Interferonopathies at the crossroads of monogenic lupus and autoinflammation: A case study

Abstract

Monogenic lupus is a highly complex condition with marked variability, resulting from diverse immune system etiopathogenesis linked to various pathogenic genetic variants. There is substantial overlap with newly described systemic autoinflammatory disorders. We present two cases of monogenic lupus and highlight the intersection between monogenic lupus and autoinflammatory disorders. This report emphasizes the concept of monogenic interferonopathies as an umbrella term for various conditions arising from genetic aberrations in type I interferon (IFN-I) signaling, which are associated with significant IFN-I activation.

Keywords

Monogenic lupus / Systemic lupus erythematosus / Type I interferon / Interferonopathies

Acknowledgments

None.

Funding

None.

Conflict of interest

The authors declare that they have no competing interests.

Author contributions

Conceptualization: All authors

Investigation: All authors

Methodology: Sulaiman M. Al-Mayouf

Writing - original draft: Sulaiman M. Al-Mayouf

Writing - review & editing: All authors

Ethics approval and consent to participate

This study adheres to the ethical principles outlined in the Declaration of Helsinki (2000); the Research Advisory Council guidelines of King Faisal Specialist Hospital and Research Center, Riyadh; and the Saudi Arabian legislation. This work was conducted as part of a previously approved study (study number 2221105). All clinical and laboratory assessments were performed as part of the standard medical care. Informed consent for genetic testing was obtained from the parents during blood extraction, as part of patient care. All collected data were examined under confidentiality practices, ensuring no personal information was disclosed.

Consent for publication

Verbal consent was obtained from each patient’s parents for publication of their data and/or images.

Availability of data

Data are available from the corresponding author upon reasonable request.

References

[1] Hedrich CM. Shaping the spectrum-from autoinflammation to autoimmunity. Clin Immunol. 2016; 165:21-28. doi: 10.1016/j.clim.2016.03.002

[2] Arakelyan A, Nersisyan L, Poghosyan D, et al. Autoimmunity and autoinflammation: A systems view on signaling pathway dysregulation profiles. PLoS One. 2017; 12(11):e0187572. doi: 10.1371/journal.pone.0187572

[3] Szekanecz Z, McInnes IB, Schett G, Szamosi S, Benkő S, Szűcs G. Autoinflammation and autoimmunity across rheumatic and musculoskeletal diseases. Nat Rev Rheumatol. 2021; 17(10):585-595. doi: 10.1038/s41584-021-00652-9

[4] Manthiram K, Zhou Q, Aksentijevich I, Kastner DL. The monogenic autoinflammatory diseases define new pathways in human innate immunity and inflammation. Nat Immunol. 2017; 18(8):832-842. doi: 10.1038/ni.3777

[5] Lucherini OM, Rigante D, Sota J, et al. Updated overview of molecular pathways involved in the most common monogenic autoinflammatory diseases. Clin Exp Rheumatol. 2018 Jan-Feb; 36 Suppl 110(1):3-9.

[6] Başaran Ö, Bilginer Y, Özen S. Rare autoinflammatory diseases. Turk Arch Pediatr. 2022; 57(1):18-25. doi: 10.5152/Turk Arch Pediatr.2022.21303

[7] Mendonça LO, Frémond ML. Interferonopathies: From concept to clinical practice. Best Pract Res Clin Rheumatol. 2024;38:101975. doi: 10.1016/j.berh.2024.101975

[8] Lo MS. Concepts in lupus pathophysiology: Lessons learned from disease across the spectrum. Clin Immunol. 2022;238:109021. doi: 10.1016/j.clim.2022.109021

[9] Catalina MD, Owen KA, Labonte AC, Grammer AC, Lipsky PE. The pathogenesis of systemic lupus erythematosus: Harnessing big data to understand the molecular basis of lupus. J Autoimmun. 2020;110:102359. doi: 10.1016/j.jaut.2019.102359

[10] Adams DE, Shao WH. Epigenetic alterations in immune cells of systemic lupus erythematosus and therapeutic implications. Cells. 2022; 11(3):506. doi: 10.3390/cells11030506

[11] Araki Y, Mimura T. Epigenetic dysregulation in the pathogenesis of systemic lupus erythematosus. Int J Mol Sci. 2024; 25(2):1019. doi: 10.3390/ijms25021019

[12] Alperin JM, Ortiz-Fernández L, Sawalha AH. Monogenic lupus: A developing paradigm of disease. Front Immunol. 2018;9:2496. doi: 10.3389/fimmu.2018.02496

[13] Omarjee O, Picard C, Frachette C, et al. Monogenic lupus: Dissecting heterogeneity. Autoimmun Rev. 2019; 18(10):102361. doi: 10.1016/j.autrev.2019.102361

