Rheumatology Research Highlights
Featured Highlights:
Featuring Yu Qiao, PhD; Eugenia G. Giannopoulou, PhD; Chun Hin Chan; Sung-ho Park; Shiaoching Gong; Janice Chen; Xiaoyu Hu, MD, PhD; Olivier Elemento, PhD; Lionel B. Ivashkiv, MD
The identification of molecular mechanisms involving chromatin that act synergistically during the inflammatory process may help reveal potential new therapies to arrest tissue damage.
A team of HSS researchers conducted a genome-wide analysis to better understand the strong synergistic activation of cytokine production in human macrophages. Their findings showed that linked actions between signaling mechanisms that call for increased inflammation and epigenetic actions prepare genes for increased transcriptional activation. The team further found that interferon-gamma (IFN-γ) primes the chromatin for key promoters and enhancers of inflammation—including TNF, IL6, IL12B—preparing the genes for transcription. The primed chromatin enables increased response to the signaling for more transcription that comes from Toll-like Receptors (TLR). Priming is mediated by pathways and mechanisms used in inflammatory signaling, including a stable STAT1 and IRF1 occupancy and histone acetylation.
This priming process also makes cells more susceptible to inhibition by two categories of drugs, Janus kinase (Jak) inhibitors and Bromodomain and Extra-Terminal (BET) inhibitors. By selectively targeting priming mechanisms while leaving residual TLR functions intact, new therapeutic approaches may be less toxic to the patient.
Featuring Josephine Isgro, MD; Sanjay Gupta, PhD; Elzbieta Jacek, BA; Tanya Pavri, BA; Roland Duculan, MD; Mimi Kim, ScD; Kyriakos A. Kirou, MD, ScD; Jane E. Salmon, MD; Alessandra B. Pernis, MD
A study that found higher levels of Rho-associated protein kinase (ROCK) in patients with systemic lupus erythematosus (SLE) versus healthy controls, suggests a potentially significant therapeutic target for the treatment of SLE
Because of its role in the differentiation of TH17 cells and the production of two key cytokine messengers in the pathogenesis of systemic lupus erythematosus—interleukin 17 (IL-17) and interleukin 21 (IL-21)—enhanced ROCK activity has been identified as an area of interest in SLE research. In an analysis completed by HSS investigators, this association was confirmed both in an in vitro assessment of increased ROCK activation in TH17 differentiation using purified human cord blood, and in a cross-sectional evaluation of 28 SLE patients with 25 healthy matched controls.
Overall, the SLE patients expressed significantly higher median ROCK levels than that of healthy controls, 1.251 versus 0.5645, respectively. (these values were obtained by using ann ELISA-based ROCK kinase activity assay to measure ROCK activation.) Among the SLE patients, two subgroups were found, one with high ROCK values (16 of the 28 patients, or 57%) and one with low ROCK values. No healthy control had a high ROCK value.
A series of analyses were also performed to find possible correlations between level of ROCK activation and clinical manifestations and or immunologic characteristics of SLE. Although no association with known measures of disease activity (and only one clinical variable—absolute lymphocyte count) was found in this study, the team plans to follow patients longitudinally to assess any possible correspondence between fluctuations in ROCK activity and manifestations of SLE over time.
Moreover, because statins have been shown in vitro to inhibit ROCK activity, study of the potential role of these drugs as well as other ROCK inhibitors may eventually yield new therapeutic alternatives in the treatment of SLE.
Featuring Christina Mertelsmann-Voss, MD; Stephen Lyman, PhD; Ting Jung Pan, MPH; Susan Goodman, MD; Mark P. Figgie, MD; Lisa Mandl, MD MPH
An analysis of discharge data for arthroplasty patients with systemic lupus erythematosus (SLE) compared with those who had no inflammatory or autoimmune conditions showed an almost two-fold increase in the SLE group from 1991 to 2005
A team of HSS researchers has found that arthroplasty rates among patients with SLE increased in similar proportions to overall joint replacement rates.
