The study, published in Science Translational Medicine, reveals that a subset of immune cells known as SPP1ʰⁱ macrophages work in tandem with structural cells and protein scaffolds to promote excessive tissue expansion in the joints of patients with RA.

RA is a chronic autoimmune disease that causes inflammation of the synovium—the tissue lining the joints—leading to pain, swelling, and eventual damage to cartilage and bone. While current therapies largely focus on controlling inflammation, the mechanisms that drive the abnormal growth of synovial tissue—and its invasive portion, known as pannus, which erodes cartilage and bone—have remained poorly understood.

A New Model of Tissue Growth in RA

Using advanced spatial transcriptomics to analyze human tissue samples, the HSS research team discovered that SPP1ʰⁱmacrophages cluster within fibrin-rich niches in the synovium. Fibrin, a protein typically involved in blood clotting and wound healing, appears to act as a temporary scaffold that supports new tissue formation.

Within these niches, the macrophages were found to:

• break down fibrin scaffolds through enzymatic activity and cellular uptake;
• stimulate nearby fibroblasts, key structural cells, to proliferate; and
• promote tissue remodeling and expansion independent of traditional inflammatory pathways.

“This work suggests that rheumatoid arthritis is not only driven by inflammation, but also by dysregulated tissue repair processes,” said Laura Donlin, PhD, senior author and scientist at the HSS Research Institute. “We are seeing a coordinated interaction between immune cells, structural cells, and the extracellular matrix that fuels abnormal growth.”

Beyond Fibrosis: A Distinct Pathway

Interestingly, while SPP1ʰⁱmacrophages resemble cells involved in fibrotic diseases such as lung or liver fibrosis, the RA tissue environment lacks the dense collagen buildup characteristic of fibrosis. Instead, the researchers describe this process as “pro-generative” tissue remodeling, more closely resembling wound healing gone awry.

Therapeutic Implications

The findings also suggest that targeting SPP1ʰⁱmacrophages and their signaling pathways could represent a new therapeutic approach. The study highlights the role of IL-6 signaling in sustaining these cells, offering further insight into why IL-6–targeting therapies, already used in RA, may be particularly effective in certain patient populations.

“Current treatments focus on suppressing inflammation, but our findings point to additional pathways that drive disease progression,” said Dr. Donlin. “Targeting these tissue remodeling processes could open the door to more precise and effective therapies.”

Broader Impact

The study’s findings may extend beyond RA. Similar immune cell populations and fibrin-based remodeling processes have been implicated in other conditions, including interstitial lung disease, lupus, cancer, and traumatic injury, suggesting a broader role for this pathway in human disease.

RA is a chronic disease characterized by inflammation in the synovium, the tissue that covers the inner surface of the joint cavity. Although usually accompanied by joint pain, swelling and deterioration, the level of inflammation varies from patient to patient, potentially requiring customized treatment plans. “What is surprising to us is that there are some patients who have clinical remission, yet continue to experience pain and show radiographic progression of the disease with high levels of synovial inflammation, while others have high disease activity with many swollen and tender joints and little inflammation in the synovial tissue” said Susan M. Goodman, MD, rheumatologist at HSS and principal investigator of the study. She explained that even when standard tests suggest the disease is under control, the joint fluid can still show high levels of inflammation. “By analyzing synovial fluid characteristics, we expected it might give us some insight into the disparity between disease progression and apparent remission,” she added.

The team analyzed samples from 64 patients with RA, 90.6% of whom were women, and with a median age of 65.3 ±11.7 years. The physicians collected synovial fluid samples to analyze and compare with the synovial tissue biopsy counterpart, which defines the inflammatory profile of the disease.

Dr. Goodman and the team measured the total white blood cell count, as well as the percentage of neutrophils, lymphocytes and monocytes in each synovial fluid sample. They then compared those findings to two additional key pieces of clinical information: the patient’s disease activity (such as joint swelling, pain, etc.) and the level of inflammation seen in the tissue.

Their analysis revealed that the total white blood cell count in the synovial fluid did not correlate with disease activity, however, the counting of individual cell types gave insights into tissue inflammation. As such, a higher percentage of neutrophils was associated with increased inflammation in the tissue, while a higher percentage of monocytes was associated with lower inflammation in the tissue.

Because the white blood cell counts in synovial fluid provided distinct and different information from standard disease activity measures and correlated well with tissue inflammation, the team believes it could help guide the selection of personalized anti-inflammatory therapies more efficiently.

“Synovial fluid extraction is already a routine part of care, but until now, it has never been used to analyze disease state in this way,” explained Dr. Goodman. In other words, the approach could be adopted without placing additional burden on healthcare providers.

"It's important that we're gaining new methods of investigating patients with RA,” Dr. Goodman added, “since choosing the appropriate therapy and choosing it in an efficient way is clearly the best way to achieve the best outcomes.”

