Systemic Autoimmunity Branch

The broad and long-term objectives of the Systemic Autoimmunity Branch are to further the understanding of the pathophysiology and clinical spectrum of systemic autoimmune diseases and to translate this knowledge into better therapies that improve outcomes for patients with these conditions. A major goal of the branch is to combine natural history or treatment studies with basic investigations into the etiology and/or pathophysiology of rheumatic diseases, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

Additionally, the branch works to train the next generation of scientists and physician-scientists focused on the understanding of the pathogenesis and advancement in the treatments of patients afflicted by systemic autoimmune diseases.

Our research focuses on unraveling fundamental mechanisms underlying immunologic tolerance and understanding innate and adaptive immune pathways crucial to these autoimmune responses in SLE and other autoimmune diseases.

Lupus neutrophils form NETs and extrude nucleic acids

As treatments to suppress aberrant immune responses improve, patients with systemic autoimmunity are able to survive for longer periods of time. As a result, the prevalence of end-stage complications, including the development of accelerated atherosclerosis and myocardial infarction, has increased. We are interested in identifying the immune pathways that promote premature vascular damage in systemic autoimmunity to identify potential preventive strategies.

Current areas of interest

  • The role of neutrophils and neutrophil extracellular traps (NETs) in the induction of loss of immunologic tolerance and acceleration of organ and vascular damage in autoimmune diseases.
  • How type I Interferons (IFNs) contribute to the development of premature atherogenesis and vasculopathy in SLE and other connective tissue diseases.
  • Alterations of immunometabolism in autoimmunity.
  • The identification of novel biomarkers and therapeutic targets to mitigate cardiovascular damage and induce immunomodulation in SLE and other systemic rheumatic diseases.

Related NIAMS Labs

Scientific Advances block_2 a:6:{s:6:"header";N;s:5:"title";i:0;s:5:"limit";N;s:8:"argument";N;s:6:"offset";N;s:5:"pager";N;}

Postdoctoral Students and Scholars

  • Eduardo Patino-Martinez, Ph.D., 2020-2025
  • Shuichiro Nakabo , M.D., PH.D., 2018-2024 (Assistant Professor, University of Kyoto, Japan)
  • Mingzeng Zhang, M.D., PH.D., 2021-2022 (Postdoctoral fellow, Dana Farber Cancer Institute)
  • Gustaf Wigerblad, Ph.D., 2018-2023 (Research Fellow, Genomic Technology Section, NIAMS)
  • Hege Lynum Pedersen, Ph.D., 2018-2019 (Research Scientist, UiT The Artic University of Norway, Tromso, Norway)
  • Jose Jiram Torres-Ruiz, M.D., 2018 (Ph.D. student, UNAM, Mexico City)
  • Liam O’Neill, M.D., 2017-2019 (Rheumatologist and Clinician-Scientist, University of Manitoba, Canada)
  • Yaima Lightfoot, Ph.D., 2015-2017 (Research Scientist, MD Anderson Cancer Center)
  • Yudong Liu, M.D., Ph.D., 2015-2018 (Attending Physician, Peking University, China)
  • Pragnesh Mistry, Ph.D., 2015-2018 (Technology Transfer and Patent Specialist, NHLBI, NIH)
  • John Reynolds, MRCP, Ph.D., 2014 (Clinical Senior Lecturer in Rheumatology, University of Birmingham, UK)
  • Ana Barrera, M.D., 2014-2016 (Attending Physician, Hospital ABC, Mexico City)