Hospital discharge databases from 10 American states were used to compare knee, hip, and shoulder arthroplasty rates. Among patients with non-inflammatory conditions the rate almost doubled, increasing from 124.5 cases/100,000 people to 247.5/100,000 (p < 0.001). Similarly, arthroplasty rates for patients with SLE increased from 0.17/100,000 to 0.38/100,000 (p < 0.001).
Researchers also found that the mean age in arthroplasty patients with SLE increased from 47.3 ± 17.0 in 1991 to 56.8± 16.0 in 2005. When stratified by age and sex, arthroplasty in SLE patients increased in all groups except women younger than 44 years old. (In contrast, arthroplasties associated with non-inflammatory conditions increased in this age group.)
A shift was also observed in the indications for joint replacement surgery among patients with SLE. In 1991, a diagnosis of osteonecrosis accounted for 53% of cases of arthroplasty and a diagnosis of osteoarthritis accounted for 23% of cases. This relationship was reversed by 2005, with osteonecrosis accounting for 24% and osteoarthritis accounting for 61% of joint replacement surgeries. Reduced reliance on high-dose corticosteroids, which are associated with osteonecrosis of the hip, has been proposed as one reason for this finding.
The shift in indications for arthroplasty in patients with SLE also suggests that increased longevity has resulted in more age-related osteoarthritis. Moreover, reduced morbidity has permitted more elective joint replacement surgeries.
Although individuals with SLE continue to represent only a small proportion of the total number of arthroplasties performed annually, their growing numbers underscore the need for widespread training in the care of these potentially complex cases.
Featuring Susan M. Goodman, MD; Lisa A. Mandl, MD, MPH; Mark P. Figgie, MD; Beverly K. Johnson, MD, MS; Michael Alexiades, MD; Hassan Ghomrawi, PhD, MPH
Rheumatoid arthritis patients on biologic DMARD therapy have more optimistic expectations about knee replacement surgery—comparable to those of osteoarthritis patients—than do RA patients not on biologics
Although patients with rheumatoid arthritis have been shown to have lower expectations of total knee arthroplasty, than do patients with osteoarthritis, recent findings showed no significant difference between these two groups when RA patients were taking DMARD therapy.
HSS investigators analyzed data from patients matched by age, sex, prior TKA, and preoperative function, who were enrolled in the Hospital’s TKA registry. All patients completed the Hospital’s Knee Expectations Survey, which employs a Likert scale to measure responses. Questions were designed to elicit preoperative expectations about pain relief, as well as a range of physical and psychosocial activities associated with mobility, including fitness for employment, ability to use public transportation and ability to participate in social activities.
An analysis of results gathered from 114 patients with RA (46.5T were taking biologics) and 228 patients with osteoarthritis showed no significant difference in expectations score (p=0.71) between OA patients and those RA patients taking biologics. RA patients not on biologics had expectation scores that were significantly lower (p=0.03) than these other groups.
Interestingly, there was a significant relationship between expectations and post-operative pain and function outcomes only in those patients who were not on biologic DMARDs. For patients with osteoarthritis or patients who were treated with biologic DMARDs, there was no relationship between expectations and post-operative pain and function.
Featuring Michael D. Lockshin, MD
Clinical trials based on risk stratification and long-term follow-up of infants born to mothers with APS may result in more effective management during pregnancy
Adverse pregnancy outcome in patients with Antiphospholipid Syndrome (APS)—including fetal death, fetal growth restriction, prematurity, and early or severe preeclampsia—is associated with antiphospholipid antibodies (aPL). However, recent research suggests that not all aPL confer the same degree of risk, findings that may help guide future research and treatment.
