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Extrarenal symptoms associate with worse quality of life in patients enrolled in the AMP RA/SLE Lupus Nephritis Network

Carlucci, Philip M; Preisinger, Katherine; Deonaraine, Kristina K; Zaminski, Devyn; Dall'Era, Maria; Gold, Heather T; Kalunian, Kenneth; Fava, Andrea; Belmont, H Michael; Wu, Ming; Putterman, Chaim; Anolik, Jennifer; Barnas, Jennifer L; Furie, Richard; Diamond, Betty; Davidson, Anne; Wofsy, David; Kamen, Diane; James, Judith A; Guthridge, Joel M; Apruzzese, William; Rao, Deepak; Weisman, Michael H; ,; Izmirly, Peter M; Buyon, Jill; Petri, Michelle
OBJECTIVE:Lupus nephritis (LN) can occur as an isolated component of disease activity or be accompanied by diverse extrarenal manifestations. Whether isolated renal disease is sufficient to decrease health related quality of life (HRQOL) remains unknown. This study compared Patient-Reported Outcomes Measurement Information System 29-Item (PROMIS-29) scores in LN patients with isolated renal disease to those with extrarenal symptoms to evaluate the burden of LN on HRQOL and inform future LN clinical trials incorporating HRQOL outcomes. METHODS:A total of 181 LN patients consecutively enrolled in the multicentre multi-ethnic/racial Accelerating Medicines Partnership completed PROMIS-29 questionnaires at the time of a clinically indicated renal biopsy. Raw PROMIS-29 scores were converted to standardized T scores. RESULTS:Seventy-five (41%) patients had extrarenal disease (mean age 34, 85% female) and 106 (59%) had isolated renal (mean age 36, 82% female). Rash (45%), arthritis (40%) and alopecia (40%) were the most common extrarenal manifestations. Compared with isolated renal, patients with extrarenal disease reported significantly worse pain interference, ability to participate in social roles, physical function, and fatigue. Patients with extrarenal disease had PROMIS-29 scores that significantly differed from the general population by > 0.5 SD of the reference mean in pain interference, physical function, and fatigue. Arthritis was most strongly associated with worse scores in these three domains. CONCLUSION/CONCLUSIONS:Most patients had isolated renal disease and extrarenal manifestations associated with worse HRQOL. These data highlight the importance of comprehensive disease management strategies that address both renal and extrarenal manifestations to improve overall patient outcomes.
PMID: 38530774
ISSN: 1462-0332
CID: 5644732

Longitudinal patterns and predictors of response to standard-of-care therapy in lupus nephritis: data from the Accelerating Medicines Partnership Lupus Network

Izmirly, Peter M; Kim, Mimi Y; Carlucci, Philip M; Preisinger, Katherine; Cohen, Brooke Z; Deonaraine, Kristina; Zaminski, Devyn; Dall'Era, Maria; Kalunian, Kenneth; Fava, Andrea; Belmont, H Michael; Wu, Ming; Putterman, Chaim; Anolik, Jennifer; Barnas, Jennifer L; Diamond, Betty; Davidson, Anne; Wofsy, David; Kamen, Diane; James, Judith A; Guthridge, Joel M; Apruzzese, William; Rao, Deepak A; Weisman, Michael H; ,; Petri, Michelle; Buyon, Jill; Furie, Richard
BACKGROUND:Leveraging the Accelerating Medicines Partnership (AMP) Lupus Nephritis (LN) dataset, we evaluated longitudinal patterns, rates, and predictors of response to standard-of-care therapy in patients with lupus nephritis. METHODS:Patients from US academic medical centers with class III, IV, and/or V LN and a baseline urine protein/creatinine (UPCR) ratio ≥ 1.0 (n = 180) were eligible for this analysis. Complete response (CR) required the following: (1) UPCR < 0.5; (2) normal serum creatinine (≤ 1.3 mg/dL) or, if abnormal, ≤ 125% of baseline; and (3) prednisone ≤ 10 mg/day. Partial response (PR) required the following: (1) > 50% reduction in UPCR; (2) normal serum creatinine or, if abnormal, ≤ 125% of baseline; and (3) prednisone dose ≤ 15 mg/day. RESULTS: = 2.61 [95%CI = 0.93-7.33]; p = 0.069). CONCLUSIONS:CR and PR rates at week 52 were consistent with the standard-of-care response rates observed in prospective registrational LN trials. Low sustained response rates underscore the need for more efficacious therapies and highlight how critically important it is to understand the molecular pathways associated with response and non-response.
PMID: 38378664
ISSN: 1478-6362
CID: 5634232