Postbaccalaureate Students

  • Christopher Oliveira, B.S., 2910-2021 (M.D. Student, University of Washington)
  • Alexandra Woo , B.S., 2022-2024 (M.D., Ph.D. Student, Northwestern University)
  • Dillon Claybaugh, B.S., 2020-2023 (M.D. student, University of Oregon)
  • Donavon Sandoval-Heglund, B.S., 2019-2020 (M.D. Student, UCSF)
  • Xinghao Wang, B.S., 2018-2021 (M.D., Ph.D. student, University of Michigan)
  • Rishi Goel, Sc.M., 2018-2019 (Internal Medicine Resident, Mass General)
  • Phillip Carlucci, B.S., 2016-2018 (Rheumatology Fellow, NYU)
  • Diana Chan, B.S., 2016-2018 (D.D.S. student, University of Washington)
  • Nickie Seto, B.S., 2015-2018
  • Erica Moore, B.S., 2014-2016 (M.D., Ph.D. student, Albert Einstein College of Medicine)
  • Jorge Irizarry Caro, 2014-2016 (Cardiology Fellow, UT Southwestern)
  • Monica Purmalek, B.A., 2014-2016 (Resident in Obstetrics and Gynecology, USUHS)

Graduate Students

  • Kathleen Bashant, Ph.D., Cambridge/NIH partnership, 2016-2020 (Research Scientist, Vow, Sydney, Australia)
  • Carolyne Smith, Ph.D., University of Michigan GPP program, 2010-2015 (Scientist, SQZ Biotechnologies)

Clinical Fellows

  • Kathleen Vazzana, M.D., 2019-2021 (Practicing Pediatric Rheumatology at Orlando Health Arnold Palmer Hospital for Children)

Staff Scientists

  • Luz Blanco Ph.D., 2013-2025

block_2 a:6:{s:6:"header";N;s:5:"title";i:0;s:5:"limit";N;s:8:"argument";s:3:"419";s:6:"offset";N;s:5:"pager";N;} Cell Biology Clinical Research Immunology Molecular Biology and Biochemistry Systems Biology block_5 a:6:{s:6:"header";N;s:5:"title";i:0;s:5:"limit";N;s:8:"argument";s:7:"137+144";s:6:"offset";N;s:5:"pager";N;}

The Aconitate Decarboxylase 1/Itaconate Pathway Modulates Immune Dysregulation and Associates with Cardiovascular Disease Markers and Disease Activity in Systemic Lupus Erythematosus.

Patiño-Martinez E, Nakabo S, Jiang K, Carmona-Rivera C, Tsai WL, Claybaugh D, Yu ZX, Romero A, Bohrnsen E, Schwarz B, Solís-Barbosa MA, Blanco LP, Naqi M, Temesgen-Oyelakin Y, Davis M, Manna Z, Gupta S, Mehta N, Naz F, dell'Orso S, Hasni S, Kaplan MJ

J Immunol.

2024 Aug 15;

213(4).

doi: 10.4049/jimmunol.2400241

PMID: 38949522

Modulation of cardiometabolic disease markers by type I interferon inhibition in systemic lupus erythematosus.

Casey KA, Smith MA, Sinibaldi D, Seto NL, Playford MP, Wang X, Carlucci PM, Wang L, Illei G, Yu B, Wang S, Remaley AT, Mehta NN, Kaplan MJ, White WI

Arthritis Rheumatol.

2020 Sep 10;

doi: 10.1002/art.41518

PMID: 32909675

Sex differences in neutrophil biology modulate response to type I interferons and immunometabolism.

Gupta S, Nakabo S, Blanco LP, O'Neil LJ, Wigerblad G, Goel RR, Mistry P, Jiang K, Carmona-Rivera C, Chan DW, Wang X, Pedersen HL, Gadkari M, Howe KN, Naz F, Dell'Orso S, Hasni SA, Dempsey C, Buscetta A, Frischmeyer-Guerrerio PA, Kruszka P, Muenke M, Franco LM, Sun HW, Kaplan MJ

Proc Natl Acad Sci U S A.

2020 Jul 14;

117(28).

doi: 10.1073/pnas.2003603117

PMID: 32601182

VDAC oligomers form mitochondrial pores to release mtDNA fragments and promote lupus-like disease.