A review of the literature by HSS rheumatologist Michael Lockshin, MD, supports the conclusion that among aPLs, LAC is the most powerful predictor of pregnancy loss. However, anticardiolipin antibody (aCL) and antibody to β2 glycoprotein I (aβ2GP-I) are also associated with adverse outcome. (The available data on aCL isotypes suggests that IgG carries more importance than IgM, and that IgA is not independently a predictor.) In addition, other clinical features, specifically coexisting SLE, contribute to pregnancy risk. (Prior thrombosis history, smoking, and trigger factors such as surgery, trauma, severe infections of any kind and oral contraceptive therapy also appear to increase risk.) In addition, Dr. Lockshin found that no study to date has sufficiently stratified patients to support an unequivocal recommendation of heparin treatment for prophylaxis against thrombosis and associated pregnancy loss, nor are clear guidelines for either dose or type—low-molecular weight or unfractionated—of heparin available. Concerns about the validity of findings from earlier studies include the omission of the role of additional risk factors as well as the potential role of aβ2GP-I, which was not identified until 1990.
Current treatment regimens for pregnant women with APS are based primarily on consensus data rather than on clinical trials and are guided by patient history; in those with no prior thrombosis, prophylactic doses of low molecular weight heparin or unfractionated heparin with low-dose aspirin are given, with treatment beginning at conception and continuing for 4-6 weeks post-partum. In patients with a history of thrombosis, full anticoagulant doses of low molecular weight heparin or unfractionated heparin are given, with treatment beginning at conception and continuing indefinitely. Dosing is reduced in the presence of renal impairment.
More recent outcomes studies at HSS suggest that LAC is the primary predictor of adverse pregnancy outcome after 12 weeks’ gestation. If LAC is not present, aCL and aβ2GP-1do not predict adverse pregnancy outcome.
Recommended areas of exploration for future study include possible alternatives to anticoagulation therapy (including those based on new findings about the biology of aPL- associated tissue damage.) For example, products that prevent complement activation may be of benefit. These therapies would seek to address injury or activation that may trigger clotting, and thereby stop the process before clotting occurs. However, designing safe and ethical clinical trials is complicated by multiple factors, including the need for very large numbers of patients to demonstrate success, and a high-level guarantee of the safety of intervention. In addition, owing to advances in neonatology, survival rates for premature or ill infants have increased. Therefore outcome criteria must include prematurity, growth restriction, and preeclampsia, as well as fetal death. Researchers should also follow infants through childhood and possibly into the teen years to determine long-term outcomes of intervention. .
Featuring Cassyanne L. Aguiar, MD; Doruk Erkan, MD
A step-by-step clinical approach can address the diagnostic challenges of Catastrophic Antiphospholipid Syndrome (CAPS)
Catastrophic Antiphospholipid Syndrome (CAPS), the most severe form of the multisystem autoimmune disease, Antiphospholipid Syndrome (APS), can present the clinician with a number of diagnostic challenges, including the absence of a history of significant antiphospholipid antibody (aPL) positivity in almost half of all patients. In addition to the vascular thrombosis and/or pregnancy loss associated with persistently positive aPL, patients with CAPS have multiple organ involvement that develops over a short period of time, usually associated with microthrombosis.
Based on the classification criteria for CAPS[1] that were first proposed during the 10th International Congress on aPL, “Definite CAPS” is defined as: thromboses in three or more organs that develop in less than a week, microthrombosis in at least one organ, and persistent aPL positivity. “Probable CAPS” is when the patient develops only three out of four of these criteria. The authors refer to aPL-positive patients with multiple and/or life-threatening events who do not fulfill all of these criteria as “CAPS-like”—a term signaling the need for close monitoring for the development of CAPS, and aggressive treatment where indicated.
Diagnostic challenges in CAPS include: false-positive or negative aPL results during the acute event; overlapping features of other thrombotic microangiopathies; similarities between CAPS and features of sepsis associated with Disseminated Intravascular Coagulation (DIC); and similarities between CAPS and Heparin-induced Thrombocytopenia (HIT).