According to Dr. Goodman, the next phase of this study, led by HSS rheumatologists Melanie H. Smith, MD, MPH, and Dana Orange, MD, MS, will look at both the proteomics and genetics of the cells within the fluid with more molecular and immunologic techniques, with the goal of finding even more clinically relevant and important information.

Poster details

Title: Can synovial fluid features be used to predict synovial tissue pathotype?

Authors: Susan M. Goodman, Michael Parides, Solana Cushing, Daniel Ramirez, Edward DiCarlo, Rebecca B. Blank, Laura Donlin, Anna Helena Jonsson, Amit Lakhanpal, Bella Mehta, Dana Orange, Melanie Smith.

Abstract n°: 2057

Presentation: June 12^th, 2025. 2:45 PM CEST

Advancements in surgical techniques and the increased use of a medication called tranexamic acid for preventing and controlling bleeding have made it possible for many patients undergoing knee replacement to avoid needing a transfusion, which requires hospital admission for at least a day.

Despite these advancements, it was believed that patients with RA undergoing orthopedic surgeries had an elevated risk of transfusion since they tend to have higher rates of anemia compared to the individuals without the disease. RA occurs in about 1% of the general American population.² About 4% of patients having joint replacement surgeries at HSS have the disease.

“Learning that rheumatoid arthritis was not a transfusion risk factor was unexpected,” said HSS rheumatologist Susan M. Goodman, MD, co-author of the study. “However, we believe presurgical care, including proactively managing chronic anemia before surgery, played a key role in minimizing transfusion risk.”

For their study, Dr. Goodman, HSS rheumatologist Linda A. Russell, MD, and colleagues analyzed hospital records for more than 29,000 patients who had a single total knee arthroplasty procedure at HSS from February 2016 to December 2022. A total of 822 patients, or 2.8%, received transfusions. The transfusion rate declined significantly during the study period from 5.7% in 2016 to 0.9% in 2022.

The investigators reviewed patient demographics such as age and sex, preoperative hemoglobin levels, RA diagnosis and the use of tranexamic acid during surgery, and then looked for associations with transfusion risk.

“In addition to finding that rheumatoid arthritis was not a transfusion risk factor, analysis revealed that a higher preoperative hemoglobin level and the use of tranexamic acid significantly decreased transfusion risk, while being male and having a greater burden of other diseases increased risk,” said HSS pre-doctoral student and research assistant Stephen Batter, BA, the presenting author of the poster summarizing the study.

The research team plans to use their unexpected findings to develop a tool to identify patients with different levels of transfusion risk based on preoperative hemoglobin level, sex, age and health status. This initiative may help orthopedic surgeons better anticipate which patients can safely avoid transfusion and may be suitable candidates for outpatient knee replacement surgery.

Authors: Stephen Batter, BA, Huong Do, MA, Dongmei Sun, PhD, Ahmed Deeb, BA, Trang Bui, MD, Jason L. Blevins, MD, Mark P. Figgie, MD, Gwo-Chin Lee, MD, J. Alex B. Gibbons, BA, Bella Mehta, MD, MS, MBBS, Susan M. Goodman, MD, Linda Russell, MD.

Reference:

¹ Batter S, Do H, Sun D, Deeb A, Bui T, Blevins J, Figgie M, Lee G, Gibbons J, Mehta B, Goodman S, A Russell L. Investigating Predictors of Transfusion in Rheumatoid Arthritis and Osteoarthritis Patients Undergoing Knee Arthroplasty [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/investigating-predictors-of-transfusion-in-rheumatoid-arthritis-and-osteoarthritis-patients-undergoing-knee-arthroplasty/. Accessed October 10, 2024.

² Xu Y, Wu Q. Prevalence Trend and Disparities in Rheumatoid Arthritis among US Adults, 2005-2018. J Clin Med. 2021;10(15):3289. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348893/. Accessed October 10, 2024.

The study, presented today at the annual meeting of the American College of Rheumatology, ACR Convergence 2024, was led by researchers at the University of Colorado School of Medicine in collaboration with investigators from HSS and other centers within the Accelerating Medicines Partnership® Program: Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP® RA/SLE) Network.¹

“These research findings validate the importance of certain immune cells in the development of RA, particularly in how they drive the change from asymptomatic to symptomatic,” said Laura Donlin, PhD, scientist and co-director of the HSS Precision Medicine Program and co-principal investigator of the National Institutes of Health-supported AMP Rheumatoid Arthritis research consortium. “We hope that one day we can use these insights to stop RA before it even begins.”

Rheumatoid arthritis is a type of inflammatory arthritis that can occur when specific types of immune cells attack the body’s healthy tissues, resulting in pain, swelling and stiffness in joints. It can also result in problems in other areas of the body, such as the heart, lungs, eyes, nerves and skin. Diagnosis typically relies on an evaluation by a rheumatologist for clinical signs and symptoms supported by further evidence from X-rays and blood tests.