Urine proteomic signatures of histological class, activity, chronicity, and treatment response in lupus nephritis

Fava, Andrea; Buyon, Jill; Magder, Laurence; Hodgin, Jeff; Rosenberg, Avi; Demeke, Dawit S; Rao, Deepak A; Arazi, Arnon; Celia, Alessandra Ida; Putterman, Chaim; Anolik, Jennifer H; Barnas, Jennifer; Dall'Era, Maria; Wofsy, David; Furie, Richard; Kamen, Diane; Kalunian, Kenneth; James, Judith A; Guthridge, Joel; Atta, Mohamed G; Monroy Trujillo, Jose; Fine, Derek; Clancy, Robert; Belmont, H Michael; Izmirly, Peter; Apruzzese, William; Goldman, Daniel; Berthier, Celine C; Hoover, Paul; Hacohen, Nir; Raychaudhuri, Soumya; Davidson, Anne; Diamond, Betty; ,; Petri, Michelle
Lupus nephritis (LN) is a pathologically heterogenous autoimmune disease linked to end-stage kidney disease and mortality. Better therapeutic strategies are needed as only 30%-40% of patients completely respond to treatment. Noninvasive biomarkers of intrarenal inflammation may guide more precise approaches. Because urine collects the byproducts of kidney inflammation, we studied the urine proteomic profiles of 225 patients with LN (573 samples) in the longitudinal Accelerating Medicines Partnership in RA/SLE cohort. Urinary biomarkers of monocyte/neutrophil degranulation (i.e., PR3, S100A8, azurocidin, catalase, cathepsins, MMP8), macrophage activation (i.e., CD163, CD206, galectin-1), wound healing/matrix degradation (i.e., nidogen-1, decorin), and IL-16 characterized the aggressive proliferative LN classes and significantly correlated with histological activity. A decline of these biomarkers after 3 months of treatment predicted the 1-year response more robustly than proteinuria, the standard of care (AUC: CD206 0.91, EGFR 0.9, CD163 0.89, proteinuria 0.8). Candidate biomarkers were validated and provide potentially treatable targets. We propose these biomarkers of intrarenal immunological activity as noninvasive tools to diagnose LN and guide treatment and as surrogate endpoints for clinical trials. These findings provide insights into the processes involved in LN activity. This data set is a public resource to generate and test hypotheses and validate biomarkers.
PMID: 38258904
ISSN: 2379-3708
CID: 5624822

Prevalence of concomitant rheumatologic diseases and autoantibody specificities among racial and ethnic groups in SLE patients