To address these potential diagnostic challenges in patients with suspected CAPS and multi-organ thrombosis, the authors review updated algorithms (2010)[2] for both those individuals with and without history of aPL positivity. They further advocate maintaining a high degree of suspicion in patients who meet some, but not all of the established diagnostic criteria for CAPS. Both diagnosis and management of CAPS are most effectively supported by a team approach including, but not limited to rheumatology, hematology, intensive care, infectious disease, nephrology, and a plasma exchange team, as well as obstetrics when relevant.
1) Asherson RA, Cervera R, de Groot PG, Erkan D, et al. Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines. Lupus. 2003;12;530-534.
2) Erkan D, Espinosa G, Cervera R. Catastrophic antiphospholipid syndrome: Updated diagnostic algorithms. Autoimmunity Reviews. 2010;10(2):74-79.
Featuring Nancy Pan, MD; Isabelle Amigues, MD; Stephen Lyman, PhD; Roland Duculan, MD; Faisal Aziz, MD; Mary K. Crow, MD; Kyriakos A. Kirou, MD
Rapid and substantial rises in Anti-dsDNA suggests utility of prompt close monitoring for SLE flares Rapid and substantial rises in Anti-dsDNA suggests utility of prompt close monitoring for SLE flares
A surge in anti-double-stranded (ds) DNA titers (anti-dsDNA) is a good predictor of a clinically important SLE flare and signals the need for close monitoring and prompt treatment, an HSS study has revealed. Anti-dsDNA is an anti-nuclear antibody that is present in 97% of people with systemic lupus erythematosus (SLE) and has long been used as part of the diagnostic work-up. However, results from previous studies have differed on the importance of the titer in predicting disease flares in patients already diagnosed with SLE.
Now a study conducted by a team of HSS rheumatologists has found an association between anti-dsDNA surge and the subsequent development of a severe flare within six months as measured by the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI or SS.) A surge of anti-dsDNA was defined as an increase of anti-dsDNA titer by the Crithidia luciliae immunofluorescence (CLIF) assay from 0 to 3+/4+, or from 1+to 4+ within a period of less than 12 months. The study also looked at the relationship of anti-dsDNA surges to mild/moderate SS flares, and renal flares—increased clinical activity in patients with lupus nephritis—as measured by the British Isles Lupus Assessment Group Index (BILAG) A and B.
Results of the HSS matched case-control study showed a higher proportion of SLE patients, in whom a rapid and sudden anti-dsDNA surge was detected, experienced a severe SS flare within 6 months, as compared to a control group. The study also found an association with mild/moderate flares and hospitalizations for flares. However, surges in anti-dsDNA did not predict renal flares.
Featuring Laura T. Donlin, PhD; Arundathi Jayatilleke, MD; Eugenia G. Giannopoulou, PhD; George D. Kalliolias, MD, PhD; Lionel B. Ivashkiv, MD
Synovial fibroblast modulation of macrophage function may play a role in the pathogenesis of inflammatory arthritis
Synovial fibroblasts, primarily known as structural support cells in the membrane that line the joints, appear to regulate the activity of macrophages, white blood cells that play a key role in the immune response, a new HSS study shows.
Building on previous findings that demonstrated the potential significance of these two types of cells in joint inflammation, the team led by Laura T. Donlin, PhD and Lionel B. Ivashkiv, MD, explored how synovial fibroblasts affect the macrophage response to tumor necrosis factor (TNF)—an agent that induces inflammation—during an inflammatory response.
Results of their study showed that synovial fibroblast suppression of specific types of macrophage activity may also play a role in the development of rheumatoid arthritis. The team’s finding contributes to an understanding of the disease process at the cellular level and may lead to new therapeutic alternatives for patients with rheumatoid arthritis.
The researchers established this relationship through RNA sequencing of human donor tissue, which allowed them to look at the activity of all of the genes in the cells’ genomes at the same time.
