Dr. Chaichian specializes in the diagnosis and management of all rheumatic diseases. As Director of the Stanford Lupus Clinic, he has a particular clinical, research, and teaching interest in systemic lupus erythematosus (SLE). He also has a secondary interest in connective tissue disease-associated interstitial lung disease (CTD-ILD). Along with Dr. Jennifer Yeh (Dermatology), he co-directs a Rheumatology-Dermatology multidisciplinary clinic at Stanford to facilitate expert management of patients with various skin/autoimmune overlap conditions including SLE with cutaneous manifestations.

He serves on the OMERACT 2022 SLE Working Group, an international collaborative effort that is aiming to revisit and update the core set domain of outcome measures to be assessed in randomized controlled trials and longitudinal observational studies in SLE. He has served as a principal investigator on clinical trials in SLE, and is involved in the Lupus Clinical Investigators Network (LuCIN). He has an ongoing interest in clinical/translational team science approaches that answer important questions relevant to lupus. He works closely with Dr. Julia Simard and other research collaborators on various projects, including studying pregnancy outcomes in SLE, the role of cognitive bias in the evaluation of lupus/other autoimmune conditions, and work centered around COVID-19 and autoimmunity. In addition, he serves as the Faculty Lead for the Division of Immunology and Rheumatology’s Clinical Research Unit (CRU) at Stanford University School of Medicine.

From a teaching standpoint, he is actively involved in the education of medical students, PA students, residents, and rheumatology fellows on topics related to rheumatology including SLE. He is also engaged in educational outreach for patients with SLE through several forums including the Lupus Foundation of Northern California.

Clinical Focus

  • Rheumatology
  • Systemic Lupus Erythematosus

Academic Appointments

Honors & Awards

  • Department of Medicine Teaching Award recipient, Stanford University School of Medicine (2019)
  • Award recipient, Abstract Discussion Group, ACR Rheumatology Research Workshop (2014)
  • Distinction in Research, completion of Research Distinction Track, University of Iowa Roy J. and Lucille A. Carver College of Medicine (2008)
  • Graduation with Honors and Highest Distinction, University of Iowa (2004)
  • Student Leadership Award, University of Iowa, Multicultural Graduation Recognition Banquet (2004)
  • Bill and John Fenton Scholarship, University of Iowa (2003-2004)
  • Rhodes Dunlop Honors Program Scholarship, University of Iowa (2002-2004)
  • Dewey Stuit Award for Sophomore Honors Student, University of Iowa (2002-2003)
  • Rhodes Dunlap First-Year Honors Student Award, University of Iowa (2001-2002)

Boards, Advisory Committees, Professional Organizations

  • Faculty Lead, Clinical Research Unit (CRU), Division of Immunology and Rheumatology, Stanford University School of Medicine (2022 - Present)
  • Member, OMERACT 2022 SLE Working Group (2021 - Present)
  • Member, Arthritis Foundation Pain Management Expert Panel (2021 - Present)
  • Member, Clinician Educator (CE) Advisory Committee, Stanford University Department of Medicine (2020 - Present)
  • Member, Arthritis Foundation Northern California’s Medical & Scientific Committee (2020 - Present)

Professional Education

  • Board Certification: American Board of Internal Medicine, Rheumatology (2014)
  • Fellowship, University of Chicago Medical Center, IL, Rheumatology (2014)
  • Primary Care Chief Resident, William S. Middleton Memorial Veterans Hospital, WI (2012)
  • Board Certification: American Board of Internal Medicine, Internal Medicine (2011)
  • Residency: University of Wisconsin Hospital and Clinics (2011) WI United States of America
  • Internship: University of Wisconsin Hospital and Clinics (2009) WI United States of America
  • Medical Education: University of Iowa Carver College of Medicine (2008) IA

Current Research and Scholarly Interests

Systemic lupus erythematosus
CTD-associated interstitial lung disease

Clinical Trials

  • A Study of LY3471851 in Adults With Systemic Lupus Erythematosus (SLE) Not Recruiting

    The reason for this study is to see if the study drug LY3471851 (NKTR-358) is safe and effective in adults with systemic lupus erythematosus (SLE).

    Stanford is currently not accepting patients for this trial.

    View full details

All Publications

  • Impact of Incentives on Physician Participation in Research Surveys: Randomized Experiment. JMIR formative research Hawa, S., Bane, S., Kinsler, K., Rector, A., Chaichian, Y., Falasinnu, T., Simard, J. F. 2024; 8: e54343