For the study, the participating rheumatologists collected tissue and blood samples from patients who either had RA or were considered at risk due to specific antibodies, called ACPA, in their blood and having a first-degree relative with the disease. Researchers at the Broad Institute of MIT and Harvard then used advanced single-cell sequencing techniques to analyze the samples and compared the results to those from healthy individuals.

The analysis found higher numbers of certain immune cells in the patients at risk for RA, including CCR2+ T helper cells, T peripheral helper cells, type 1 T helper cells, and granzyme B-positive memory T helper cells. Advanced sequencing also gave the investigators a better understanding of which genes were activated in these cells, offering insight into how the immune cells in patients with RA differ from those in at-risk individuals and healthy people.

“We knew that the presence of ACPA in blood and having a first-degree relative with rheumatoid arthritis indicate risk, but this new research has allowed us to learn more about the underlying biology driving increased risk,” said HSS rheumatologist Susan M. Goodman, MD, a co-author of the study. “These insights will pave the way toward helping us develop a new tool for determining which patients may benefit from early intervention.”

“There is some evidence that existing RA drugs, such as abatacept or rituximab, may help prevent the disease, but they are relatively expensive and come with side effects,” said co-author S. Louis Bridges, Jr., MD, PhD, physician-in-chief and chief of the Division of Rheumatology at HSS. “Pending validation in larger studies, the new patterns of immune cells identified in this research could represent potential targets for the development of new, more effective therapies.”

HSS Authors: S. Louis Bridges, Jr., MD, PhD, Vivian P. Bykerk, BSc, MD, FRCPC, Susan M. Goodman, MD, Laura Donlin, PhD.

Reference:

¹ Inamo J, Keegan J, Griffith A, Ghosh T, Horisberger A, Howard K, Pulford J, Murzin E, Hancock B, Eisenhaure T, Dominguez S, Gurra M, Gurajala S, Jonsson A, Seifert J, Feser M, Norris J, Cao Y, Apruzzese W, Bridges S, Bykerk V, Goodman S, Donlin L, Firestein G, Bathon J, Hughes L, Tabechian D, Filer A, Pitzalis C, Anolik J, Moreland L, Hacohen N, Guthridge J, James J, Cuda C, Perlman H, Brenner M, Raychaudhuri S, Sparks J, Holers M, Deane K, Lederer J, Rao D, Zhang F. Deciphering Pathogenic Phenotypes by Multi-modal Deep Single-cell Blood Immunophenotyping in Individuals At-risk for Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/deciphering-pathogenic-phenotypes-by-multi-modal-deep-single-cell-blood-immunophenotyping-in-individuals-at-risk-for-rheumatoid-arthritis/. Accessed October 10, 2024.

The study examined how patients engage with the digital world using real-time data from Google Trends. The patterns reveal not only how rheumatoid conditions affect daily life, but also reflect patients’ digital behavior as they turn to online resources for answers and support.

“Our work provides a clearer view of what patients are actually searching for and enables us to address their needs more effectively,” says Bella Mehta, MBBS, MS, MD, rheumatologist at HSS and senior author of the study.

Researchers selected a range of keywords and topics related to symptoms and treatment of rheumatic diseases. They found that online searches for symptoms consistent with rheumatoid or inflammatory arthritis, such as joint pain and swollen hands, spiked between 5:00 am and 7:00 am, when patients are likely at peak discomfort. In contrast, searches for medications like methotrexate, which is one of the standard medications for RA, were higher at night. This indicates that patients are actively seeking relief after experiencing pain throughout the day and into the evening.

“By identifying the times when patients most frequently experience and seek relief for their symptoms, we can optimize medication schedules and enhance patient support to provide more targeted care,” says Dr. Mehta. “This personalized approach not only improves the effectiveness of treatments but also helps patients better manage their conditions.”

This data-driven approach also fosters better communication between patients and providers, opening the door for more-informed discussions about symptom patterns and treatment options. “This allows us to be more responsive to patients’ needs and offer interventions that align with their daily challenges, leading to better health outcomes,” explains Dr. Mehta.

For example, many people with rheumatoid diseases search for dietary advice or other alternative treatments online, yet this is a conversation that rarely happens during clinical visits. Research studies like this can help bridge these gaps, creating more opportunities for physicians to talk to their patients about appropriate care options, rather than patients relying on potentially ineffective or harmful information online.

“By paying attention to these online behaviors, we can reduce the disconnect between the healthcare system and the individuals we serve, ensuring that we provide more empathetic, timely, and patient-centered care,” says Dr. Mehta.

Developing SR-878, a novel monoclonal antibody drug candidate targeting inflammation

SR-878, which builds upon foundational basic research discoveries made in the lab of Carl P. Blobel, MD, PhD, director of the Arthritis and Tissue Degeneration Program at the HSS Research Institute, is a monoclonal antibody drug candidate that targets inflammation in a new way.  More specifically, SR-878 targets a complex consisting of inactive Rhomboid 2 (iRhom2) and TACE/ADAM17 (ADAM17), a “master switch” for regulating the inflammatory response that is overactive in many autoimmune diseases.