Featuring Theodore R. Fields, MD; Anne R. Bass, MD; Juliet Aizer, MD, MPH; Stephen A. Paget, MD; Jessica Berman, MD
Study finds clear communication matters
Rheumatology fellows training in New York recently learned some important news with implications for all clinicians, not just fellows: excessive use of medical jargon makes a doctor seem less professional.
Since 2004, fellows from many NYC hospitals participate in a structured, clinical exam called New York City Rheumatology Objective Self Assessment Clinical Exam or NYC-ROSCE. Real-life patients with rheumatic conditions are recruited and trained to be examined by the fellows, simulating many different rheumatic issues and patient temperaments, while a board-certified rheumatologist observes.
The patient-actors and observing MDs give immediate oral feedback, then later fill-in written evaluations and questionnaires. The fellows also rate their own performances. Discussing the results helps the fellows become better doctors.
This year, an evaluation was added to see which particular skills correlated highest with professionalism. Results: clear communication matters. Both the patient-actors and MD-evaluators correlated jargon reliance inversely with the ratings of professionalism. The patients considered ability to minimize medical jargon to be one of the most important markers of professional competency.
This study was presented at the 2013 ACR Annual Meeting.
Featuring Katherine C. Hall; Daniel Hill; Miguel Otero, PhD; Darren A. Plumb, PhD; Dara Froemel, MD; Cecilia L. Dragomir, MD; Thorsten Maretzky, PhD; Adele Boskey, PhD; Licia Selleri, MD, PhD; Mary B. Goldring, PhD; Carl P. Blobel, MD, PhD
Mice whose cartilage cells were missing ADAM17 did not experience proper long bone growth.
ADAM17, a crucial regulator of cell-to-cell interaction in inflammation, has been found to control cellular signaling in terminal differentiation of chrondrocytes a key process of new bone growth.
The long bones of the skeleton are formed through a complex process called endochondral ossification, in which the matrix made by cartilage cells known as chondrocytes is transformed into hard, new bone. Terminal differentiation refers to the final maturation process of chondrocytes, which allows these cells to synthesize a matrix that can be mineralized as part of the formation of new bone.
A recent HSS-led study has shown that ADAM17 controls cellular signaling during terminal differentiation of chondrocytes in the growth plate of long bones, specifically along the growth factor TGFα/EGFR axis.
Mice bred without ADAM17 in their endochondral chondrocytes did not have proper ossification or normal long bone growth because the cellular signaling that ADAM17 would normally send to regulate the differentiation of chondrocytes and permit the deposition of new bone was disrupted in these animals.
This study was presented at the 2013 ACR Annual Meeting.
Featuring Priya Darshinee A. Issuree, PhD; Thorsten Maretzky, PhD; Xiaoping Qing, MD, PhD; Steven L. Swendeman, PhD; Kyung-Hyun Park-Min, MD; Nikolaus Binder, PhD; George D. Kalliolias, MD, PhD; Anna Yarilina, PhD; Lionel B. Ivashkiv, MD; Jane E. Salmon, MD; Carl P. Blobel, MD, PhD
Selectively targeting iRHOM2 could create new therapies to treat RA with less side effects
Two exciting studies at HSS have shown that inactive rhomboid protein 2 – or iRHOM2 – is a promising target for new therapies to treat rheumatoid arthritis (RA). Currently, biologic drugs used to treat RA block the cytokine tumor necrosis factor alpha (TNF-α) from signaling for inflammation. New iRHOM2 therapies would intervene earlier in the inflammatory process.
TNF-α is released into signaling action by a process known as shedding. A kind of molecular scissors called TACE, or tumor necrosis factor-α converting enzyme, snips the tether that holds TNF-α on the membranes of macrophage cells of the immune system. TNF-α “sheds” into the bloodstream. However, any drug that blocked TACE system-wide to prevent shedding would also block TACE’s other important functions like protecting skin and the intestinal barrier.