    Web-based surveys can be effective data collection instruments; however, participation is notoriously low, particularly among professionals such as physicians. Few studies have explored the impact of varying amounts of monetary incentives on survey completion.This study aims to conduct a randomized study to assess how different incentive amounts influenced survey participation among neurologists in the United States.We distributed a web-based survey using standardized email text to 21,753 individuals randomly divided into 5 equal groups (≈4351 per group). In phase 1, each group was assigned to receive either nothing or a gift card for US $10, $20, $50, or $75, which was noted in the email subject and text. After 4 reminders, phase 2 began and each remaining individual was offered a US $75 gift card to complete the survey. We calculated and compared the proportions who completed the survey by phase 1 arm, both before and after the incentive change, using a chi-square test. As a secondary outcome, we also looked at survey participation as opposed to completion.For the 20,820 emails delivered, 879 (4.2%) recipients completed the survey; of the 879 recipients, 622 (70.8%) were neurologists. Among the neurologists, most were male (412/622, 66.2%), White (430/622, 69.1%), non-Hispanic (592/622, 95.2%), graduates of American medical schools (465/622, 74.8%), and board certified (598/622, 96.1%). A total of 39.7% (247/622) completed their neurology residency more than 20 years ago, and 62.4% (388/622) practiced in an urban setting. For phase 1, the proportions of respondents completing the survey increased as the incentive amount increased (46/4185, 1.1%; 76/4165, 1.8%; 86/4160, 2.1%; 104/4162, 2.5%; and 119/4148, 2.9%, for US $0, $10, $20, $50, and $75, respectively; P<.001). In phase 2, the survey completion rate for the former US $0 arm increased to 3% (116/3928). Those originally offered US $10, $20, $50, and $75 who had not yet participated were less likely to participate compared with the former US $0 arm (116/3928, 3%; 90/3936, 2.3%; 80/3902, 2.1%; 88/3845, 2.3%; and 74/3878, 1.9%, for US $0, $10, $20, $50, and $75, respectively; P=.03). For our secondary outcome of survey participation, a trend similar to that of survey completion was observed in phase 1 (55/4185, 1.3%; 85/4165, 2%; 96/4160, 2.3%; 118/4162, 2.8%; and 135/4148, 3.3%, for US $0, $10, $20, $50, and $75, respectively; P<.001) and phase 2 (116/3928, 3%; 90/3936, 2.3%; 80/3902, 2.1%; 88/3845, 2.3%; and 86/3845, 2.2%, for US $0, $10, $20, $50, and $75, respectively; P=.10).As expected, monetary incentives can boost physician survey participation and completion, with a positive correlation between the amount offered and participation.

    View details for DOI 10.2196/54343

    View details for PubMedID 38743466

  • Impaired innate and adaptive immune responses to BNT162b2 SARS-CoV-2 vaccination in systemic lupus erythematosus. JCI insight Sarin, K. Y., Zheng, H., Chaichian, Y., Arunachalam, P. S., Swaminathan, G., Eschholz, A., Gao, F., Wirz, O. F., Lam, B., Yang, E., Lee, L. W., Feng, A., Lewis, M. A., Lin, J., Maecker, H. T., Boyd, S. D., Davis, M. M., Nadeau, K. C., Pulendran, B., Khatri, P., Utz, P. J., Zaba, L. C. 2024; 9 (5)


    Understanding the immune responses to SARS-CoV-2 vaccination is critical to optimizing vaccination strategies for individuals with autoimmune diseases, such as systemic lupus erythematosus (SLE). Here, we comprehensively analyzed innate and adaptive immune responses in 19 patients with SLE receiving a complete 2-dose Pfizer-BioNTech mRNA vaccine (BNT162b2) regimen compared with a control cohort of 56 healthy control (HC) volunteers. Patients with SLE exhibited impaired neutralizing antibody production and antigen-specific CD4+ and CD8+ T cell responses relative to HC. Interestingly, antibody responses were only altered in patients with SLE treated with immunosuppressive therapies, whereas impairment of antigen-specific CD4+ and CD8+ T cell numbers was independent of medication. Patients with SLE also displayed reduced levels of circulating CXC motif chemokine ligands, CXCL9, CXCL10, CXCL11, and IFN-γ after secondary vaccination as well as downregulation of gene expression pathways indicative of compromised innate immune responses. Single-cell RNA-Seq analysis reveals that patients with SLE showed reduced levels of a vaccine-inducible monocyte population characterized by overexpression of IFN-response transcription factors. Thus, although 2 doses of BNT162b2 induced relatively robust immune responses in patients with SLE, our data demonstrate impairment of both innate and adaptive immune responses relative to HC, highlighting a need for population-specific vaccination studies.

    View details for DOI 10.1172/jci.insight.176556

    View details for PubMedID 38456511

  • Hydroxychloroquine in lupus pregnancy and risk of preeclampsia. Arthritis & rheumatology (Hoboken, N.J.) Rector, A., Maric, I., Chaichian, Y., Chakravarty, E., Cantu, M., Weisman, M. H., Shaw, G. M., Druzin, M., Simard, J. F. 2024


    OBJECTIVE: Systemic lupus (SLE) disproportionately affects females during childbearing years, and hydroxychloroquine (HCQ) is the standard first-line treatment. Preeclampsia complicates up to one-third of lupus pregnancies, although reports vary by parity and multi-fetal gestation. We investigated whether HCQ use early in pregnancy may reduce the risk of preeclampsia.METHODS: We studied 1068 livebirth singleton pregnancies among 1020 privately insured patients with SLE (2007-2016). HCQ use was defined as 3 months preconception through the first trimester and prescription fills were a proxy for use. Modified Poisson regression estimated risk ratios (RRs) and 95% confidence intervals (95% CI) stratified by parity. Propensity scores accounted for confounders and stratified analyses examined effect modification.RESULTS: Approximately 15% of pregnancies were diagnosed with preeclampsia. 52% of pregnancies had ≥1 HCQ fill. HCQ-exposed pregnancies had more comorbidities, SLE activity, and azathioprine use. We found no evidence of a statistical association between HCQ and preeclampsia among nulliparous (RR=1.26, 95% CI 0.82, 1.93) and multiparous pregnancies (RR=1.20, 95% CI 0.80, 1.70). Additional control for confounding decreased the RRs towards the null (nulliparous: PS-adj RR=1.09, 95% CI 0.68, 1.76 and multiparous: PS-adj RR=1.01, 95% CI 0.66, 1.53).CONCLUSION: Using a large insurance-based database, we did not observe a decreased risk of preeclampsia associated with HCQ use in pregnancy, although we cannot rule out residual and unmeasured confounding and misclassification. Further studies leveraging large population-based data and prospective collection could characterize how HCQ influences preeclampsia risk in SLE pregnancy and among persons at greater risk of hypertensive disorders of pregnancy.

