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          NIAMS Scientific Advances
          Loss of an Enzyme in the Endoplasmic Reticulum—a Cell’s Transportation System—Might Play a Protective Role in Spondyloarthritis








NIAMS Advances


Loss of an Enzyme in the Endoplasmic Reticulum—a Cell’s Transportation System—Might Play a Protective Role in Spondyloarthritis February 1, 2023
                                TRANSLATIONAL
        Robert A. Colbert, M.D., Ph.D.
                                          |
              Pediatric Translational Research Branch
                                          |
              NIAMS IRP
        Description

Spondyloarthritis (SpA) is a family of inflammatory rheumatic diseases that share common features including inflammation, pain, and stiffness in the spine, pelvic joints, shoulders, and knees. Defects in the gene HLA-B27 are common in people with certain types of arthritis and other inflammatory diseases including SpA, yet the role of HLA-B27 in SpA is not clear. On the other hand, variants of endoplasmic reticulum aminopeptidase 1 (ERAP1) are associated with several HLA class I-linked inflammatory diseases. Using an animal model, the authors of this report demonstrated for the first time that a complete loss of the ERAP1 gene partially protects against SpA by altering HLA-B27 protein conformation.

What is exciting about this article?

Endoplasmic reticulum aminopeptidase 1 (ERAP1) is part of the machinery in the endoplasmic reticulum that controls the processing of antigens to be presented on the cell surface within HLA class I protein molecules. This study demonstrated that altering the expression of ERAP1 may protect against arthritis.

How does this fit into the larger NIAMS portfolio?

In line with NIAMS’ mission, Dr. Colbert’s research is focused on understanding the genetic causes of juvenile SpA. In this study, his group identified a novel effect of an endoplasmic reticulum enzyme (ERAP1) on HLA-B27 protein conformation and demonstrated how it regulates the folding of HLA-B27 protein to control immune responses. These findings may have important translational implications for SpA.

Grant support

AR041180
        Research Areas:
            Cell Biology
      Clinical Research
      Genetics and Genomics
      Immunology
      Molecular Biology and Biochemistry
                                        Reference:
            Paradoxical Effects of Endoplasmic Reticulum Aminopeptidase 1 Deficiency on HLA-B27 and Its Role as an Epistatic Modifier in Experimental Spondyloarthritis.

    Tran TM, Gill T, Bennett J, Hong S, Holt V, Lindstedt AJ, Bakshi S, Sikora K, Taurog JD, Breban M, Navid F, Colbert RA
        

                    Arthritis Rheumatol.
        
                    2023 Feb;
        
                    75(2).
        
                    doi: 10.1002/art.42327
                            PMID: 36577442
        Research reported in this publication was supported by the Intramural Research Program of the NIHʼs National Institute of Arthritis and Musculoskeletal and Skin Diseases.
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