Making Inroads to Precision Medicine for the Treatment of Autoimmune Diseases: Harnessing Genomic Studies to Better Diagnose and Treat Complex Disorders

Overview

Journal Camb Prism Precis Med

Publisher Cambridge University Press

Date 2024 Mar 29

PMID 38550937

Authors

Yuriy Baglaenko

Catriona Wagner

Vijay G Bhoj

Petter Brodin

M Eric Gershwin

Daniel Graham

Pietro Invernizzi

Kenneth K Kidd

Ilya Korsunsky

Michael Levy

Andrew L Mammen

Victor Nizet

Francisco Ramirez-Valle

Edward C Stites

Marc S Williams

Michael Wilson

Noel R Rose

Virginia Ladd

Marina Sirota

Affiliations

Soon will be listed here.

Abstract

Precision Medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle. Autoimmune diseases are those in which the body's natural defense system loses discriminating power between its own cells and foreign cells, causing the body to mistakenly attack healthy tissues. These conditions are very heterogeneous in their presentation and therefore difficult to diagnose and treat. Achieving precision medicine in autoimmune diseases has been challenging due to the complex etiologies of these conditions, involving an interplay between genetic, epigenetic, and environmental factors. However, recent technological and computational advances in molecular profiling have helped identify patient subtypes and molecular pathways which can be used to improve diagnostics and therapeutics. This review discusses the current understanding of the disease mechanisms, heterogeneity, and pathogenic autoantigens in autoimmune diseases gained from genomic and transcriptomic studies and highlights how these findings can be applied to better understand disease heterogeneity in the context of disease diagnostics and therapeutics.

References

Goronzy J, Bartz-Bazzanella P, Hu W, Jendro M, Weyand C . Dominant clonotypes in the repertoire of peripheral CD4+ T cells in rheumatoid arthritis. J Clin Invest. 1994; 94(5):2068-76. PMC: 294644. DOI: 10.1172/JCI117561. View

Goutsouliak K, Veeraraghavan J, Sethunath V, De Angelis C, Osborne C, Rimawi M . Towards personalized treatment for early stage HER2-positive breast cancer. Nat Rev Clin Oncol. 2019; 17(4):233-250. PMC: 8023395. DOI: 10.1038/s41571-019-0299-9. View

Cordova K, Willis V, Haskins K, Holers V . A citrullinated fibrinogen-specific T cell line enhances autoimmune arthritis in a mouse model of rheumatoid arthritis. J Immunol. 2013; 190(4):1457-65. PMC: 4108985. DOI: 10.4049/jimmunol.1201517. View

Toro-Dominguez D, Martorell-Marugan J, Goldman D, Petri M, Carmona-Saez P, Alarcon-Riquelme M . Stratification of Systemic Lupus Erythematosus Patients Into Three Groups of Disease Activity Progression According to Longitudinal Gene Expression. Arthritis Rheumatol. 2018; 70(12):2025-2035. PMC: 8326877. DOI: 10.1002/art.40653. View

Furie R, Khamashta M, Merrill J, Werth V, Kalunian K, Brohawn P . Anifrolumab, an Anti-Interferon-α Receptor Monoclonal Antibody, in Moderate-to-Severe Systemic Lupus Erythematosus. Arthritis Rheumatol. 2017; 69(2):376-386. PMC: 5299497. DOI: 10.1002/art.39962. View

Ellinghaus D, Ellinghaus E, Nair R, Stuart P, Esko T, Metspalu A . Combined analysis of genome-wide association studies for Crohn disease and psoriasis identifies seven shared susceptibility loci. Am J Hum Genet. 2012; 90(4):636-47. PMC: 3322238. DOI: 10.1016/j.ajhg.2012.02.020. View

Sohn S, Barrett K, Van Abbema A, Chang C, Kohli P, Kanda H . A restricted role for TYK2 catalytic activity in human cytokine responses revealed by novel TYK2-selective inhibitors. J Immunol. 2013; 191(5):2205-16. PMC: 3748334. DOI: 10.4049/jimmunol.1202859. View

Raychaudhuri S, Sandor C, Stahl E, Freudenberg J, Lee H, Jia X . Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis. Nat Genet. 2012; 44(3):291-6. PMC: 3288335. DOI: 10.1038/ng.1076. View

Zhang F, Wei K, Slowikowski K, Fonseka C, Rao D, Kelly S . Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry. Nat Immunol. 2019; 20(7):928-942. PMC: 6602051. DOI: 10.1038/s41590-019-0378-1. View

10.

