J Rheum Dis.  2023 Jan;30(1):58-64. 10.4078/jrd.22.0027.

Development of Spondyloarthritis After COVID-19 in HLAB27-Positive Monozygotic Twins: Case Reports With Single Cell Transcriptome Profiling

Affiliations
  • 1Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
  • 2Division of Rheumatology, Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Korea
  • 3YiPSCELL, Inc., Seoul, Korea

Abstract

A subset of spondyloarthritis (SpA) called ‘reactive arthritis’ is triggered by causal pathogens, usually bacteria related to venereal disease or gastrointestinal infection. During the outbreak of coronavirus disease 2019 (COVID-19), there have been case reports about SpA after COVID-19, but the causality is still elusive. We described cases of 23-year-old monozygotic twins both diagnosed with SpA after COVID-19. The probable linkage between SpA and COVID-19 was elaborated with our cases as well as literature reviews. Of note, shared genetic traits by monozygotic twins, particularly HLA-B27 positivity, might have contributed to their susceptibility to COVID-19-induced SpA. Moreover, single-cell transcriptome analysis revealed that the transcriptomic profile of peripheral compartment of SpA after COVID-19 was distinctive from that of typical radiographic axial SpA as shown by differential expression of ribosomal protein S26 (RPS26) and small nucleolar RNA host gene 5 (SNHG5) in nearly all subsets of peripheral blood mononuclear cells.

Keyword

Arthritis; reactive; COVID-19

Figure

  • Fig. 1 MRI of the ankle and sacroiliac joints in Twin A and Twin B. (A) Sagittal plain T2-weighted images of Twin A displaying tendinopathy of the left Achilles tendon (white arrow). (B) STIR images of Twin A displaying the sacroiliac bone marrow edema (white arrow). (C) Sagittal plain T2-weighted images of Twin B displaying synovial proliferation and joint effusion (white arrow). (D) STIR images of Twin B displaying bilateral sacroiliac bone marrow edema (white arrows). MRI: magnetic resonance imaging, STIR: short tau inversion recovery.

  • Fig. 2 Cell clusters identified by single-cell RNA sequencing analysis. (A) Identification of 14 clusters in pooled peripheral blood mononuclear cells from twins who developed spondyloarthritis after COVID-19 and one patient with typical radiographic axial spondyloarthritis. (B) Difference in frequency of cell population is displayed in bar plots. COVID-19: coronavirus disease 2019, UMAP: Uniform Manifold Approximation and Projetion.

  • Fig. 3 The differentially expressed genes from single-cell RNA sequencing analysis. (A) The mRNA expression of ribosomal protein S26 (RPS26) is systematically down-regulated in most subsets of spondyloarthritis (SpA) after coronavirus disease 2019 (COVID-19) compared to that in typical axial spondyloarthritis. (B) The expression of small nucleolar RNA host gene 5 (SNHG5) is consistently upregulated in most subsets of SpA after COVID-19 compared to that in typical axial spondyloarthritis.

  • Fig. 4 Continued.


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