    View details for DOI 10.1002/art.42793

    View details for PubMedID 38272838

  • OMERACT 2023 Systemic Lupus Erythematosus Special Interest Group: Winnowing and Binning Preliminary Candidate Domains for the Core Outcome Set. Seminars in arthritis and rheumatism Nielsen, W., Strand, V., Simon, L. S., Parodis, I., Kim, A. H., Desai, M., Enman, Y., Wallace, D., Chaichian, Y., Navarra, S., Aranow, C., MacKay, M., Trotter, K., Tayer-Shifman, O. E., Duarte-Garcia, A., Shan Tam, L., Ugarte-Gil, M. F., PonsEstel, G. J., Reynolds, J. A., Nikpour, M., Hoi, A., Romero-Diaz, J., Papachristos, D., Aggarwal, A., Mok, C. C., Fujio, K., Ramsey-Goldman, R., Howe, A., Kia, B. N., Bonilla, D., Thumboo, J., Mosca, M., Aringer, M., Johnson, S. R., Drucker, A. M., Morand, E., Bruce, I., Touma, Z. 2024; 65: 152380


    The Outcome Measures in Rheumatology (OMERACT) Systemic Lupus Erythematosus (SLE) Working Group held a Special Interest Group (SIG) at the OMERACT 2023 conference in Colorado Springs where SLE collaborators reviewed domain sub-themes generated through qualitative research and literature review.The objective of the SIG and the subsequent meetings of the SLE Working Group was to begin the winnowing and binning of candidate domain sub-themes into a preliminary list of candidate domains that will proceed to the consensus Delphi exercise for the SLE COS.Four breakout groups at the SLE SIG in Colorado Springs winnowed and binned 132 domain sub-themes into candidate domains, which was continued with a series of virtual meetings by an advisory group of SLE patient research partners (PRPs), members of the OMERACT SLE Working Group Steering Committee, and other collaborators.The 132 domain sub-themes were reduced to a preliminary list of 20 candidate domains based on their clinical and research relevance for clinical trials and research studies.A meaningful and substantial winnowing and binning of candidate domains for the SLE COS was achieved resulting in a preliminary list of 20 candidate domains.

    View details for DOI 10.1016/j.semarthrit.2024.152380

    View details for PubMedID 38281467

  • The Problem of Pain in Rheumatology: Variations in Case Definitions Derived From Chronic Pain Phenotyping Algorithms Using Electronic Health Records. The Journal of rheumatology Falasinnu, T., Nguyen, T., En Jiang, T., Tamang, S., Chaichian, Y., Darnall, B. D., Mackey, S., Simard, J. F., Chen, J. H. 2023


    The aim of this study was to investigate and compare different case definitions for chronic pain to provide estimates of possible misclassification when researchers are limited by available electronic health record and administrative claims data, allowing for greater precision in case definitions.We compared the prevalence of different case definitions for chronic pain (N = 3042) in patients with autoimmune rheumatic diseases. We estimated the prevalence of chronic pain based on 15 unique combinations of pain scores, diagnostic codes, analgesic medications, and pain interventions.Chronic pain prevalence was lowest in unimodal pain phenotyping algorithms: 15% using analgesic medications, 18% using pain scores, 21% using pain diagnostic codes, and 22% using pain interventions. In comparison, the prevalence using a well-validated phenotyping algorithm was 37%. The prevalence of chronic pain also increased with the increasing number (bimodal to quadrimodal) of phenotyping algorithms that comprised the multimodal phenotyping algorithms. The highest estimated chronic pain prevalence (47%) was the multimodal phenotyping algorithm that combined pain scores, diagnostic codes, analgesic medications, and pain interventions. However, this quadrimodal phenotyping algorithm yielded a 10% overestimation of chronic pain compared to the well-validated algorithm.This is the first empirical study to our knowledge that shows that established common modes of phenotyping chronic pain can lead to substantially varying estimates of the number of patients with chronic pain. These findings can be a reference for biases in case definitions for chronic pain and could be used to estimate the extent of possible misclassifications or corrections in using datasets that cannot include specific data elements.

