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.”  

In their paper, published online ahead of print on November 30, 2020, in Arthritis Care & Research, the investigators reported on the first two of four phases of criteria development. Phase I and II involved generating 261 candidate criteria for defining APS and reducing the list to 27 finalist criteria, grouped into six specific categories: laboratory tests, macrovascular, microvascular, obstetric, cardiac and hematologic. The ultimate goal is to develop a threshold-based scoring system that will allow researchers worldwide to determine which patients most likely have APS and should be included in research studies.

APS is an autoimmune disorder in which the immune system produces antibodies against specific normal proteins in the blood, causing clots in blood vessels, low platelet counts, heart valve abnormalities and pregnancy complications. It is the leading cause of stroke in young people, causing one in three strokes in people under the age of 50, one in five recurrent miscarriages and up to 20 percent of all deep vein thromboses. The disease is often found in patients with other autoimmune conditions, especially lupus.

The current APS Sapporo Classification System was published in 1999, validated in 2000, and revised in 2006. “The previous classification system was based on the available evidence at the time,” says lead author Medha Barbhaiya, MD, MPH, rheumatologist at the Barbara Volcker Center for Women and Rheumatic Diseases at HSS and assistant professor of medicine and population health sciences at Weill Cornell Medicine. “In the last decade, researchers have identified additional features of APS that deserve inclusion. We also now have more rigorous methods for developing and validating disease classification criteria.”

The international initiative is jointly funded by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR), in recognition of the need for improving the method of classifying patients for APS research to be used worldwide. Doruk Erkan, MD, MPH, rheumatologist at the Barbara Volcker Center for Women and Rheumatic Diseases at HSS and associate professor of medicine at Weill Cornell Medicine, is the senior author and co-principal investigator together with Stephane Zuily, MD, MPH, PhD, a vascular medicine specialist and professor of medicine at the Université de Lorraine, Nancy, France.

Emphasizing the difference between classification versus diagnosis criteria for APS, Dr. Erkan says, “Classification criteria are intended to be used in a research setting whereas diagnostic criteria are used in a clinical setting for the purpose of managing diseases; the two sets of criteria may have overlapping elements, but they have separate goals. The goal of classification criteria is to ensure that patients with common characteristics, thought to be specific for a certain disease, are included in appropriate research studies. In contrast, the goal of diagnostic criteria is to identify, as accurately as possible, whether patients have that particular disease.”

The next phase of the new APS classification criteria methodology involves defining, refining, and weighting the candidate criteria and assigning a threshold score for identifying APS using real-world cases and a computer-based decision tool. Following the final validation phase of the project, researchers plan to report their results in 2021. Dr. Barbhaiya is also supported by a separate but related grant, the 2018 Rheumatology Research Foundation Investigator Award, to investigate risk factors for APS using the data collected during new classification criteria development.

“We are excited to be developing validated classification criteria for APS as previously done for other rheumatologic diseases, such as lupus and rheumatoid arthritis,” says Dr. Erkan, who is also co-chair of the AntiPhospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION). “A threshold score for identifying patients with the disease will go a long way to advancing APS research, with the ultimate goal of high-quality research to improve APS prevention and treatment options for patients.”

“In APS, we haven’t known what triggers the antiphospholipid antibodies. This study sheds light on an important area to understand the mechanisms of APS,” said Doruk Erkan, MD, MPH, a rheumatologist at the Barbara Volcker Center for Women and Rheumatic Diseases, Hospital for Special Surgery, in New York City, an APS expert, and a coauthor of the research. “Millions of microorganisms exist in our gastrointestinal system, and usually these microorganisms are harmless. However if they elicit systemic immune responses, these microorganisms can be problematic by triggering autoimmunity outside the gut.”

APS can occur in patients with or without other systemic autoimmune diseases, such as lupus. In addition to blood clots, APS increases the risk for pregnancy complications, low platelet counts, anemia, kidney disease, and heart valve disease. Antiphospholipid antibodies mainly bind to the antigen β₂-glycoprotein-I, a phospholipid binding protein in the blood, and this binding triggers blood clotting and inflammation.

In the new study, the researchers investigated whether APS can be triggered by gut microorganisms, because other research has implicated the role of certain gut bacteria in autoimmune diseases such as lupus. The investigators searched a bacterial protein database to identify bacteria that had a similar snippet in their molecules to the APS-associated self molecule β₂-glycoprotein-I targeted in patients by their immune system. This snippet, called epitope, is the part of an antigen molecule to which an antibody attaches itself. They found that core epitopes of β₂-glycoprotein-I are conserved in Roseburia intestinalis, paving the way for cross reactivity. In other words, antibodies produced against this bacteria can also dock and bind on β₂-glycoprotein-I.

The researchers then recruited, from HSS and Yale, 20 healthy controls and 15 individuals who were persistently antiphospholipid antibody-positive. Cassyane Aguiar, MD a previous HSS fellow and currently a pediatric rheumatologist at Children’s Hospital for the King’s Daughters, Norfolk, VA, was also part of the research team helping with the HSS patient recruitment and follow-up. They collected blood and stool samples at baseline (month 1), and then at month 2 and month 3, to capture microbial and immune marker variability over time. They gathered information on health status, medications, 24-hour diet history, and APS-relevant genetic and immune markers such as other antibodies against self molecules.

Based on studies completed in the laboratory of Martin Kriegel, MD, PhD, at Yale School of Medicine, researchers found that Roseburia intestinalis was capable of eliciting an immune response in humans and that T cells from APS patients respond systemically to the bacteria in a manner that depended on the patient’s genetic predisposition. They found long-lasting T and B cell immune responses against this bug in APS patients. Studies in mice further supported this hypothesis and linked the cross-reactive immune responses with tissue damage. “Benign cross-reactive immune responses to gut microbes is probably very common given that we have so many of them living inside of us,” said Dr. Kriegel, who is the lead investigator on the project. “Some of them, however, can lead to damaging immune responses in predisposed individuals, which we have shown here.”