Denvir, Brendan; Carlucci, Philip M; Corbitt, Kelly; Buyon, Jill P; Belmont, H Michael; Gold, Heather T; Salmon, Jane E; Askanase, Anca; Bathon, Joan M; Geraldino-Pardilla, Laura; Ali, Yousaf; Ginzler, Ellen M; Putterman, Chaim; Gordon, Caroline; Barbour, Kamil E; Helmick, Charles G; Parton, Hilary; Izmirly, Peter M
OBJECTIVE/UNASSIGNED:Leveraging the Manhattan Lupus Surveillance Program (MLSP), a population-based registry of cases of systemic lupus erythematosus (SLE) and related diseases, we investigated the proportion of SLE with concomitant rheumatic diseases, including Sjögren's disease (SjD), antiphospholipid syndrome (APLS), and fibromyalgia (FM), as well as the prevalence of autoantibodies in SLE by sex and race/ethnicity. METHODS/UNASSIGNED:Prevalent SLE cases fulfilled one of three sets of classification criteria. Additional rheumatic diseases were defined using modified criteria based on data available in the MLSP: SjD (anti-SSA/Ro positive and evidence of keratoconjunctivitis sicca and/or xerostomia), APLS (antiphospholipid antibody positive and evidence of a blood clot), and FM (diagnosis in the chart). RESULTS/UNASSIGNED:1,342 patients fulfilled SLE classification criteria. Of these, SjD was identified in 147 (11.0%, 95% CI 9.2-12.7%) patients with women and non-Latino Asian patients being the most highly represented. APLS was diagnosed in 119 (8.9%, 95% CI 7.3-10.5%) patients with the highest frequency in Latino patients. FM was present in 120 (8.9%, 95% CI 7.3-10.5) patients with non-Latino White and Latino patients having the highest frequency. Anti-dsDNA antibodies were most prevalent in non-Latino Asian, Black, and Latino patients while anti-Sm antibodies showed the highest proportion in non-Latino Black and Asian patients. Anti-SSA/Ro and anti-SSB/La antibodies were most prevalent in non-Latino Asian patients and least prevalent in non-Latino White patients. Men were more likely to be anti-Sm positive. CONCLUSION/UNASSIGNED:Data from the MLSP revealed differences among patients classified as SLE in the prevalence of concomitant rheumatic diseases and autoantibody profiles by sex and race/ethnicity underscoring comorbidities associated with SLE.
PMID: 38516120
ISSN: 2674-1199
CID: 5640792

Risk Assessment Model for Postpartum Venous Thromboembolism Prevention in Patients with Systemic Lupus Erythematosus

Griffin, Myah M; Engel, Alexis; Mehta-Lee, Shilpi S; Nusbaum, Julie; Golpanian, Michael; Izmirly, Peter; Belmont, H Michael; Buyon, Jill P
OBJECTIVE:This article assesses the application of the Royal College of Obstetricians and Gynaecologists (RCOG) venous thromboembolism (VTE) risk model on a cohort of postpartum patients with a history of systemic lupus erythematosus (SLE). STUDY DESIGN: < 0.05. RESULTS: = 3) were nevertheless recommended for VTE prophylaxis. No patients had a postpartum VTE regardless of therapy. CONCLUSION:These data reveal a need to improve upon providing postpartum VTE prophylaxis to SLE patients not in remission while also recognizing a diagnosis of SLE alone should not equate with active disease. Moreover, SLE patients in remission may still warrant VTE prophylaxis if other non-SLE-related risk factors are present. KEY POINTS:· Those with SLE are at increased risk for VTE postpartum.. · VTE prophylaxis should be instituted when clinically appropriate.. · Caution should be exercised in broadly assigning disease activity for SLE diagnosis only.. · This study supports VTE prophylaxis use in postpartum patients with SLE..
PMID: 37494484
ISSN: 1098-8785
CID: 5618842

Clinical implications of discordance between anti-dsDNA antibodies by multiplex flow immunoassay and Crithidia luciliae assay in a multiethnic racial cohort of patients with SLE

Zaminski, Devyn; Saxena, Amit; Izmirly, Peter; Buyon, Jill P; Belmont, H Michael
OBJECTIVE:immunofluorescence test (CLIFT). To address the clinical impact of measuring these antibodies by two different assays, this study leveraged a well-phenotyped multiethnic/racial cohort. METHODS:All patients fulfilled the classification criteria for SLE by at least one of the validated schemes: American College of Rheumatology, Systemic Lupus Erythematosus International Collaborating Clinics and/or American College of Rheumatology/European League Against Rheumatism classification criteria. Patients with one or more simultaneously paired anti-dsDNA by multiplex EIA and CLIFT were identified. Analysis of concordance or discordance, titre comparability of assays and association with hybrid SLE Disease Activity Index score, prevalence of lupus nephritis (LN), ability to predict a flare and classification criteria was performed. RESULTS:207 patients were simultaneously tested by EIA and CLIFT at least once for anti-dsDNA, generating 586 paired results. 377 pairs were concordant and 209 were discordant. 41 of 207 patients always had discordant paired results and 39 patients always had results with titre discordance. In 100 patients with LN, 60 were positive by EIA and 72 by CLIFT. Sensitivities and specificities for patients with LN versus patients without LN were EIA 60% and 47%, and CLIFT 72% and 37%, respectively. 42 patients had flare assessment within 90 days of their paired result. Six of seven patients with mild flares and all four patients with severe flares had concordant positive results. CONCLUSION:Our data demonstrate that discordance of positivity between both assays for anti-dsDNA is relatively common, occurring in a fifth of patients overall and a third of visits. EIA positivity is associated with LN less often than CLIFT positivity. With the significant discordance of results between anti-dsDNA assays, obtaining both CLIFT and EIA assays may be beneficial for classification and routine monitoring of SLE.
PMID: 37963669
ISSN: 2053-8790
CID: 5610132