    View details for DOI 10.3899/jrheum.2023-0416

    View details for PubMedID 38101917

  • Exploring Reasons for Non-Use of Hydroxychloroquine in SLE Pregnancy Chan, A., Hirz, A., Chaichian, Y., Rector, A., Druzin, M., Simard, J. WILEY. 2022: 1901-1902
  • The Problem of Pain in Rheumatology: Clinical Profiles Associated with Concomitant Diagnoses with Chronic Overlapping Pain Conditions Falasinnu, T., Chaichian, Y., Simard, J. WILEY. 2022: 2392-2394
  • Assessing the Association Between Hydroxychloroquine and Preeclampsia Risk in SLE Pregnancies Using Administrative Claims Data Rector, A., Maric, I., Chaichian, Y., Chakravarty, E., Cantu, M., Weisman, M., Shaw, G., Druzin, M., Simard, J. WILEY. 2022: 1890-1893
  • The Problem of Pain in Rheumatology: Clinical Profiles Associated With Concomitant Diagnoses With Chronic Overlapping Pain Conditions. ACR open rheumatology Falasinnu, T., Nguyen, T., Jiang, T. E., Chaichian, Y., Rector, A., Darnall, B. D., Mackey, S., Simard, J. F. 2022


    OBJECTIVE: The chronification of pain is heterogeneous in rheumatology. Chronic overlapping pain conditions (COPCs) such as fibromyalgia, endometriosis, migraine, and back pain may co-occur with one another and in rheumatic diseases. We describe the sociodemographic and clinical profiles associated with concomitant COPCs among patients with rheumatic diseases.METHODS: We retrospectively identified patients visiting rheumatology clinics at a single institution from 2010 to 2020 for five common rheumatic conditions: psoriatic arthritis (PsA), rheumatoid arthritis (RA), Sjogren syndrome (SjS), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc). We compared sociodemographic, clinical, and lifestyle factors by rheumatic condition and by COPC status. We also report sex-stratified diagnosis of COPCs. The primary outcome was diagnostic validation of one or more COPCs.RESULTS: We identified 5992 rheumatology patients: 846 with PsA, 2605 with RA, 956 with SjS, 975 with SLE, and 610 with SSc. Approximately 36-62% of patients had a concomitant COPC diagnosis. Patients with SjS had the highest prevalence (62%). Diagnosis of one or more COPCs was highest among Black patients and lowest among Asian patients. Patients using public insurance had a higher prevalence of one or more COPCs compared with those with private insurance. Patients with one or more COPCs had more depression and anxiety and more frequent emergency department visits, surgeries, and hospitalizations.CONCLUSION: Our findings suggest that COPCs are strikingly common among patients with rheumatic disease and are associated with lower quality of life and greater health care needs. Future research may elucidate drivers of chronic pain and how to best address the unique analgesic needs of this multimorbid population.

    View details for DOI 10.1002/acr2.11488

    View details for PubMedID 35872631

  • The Burden of Systemic Lupus in Five Distinct Racial and Ethnic Groups in Israel: A Population-based Study Falasinnu, T., Rizk, N., Feldman, B., Zisman, D., Leshchinsky, M., Lawrence, G., Chaichian, Y., Simard, J. WILEY. 2021: 1203-1207
  • Innovative Trials and New Opportunities in SLE. Rheumatic diseases clinics of North America Chaichian, Y., Wallace, D. J. 2021; 47 (3): 481-499


    Despite progress in the treatment of systemic lupus erythematosus (SLE), remission rates and health-related quality of life remain disappointingly low. The paucity of successful SLE clinical trials reminds us that we still have a long way to go. Nevertheless, there are clear signs of hope. We highlight results from recent studies of novel therapeutic strategies based on emerging insights into our understanding of SLE disease mechanisms. We also highlight several studies that inform optimal use of existing treatments to improve efficacy and/or limit toxicity. These developments suggest we may yet unlock the key toward more satisfactory treatment outcomes in SLE.

    View details for DOI 10.1016/j.rdc.2021.04.010

    View details for PubMedID 34215375

  • Are we missing lupus in males? Evidence of cognitive bias from a randomized experiment in the US. American journal of epidemiology Simard, J. F., Chaichian, Y., Rizk, N., Rector, A., Feldman, C. H., Falasinnu, T. O. 2021

    View details for DOI 10.1093/aje/kwab199

    View details for PubMedID 34308469

  • Interferon-directed therapies for the treatment of systemic lupus erythematosus: a critical update. Clinical rheumatology Chaichian, Y., Strand, V. 2021


    The interferon (IFN) pathway, especially type I IFN, plays a critical role in the immunopathogenesis of systemic lupus erythematosus (SLE). We have gained significant insights into this pathway over the past two decades, including a better understanding of the key mediators of inflammation upstream and downstream of type I IFN. This has led to the identification of multiple potential targets for the treatment of SLE, for which a significant unmet need remains due to the failure of many patients to adequately respond to standard-of-care medications. Unfortunately, most new therapies in SLE have disappointed in preclinical or clinical trials to date, including a number that target type I IFN. Nevertheless, several IFN-directed therapies aimed at specific steps within this immunologic pathway have recently shown promise, and additional agents are in the treatment pipeline. In this review, we focus on the results of key therapeutic studies targeting the type I IFN pathway and discuss the future state of IFN-blockade in SLE.