ADAM17 is an enzyme involved in accelerating the body’s immune response, which has long held the interest of researchers due to its close association with an already proven target in the treatment of rheumatoid arthritis and other inflammatory diseases, the molecule TNF-alpha.

Researchers hypothesized that going after ADAM17 could prove even more effective than targeting TNF-alpha alone. “Beginning in the late 90s, there was an interest in targeting ADAM17 as another way to reduce TNF-alpha,” Dr. Blobel explains, “but it turns out, on its own, it wasn’t an optimal target because ADAM17 holds other important functions — such as protecting the skin and intestinal barrier.”

However, studies at HSS have since revealed that ADAM17 is regulated by its binding partner iRhom2. When iRhom2 is inactivated, those studies have demonstrated that the related iRhom1 can still protect against the problems observed when ADAM17 is blocked.  This research suggested that iRhom2 could be a safer and more effective target for drugs than ADAM17.

Collaborations with HSS rheumatologist Jane E. Salmon, MD, HSS Chief Scientific Officer Lionel B. Ivashkiv, MD, and HSS Physician-in-Chief Emerita Mary K. (Peggy) Crow, MD further supported this notion.  Those studies explored the effects of knocking out iRhom2 in preclinical mouse models with inflammatory arthritis as well as an autoimmune kidney disease called lupus glomerulonephritis. Their research demonstrated that the mouse models were protected from disease by blocking the TNF-alpha pathway and, in the case of lupus glomerulonephritis, also by inhibiting another pathway that contributes to inflammation, called the EGFR pathway. “We eventually realized that iRhom2 could be a very exciting target,” Dr. Blobel says.

The development of SR-878 underscores the importance of doing basic science research at academic institutions like HSS,” says Michael P. Ast, MD, orthopedic surgeon and Chief Medical Innovation Officer at HSS. “Scientific breakthroughs uncovered in the lab can be used to shape further studies that advance our understanding of complex diseases. Through the knowledge and expertise of investigators at HSS and SciRhom, we can build on the insights made together to ultimately benefit patients worldwide.”

Co-Founding & Advancing SciRhom

During a visiting professorship in 2015 in Munich, Germany, Dr. Blobel met two researchers, Drs. Jens Ruhe and Matthias Schneider, who have extensive experience in preclinical development of early to clinical stage antibody projects.

Together, HSS, the three researchers, and other experienced biotech entrepreneurs and investors, co-founded SciRhom in 2016 to translate Dr. Blobel’s scientific findings into novel therapies for autoimmune diseases.

Proof of concept studies performed by HSS scientist Gisela Weskamp, PhD, have since strongly supported the notions that targeting iRhom2 with SR-878 in a preclinical model of inflammatory arthritis is more effective than targeting TNF-alpha alone and is at least as effective as blocking both TNF-alpha and the EGFR pathway together. In addition, treatment with SR-878 also has potential to block another target of existing therapies, the interleukin-6 receptor. “We anticipate that SR-878 will simultaneously block multiple disease-causing pathways and therefore has potential for superior efficacy relative to current monotherapies,” she adds.

Following on the footsteps of its pre-clinical findings, SciRhom has since expanded its board and management ranks with former executives from the global pharmaceutical industry, including Chief Executive Officer Dr. Jan Poth, former Therapeutic Area Head Immunology at Boehringer Ingelheim, and board member Dr. Wolfgang Baiker, former CEO of Boehringer Ingelheim USA.

“SciRhom’s recent Series A financing and its approval to start clinical trials are pivotal milestones in the company’s journey towards commercialization” says Vijay Nair, Managing Director at the HSS Innovation Institute. “Bringing a discovery from the lab to patients requires immense dedication and collaboration across HSS and with the biotech entrepreneurial and investment communities. Their leadership and external validation have been critical in launching the company, securing funding, attracting world-class talent, pursuing pre-clinical development, and reaching this inflection point.”

“There is a lot of enthusiasm for this approach among members of the medical and investment communities. We are tremendously excited that we can now advance the study of this drug to human trials,” says Dr. Blobel.

The study published August 29 in Nature Communications shows that artificial intelligence and machine learning technologies can effectively and efficiently subtype pathology samples from patients with RA.

For this study, Dr. Richard Bell, an Instructor in the HSS Research Institute and Arthritis and Tissue Degeneration Program, and Lionel B. Ivashkiv,  MD, Chief Scientific Officer at HSS teamed up with  Dr. Fei Wang, a professor of population health sciences and the founding director of the Institute of AI for Digital Health (AIDH) in the Department of Population Health Sciences at Weill Cornell Medicine. 

