Evaluation of the European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus in a Population Based Registry
Guttmann, Allison; Denvir, Brendan; Aringer, Martin; Buyon, Jill P; Belmont, H Michael; Sahl, Sara; Salmon, Jane E; Askanase, Anca; Bathon, Joan M; Geraldino-Pardilla, Laura; Ali, Yousaf; Ginzler, Ellen M; Putterman, Chaim; Gordon, Caroline; Helmick, Charles G; Parton, Hilary; Izmirly, Peter M
OBJECTIVE:Using the Manhattan Lupus Surveillance Program (MLSP), a multi-racial/ethnic population-based registry, we compared three commonly used classification criteria for Systemic Lupus Erythematosus (SLE) to identify unique cases and determine the incidence and prevalence of SLE using the EULAR/ACR criteria. METHODS:SLE cases were defined as fulfilling 1997 ACR, SLICC, or EULAR/ACR classification criteria. We quantified the number of cases uniquely associated with each and the number fulfilling all three. Prevalence and incidence using the EULAR/ACR classification criteria and associated 95% confidence intervals (CI) were calculated. RESULTS:1,497 cases fulfilled at least one of the three classification criteria, with 1,008 (67.3%) meeting all three classifications, 138 (9.2%) fulfilling only SLICC criteria, 35 (2.3%) fulfilling only ACR criteria and 34 (2.3%) uniquely fulfilling EULAR/ACR criteria. Patients solely satisfying EULAR/ACR criteria had fewer than four manifestations. The majority classified only by the ACR criteria did not meet any of the defined immunologic criteria. Patients fulfilling only SLICC criteria did so based on the presence of features unique to this system. Using the EULAR/ACR classification criteria, age-adjusted overall prevalence and incidence rates of SLE in Manhattan were 59.6 (95%CI:55.9-63.4) and 4.9 (95%CI 4.3-5.5) per 100,000 population, with age-adjusted prevalence and incidence rates highest among non-Hispanic Black females. CONCLUSION/CONCLUSIONS:Applying the three commonly used classification criteria to a population-based registry identified patients with SLE fulfilling only one validated definition. The most recently developed EULAR/ACR classification criteria revealed similar prevalence and incidence estimates to those previously established for the ACR and SLICC classification schemes.
Platelet LGALS3BP Induces Myeloid Inflammation In Systemic Lupus Erythematosus
El Bannoudi, Hanane; Cornwell, MacIntosh; Luttrell-Williams, Elliot; Engel, Alexis; Rolling, Christina; Barrett, Tessa J; Izmirly, Peter; Belmont, H Michael; Ruggles, Kelly; Clancy, Robert; Buyon, Jill; Berger, Jeffrey S
OBJECTIVE:Platelets are mediators of inflammation with immune effector cell properties, and have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). This study investigated the role of platelet associated lectin galactoside-binding soluble 3 binding protein (LGALS3BP) as a mediator of inflammation in SLE, and a potential biomarker associated with clinical phenotypes. METHODS:We performed RNA sequencing on platelets of patients with SLE (n=54) and age, sex, and race-matched controls (n=18) and measured LGALS3BP in platelet releasate and in circulating serum. We investigated the association between levels of LGALS3BP with the prevalence, disease severity, and clinical phenotpyes of SLE, and studied platelet-mediated effects on myeloid inflammation. RESULTS:). Platelet-released LGALS3BP was highly correlated with circulating LGALS3BP (RÂ =Â 0.69, p <â€‰0.0001). Circulating LGALS3BP correlated with the SLE disease activity index (RÂ =Â 0.32, p =â€‰0.0006). Specifically, circulating LGALS3BP was higher in SLE patients with lupus nephritis than those with inactive disease (4.0 Î¼g/mL vs 2.3 Î¼g/mL, P <â€‰0.001). IFN-Î± induced LGALS3BP transcription and translation in a megakaryoblastic cell line (MEG-01) cells in a dose-dependent manner. Recombinant LGALS3BP and platelet releasates from SLE patients enhanced pro-inflammatory cytokine production by macrophages. CONCLUSIONS:These data support that platelets act as potent effector cells contributing to the pathogenesis of SLE by secreting proinflammatory LGALS3BP, which also represents a novel biomarker of SLE clinical activity.