    View details for DOI 10.1007/s10067-020-05526-1

    View details for PubMedID 33411137

  • Pulse dose steroid experience among hospitalized patients with systemic lupus erythematosus: a single-center feasibility study. Clinical rheumatology Chaichian, Y. n., Weisman, M. H., Simard, J. F. 2021


    Pulse intravenous (IV) methylprednisolone (MEP) is often used for severe SLE manifestations requiring hospitalization. However, the accuracy of pulse dose documentation extracted from the electronic health record (EHR) is unknown. We assessed the feasibility to study pulse steroid dosing among hospitalized patients with SLE at our institution. Using the Stanford Medicine Research Data Repository (STARR) extracted from the EHR, we identified patients with ≥ 1 SLE ICD code before/during hospitalization receiving steroids (1/2008-12/2017). SLE diagnosis required rheumatologist confirmation. For our feasibility study, we randomly sampled 40/747 patients meeting search criteria. Pulse IV MEP was defined as ≥ 200 mg. Pharmacy dispensation data required EHR confirmation. Forty adult and pediatric subjects were identified, passing initial criteria screen; 6 pediatric patients were excluded as EHR pharmacy confirmation was unavailable. Of the 34 adults, 14 had SLE confirmed. Among 5 adult SLE patients with pulse documentation, 3 occurred while hospitalized, for the following indications: acute renal transplant rejection (2 patients, 2 hospitalizations) and lupus flare (1 patient, 2 hospitalizations). No discrepancies were observed in pharmacy dispensation documentation of pulse dosing between EHR and STARR for all 4 hospitalizations.Assessment of pulse steroid dose dispensation among hospitalized patients with SLE can be reliably ascertained from the extracted portion of the EHR designed for research. Reliance on a single ICD code for SLE in the EHR may lead to high rate of false-positive diagnoses of SLE among hospitalized patients. We document the importance of supplementing one ICD code with additional clinical information when confirming SLE diagnosis. Key Points • Assessment of pulse steroid dosing dispensation among hospitalized patients with SLE can be reliably determined from the extracted portion of the EHR designed for research purposes. • Reliance on a single ICD code contributes to a high rate of false positive diagnoses of SLE among hospitalized patients. • Supplementing ICD coding with additional clinical information is vital when confirming SLE diagnosis.

    View details for DOI 10.1007/s10067-021-05644-4

    View details for PubMedID 33608793

  • Increasing Ancestral Diversity in Lupus Trials: Ways Forward. Rheumatic diseases clinics of North America Falasinnu, T., Chaichian, Y., Simard, J. F. 2020; 46 (4): 713–22


    Significant disparities exist in systemic lupus erythematosus (SLE) regarding prevalence, disease severity, and mortality, with race/ethnic minorities being disproportionately affected in the United States. This review highlights that despite these disparities, race/ethnic minority underrepresentation remains an issue within SLE research. Decreased race/ethnic minority involvement in SLE research has real-world implications, including less understanding of the disease and less applicability of approved therapies among diverse groups of patients. Members of the SLE research community have an obligation to narrow this gap to ensure that future advances within the field are derived from and benefit a more representative group of patients.

    View details for DOI 10.1016/j.rdc.2020.07.011

    View details for PubMedID 32981648

  • The road to rheumatoid arthritis prevention: challenges and opportunities. Clinical rheumatology Chaichian, Y., Genovese, M. C., Weisman, M. H. 2020


    Rheumatoid arthritis (RA) is the most prevalent cause of chronic arthritis worldwide and contributes substantial health burden and socioeconomic costs, issues that are magnified by the aging population. Despite significantly improved outcomes in the management of RA with earlier diagnosis and advances in treatment, there is still no cure and disease prevention remains an area of intense interest. Studies examining different treatment regimens in varied subsets of patients with pre-clinical RA have been able to delay but not prevent onset of frank RA. In this timely issue of Clinical Rheumatology, Alpziar-Rodriguez D. and Finckh A. highlight the available literature on pre-clinical RA including modifiable risk factors, results of key intervention trials, and discuss whether prevention of RA is on the horizon. We offer additional thoughts on current areas of uncertainty in RA prevention studies, lessons to be learned from prevention trials in other disease states, and future directions to consider.

    View details for DOI 10.1007/s10067-020-05016-4

    View details for PubMedID 32170486

  • CD52 Is Elevated on B cells of SLE Patients and Regulates B Cell Function. Frontiers in immunology Bhamidipati, K. n., Silberstein, J. L., Chaichian, Y. n., Baker, M. C., Lanz, T. V., Zia, A. n., Rasheed, Y. S., Cochran, J. R., Robinson, W. H. 2020; 11: 626820


    Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by B cell dysregulation and breaks in tolerance that lead to the production of pathogenic autoantibodies. We performed single-cell RNA sequencing of B cells from healthy donors and individuals with SLE which revealed upregulated CD52 expression in SLE patients. We further demonstrate that SLE patients exhibit significantly increased levels of B cell surface CD52 expression and plasma soluble CD52, and levels of soluble CD52 positively correlate with measures of lupus disease activity. Using CD52-deficient JeKo-1 cells, we show that cells lacking surface CD52 expression are hyperresponsive to B cell receptor (BCR) signaling, suggesting an inhibitory role for the surface-bound protein. In healthy donor B cells, antigen-specific BCR-activation initiated CD52 cleavage in a phospholipase C dependent manner, significantly reducing cell surface levels. Experiments with recombinant CD52-Fc showed that soluble CD52 inhibits BCR signaling in a manner partially-dependent on Siglec-10. Moreover, incubation of unstimulated B cells with CD52-Fc resulted in the reduction of surface immunoglobulin and CXCR5. Prolonged incubation of B cells with CD52 resulted in the expansion of IgD+IgMlo anergic B cells. In summary, our findings suggest that CD52 functions as a homeostatic protein on B cells, by inhibiting responses to BCR signaling. Further, our data demonstrate that CD52 is cleaved from the B cell surface upon antigen engagement, and can suppress B cell function in an autocrine and paracrine manner. We propose that increased expression of CD52 by B cells in SLE represents a homeostatic mechanism to suppress B cell hyperactivity.