“Our study addresses the analytical bottleneck of pathology research,” Dr. Bell said. “It is very time-consuming and tedious.” “Our tool automates the analysis of pathology slides, which may one day lead to more precise and efficient disease diagnosis and personalized treatment for RA,” said Dr. Wang. “It shows that machine learning can potentially transform pathological assessment of many diseases.”

There are several existing machine learning tools for automatic analysis of pathology slides in oncology. Dr. Wang and his colleagues have been working to expand the use of this technology in other clinical specialties.

Digital Pathology and Precision Medicine in RA

Distinguishing between the three subtypes of RA may help clinicians choose which therapy is most likely to be effective for a particular patient. This personalized medicine approach would represent a breakthrough in the care of patients with RA, and is a major goal of the Research Institute and Division of Rheumatology at HSS, which involves multiple laboratory and clinical investigators. “It’s the first step towards more personalized RA care,” Dr. Bell said. “If you can build an algorithm that identifies a patient’s subtype, you’ll be able to get patients the treatments they need more quickly.”

 The technology may provide new insights into the disease by detecting unexpected tissue changes that humans might miss. By saving pathologists time on subtyping, the tool may also decrease the cost and increase the efficiency of clinical trials testing treatments for patients with different subtypes of RA. “This work represents an important advance in analyzing RA tissues that can be applied for the benefit of patients” Dr. Ivashkiv said.

 Pathologists currently manually classify arthritis subtypes using a rubric to identify cell and tissue characteristics in biopsy samples from human patients—a slow process that adds to the cost of research and may lead to inconsistencies between pathologists.

 The team first trained its algorithm on RA samples from one set of preclinical models, optimizing its ability to distinguish tissue and cell types in the sample and sort them by subtype. They validated the tool on a second set of samples. The tool also yielded new insights into treatment effects in the models, such as reduced cartilage degradation within six weeks of administering commonly used RA treatments.

Then, they deployed the tool on patient biopsy samples from the NIH-supported Accelerating Medicines Partnership Rheumatoid Arthritis research consortium, of which HSS is a major participating site in research led by Laura Donlin, PhD, scientist and co-director of the HSS Precision Medicine Program and rheumatologist Susan  M. Goodman, MD. The new digital pathology approach could effectively and efficiently type human clinical samples. The researchers are now validating the tool with additional patient samples and determining the best way to incorporate this new tool into pathologists’ workflows.

 The team is working to develop similar tools for evaluating osteoarthritis, disc degeneration and tendinopathy.

The research reported in this story was supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Institute of Allergy and Infectious Diseases, the National Institute of General Medical Sciences, and the National Institute on Aging, all part of the National Institutes of Health, through grant numbers R21AR071670, R01AI175212, UH2AR067690, UC2AR081025, F30AG076326, T32GM007356, AR046713, AR050401, R01AR078268, UC2AR081025, UL1TR001866 and R01AR056702.

Current treatments for autoimmune diseases focus on suppressing the parts of the immune system that trigger inflammation and cause disease symptoms. But the immune-suppressing activity of these drugs also leads to side effects, including an increased susceptibility to infections.  New therapies are needed that are anti-inflammatory without being immunosuppressive.    The new study suggests that if immune cells and autoantibodies can be kept within the bloodstream, inflammatory damage is prevented.

“The idea is that if we can bolster the integrity of the blood vessels, we can prevent the immune components that trigger and mediate inflammation from entering tissues and attenuate disease ” says first author Nathalie Burg, MD, a rheumatologist and assistant scientist in the HSS Research Institute.

“This would be a completely new approach to treat or prevent organ damage in autoimmune diseases,” adds senior author Jane Salmon, MD, a rheumatologist and senior scientist at HSS.

The key to this research is a molecule called S1PR1 (Sphingosine 1-Phosphate Receptor 1). S1PR1 is important for maintaining vascular integrity — meaning it helps the endothelial cells lining the walls of the blood vessels stick together.

As part of the study, the scientists first developed mouse models with S1PR1 knocked out specifically in endothelial cells and determined that when these mice were exposed to serum that causes arthritis, there was more inflammation and damage in their joints.  In contrast, drugs that augment S1PR1 signaling and tighten the junctions between endothelial cells attenuated arthritis in experimental models.  Subsequently, an analysis of samples from patients with rheumatoid arthritis confirmed decreased levels of S1PR1 in the micro vessel endothelial cells lining the joints as well as lower levels of S1P and Sa1P, molecules that stimulate S1PR1, circulating in the bloodstream.

“This helps to confirm the role that S1PR1 plays,” Dr. Salmon explains.

While doing this research, Dr. Burg also discovered a mechanism by which S1PR1 regulates the integrity of the blood vessel walls: It helps to restrain the cleavage of a molecule called VE- cadherin, which acts like Velcro in holding the endothelial cells together. Thus, when S1PR1 is deleted or its function is blocked, the VE cadherin molecules are broken and the blood vessels become leaky.