Robinson W . Sequencing the functional antibody repertoire--diagnostic and therapeutic discovery. Nat Rev Rheumatol. 2014; 11(3):171-82. PMC: 4382308. DOI: 10.1038/nrrheum.2014.220. View

11.

Ogino S, Nowak J, Hamada T, Milner Jr D, Nishihara R . Insights into Pathogenic Interactions Among Environment, Host, and Tumor at the Crossroads of Molecular Pathology and Epidemiology. Annu Rev Pathol. 2018; 14:83-103. PMC: 6345592. DOI: 10.1146/annurev-pathmechdis-012418-012818. View

12.

Ikeda Y, Masuko K, Nakai Y, Kato T, Hasanuma T, Yoshino S . High frequencies of identical T cell clonotypes in synovial tissues of rheumatoid arthritis patients suggest the occurrence of common antigen-driven immune responses. Arthritis Rheum. 1996; 39(3):446-53. DOI: 10.1002/art.1780390312. View

13.

Lanata C, Paranjpe I, Nititham J, Taylor K, Gianfrancesco M, Paranjpe M . A phenotypic and genomics approach in a multi-ethnic cohort to subtype systemic lupus erythematosus. Nat Commun. 2019; 10(1):3902. PMC: 6715644. DOI: 10.1038/s41467-019-11845-y. View

14.

Kohm A, Carpentier P, Anger H, Miller S . Cutting edge: CD4+CD25+ regulatory T cells suppress antigen-specific autoreactive immune responses and central nervous system inflammation during active experimental autoimmune encephalomyelitis. J Immunol. 2002; 169(9):4712-6. DOI: 10.4049/jimmunol.169.9.4712. View

15.

Raffin C, Vo L, Bluestone J . T cell-based therapies: challenges and perspectives. Nat Rev Immunol. 2019; 20(3):158-172. PMC: 7814338. DOI: 10.1038/s41577-019-0232-6. View

16.

Baechler E, Batliwalla F, Karypis G, Gaffney P, Ortmann W, Espe K . Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci U S A. 2003; 100(5):2610-5. PMC: 151388. DOI: 10.1073/pnas.0337679100. View

17.

Steen J, Forsstrom B, Sahlstrom P, ODowd V, Israelsson L, Krishnamurthy A . Recognition of Amino Acid Motifs, Rather Than Specific Proteins, by Human Plasma Cell-Derived Monoclonal Antibodies to Posttranslationally Modified Proteins in Rheumatoid Arthritis. Arthritis Rheumatol. 2018; 71(2):196-209. PMC: 6563427. DOI: 10.1002/art.40699. View

18.

Dudley J, Sirota M, Shenoy M, Pai R, Roedder S, Chiang A . Computational repositioning of the anticonvulsant topiramate for inflammatory bowel disease. Sci Transl Med. 2011; 3(96):96ra76. PMC: 3479650. DOI: 10.1126/scitranslmed.3002648. View

19.

Elliott S, Kongpachith S, Lingampalli N, Adamska J, Cannon B, Mao R . Affinity Maturation Drives Epitope Spreading and Generation of Proinflammatory Anti-Citrullinated Protein Antibodies in Rheumatoid Arthritis. Arthritis Rheumatol. 2018; 70(12):1946-1958. PMC: 6261684. DOI: 10.1002/art.40587. View

20.

Tsoi L, Spain S, Knight J, Ellinghaus E, Stuart P, Capon F . Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity. Nat Genet. 2012; 44(12):1341-8. PMC: 3510312. DOI: 10.1038/ng.2467. View