Knowledge is power: regarding SMFM Consult Series #64: Systemic lupus erythematosus in pregnancy [Editorial]

Cuneo, Bettina F; Buyon, Jill P; Sammaritano, Lisa; Jaeggi, Edgar; Arya, Bhawna; Behrendt, Nicholas; Carvalho, Julene; Cohen, Jennifer; Cumbermack, Kristopher; DeVore, Greggory; Doan, Tam; Donofrio, Mary T; Freud, Lindsay; Galan, Henry L; Groper, Melanie R F; Haxel, Caitlin; Hornberger, Lisa K; Howley, Lisa W; Izmirly, Peter; Killen, Stacy S; Kaplinski, Michelle; Krishnan, Anita; Lavasseur, Stephanie; Lindblade, Christopher; Matta, Jyothi; Makhoul, Majd; Miller, Jena; Morris, Shaine; Paul, Erin; Perrone, Erin; Phoon, Colin; Pinto, Nelangi; Rychik, Jack; Satou, Gary; Saxena, Amit; Sklansky, Mark; Stranic, James; Strasburger, Janette F; Srivastava, Shubhika; Srinivasan, Sharda; Tacy, Theresa; Tworetzky, Wayne; Uzun, Orhan; Yagel, Simcha; Zaretsky, Michael V; Moon-Grady, Anita J
PMID: 37394327
ISSN: 1097-6868
CID: 5538952

Longitudinal gut microbiome analyses and blooms of pathogenic strains during lupus disease flares

Azzouz, Doua F; Chen, Ze; Izmirly, Peter M; Chen, Lea Ann; Li, Zhi; Zhang, Chongda; Mieles, David; Trujillo, Kate; Heguy, Adriana; Pironti, Alejandro; Putzel, Greg G; Schwudke, Dominik; Fenyo, David; Buyon, Jill P; Alekseyenko, Alexander V; Gisch, Nicolas; Silverman, Gregg J
OBJECTIVE:Whereas genetic susceptibility for systemic lupus erythematosus (SLE) has been well explored, the triggers for clinical disease flares remain elusive. To investigate relationships between microbiota community resilience and disease activity, we performed the first longitudinal analyses of lupus gut-microbiota communities. METHODS:In an observational study, taxononomic analyses, including multivariate analysis of ß-diversity, assessed time-dependent alterations in faecal communities from patients and healthy controls. From gut blooms, strains were isolated, with genomes and associated glycans analysed. RESULTS:(RG) occurred at times of high-disease activity, and were detected in almost half of patients during lupus nephritis (LN) disease flares. Whole genome sequence analysis of RG strains isolated during these flares documented 34 genes postulated to aid adaptation and expansion within a host with an inflammatory condition. Yet, the most specific feature of strains found during lupus flares was the common expression of a novel type of cell membrane-associated lipoglycan. These lipoglycans share conserved structural features documented by mass spectroscopy, and highly immunogenic repetitive antigenic-determinants, recognised by high-level serum IgG2 antibodies, that spontaneously arose, concurrent with RG blooms and lupus flares. CONCLUSIONS:Our findings rationalise how blooms of the RG pathobiont may be common drivers of clinical flares of often remitting-relapsing lupus disease, and highlight the potential pathogenic properties of specific strains isolated from active LN patients.
PMID: 37365013
ISSN: 1468-2060
CID: 5540152

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.
PMID: 36538873
ISSN: 1462-0332
CID: 5431852

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
PMID: 36997071
ISSN: 1097-6787
CID: 5463392