Now, HSS-led research has found that iRHOM2 regulates TACE’s shedding functions. Essentially, iRHOM2 wraps around TACE to help it shed TNF-α. Further, these studies suggest the exciting possibility that monocloclonal antibodies could be developed to prevent iRHOM2 from allowing TACE to shed TNF-α, but not stop TACE’s necessary and helpful functions.
Experiments at HSS with special mice who had no iRHOM2, found that the mice, when challenged to develop inflammatory arthritis, remained healthy. New iRHOM2 therapies could potentially cause less side effects than anti-TNF drugs, and benefit patients with conditions that anti-TNF drugs do not currently help.
This study was presented at the 2013 ACR Annual Meeting.
For more information about inflammatory arthritis treatment at HSS, see the Inflammatory Arthritis Center.
Featuring Vivian P. Bykerk, MD; Pooneh Akhavan, MD, FRCPC; Edward C. Keystone, MD, FRCPC; Juan Xiong, PhD; Bindee Kuriya, MD, FRCPC, MSc; Janet E Pope, MD, MPH, FRCPC; Gilles Boire, MD, MSc; Diane Tin, BPharm; Boulos Haraoui, MD, FRCPC; Carol A. Hitchon, MD
Delaying treatment for RA can increase chances of long-term joint damage
Patients with early rheumatoid arthritis (RA) who reach the treatment target of low disease activity (LDA) at 6 months show less joint damage and functional ability after two years than those who do not achieve the target. LDA means joint pain, swelling, and other markers of inflammation are markedly reduced.
These important findings are from a study using data from the Canadian early ArThritis Cohort (CATCH), an ongoing multi-center project which has been collecting information on patients with early inflammatory arthritis in Canada since 2007. HSS Associate Attending Rheumatologist Vivian Bykerk, MD, is chair and director of CATCH.
Of the 833 patients in the study, 56% achieved LDA at 6 months. Dr. Bykerk believes there is a window for RA treatment within the first three months of developing joint inflammation. During the window, patients with RA have a better chance of getting the disease under good control, with many needing less intense therapy over the long run.
This study was presented at the 2013 ACR Annual Meeting.
For more information about rheumatoid arthritis treatment at HSS, see the Inflammatory Arthritis Center.
Featuring Alessandra B. Pernis, MD; Josephine Isgro, MD; Sanjay Gupta, MD; Elzbieta Jacek; Tanya Pavri; Roland Duculan, MD; Kyriakos A. Kirou, MD; Jane E. Salmon, MD
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Comparing 28 patients with lupus to 25 healthy control patients, a research team of HSS scientists and rheumatologists found that the patients with lupus had increased activity of proteins called rho-associated kinases – or ROCKs. This enhanced activity was associated with differentiation of the Th17 cells of the immune system.
In lupus, inflammation can be triggered by signals from two key cytokine messengers – interleukin 17 (IL-17) and interleukin 21 (IL-21). To produce these cytokines the body requires a transcription factor called IRF4.
The ability of IRF4 to drive cytokine production is controlled by ROCKs – which phosphorylate IRF4. Drugs that inhibit ROCK activity are already used to treat cardiovascular and other diseases. In previous studies, using lupus mice, the HSS team showed drugs that inhibit ROCKs could reduce inflammation. In this new study, using human T cells, ROCK inhibitors reduced production of IL-17 and IL-21. These results support the idea that ROCKs could be promising therapeutic targets for treating lupus.
This study was presented at the 2013 ACR Annual Meeting.
For more information about lupus treatment at HSS, see the Lupus and APS Center of Excellence.
Featuring Danielle Ramsden-Stein, MD; Susan M. Goodman, MD; Michael M. Alexiades, MD; Wei-Ti Huang, MS; Rebecca Zhu; Mark P. Figgie, MD; Lisa A. Mandl, MD, MPH
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A large outcomes study of 223 patients with rheumatoid arthritis (RA) and 561 with osteoarthritis (OA) who underwent total hip replacement at HSS shows that being socially isolated is associated with almost three times the odds of experiencing painful results after surgery.