Kim J, Gupta R, Blanco LP, Yang S, Shteinfer-Kuzmine A, Wang K, Zhu J, Yoon HE, Wang X, Kerkhofs M, Kang H, Brown AL, Park SJ, Xu X, Zandee van Rilland E, Kim MK, Cohen JI, Kaplan MJ, Shoshan-Barmatz V, Chung JH

Science.

2019 Dec 20;

366(6472).

doi: 10.1126/science.aav4011

PMID: 31857488

Transcriptomic, epigenetic, and functional analyses implicate neutrophil diversity in the pathogenesis of systemic lupus erythematosus.

Mistry P, Nakabo S, O'Neil L, Goel RR, Jiang K, Carmona-Rivera C, Gupta S, Chan DW, Carlucci PM, Wang X, Naz F, Manna Z, Dey A, Mehta NN, Hasni S, Dell'Orso S, Gutierrez-Cruz G, Sun HW, Kaplan MJ

Proc Natl Acad Sci U S A.

2019 Dec 10;

116(50).

doi: 10.1073/pnas.1908576116

PMID: 31754025

Synovial fibroblast-neutrophil interactions promote pathogenic adaptive immunity in rheumatoid arthritis.

Carmona-Rivera C, Carlucci PM, Moore E, Lingampalli N, Uchtenhagen H, James E, Liu Y, Bicker KL, Wahamaa H, Hoffmann V, Catrina AI, Thompson P, Buckner JH, Robinson WH, Fox DA, Kaplan MJ

Sci Immunol.

2017 Apr;

2(10).

pii: eaag3358. doi: 10.1126/sciimmunol.aag3358

PMID: 28649674

Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease.

Lood C, Blanco LP, Purmalek MM, Carmona-Rivera C, De Ravin SS, Smith CK, Malech HL, Ledbetter JA, Elkon KB, Kaplan MJ

Nat Med.

2016 Feb;

22(2).

doi: 10.1038/nm.4027

PMID: 26779811

Deficiency of adenosine deaminase 2 triggers adenosine-mediated NETosis and TNF production in patients with DADA2.

Carmona-Rivera C, Khaznadar SS, Shwin KW, Irizarry-Caro JA, O'Neil LJ, Liu Y, Jacobson KA, Ombrello AK, Stone DL, Tsai WL, Kastner DL, Aksentijevich I, Kaplan MJ, Grayson PC

Blood.

2019 Jul 25;

134(4).

doi: 10.1182/blood.2018892752

PMID: 31015188

Peptidylarginine deiminases 2 and 4 modulate innate and adaptive immune responses in TLR-7-dependent lupus.

Liu Y, Lightfoot YL, Seto N, Carmona-Rivera C, Moore E, Goel R, O'Neil L, Mistry P, Hoffmann V, Mondal S, Premnath PN, Gribbons K, Dell'Orso S, Jiang K, Thompson PR, Sun HW, Coonrod SA, Kaplan MJ

JCI Insight.

2018 Dec 6;

3(23).

pii: 124729. doi: 10.1172/jci.insight.124729

PMID: 30518690

Revealing the cellular degradome by mass spectrometry analysis of proteasome-cleaved peptides.

Wolf-Levy H, Javitt A, Eisenberg-Lerner A, Kacen A, Ulman A, Sheban D, Dassa B, Fishbain-Yoskovitz V, Carmona-Rivera C, Kramer MP, Nudel N, Regev I, Zahavi L, Elinger D, Kaplan MJ, Morgenstern D, Levin Y, Merbl Y

Nat Biotechnol.

2018 Oct 22;

doi: 10.1038/nbt.4279

PMID: 30346940

Dysregulated neutrophil responses and neutrophil extracellular trap formation and degradation in PAPA syndrome.

Mistry P, Carmona-Rivera C, Ombrello AK, Hoffmann P, Seto NL, Jones A, Stone DL, Naz F, Carlucci P, Dell'Orso S, Gutierrez-Cruz G, Sun HW, Kastner DL, Aksentijevich I, Kaplan MJ

Ann Rheum Dis.