    View details for DOI 10.3389/fimmu.2020.626820

    View details for PubMedID 33658999

    View details for PubMedCentralID PMC7917337

  • Phase II, randomised, double-blind, multicentre study evaluating the safety and efficacy of filgotinib and lanraplenib in patients with lupus membranous nephropathy. RMD open Baker, M. n., Chaichian, Y. n., Genovese, M. n., Derebail, V. n., Rao, P. n., Chatham, W. n., Bubb, M. n., Lim, S. n., Hajian, H. n., Gurtovaya, O. n., Patel, U. n., Tumlin, J. n. 2020; 6 (3)


    Patients with lupus membranous nephropathy (LMN) are at risk for prolonged proteinuria and progressive chronic kidney disease. There are no proven effective treatments for LMN, and controlled trials are lacking. This trial assessed the preferential Janus kinase 1 (JAK1) inhibitor filgotinib and the spleen tyrosine kinase inhibitor lanraplenib in patients with LMN.This was a phase II, randomised, double-blind trial conducted at 15 centres in the USA to evaluate the safety and efficacy of filgotinib or lanraplenib for the treatment of LMN. Eligible patients were randomised 1:1 to receive either filgotinib or lanraplenib in a blinded fashion for up to 52 weeks. The primary endpoint was the per cent change in 24-hour urine protein from baseline to week 16.Nine patients were randomised to receive filgotinib (n=5) or lanraplenib (n=4). Four patients in the filgotinib group and one patient in the lanraplenib group completed week 16. There was a median reduction of 50.7% in 24-hour urine protein after 16 weeks of treatment with filgotinib (n=4), and the median Systemic Lupus Erythematosus Disease Activity Index from the Safety of Estrogens in Lupus National Assessment score remained stable. Filgotinib treatment was well tolerated. Limited conclusions can be drawn about treatment with lanraplenib.The number of patients treated in this study was small, and only limited conclusions can be drawn. There may be a therapeutic benefit with filgotinib treatment, which may support future investigations with filgotinib or other JAK inhibitors in patients with LMN.NCT03285711.

    View details for DOI 10.1136/rmdopen-2020-001490

    View details for PubMedID 33380521

  • Does SLE widen or narrow race/ethnic disparities in the risk of five co-morbid conditions? Evidence from a community-based outpatient care system. Lupus Falasinnu, T., Chaichian, Y., Li, J., Chung, S., Waitzfelder, B. E., Fortmann, S. P., Palaniappan, L., Simard, J. F. 2019: 961203319884646


    OBJECTIVE: The heterogeneous spectrum of systemic lupus erythematosus (SLE) often presents with secondary complications such as cardiovascular disease (CVD), infections and neoplasms. Our study assessed whether the presence of SLE independently increases or reduces the disparities, accounting for the already higher risk of these outcomes among racial/ethnic minority groups without SLE.METHODS: We defined a cohort using electronic health records data (2005-2016) from a mixed-payer community-based outpatient setting in California serving patients of diverse racial/ethnic backgrounds. The eligible population included adult patients with SLE and matched non-SLE patients (≥18 years old). SLE was the primary exposure. The following outcomes were identified: pneumonia, other infections, CVD and neoplasms. For each racial/ethnic group, we calculated the proportion of incident co-morbidities by SLE exposure, followed by logistic regression for each outcome with SLE as the exposure. We evaluated interaction on the additive and multiplicative scales by calculating the relative excess risk due to interaction and estimating the cross-product term in each model.RESULTS: We identified 1036 SLE cases and 8875 controls. The incidence for all outcomes was higher among the SLE exposed. We found little difference in the odds of the outcomes associated with SLE across racial/ethnic groups, even after multivariable adjustment. This finding was consistent on the multiplicative and additive scales.CONCLUSION: We demonstrated that SLE status does not independently confer substantial interaction or heterogeneity by race/ethnicity toward the risk of pneumonia, other infections, CVD or neoplasms. Further studies in larger datasets are necessary to validate this novel finding.