Furthermore, social isolation appears to be more significant in OA, which comprises the vast majority of hip replacement cases.
This study was presented at the 2013 ACR Annual Meeting.
For more information about rheumatoid arthritis treatment at HSS, see the Inflammatory Arthritis Center.
Featuring Jane E. Salmon, MD; Michael D. Lockshin, MD; Lisa R. Sammaritano, MD; Marta M. Guerra, MS
New biomarkers could help identify pregnancies at risk in patients with lupus or aPL.
Adult bodies form new blood vessels from existing ones through a process called angiogensis. During pregnancy, a woman’s body grows many new blood vessels to support the developing fetus. The biological molecules involved in the growth processes are called angiogenic factors.
A recent study has found that specific alterations in angiogenic factors early in pregnancy are strongly associated with preeclampsia and other poor outcomes in pregnant patients with lupus or antiphospholipid antibodies (aPL).
Increased levels of sFlt1 (an anti-angiogenic factor) and/or decreased levels of placental growth factor or PlGF (a pro-angiogenic factor) suggest that a pregnancy may be destined for complications.
Using levels of angiogenic factors as biomarkers, doctors can identify pregnancies at risk before 15 weeks, allowing early intervention and revealing novel targets for treatment.
This study was presented at the 2013 ACR Annual Meeting.
For more information about lupus treatment at HSS, see the Lupus and APS Center of Excellence.
Featuring Lindsay S. Lally, MD; Robert Lebovics, MD; Wei-Ti Huang, MS; Robert F. Spiera, MD
In this large study, patients treated with RTX were far less likely to have active ENT disease.
Ear, nose, and throat (ENT) involvement is the most prevalent manifestation of granulomatosis with polyangiitis (GPA) or Wegener’s granulomatosis.
The drug Rituximab (RTX) has proven effective in treating severe GPA involving vasculitic manifestations, but its effectiveness in treating ENT manifestations in GPA has been less certain.
Reviewing data from 99 patients and 975 office visits, RTX was found superior to conventional immunosuppressives for ENT manifestations of GPA.
Dr. Lally presented this study at the 2013 ACR Annual Meeting, where she received the Distinguished Fellow Award.
Featuring Lisa A. Mandl, MD, MPH; Rebecca Zhul; Wei-Ti Huang, MS; Michael M. Alexiades, MD; Mark P. Figgie, MD; Susan M. Goodman, MD
Having psoriatic arthritis does not prevent good outcomes in either hip or knee replacement.
Two large studies by an interdisciplinary HSS research team reviewed outcomes in total knee replacement and total hip replacement for patients with psoriatic arthritis (PsA).
Despite worse pre-operative health status, having PsA or cutaneous psoriasis with osteoarthritis (PsC+OA) were not independent risk factors for poor outcomes.
Using the large HSS patient registries, the team was able to identify 289 patients with psoriasis (69 with PsA and 167 PsC+OA) for the hip replacement study and compared their results to 771 patients with OA, alone. The knee replacement study compared 253 patients with psoriasis (76 PsA and 155 PsC+OA) to 547 patients with OA, alone.
In both studies, in 3-to-5 year follow-ups, the patient groups had equally good outcomes in pain and function scores, and were equally satisfied with the results.
This study was presented at the 2013 ACR Annual Meeting.
Read More:
- Total Knee Replacement Outcomes in Patients with Psoriatic Arthritis, Osteoarthritis with Cutaneous Psoriasis, and Osteoarthritis
- Total Hip Arthroplasty Outcomes in Patients with Psoriatic Arthritis, Osteoarthritis with Cutaneous Psoriasis, and Osteoarthritis
For more information about rheumatoid arthritis treatment at HSS, see the Inflammatory Arthritis Center.
Featuring Mikhail Olferiev, MD; Elzbieta E. Jacek; Mari Lliguicota; Margaret Robotham; Wei-Ti Huang, MS; Elena Gkrouzman, MD; Mary K. Crow, MD; Kyriakos A. Kirou, MD, DSc
Monitoring IFN-I activity in SLE plasma could help predict future disease activity, particularly involving the kidney.