2018 Dec;

77(12).

doi: 10.1136/annrheumdis-2018-213746

PMID: 30131320

Neutrophil subsets and their gene signature associate with vascular inflammation and coronary atherosclerosis in lupus.

Carlucci PM, Purmalek MM, Dey AK, Temesgen-Oyelakin Y, Sakhardande S, Joshi AA, Lerman JB, Fike A, Davis M, Chung JH, Playford MP, Naqi M, Mistry P, Gutierrez-Cruz G, Dell'Orso S, Naz F, Salahuddin T, Natarajan B, Manna Z, Tsai WL, Gupta S, Grayson P, Teague H, Chen MY, Sun HW, Hasni S, Mehta NN, Kaplan MJ

JCI Insight.

2018 Apr 19;

3(8).

pii: 99276. doi: 10.1172/jci.insight.99276

PMID: 29669944

Synovial fibroblast-neutrophil interactions promote pathogenic adaptive immunity in rheumatoid arthritis.

Carmona-Rivera C, Carlucci PM, Moore E, Lingampalli N, Uchtenhagen H, James E, Liu Y, Bicker KL, Wahamaa H, Hoffmann V, Catrina AI, Thompson P, Buckner JH, Robinson WH, Fox DA, Kaplan MJ

Sci Immunol.

2017 Apr;

2(10).

pii: eaag3358. doi: 10.1126/sciimmunol.aag3358

PMID: 28649674

A role for muscarinic receptors in neutrophil extracellular trap formation and levamisole-induced autoimmunity.

Carmona-Rivera C, Purmalek MM, Moore E, Waldman M, Walter PJ, Garraffo HM, Phillips KA, Preston KL, Graf J, Kaplan MJ, Grayson PC

JCI Insight.

2017 Feb 9;

2(3).

doi: 10.1172/jci.insight.89780

PMID: 28194438

Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease.

Lood C, Blanco LP, Purmalek MM, Carmona-Rivera C, De Ravin SS, Smith CK, Malech HL, Ledbetter JA, Elkon KB, Kaplan MJ

Nat Med.

2016 Feb;

22(2).

doi: 10.1038/nm.4027

PMID: 26779811

NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis.

Khandpur R, Carmona-Rivera C, Vivekanandan-Giri A, Gizinski A, Yalavarthi S, Knight JS, Friday S, Li S, Patel RM, Subramanian V, Thompson P, Chen P, Fox DA, Pennathur S, Kaplan MJ

Sci Transl Med.

2013 Mar 27;

5(178).

doi: 10.1126/scitranslmed.3005580

PMID: 23536012

CD11b activation suppresses TLR-dependent inflammation and autoimmunity in systemic lupus erythematosus.

Faridi MH, Khan SQ, Zhao W, Lee HW, Altintas MM, Zhang K, Kumar V, Armstrong AR, Carmona-Rivera C, Dorschner JM, Schnaith AM, Li X, Ghodke-Puranik Y, Moore E, Purmalek M, Irizarry-Caro J, Zhang T, Day R, Stoub D, Hoffmann V, Khaliqdina SJ, Bhargava P, Santander AM, Torroella-Kouri M, Issac B, Cimbaluk DJ, Zloza A, Prabhakar R, Deep S, Jolly M, Koh KH, Reichner JS, Bradshaw EM, Chen J, Moita LF, Yuen PS, Li Tsai W, Singh B, Reiser J, Nath SK, Niewold TB, Vazquez-Padron RI, Kaplan MJ, Gupta V

J Clin Invest.

2017 Apr 3;

127(4).

doi: 10.1172/JCI88442

PMID: 28263189

Our lab is always seeking to recruit the best talent in the scientific community. If you are interested in joining our team, please contact us .

A group of diverse scientists, standing shoulder to shoulder.
See all Publications on PubMed