    View details for DOI 10.1177/0961203319884646

    View details for PubMedID 31660790

  • Preterm birth phenotypes in women with autoimmune rheumatic diseases: A population based cohort study. BJOG : an international journal of obstetrics and gynaecology Kolstad, K. D., Mayo, J. A., Chung, L., Chaichian, Y., Kelly, V. M., Druzin, M., Stevenson, D. K., Shaw, G. M., Simard, J. F. 2019


    OBJECTIVE: To investigate preterm birth (PTB) phenotypes in women with different autoimmune rheumatic diseases in a large population-based cohort.DESIGN: Retrospective cohort study.SETTING: California, USA.POPULATION: All live singleton births in California between 2007 and 2011 were analyzed. Patients with autoimmune disease at delivery were identified by ICD-9 codes for systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), polymyositis/dermatomyositis (DM/PM), and juvenile idiopathic arthritis (JIA).METHODS: Maternally linked hospital and birth certificate records of 2,481,516 deliveries were assessed (SLE n=2,272, RA n=1,501, SSc n=88, JIA n=187, DM/PM n=38). Multivariable Poisson regression models estimated risk ratios (RRs) for different PTB phenotypes (relative to term deliveries) for each autoimmune disease compared to the general obstetric population adjusting for maternal age, race/ethnicity, body mass index, smoking, education, payer, parity, and prenatal care.MAIN OUTCOME MEASURES: PTB was assessed overall (20-36 weeks) and by subphenotype: pre-term premature rupture of membranes (PPROM), spontaneous, or medically indicated PTB. Risk of PTB overall and each phenotype was partitioned by gestational age: early (20-31 weeks) and late (32-36 weeks).RESULTS: Risks for PTB were elevated for each autoimmune disease evaluated: SLE (RR 3.27 95%CI 3.01-3.56), RA (RR 2.04 95%CI 1.79-2.33), SSc (RR 3.74 95%CI 2.51-5.58), JIA (RR 2.23 95%CI 1.54-3.23), and DM/PM (RR 5.26 95%CI 3.12-8.89). These elevated risks were observed for the majority of PTB phenotypes as well.CONCLUSIONS: Women with systemic autoimmune diseases appear to have an elevated risk of various PTB phenotypes. Therefore, preconception counseling and close monitoring during pregnancy is crucial.

    View details for DOI 10.1111/1471-0528.15970

    View details for PubMedID 31571337

  • Preterm Delivery Phenotypes in Systemic Lupus Erythematosus Pregnancies AMERICAN JOURNAL OF PERINATOLOGY Simard, J. F., Chaichian, Y., Rossides, M., Wikstrom, A., Shaw, G. M., Druzin, M. L. 2019; 36 (9): 964–68
  • A promising approach to targeting type 1 IFN in systemic lupus erythematosus. The Journal of clinical investigation Chaichian, Y., Wallace, D. J., Weisman, M. H. 2019


    Despite advances in understanding systemic lupus erythematosus (SLE) pathogenesis, most clinical trials of new targeted therapies have been met with disappointment. The type I IFN pathway is believed to play an important role in SLE, and the proposed involvement of this pathway helps explain the frustration behind the failure at targeting either IFN-alpha or the type 1 IFN receptor itself. In this issue of the JCI, Furie et al. report on an intriguing phase 1b study that demonstrates an approach for inhibiting this pathway in the skin using an mAB (BIIB059) that targets the blood DC antigen 2 (BDCA-2) receptor on plasmacytoid DCs (pDCs). BIIB059 decreased IFN expression and improved cutaneous lupus disease activity, with a favorable safety profile. Whether or not this strategy will be effective in managing SLE in other organs remains unanswered. However, these results suggest that closing the door on targeting the type 1 IFN pathway in SLE may be premature and highlight the emerging question of whether an organ-specific approach toward lupus trials and treatment should be the wave of the future.

    View details for PubMedID 30776023

  • Unraveling Race, Socioeconomic Factors, and Geographical Context in the Heterogeneity of Lupus Mortality in the United States. ACR open rheumatology Falasinnu, T. n., Chaichian, Y. n., Palaniappan, L. n., Simard, J. F. 2019; 1 (3): 164–72


    Systemic lupus erythematosus (SLE) is a chronic autoimmune disease disproportionately affecting women and racial/ethnic minorities. We examined SLE-related mortality over time to assess whether the impact of race is attenuated when social economic status (SES) and geographic context are also considered.This study examined whether social environment attenuates racial disparities in SLE-related mortality using race-geographical combinations of the US population known as the "Eight Americas." This framework jointly characterizes race, SES, and geographical location in relation to health disparities in the United States. Using National Vital Statistics and US Census data, we estimated mortality parameters for each of the Eight Americas.We identified 24 773 SLE deaths (2003-2014). Average annual mortality rates were highest among blacks in three race-geographical contexts: average-income blacks, southern low-income blacks, and high-risk urban blacks (14 to 15 deaths per million population) and lowest among nonblacks living in average-income settings (3 to 4 deaths per million population). Age at death was lowest (~47.5 years) for blacks and Asians and highest among low-income rural whites (~64.8 years).Blacks sharing the same social and geographical contexts as whites were disproportionately more likely to die young. Although blacks inhabited three vastly different contexts, SLE-related mortality parameters did not vary among socially advantaged and disadvantaged blacks. These findings suggest that race may transcend SES and geographical parameters as a key determinant of SLE-related mortality.