The kidney disease lupus nephritis is the most common severe manifestation of systemic lupus erythematosus (SLE). It confers an increased risk of end-stage renal disease and death.
One of the key cytokines that signals for an inflammatory response in the body – type I interferon (IFN-1) – is found at elevated levels in patients with lupus.
Now, a new HSS study has discovered that high IFN-I activity in the plasma of patients with lupus indicates higher likelihood of disease activity, particularly increasing the chances of the patient developing future lupus nephritis.
Furthermore, patients with higher plasma IFN-I activity at study initiation maintained elevated levels at future visits.
Higher IFN-I activity in the plasma of patients with lupus may serve as an important disease monitoring biomarker and help identify patients at risk for lupus nephritis.
This study was presented at the 2013 ACR Annual Meeting.
Featuring P. Edward Purdue, PhD; Steven R. Goldring, MD
Netrin1 may be a novel therapeutic target to prevent bone loss leading to loosening of joint replacements in osteolysis.
Netrins are a class of proteins called chemorepulsants that can chemically affect the movement of other cells. Netrins are known to guide axons during fetal brain development. Netrins are also thought to suppress inflammation and affect migration of the immune system’s macrophage cells.
A recent collaborative study between HSS and NYU Medical Center asked whether netrins might be involved in the development of osteoclasts, the cells responsible for dismantling old bone cells to make way for new bone. The answer is yes. Without netrin1, the body cannot properly create new osteoclast cells.
The study found that netrin1 is required for osteoclast differentiation and stimulates that process by an autocrine mechanism.
This study was presented at the 2013 ACR Annual Meeting.
Featuring Milena Vukelic, MD; Xiaoping Qing, MD, PhD; Patricia Redecha; Gloria Koo, PhD; Jane E. Salmon, MD
New therapies stimulating neurotransmitters may be able to reduce inflammation.
There are neurotransmitter receptors on the immune cells that cause inflammation in lupus. A new HSS study, sponsored in part by the Lupus Research Institute, has revealed that stimulating these cholinergic neurotransmitter receptors resulted in less immune complex-induced inflammation in cultured human cells and less organ damage in mouse models.
The team plans to investigate ways to turn this discovery into treatment. Possibilities include using existing drugs that directly activate cholinergic receptors or cause production of more cholinergic neurotransmitters. Another avenue may be electrically stimulating the vagus nerve, which carries a wide assortment of signals to and from the brain, and governs many reflex responses, to calm inflammation and limit tissue damage.
Patients may also benefit from activities that naturally stimulate the vagal nerve, like aerobic exercise, meditation, acupuncture, and relaxation training.
This study was presented at the 2013 ACR Annual Meeting.
For more information about lupus treatment at HSS, see the Lupus and APS Center of Excellence.
Featuring Yuo-Yu Lee; Stephen Lyman, PhD; Geoffrey H. Westrich, MD; Brian F. Gage, MD, MSc; Anne R. Bass, MD
Statins shown to protect against PE although not total VTE following hip or knee replacement.
An interdisciplinary HSS research team has found that statin drug therapy can protect against pulmonary embolism (PE) although not total venous thromboembolism (VTE) following hip or knee total joint replacement.
The team reviewed 16,183 returned 6-month questionnaires from patients who had total hip or knee replacement at HSS. 40% of the patients were on statin therapy.
Other findings included that patients on statins were older (68.9 vs 63 years), heavier (BMI 29.6 vs 28.3), more commonly male (49.2% vs 38.5%), had a longer length of stay (5.0 vs 4.9 days), and were more commonly discharged to a rehabilitation center (46.9% vs 37.9%). venous thromboembolism (VTE) following hip or knee total joint replacement.
This study was presented at the 2013 ACR Annual Meeting.