“This study is important because if we can eliminate Roseburia, then we may be able to decrease the levels of antiphospholipid antibodies,” said Dr. Erkan. “The similar epitopes between β₂-glycoprotein-I and the gut microbiome can help us better understand the mechanisms of antiphospholipid antibody production and also open doors for future treatment options.” This includes the use of antibiotics or the development of vaccines for APS and APS-associated autoimmune diseases.

According to Michael Lockshin, MD, Director of Barbara Volcker Center for Women and Rheumatic Diseases, at Hospital for Special Surgery, moving the research forward will require verifying that Roseburia intestinalis is a major, if not the most important, trigger for antiphospholipid antibodies. Since most people with this bacterium do not develop antiphospholipid syndrome, the next step will be to determine why patients develop disease.

“The microbiome itself and the concept of cross-reactivity is hard to study in humans,” said Dr. Kriegel. “We have used molecular approaches and supported our culture dish findings with animal models to show that cross-reactivity induced by a common gut bacterium in APS patients can lead to tissue damage. This study thus went far beyond the typical microbiome surveying studies and made causal links to disease, something still lacking in many studies in the field.”

The current study was a collaborative effort with researchers from HSS; Yale School of Medicine, in New Haven, Connecticut; Benaroya Research Institute, in Seattle, Washington; the Frederick National Laboratory for Cancer Research, in Frederick, Maryland; and Sackler School of Medicine, in Tel Aviv, Israel.

HSS rheumatologist Michael D. Lockshin, MD, and director of the Center, shared his conversations with patient Barbara Volcker, wife of former U.S. Federal Reserve Chairman Paul Volcker. According to the article, Mrs. Volcker met Dr. Lockshin in the 1970s to treat her rheumatoid arthritis.

"She was the type of patient that I really enjoyed taking care of because she challenged me on everything. She would say, 'But that answer doesn't make sense. Give me the information behind it. Convince me.' She drove me to question my own assumptions to respond to her," said Dr. Lockshin.

In the late 1990s, Mrs. Volcker's health worsened, and the Volckers offered to establish a center at HSS to honor her. Dr. Steven Paget, who was physician in chief at HSS, and Dr. Charles Christian, who was the emeritus physician in chief, invited Dr. Lockshin, then acting director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), to discuss the center's mission, and he was ultimately offered the job as director, a position he still holds.

The Center was established in 1997. Mrs. Volcker passed away the following year at the age of 68.

"Her questions are the core of the Center that bears her name," noted Dr. Lockshin.

The Center convened a conference on the biology of sex differences in autoimmune illness—the first of its kind—within a year of opening its doors, notes Dr. Lockshin. The topic later gained national attention for all human health when the Institute of Medicine (later renamed the National Academy of Medicine) convened a committee to address the same question and published a report in 2001, according to Dr. Lockshin, who served on the committee. Doruk Erkan, MD, MPH, a rheumatologist at HSS whose early research focused on antiphospholipid syndrome, joined the Center in 2005 as physician-scientist.

Today, the Center is marking 20 years of research and clinical work devoted to women with various rheumatic conditions. According to Dr. Lockshin, physicians at the Center see more than 3,000 individual patients for issues of pregnancy and contraception, antiphospholipid syndrome, and other rheumatic illnesses.

As part of the Center's research, HSS rheumatologists Jane E. Salmon, MD and Lisa R. Sammaritano, MD are co-investigators of a study on hormone treatment in lupus as well as pregnancy in lupus patients.

Additionally, HSS research associate Mikhail Olferiev, MD received a grant from the center to study the expression of genes across health donors and patients with lupus. "I hope that my study will contribute to a better understanding of an autoimmune disease and possibly identify new therapeutic targets," Dr. Olferiev said.

HSS scientist Theresa T. Lu, MD, PhD also received a grant to study whether fat tissue might influence stromal cells in lymph nodes to contribute to sex differences in rheumatic diseases.

Dr. Lockshin explained that concepts and ideas about pregnancy and issues related to women with rheumatic diseases have changed over time in part because of research discoveries coming out of HSS.

Additionally, the Center recently welcomed a new member, HSS rheumatologist Medha Barbhaiya, MD, MPH. Dr. Barbhaiya explained that she joined HSS because of the Center's strong emphasis on clinical care and clinical research related to lupus, antiphospholipid syndrome, and pregnancy in rheumatic diseases.

Several of its members hold leadership positions associated with the Center's mission, according to Dr. Lockshin. For example, Dr. Erkan chairs both the Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking, headquartered at the Center, and the 15th International Congress on Antiphospholipid Antibodies. Kyriakos Kirou, MD, conducts lupus nephritis clinical trials, and Dr. Sammaritano chairs the ACR Reproductive Health Guideline Project. With a background in environmental causes of autoimmune illnesses, Dr. Barbhaiya is involved with the ACR. In addition, Dr. Lockshin served on committees with a focus on pregnancy, sex differences, and other aspects of autoimmune illness and he is past editor in chief of Arthritis & Rheumatism (now Arthritis & Rheumatology).

In a phone interview, Mr. Volcker said that he is delighted with the Center's accomplishments over the years. Furthermore, he said he is sure if Mrs. Volcker were alive she would be "very pleased and happy that her name was attached to it, no doubt in my mind".

Read the full article at the-rheumatologist.org. This also appeared in the January 2018 print issue.