    View details for DOI 10.1002/acr2.1024

    View details for PubMedID 31777791

    View details for PubMedCentralID PMC6858029

  • Do Death Certificates Underestimate the Burden of Rare Diseases? The Example of Systemic Lupus Erythematosus Mortality, Sweden, 2001-2013. Public health reports (Washington, D.C. : 1974) Falasinnu, T., Rossides, M., Chaichian, Y., Simard, J. F. 2018: 33354918777253


    OBJECTIVES: Mortality due to rare diseases, which are substantial sources of premature mortality, is underreported in mortality studies. The objective of this study was to determine the completeness of reporting systemic lupus erythematosus (SLE) as a cause of death.METHODS: In 2017, we linked data on a Swedish population-based cohort (the Swedish Lupus Linkage, 2001-2013) comprising people with SLE (n = 8560) and their matched general population comparators (n = 37717) to data from the Cause of Death Register. We reviewed death records of deceased people from the cohort (n = 5110) and extracted data on patient demographic characteristics and causes of death. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for not reporting SLE as a cause of death by using multivariable-adjusted logistic regression models.RESULTS: Of 1802 deaths among SLE patients in the study, 1071 (59%) did not have SLE reported on their death records. Most SLE decedents were aged 75-84 at death (n = 584, 32%), female (n = 1462, 81%), and born in Nordic countries (n = 1730, 96%). Decedents aged ≥85 at death were more likely to have SLE not reported on their death records than were decedents aged <50 (OR = 2.34; 95% CI, 1.48-3.68). Having renal failure listed as a cause of death decreased the likelihood of SLE not being reported on the death record (OR = 0.54; 95% CI, 0.40-0.73), whereas having cancer listed as a cause of death increased this likelihood (OR = 2.39; 95% CI, 1.85-3.07).CONCLUSIONS: SLE was greatly underreported as a cause of mortality on death records of SLE patients, particularly in older decedents and those with cancer, thereby underestimating the true burden of this disease. Public health resources need to focus on improving the recording of rare diseases in order to enhance the epidemiological utility of mortality data.

    View details for DOI 10.1177/0033354918777253

    View details for PubMedID 29928843

  • The Representation of Gender and Race/Ethnic Groups in Randomized Clinical Trials of Individuals with Systemic Lupus Erythematosus. Current rheumatology reports Falasinnu, T. n., Chaichian, Y. n., Bass, M. B., Simard, J. F. 2018; 20 (4): 20


    This review evaluated gender and race/ethnic representation in randomized controlled trials (RCTs) of patients with systemic lupus erythematosus (SLE).Whites comprise 33% of prevalent SLE cases and comprised 51% of RCT enrollees. Blacks encompass 43% of prevalent SLE cases, but only represented 14% of RCT enrollees. Hispanics comprise 16% of prevalent SLE cases and 21% of RCT enrollees, while Asians comprise 13% of prevalent SLE cases and 10% of RCT enrollees. Males encompass 9% of SLE cases and 7% of RCT enrollees. The reporting and representation of males have remained stable over time, although their representation in RCTs is slighter lower than the prevalence of SLE in males. The representation of Hispanics, Asians, and Native Americans increased over time. However, the representation of blacks among RCT participants has decreased since 2006-2011. RCTs among SLE patients need larger sample sizes in order to evaluate heterogeneity in outcomes among racial subgroups. It is imperative that novel strategies be developed to recruit racial minorities with SLE by identifying and improving barriers to RCT enrollment in order to better understand the disease's diverse population.

    View details for PubMedID 29550947

  • Impact of Sex on Systemic Lupus Erythematosus-Related Causes of Premature Mortality in the United States. Journal of women's health (2002) Falasinnu, T. n., Chaichian, Y. n., Simard, J. F. 2017


    Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is a source of significantly decreased life expectancy in the United States. This study investigated causes of deaths among males and females with SLE.This cross-sectional study used the national death certificate database of ∼2.7 million death records in the United States, 2014. SLE was defined using Tenth Revision of the International Classification of Diseases codes: M32.1, M32.9, and M32.8. We compared sex-stratified demographic characteristics and the most commonly listed comorbidities in decedents with and without SLE. Relative risks (RRs) quantified the risk of dying with the most commonly listed comorbidities among decedents with SLE aged ≤50 years compared with non-SLE decedents.There were 2,036 decedents with SLE in the United States (86.2% female). Female SLE decedents were 22 years younger than non-SLE females (median: 59 years vs. 81 years). This difference was 12 years among male decedents (median: 61 years vs. 73 years). The most frequently listed causes of death among female SLE decedents were septicemia (4.32%) and hypertension (3.04%). In contrast, heart disease (3.70%) and diabetes mellitus with complications (3.61%) were the most common among male SLE decedents. Among younger male decedents, SLE had higher co-occurrence of coagulation/hemorrhagic disorders and chronic renal failure compared with non-SLE (RR = 16.69 [95% confidence interval {CI} = 10.50-27.44] and RR = 5.76 [95% CI = 2.76-12.00], respectively). These also contributed to premature mortality among women (RR = 4.98 [95% CI = 3.69-6.70] and 8.55 [95% CI = 6.89-10.61], respectively).Our findings identify clinically relevant comorbidities that may warrant careful consideration in patients' clinical management and the natural history of SLE.

    View details for DOI 10.1089/jwh.2017.6334

    View details for PubMedID 28891746

  • Long-term Management of Gout: Nonpharmacologic and Pharmacologic Therapies Rheumatic Disease Clinics of North America Chaichian, Y., Chohan, S., Becker, M. A. 2014; 40 (2)
  • Targeted Therapies in Systemic Lupus Erythematosus: A State-of-the-Art Review Journal of Clinical & Cellular Immunology Chaichian, Y., Utset, T. O. 2013; 4 (S6)