Modeling of clinical phenotypes in systemic lupus erythematosus based on the platelet transcriptome and FCGR2a genotype
Cornwell, MacIntosh G; Bannoudi, Hanane El; Luttrell-Williams, Elliot; Engel, Alexis; Barrett, Tessa J; Myndzar, Khrystyna; Izmirly, Peter; Belmont, H Michael; Clancy, Robert; Ruggles, Kelly V; Buyon, Jill P; Berger, Jeffrey S
BACKGROUND:The clinical heterogeneity of SLE with its complex pathogenesis remains challenging as we strive to provide optimal management. The contribution of platelets to endovascular homeostasis, inflammation and immune regulation highlights their potential importance in SLE. Prior work from our group showed that the Fcγ receptor type IIa (FcγRIIa)-R/H131 biallelic polymorphism is associated with increased platelet activity and cardiovascular risk in SLE. The study was initiated to investigate the platelet transcriptome in patients with SLE and evaluate its association across FcγRIIa genotypes and distinct clinical features. METHODS:Fifty-one patients fulfilling established criteria for SLE (mean age = 41.1 ± 12.3, 100% female, 45% Hispanic, 24% black, 22% Asian, 51% white, mean SLEDAI = 4.4 ± 4.2 at baseline) were enrolled and compared with 18 demographically matched control samples. The FCGR2a receptor was genotyped for each sample, and RNA-seq was performed on isolated, leukocyte-depleted platelets. Transcriptomic data were used to create a modular landscape to explore the differences between SLE patients and controls and various clinical parameters in the context of FCGR2a genotypes. RESULTS:There were 2290 differentially expressed genes enriched for pathways involved in interferon signaling, immune activation, and coagulation when comparing SLE samples vs controls. When analyzing patients with proteinuria, modules associated with oxidative phosphorylation and platelet activity were unexpectedly decreased. Furthermore, genes that were increased in SLE and in patients with proteinuria were enriched for immune effector processes, while genes increased in SLE but decreased in proteinuria were enriched for coagulation and cell adhesion. A low-binding FCG2Ra allele (R131) was associated with decreases in FCR activation, which further correlated with increases in platelet and immune activation pathways. Finally, we were able to create a transcriptomic signature of clinically active disease that performed significantly well in discerning SLE patients with active clinical disease form those with inactive clinical disease. CONCLUSIONS:In aggregate, these data demonstrate the platelet transcriptome provides insight into lupus pathogenesis and disease activity, and shows potential use as means of assessing this complex disease using a liquid biopsy.
Cutaneous neonatal lupus in patients with skin of color: A retrospective cohort study from a national registry
Kleitsch, Julianne; Mazori, Daniel R; Masson, Mala; Izmirly, Peter M; Saxena, Amit; Buyon, Jill P; Glick, Sharon A
The modifying influence of HLA class II DQB1âˆ—06:02 on the Streptococcus and clinical phenotype correlation among anti-Ro+ mothers of children with neonatal lupus
Clancy, Robert M.; Guthridge, Carla J.; Marion, Miranda C.; Guthridge, Joel; Howard, Timothy D.; Izmirly, Peter M.; Masson, Mala; Buyon, Jill P.; James, Judith A.; Langefeld, Carl D.
Low incidence and transient elevation of autoantibodies post mRNA COVID-19 vaccination in inflammatory arthritis
Blank, Rebecca B; Haberman, Rebecca H; Qian, Kun; Samanovic, Marie; Castillo, Rochelle; Jimenez Hernandez, Anthony; Vasudevapillai Girija, Parvathy; Catron, Sydney; Uddin, Zakwan; Rackoff, Paula; Solomon, Gary; Azar, Natalie; Rosenthal, Pamela; Izmirly, Peter; Samuels, Jonathan; Golden, Brian; Reddy, Soumya; Mulligan, Mark J; Hu, Jiyuan; Scher, Jose U
OBJECTIVES/OBJECTIVE:Autoantibody seroconversion has been extensively studied in the context of COVID-19 infection but data regarding post-vaccination autoantibody production is lacking. Here we aimed to determine the incidence of common autoantibody formation following mRNA COVID-19 vaccines in patients with inflammatory arthritis (IA) and in healthy controls. METHODS:Autoantibody seroconversion was measured by serum ELISA in a longitudinal cohort of IA participants and healthy controls before and after COVID-19 mRNA-based immunization. RESULTS:Overall, there was a significantly lower incidence of ANA seroconversion in participants who did not contract COVID-19 prior to vaccination compared with those who been previously infected (7.4% vs 24.1%, p= 0.014). Incidence of de novo anti-cyclic citrullinated protein (CCP) seroconversion in all participants was low at 4.9%. Autoantibody levels were typically of low titer, transient, and not associated with increase in IA flares. CONCLUSIONS:In both health and inflammatory arthritis, the risk of autoantibody seroconversion is lower following mRNA-based immunization than following natural SARS-CoV-2 infection. Importantly, seroconversion does not correlate with self-reported IA disease flare risk, further supporting the encouragement of mRNA-based COVID-19 immunization in the IA population.
