheostosis exhibit exuberant bone overgrowth in the appendicular skeleton, resulting in pain and deformity with no known treatment. Most patients have somatic, mosaic mutations in MAP2K1 (encoding the MEK1 protein) in osteoblasts and overlying skin. As with most rare bone diseases, lack of affected tissue has limited the opportunity to understand how the mutation results in excess bone formation.
View Article and Find Full Text PDFObjective: Stakeholders met to address persistent challenges facing the development of therapeutics for polyarticular juvenile idiopathic arthritis (pJIA), which result in fewer approved therapies for children with pJIA than adults with rheumatoid arthritis (RA) and long lag times from adult RA approval to pediatric labeling. Ensuring that new medications are authorized in a timely manner to meet the needs of JIA patients worldwide is critically important to multiple stakeholders.
Methods: The Food and Drug Administration in collaboration with the University of Maryland Center for Regulatory Science and Innovation held a public workshop entitled "Accelerating Drug Development for pJIA" on October 2, 2019, to address challenges surrounding access to new medications for children and adolescents with pJIA.
Objective: We undertook this study to examine the functional basis for epistasis between endoplasmic reticulum aminopeptidase 1 (ERAP1) and HLA-B27 in experimental spondyloarthritis (SpA).
Methods: ERAP1-knockout rats were created using genome editing and bred with HLA-B27/human β -microglobulin-transgenic (HLA-B27-Tg) rats and HLA-B7-Tg rats. The effects of ERAP1 deficiency on HLA allotypes were determined using immunoprecipitation and immunoblotting, flow cytometry, allogeneic T cell proliferation assays, and gene expression analyses.
Objective: To validate the Juvenile Spondyloarthritis Disease Activity Index (JSpADA), and modified versions thereof, in a North American cohort of patients with enthesitis-related arthritis (ERA).
Methods: We utilized the Childhood Arthritis and Rheumatology Research Alliance Registry database ERA cohort to validate the JSpADA and its modifications (JSpADA6-no Schober, no C-reactive protein [CRP]/erythrocyte sedimentation rate [ESR]; JSpADA7-no Schober; and JSpADA7-no CRP/ESR) using the Outcome Measures in Rheumatology principles of face validity, discriminative validity, and responsiveness to change.
Results: There were 51 subjects (64 visits) with complete JSpADA data with a mean age of 13.
During inflammation, cellular glucose uptake and glycolysis are upregulated to meet an increased energy demand. For example, keratinocyte glycolysis is essential for progression of psoriasis. Therefore, understanding the regulation of glucose metabolism in keratinocytes is of importance.
View Article and Find Full Text PDFArticle Synopsis
- The study aimed to assess how doctors manage juvenile spondyloarthritis (JSpA) patients who don’t respond to anti-TNF treatments.
- An online survey with a 36% response rate revealed that 63% of pediatric rheumatologists reported having JSpA patients who failed anti-TNF therapy, primarily due to secondary non-response.
- Sacroiliitis was a key factor in evaluating treatment effectiveness, with many doctors opting to try a second anti-TNF agent before switching to different medications after failures.
Melorheostosis is a rare sclerosing bone disease with associated vascular abnormalities in skin and bone, which is caused by somatic mosaic single nucleotide variations in the MAP2K1 gene, which encodes MAPK/extracellular signal‒regulated kinase (ERK) kinase 1. However, disease pathogenesis is poorly understood. Using patient-derived cells, we found that affected skin fibroblasts carrying the single nucleotide variations have increased activation of ERK1/2, which results in increased expression and secretion of proangiogenic factors, including VEGF.
View Article and Find Full Text PDFEvenings with Molly: Adult Couples' Use of MDMA for Relationship Enhancement.
Cult Med Psychiatry
March 2023
Within the modern resurgence of psychedelics as medicinal agents for a range of conditions, the story of MDMA (Ecstasy, Molly) has been re-narrated from a dangerous street drug to a breakthrough mental health therapy. Even still, the story of MDMA remains incomplete within a binary discourse of deviant recreational use versus psychotherapeutic-medical use. The present research aimed to uncover an emerging model of MDMA use grounded in the experiences of adult couples using MDMA privately and in the context of their committed relationships.
View Article and Find Full Text PDFSpondyloarthritis represents a group of disorders characterized by enthesitis and axial skeletal involvement. Juvenile spondyloarthritis begins before age 16. Joint involvement is usually asymmetric.