[14] Demirkaya E, Sahin S, Romano M, Zhou Q, Aksentijevich I. New horizons in the genetic etiology of systemic lupus erythematosus and lupus-like disease: Monogenic lupus and beyond. J Clin Med. 2020; 9(3):712. doi: 10.3390/jcm9030712

[15] Al-Mayouf SM, Akbar L, Abdwani R, et al.Performance of the EULAR/ACR 2019 classification criteria for systemic lupus erythematous in monogenic lupus. Clin Rheumatol. 2022; 41(9):2721-2727. doi: 10.1007/s10067-022-06209-9

[16] Tusseau M, Khaldi-Plassart S, Cognard J, et al. Mendelian causes of autoimmunity: The lupus phenotype. J Clin Immunol. 2024; 44(4):99. doi: 10.1007/s10875-024-01696-8

[17] Al-Mayouf SM, Akbar L, AlEnazi A, Al-Mousa H. Autosomal recessive ISG15 deficiency underlies type I interferonopathy with systemic lupus erythematosus and inflammatory myositis. J Clin Immunol. 2021; 41(6):1361-1364. doi: 10.1007/s10875-021-01019-1

[18] Al-Mayouf SM, Alkhars F, AlSaleem A. Phenotype and disease course differences in monogenic and sporadic childhood lupus. Lupus. 2023; 32(13):1548-1554. doi: 10.1177/09612033231211065

[19] Tirosh I, Spielman S, Barel O, et al. Whole exome sequencing in childhood-onset lupus frequently detects single gene etiologies. Pediatr Rheumatol Online J. 2019; 17(1):52. doi: 10.1186/s12969-019-0349-y

[20] Misztal MC, Liao F, Couse M, et al. Genome-wide sequencing identified rare genetic variants for childhood-onset monogenic lupus. J Rheumatol. 2023; 50(5):671-675. doi: 10.3899/jrheum.220513

[21] Kim H, Sanchez GA, Goldbach-Mansky R. Insights from Mendelian interferonopathies: Comparison of CANDLE, SAVI with AGS, monogenic lupus. J Mol Med (Berl). 2016; 94(10):1111-1127. doi: 10.1007/s00109-016-1465-5

[22] Gagne S, Sivaraman V, Akoghlanian S. Interferonopathies masquerading as non-Mendelian autoimmune diseases: Pattern recognition for early diagnosis. Front Pediatr. 2023;11:1169638. doi: 10.3389/fped.2023.1169638

[23] Volpi S, Picco P, Caorsi R, Candotti F, Gattorno M. Type I interferonopathies in pediatric rheumatology. Pediatr Rheumatol Online J. 2016; 14(1):35. doi: 10.1186/s12969-016-0094-4

[24] Rodero MP, Tesser A, Bartok E, et al. Type I interferon-mediated autoinflammation due to DNase II deficiency. Nat Commun. 2017; 8(1):2176. doi: 10.1038/s41467-017-01932-3

[25] Bai Y, Tong Y, Liu Y, Hu H. Self-dsDNA in the pathogenesis of systemic lupus erythematosus. Clin Exp Immunol. 2018; 191(1):1-10. doi: 10.1111/cei.13041

[26] Qin Y, Ma J, Vinuesa CG. Monogenic lupus: Insights into disease pathogenesis and therapeutic opportunities. Curr Opin Rheumatol. 2024; 36(3):191-200. doi: 10.1097/BOR.0000000000001008.

[27] Murdaca G, Colombo BM, Puppo F. The role of Th17 lymphocytes in the autoimmune and chronic inflammatory diseases. Intern Emerg Med. 2011; 6(6):487-495. doi: 10.1007/s11739-011-0517-7

[28] Contini P, Murdaca G, Puppo F, Negrini S. HLA-G expressing immune cells in immune mediated diseases. Front Immunol. 2020;11:1613. doi: 10.3389/fimmu.2020.01613

[29] Wilkinson C, Henderson RB, Jones-Leone AR, et al. The role of baseline BLyS levels and type 1 interferon-inducible gene signature status in determining belimumab response in systemic lupus erythematosus: A post hoc meta-analysis. Arthritis Res Ther. 2020; 22(1):102. doi: 10.1186/s13075-020-02177-0

[30] Mohan S. Targeted treatment of diseases of immune dysregulation. Rheum Dis Clin North Am. 2023; 49(4): 913-929. doi: 10.1016/j.rdc.2023.07.002

[31] Furie RA, Morand EF, Bruce IN, et al. TULIP-1 study investigators. Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1): A randomised, controlled, phase 3 trial. Lancet Rheumatol. 2019; 1(4): e208-e219. doi: 10.1016/S2665-9913(19)30076-1