Population-based prevalence and incidence estimates of mixed connective tissue disease from the Manhattan Lupus Surveillance Program
Hasan, Ghadeer; Ferucci, Elizabeth D; Buyon, Jill P; Belmont, H Michael; Salmon, Jane E; Askanase, Anca; Bathon, Joan M; Geraldino-Pardilla, Laura; Ali, Yousaf; Ginzler, Ellen M; Putterman, Chaim; Gordon, Caroline; Helmick, Charles G; Parton, Hilary; Izmirly, Peter M
OBJECTIVE:Epidemiologic data for mixed connective tissue disease (MCTD) are limited. Leveraging data from the Manhattan Lupus Surveillance Program (MLSP), a racially/ethnically diverse population-based registry of cases with SLE and related diseases including MCTD, we provide estimates of the prevalence and incidence of MCTD. METHODS:MLSP cases were identified from rheumatologists, hospitals, and population databases using a variety of ICD-9 codes. MCTD was defined as one of the following: 1) fulfillment of our modified Alarcon-Segovia and Kahn criteria which required a positive RNP antibody and the presence of synovitis, myositis, and Raynaud's phenomenon, 2) a diagnosis of MCTD and no other diagnosis of another connective tissue disease (CTD), and 3) a diagnosis of MCTD regardless of another CTD diagnosis. RESULTS:Overall, 258 (7.7%) of cases met a definition of MCTD. Using our modified Alarcon-Segovia and Kahn criteria for MCTD, the age-adjusted prevalence was 1.28 (95%CI 0.72-2.09) per 100 000. Using our definition of a diagnosis of MCTD and no other diagnosis of another CTD yielded an age-adjusted prevalence and incidence of MCTD of 2.98 (95%CI 2.10-4.11) per 100 000 and 0.39 (95%CI 0.22-0.64) per 100 000, respectively. The age-adjusted prevalence and incidence were highest using a diagnosis of MCTD regardless of other CTD diagnoses and were 16.22 (95%CI 14.00-18.43) per 100 000 and 1.90 (95%CI 1.49-2.39) per 100 000 respectively. CONCLUSIONS:The MLSP provided estimates for prevalence and incidence of MCTD in a diverse population. The variation in estimates using different case definitions is reflective of the challenge of defining MCTD in epidemiologic studies.
High incidence of proliferative and membranous nephritis in SLE patients with low proteinuria in the Accelerating Medicines Partnership
Carlucci, Philip M; Li, Jessica; Fava, Andrea; Deonaraine, Kristina K; Wofsy, David; James, Judith A; Putterman, Chaim; Diamond, Betty; Davidson, Anne; Fine, Derek M; Monroy-Trujillo, Jose; Atta, Mohamed G; DeJager, Wade; Guthridge, Joel M; Haag, Kristin; Rao, Deepak A; Brenner, Michael B; Lederer, James A; Apruzzese, William; Belmont, H Michael; Izmirly, Peter M; Zaminski, Devyn; Wu, Ming; Connery, Sean; Payan-Schober, Fernanda; Furie, Richard; Dall'Era, Maria; Cho, Kerry; Kamen, Diane; Kalunian, Kenneth; Anolik, Jennifer; Barnas, Jennifer; Ishimori, Mariko; Weisman, Michael H; Buyon, Jill P; Petri, Michelle
OBJECTIVE:Delayed detection of lupus nephritis associates with worse outcomes. There are conflicting recommendations regarding a threshold level of proteinuria at which biopsy will likely yield actionable management. This study addressed the association of urine protein creatinine ratios (UPCR) with clinical characteristics and investigated the incidence of proliferative and membranous histology in patients with a UPCR between 0.5 and 1. METHODS:275 SLE patients (113 first biopsy, 162 repeat) were enrolled in the multicentre multi-ethnic/racial Accelerating Medicines Partnership across 15â€‰U.S. sites at the time of a clinically indicated renal biopsy. Patients were followed for 1â€‰year. RESULTS:At biopsy, 54 patients had UPCR <1 and 221 had UPCR >1. Independent of UPCR or biopsy number, a majority (92%) of patients had class III, IV, V or mixed histology. Moreover, patients with UPCR <1 and class III, IV, V, or mixed had a median activity index of 4.5 and chronicity index of 3, yet 39% of these patients had an inactive sediment. Neither anti-dsDNA nor low complement distinguished class I or II from III, IV, V, or mixed in patients with UPCR <1. Of 29 patients with baseline UPCR <1 and class III, IV, V or mixed, 23 (79%) had a UPCR <0.5 at one year. CONCLUSION/CONCLUSIONS:In this prospective study three quarters of patients with UPCR <1 had histology showing class III, IV, V or mixed with accompanying activity and chronicity despite an inactive sediment or normal serologies. These data support renal biopsy at thresholds lower than a UPCR of 1.
COVID-19 outcomes in patients with psoriasis and psoriatic arthritis: A prospective cohort study
Yan, Di; Kolla, Avani M; Young, Trevor; Fried, Lauren; Shankar, Shruthi; Rangel, Lauren; Yin, Lu; Castillo, Rochelle; Steuer, Alexa; Svigos, Katerina; Izmirly, Peter; Sekar, Vaish; Lesser, Robert; Solomon, Gary; Blank, Rebecca B; Haberman, Rebecca H; Neimann, Andrea L; Scher, Jose U
Breakthrough SARS-CoV-2 infections, morbidity, and seroreactivity following initial COVID-19 vaccination series and additional dose in patients with SLE in New York City
Saxena, Amit; Engel, Alexis J; Banbury, Brittany; Hasan, Ghadeer; Fraser, Nicola; Zaminski, Devyn; Masson, Mala; Haberman, Rebecca H; Scher, Jose U; Ho, Gary; Law, Jammie; Rackoff, Paula; Tseng, Chung-E; Belmont, H Michael; Clancy, Robert M; Buyon, Jill P; Izmirly, Peter M