View Article and Find Full Text PDFObjectives: Whole body-MRI is helpful in directing diagnostic and treatment approaches, and as a research outcome measure. We describe our initial consensus-driven phase towards developing a whole body-MRI scoring system for juvenile idiopathic arthritis.
Methods: An iterative approach using three rounds of anonymous Delphi surveys followed by a consensus meeting was used to draft the structure of the whole body-MRI scoring system, including the relevant anatomic joints and entheses for assessment, diagnostic item selection, definition and grading, and selection of appropriate MRI planes and sequences.
Several cytokines involved in inflammatory pathologies signal via the Janus kinase-signal transducer and activator of transcription pathway. Four JAKs are known: JAK1, JAK2, JAK3 and TYK2. The specific activation of JAKs and STATs determines the biological effects of each cytokine.
View Article and Find Full Text PDFArticle Synopsis
- A study identified somatic mutations in the UBA1 gene as the cause of a newly recognized syndrome called VEXAS, which affects a significant portion of patients diagnosed with relapsing polychondritis (RP).
- Of the 92 RP patients tested, 7.6% had UBA1 mutations, with notable differences in clinical features, mortality rates, and accompanying health issues compared to those with typical RP.
- A clinical algorithm was developed to help identify patients with VEXAS among those diagnosed with RP, showing high sensitivity and specificity based on factors like male sex and specific blood test results.
Article Synopsis
- Chronic inflammatory arthritis in children, known as juvenile idiopathic arthritis (JIA), shows diverse presentations but shares similarities with adult-onset arthritis, except for some unique pediatric forms.
- Traditional approaches have treated JIA and adult arthritis as separate entities, leading to a lack of overlap in classification terms between the two groups.
- Recent research highlights the need for a revised approach that integrates biological categories and genetic data to better understand and categorize inflammatory arthritis in both children and adults.
Article Synopsis
- In 2008, guidelines were established for researching autophagy, which has since gained significant interest and new technologies, necessitating regular updates to monitoring methods across various organisms.
- The new guidelines emphasize selecting appropriate techniques to evaluate autophagy while noting that no single method suits all situations; thus, a combination of methods is encouraged.
- The document highlights that key proteins involved in autophagy also impact other cellular processes, suggesting genetic studies should focus on multiple autophagy-related genes to fully understand these pathways.
Article Synopsis
- - The study examined the responses of 20 volunteers who received the Moderna or Pfizer-BioNTech vaccines against SARS-CoV-2 and found that after eight weeks, they had high levels of anti-SARS-CoV-2 antibodies and memory B cells similar to those who recovered from infection.
- - While the vaccines produced potent neutralizing antibodies targeting the virus, their effectiveness against certain variants with mutations (E484K, N501Y, K417N) was notably reduced.
- - The findings indicate that it’s crucial to evaluate the effectiveness of monoclonal antibodies against new variants and suggest that mRNA vaccines may require updates over time to maintain their effectiveness.
Article Synopsis
- Over 100 million people have been infected by SARS-CoV-2, resulting in over two million deaths, prompting the use of mRNA vaccines like Moderna and Pfizer-BioNTech to combat COVID-19.
- A study of 20 volunteers showed that both vaccines produced strong antibody responses and memory B cells, comparable to those seen in individuals recovered from natural infections.
- However, the effectiveness of these vaccine-induced antibodies was slightly reduced against certain SARS-CoV-2 variants, indicating that continuous monitoring and potential updates to vaccines may be necessary to maintain their efficacy.
Establishing a clear role for HLA-B*27 in the pathogenesis of spondyloarthritis continues to be challenging. Aberrant properties of the heavy chain as well as a potential role presenting arthritogenic peptides continue to be pursued as plausible mechanisms. Recent studies implicate HLA-B*27 in aberrant bone formation.
View Article and Find Full Text PDFArticle Synopsis
- This review compares clinical, genetic, and pathophysiologic features of enthesitis-related arthritis (ERA) in children with axial involvement to adult forms of axial and peripheral spondyloarthritis (SpA).
- It highlights that current FDA regulations exempt pediatric studies for new medications targeting axial spondyloarthropathies, limiting treatment options for children with ERA despite similarities to adult conditions.
- The paper advocates for studying existing adult SpA medications in children with ERA to ensure effective treatments are available, emphasizing the need for pediatric investigations by the FDA for already approved adult therapies.