“This research is truly multidisciplinary and also unconventional,” Dr. Salmon says. “It represents the capacity to apply one field — vascular biology — to another — immunology. It is really done at the interface of the two disciplines.” Dr. Burg learned many of the techniques used in this research in the laboratory of Timothy Hla, PhD, a leading vascular biologist and investigator at Harvard Medical School. Dr. Hla and members of his team are co-authors of The Journal of Clinical Investigation Insight paper.

The investigators plan to continue studying this approach, with the goal of designing clinical trials of drugs that boost endothelial cell S1PR1. Such drugs already exist.  

Drs. Burg and Salmon posit that these interventions would likely be used in combination with existing drugs, especially in early disease, before longstanding damage has occurred. “We don’t think this pathway is powerful enough to prevent these diseases on its own, but by combining this type of drug with an immunosuppressant, we might get a synergistic effect,” Dr. Burg says. “This might allow us to reduce the amount of immunosuppression that is needed to keep autoimmune disease under control.   We are testing the role of endothelial S1PR1 in other models of inflammatory arthritis.

Approximately 1.3 million individuals in the U.S. live with rheumatoid arthritis and 18 million worldwide. Considered a systemic autoimmune inflammatory disease, RA primarily affects the joints, causing pain, stiffness and swelling. While treatment strategies have improved in recent years, a process of trial and error is often required to alleviate symptoms and slow the progression of disease. It remains common for patients to switch medications several times over the course of months to years, with some not finding an effective therapy.

The new study, funded by the National Institutes of Health (NIH) and pharmaceutical industry partners, suggests that RA can be characterized into at least four distinct subtypes. Notably, the underlying biology of each corresponds to a different drug target. By comparing the targets in a patient’s joint with the medications to which they respond, doctors may begin to tailor treatments, potentially leading to more rapidly effective treatment outcomes.

"We believe this work lays the foundation for a new era in the treatment of rheumatoid arthritis,” said Laura Donlin, PhD, Co-Senior author and Co-Director of the Derfner Foundation Precision Medicine Laboratory at Hospital for Special Surgery (HSS). “While we have numerous medications available, the chance we'll choose the right one the first time is fairly low, around 40%. It's critical that we get patients the best medication possible as quickly as possible to slow the progression of disease. By understanding the unique features of a patient's condition, we can make more informed decisions and, hopefully, produce more successful  outcomes for patients.”

Dr. Donlin and her team at HSS are hopeful these results will lead to new standards of personalized care for RA.

Their research was made possible by generous support from The Ambrose Monell Foundation, The Carson Family Charitable Trust, and The Tow Foundation.

About HSS Research Enterprise

HSS Research Enterprise stands as the largest musculoskeletal research facility globally. With over 300 dedicated researchers and 20 state-of-the-art laboratories, HSS Research Institute leads in research aimed at enhancing the lives of patients afflicted by debilitating orthopedic and rheumatic conditions, including arthritis, bone and soft tissue injuries, autoimmune diseases, and musculoskeletal pain.

Research highlights include studies that have found an initial high-risk antibody profile for antiphospholipid syndrome (APS) tended to remain high in pediatric patients, a correlation between obesity and more severe disease flare symptoms in patients with early rheumatoid arthritis (RA), people with inflammatory arthritis face challenges in maintaining employment, a link between aging and physical activity, and people with vasculitis frequently suffer from frailty, new research findings in antiphospholipid syndrome (APS)  insights on improving communications with diverse patient populations, and and new research on reproductive health.

A High-Risk Antiphospholipid Antibody Profile Matters in Pediatric Patients with Antiphospholipid Syndrome

A new study by HSS investigators including Jheel Pandya, MD, Karen Onel, MD, Doruk Erkan, MD, MPH has found that an initial high-risk antibody profile for APS tended to remain high in pediatric patients.

HSS Research Shows Obesity Is Associated with Worse Flare Symptoms and Quality of Life in People with Early Rheumatoid Arthritis 

A recent study from HSS and others has found a correlation between obesity and more severe disease flare symptoms that negatively affect quality of life in patients with early RA, a systemic, autoimmune, inflammatory disorder affecting multiple joints in the body. 

Study Finds People with Inflammatory Arthritis Face Significant Psychological Challenges in Maintaining Employment

An HSS study presented by Joan Westreich, MSW, LCSW, social work coordinator, Early Arthritis Initiative at HSS reveals a significant psychological impact related to inflammatory arthritis patients’ efforts to maintain employment while coping with the challenges of their illness.

New Study Shows Perception of Aging is Linked to Level of Physical Activity in Arthritis Patients

People with arthritis who report more negative feelings about how they are aging tend to get less physical activity and perceive themselves as less healthy, according to a new study by researchers at HSS and Weill Cornell Medicine. However, self-perception of good health explained the effect of negative thinking – providing an opportunity for clinicians to focus on a patient’s outlook on aging as well as their overall health. 

New Study Identifies Outcomes Associated With Frailty in Patients With Vasculitis

According to a new study from researchers at HSS and colleagues from the University of Pittsburgh and the University of Pennsylvania, people with vasculitis frequently suffer from frailty, a process that can affect our ability to recover after an illness or a fall, which in turn is linked to poor health outcomes.

New Antiphospholipid Syndrome Research Findings Presented at ACR Convergence 2023

Investigators from the Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) presented new research findings in antiphospholipid syndrome (APS) at the American College of Rheumatology (ACR) Convergence 2023, the ACR’s annual meeting.

HSS Shares Strategies to Enhance and Enable Communication with Language-Diverse Patients at Annual ACR Convergence

Bella Elogoodin, vice president, Service Excellence & Language Access at HSS, shared strategies to enhance and enable communication with language-diverse patients at the American College of Rheumatology (ACR) Convergence 2023 in a session titled, “Lost in Translation: Creating Access Pathways for Language-Diverse Patients in Rheumatic Care Settings.”

HSS Presents New Reproductive Health Research at the ACR Convergence 2023  

At this year’s American College of Rheumatology (ACR) annual meeting, HSS presented a number of studies focused on reproductive health for patients with systemic lupus erythematosus, rheumatoid arthritis, and other rheumatic diseases, including issues related to fertility, sexual function, use of contraception and HPV vaccination.

In the study, Dr. Park-Min and her team examined human bone resorbing cells called osteoclasts and identified a new way to specifically target osteoclasts of patents without affecting other cells. Dysregulated osteoclasts led to bone destruction, limited mobility, and pain. Their findings lead them to believe that ASO therapy could be used to target bone diseases associated with hyperactive osteoclasts, including osteoporosis and rheumatoid arthritis. This is impactful as an estimated 1.3 million Americans have Rheumatoid Arthritis (RA) and suffer from the disease’s debilitating symptoms.

Dr. Park-Min shared, “While regulators of osteoclast formation are well defined, the cell-specific regulatory mechanism controlling osteoclasts remains fairly unknown. By defining cell-specific targets, we can provide novel therapies and improve patient outcomes.”

The team found high expression of osteoclast-specific signature in RA synovial fluid cells by real-time PCR analysis, which provided unprecedented insight that suggests manipulating SE-eRNAs may offer a novel, osteoclast-specific therapeutic strategy for treating dysregulated osteoclast-mediated bone diseases. 

Dr. Park- Min’s team includes HSS Alumni Researchers, Dr. Sungho Park of Ulsan National Institute of Science & Technology and Dr. Eun Young Lee of Seoul National University College of Medicine, in the Republic of Korea. Their work is supported by Rosensweig Genomics Center from The Tow Foundation.

Critical issues included a lack of health education and awareness in managing arthritis and other painful conditions; a high incidence of falls in the community; and limited access to care among underserved populations.

The study, “Assessing Musculoskeletal Health Needs of Underserved Patients & Community Members Using a Community Based Participatory Research Approach,” was presented virtually at ACR Convergence 2022, the annual meeting of the American College of Rheumatology in Philadelphia.

“Musculoskeletal disorders are the most prevalent health conditions in the United States, resulting in financial and social burdens, especially in underserved communities,” explained Titilayo Adeniran, MPH, director of outcomes & data analytics at the HSS Education Institute. “Studies show that musculoskeletal health disparities disproportionately affect women, older adults and racial/ethnic minorities.”

HSS researchers used a mixed-method approach to develop a Community Health Needs Assessment (CHNA). “For quantitative data, we distributed a community survey in four languages—English, Spanish, Chinese and Russian—to assess the socio-demographic characteristics of the populations we serve; health status and quality of life; health behavior and lifestyle; use of and access to care; and health education needs,” explained Adeniran. “For qualitative data, we conducted interviews with 22 community partners, including community-based organizations, city and state agencies and universities.”

The survey was distributed in various ways, including online, via email, using Alchemer panels, in person, and through the mail over a four-week period from January 15 to February 15, 2022. A total of 18,248 patients and community members completed the surveys, with 57% representing a diverse and underserved population.

In addition to the surveys, interviews with community partners provided valuable insights into unmet health needs, Adeniran noted. Community organizations represented all five boroughs of New York City, as well as surrounding areas serving racially/ethnically diverse populations. They represented all age, gender, and socioeconomic groups.

Key findings:

- Chronic pain, osteoarthritis or another form of arthritis were the most common musculoskeletal conditions reported in the survey.
- Among respondents with a musculoskeletal condition, a lack of confidence in managing symptoms emerged as a health need, particularly among medically underserved community members.
- Almost one-third of all respondents reported falling in the past year.
- Those with chronic pain, fibromyalgia or lupus were more likely to report two or more weeks of poor physical and mental health.
- Medically underserved respondents diagnosed with lupus, chronic pain or rheumatoid arthritis were more likely to have used a prescription opioid to manage pain.
- Health education emerged as a major need, with 70% of respondents reporting no participation in health education in the past 12 months. The top reasons were fear of COVID-19 and not knowing about educational programs.
- The top issues impacting respondents’ health and well-being were COVID-19 related issues, social isolation/loneliness, limited places to exercise, and limited access to healthy foods.
- The survey identified a need to address access to healthcare, with 42% of respondents reporting they could not access healthcare in the past 12 months, compared to 8% in a previous survey conducted in 2019. The top barriers were difficulty getting an appointment, lack of affordability or a service not covered by insurance. The need for transportation was also cited among the medically underserved.
- The most common type of discrimination reported in medical settings was that a doctor or nurse was not listening to the respondent. More than half of those taking the survey cited this issue.

“Broad community engagement is crucial to the success of any CBPR approach when assessing the health needs of the community and identifying health disparities,” said Sandra Goldsmith, MA, MS, RD, assistant vice president at the HSS Education Institute. “The results of our study will enable us to raise awareness about disparities that continue to affect our diverse and underserved populations and help us develop community-based initiatives to promote health equity.”

Authors: Titilayo Adeniran, Bertilia Trieu, Sandra Goldsmith and Laura Robbins, Hospital for Special Surgery, New York, NY

Michael Lockshin, MD, received the ACR Distinguished Clinician Scholar Award, which honors a rheumatologist who has made outstanding contributions in clinical medicine, clinical scholarship or education.

Melanie Smith, MD, PhD, received the ACR Distinguished Fellow Award, which recognizes clinical and research fellows who are in a rheumatology fellowship training program and have performed meritoriously.

Adena Batterman, LCSW, MSW, received the ARP Distinguished Clinician Award. It is presented to an ARP member who is engaged in clinical practice and demonstrates outstanding clinical expertise in arthritis and the rheumatic diseases.

"HSS is extremely proud of our team members who have been honored with these notable awards,” said Louis A. Shapiro, president and CEO of HSS. “We warmly congratulate them for their contributions and achievements in patient care, research, support and education.”

Michael Lockshin, MD

Dr. Lockshin’s award follows a career spanning more than four decades at HSS. When asked about receiving the honor, he said, “I think it honors those who surrounded and challenged me more than it does me—patients who asked hard questions; the team led by Charles Christian that trained me and with whom I was privileged to work; intellectually curious colleagues, students and fellows; Hospital for Special Surgery, which gave me freedom to pursue goals I thought were worthwhile; and my wonderful family.”

Director emeritus of the Barbara Volcker Center for Women and Rheumatic Disease at HSS, Dr. Lockshin is a preeminent expert in the long-term care of chronically ill patients. His research enabled him to develop special expertise in solving health-care issues associated with systemic lupus erythematosus, antiphospholipid antibody syndrome and other autoimmune diseases that predominantly affect women.

Dr. Lockshin continues to conduct research and engage in mentoring activities at HSS. His current work focuses on diagnostic uncertainty, the topic of an international conference he organized last year. He has also published a white paper and written a book on the subject.

Melanie Smith, MD, PhD

Dr. Smith describes her Distinguished Fellow award as an incredible honor. “It is a testament to the opportunities I have had during my fellowship training and the amazing group of mentors that have supported my development as both a physician and a scientist,” she said. “I am excited to embark on a career dedicated to understanding mechanisms of disease with the goal of improving care for our patients.”

Dr. Smith, now a staff rheumatologist at HSS, specializes in treating inflammatory arthritic conditions such as rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Sjogren's syndrome and gout/pseudogout. She also treats patients with osteoarthritis. Her research focuses on how cells that make up the healthy joint lining change when an individual develops rheumatoid arthritis.

Adena Batterman, LCSW, MSW

Adena Batterman, recognized with the ARP Distinguished Clinician Award, is senior manager of the Inflammatory Arthritis Support and Education Programs at HSS. “I feel honored and grateful to be recognized for clinical work and research that enhances the lives, and elevates the voices, of patients,” she said. “I’m grateful to be engaged in work made possible by colleagues and mentors that continues to have deep personal and professional meaning to me.”

Ms. Batterman develops and oversees support and education programs designed to address the multifaceted needs of patients with inflammatory arthritis during the many stages of their illness. The programs provide essential information to help participants make informed decisions about management and treatment; offer peer support and coping strategies; and create a forum in which members can share their experiences and feelings.

“I commend our HSS colleagues who have been honored by two of the foremost organizations advancing the field of rheumatology,” said S. Louis Bridges, Jr., MD, PhD, physician-in-chief and chief of the Division of Rheumatology at HSS. "Our colleagues’ hard work, skill and dedication have enabled them to excel in their respective specialties. Their contributions have helped HSS achieve a leadership role in rheumatology to improve the lives of patients with exceptional care and vital research.”