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Shedding of mutant tumor necrosis factor receptor superfamily 1A associated with tumor necrosis factor receptor-associated periodic syndrome: differences between cell types.
Arthritis Rheum 2004; 50(8):2651-9AR

Abstract

OBJECTIVE

To investigate the effect of mutations in tumor necrosis factor receptor superfamily 1A (TNFRSF1A) on the ability of the receptors to be cleaved from the cell surface upon stimulation. The mutations we studied are associated with clinically distinct forms of TNF receptor-associated periodic syndrome (TRAPS). We also investigated different cell types within the same form of TRAPS.

METHODS

The shedding of TNFRSF1A in response to stimulation with phorbol myristate acetate was assessed in leukocytes and dermal fibroblasts from patients with C33Y TRAPS, and in HEK 293 cell lines stably transfected with constructs containing wild-type TNFRSF1A and/or TNFRSF1A mutants identified in TRAPS patients.

RESULTS

The shedding of TNFRSF1A differed between cell types within the same form of TRAPS. In particular, dermal fibroblasts, but not leukocytes, from C33Y TRAPS patients demonstrated reduced shedding of TNFRSF1A. Shedding of both wild-type and mutant TNFRSF1A from the transfected HEK 293 cells showed minor differences, but was in all cases induced to a substantial extent.

CONCLUSION

Differences in TNFRSF1A shedding are not purely a function of the TNFRSF1A structure, but are also influenced by other features of genetic makeup and/or cellular differentiation. It is unlikely that a defect in TNFRSF1A shedding per se can fully explain the clinical features that are common to TRAPS patients with different TNFRSF1A mutations.

Authors+Show Affiliations

Division of Immunology, Queen's Medical Centre, University of Nottingham, Nottingham, UK. mary.huggins@nottingham.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15334481

Citation

Huggins, Mary L., et al. "Shedding of Mutant Tumor Necrosis Factor Receptor Superfamily 1A Associated With Tumor Necrosis Factor Receptor-associated Periodic Syndrome: Differences Between Cell Types." Arthritis and Rheumatism, vol. 50, no. 8, 2004, pp. 2651-9.
Huggins ML, Radford PM, McIntosh RS, et al. Shedding of mutant tumor necrosis factor receptor superfamily 1A associated with tumor necrosis factor receptor-associated periodic syndrome: differences between cell types. Arthritis Rheum. 2004;50(8):2651-9.
Huggins, M. L., Radford, P. M., McIntosh, R. S., Bainbridge, S. E., Dickinson, P., Draper-Morgan, K. A., ... Todd, I. (2004). Shedding of mutant tumor necrosis factor receptor superfamily 1A associated with tumor necrosis factor receptor-associated periodic syndrome: differences between cell types. Arthritis and Rheumatism, 50(8), pp. 2651-9.
Huggins ML, et al. Shedding of Mutant Tumor Necrosis Factor Receptor Superfamily 1A Associated With Tumor Necrosis Factor Receptor-associated Periodic Syndrome: Differences Between Cell Types. Arthritis Rheum. 2004;50(8):2651-9. PubMed PMID: 15334481.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Shedding of mutant tumor necrosis factor receptor superfamily 1A associated with tumor necrosis factor receptor-associated periodic syndrome: differences between cell types. AU - Huggins,Mary L, AU - Radford,Paul M, AU - McIntosh,Richard S, AU - Bainbridge,Susan E, AU - Dickinson,Peter, AU - Draper-Morgan,Kelly-Ann, AU - Tighe,Patrick J, AU - Powell,Richard J, AU - Todd,Ian, PY - 2004/8/31/pubmed PY - 2004/9/25/medline PY - 2004/8/31/entrez SP - 2651 EP - 9 JF - Arthritis and rheumatism JO - Arthritis Rheum. VL - 50 IS - 8 N2 - OBJECTIVE: To investigate the effect of mutations in tumor necrosis factor receptor superfamily 1A (TNFRSF1A) on the ability of the receptors to be cleaved from the cell surface upon stimulation. The mutations we studied are associated with clinically distinct forms of TNF receptor-associated periodic syndrome (TRAPS). We also investigated different cell types within the same form of TRAPS. METHODS: The shedding of TNFRSF1A in response to stimulation with phorbol myristate acetate was assessed in leukocytes and dermal fibroblasts from patients with C33Y TRAPS, and in HEK 293 cell lines stably transfected with constructs containing wild-type TNFRSF1A and/or TNFRSF1A mutants identified in TRAPS patients. RESULTS: The shedding of TNFRSF1A differed between cell types within the same form of TRAPS. In particular, dermal fibroblasts, but not leukocytes, from C33Y TRAPS patients demonstrated reduced shedding of TNFRSF1A. Shedding of both wild-type and mutant TNFRSF1A from the transfected HEK 293 cells showed minor differences, but was in all cases induced to a substantial extent. CONCLUSION: Differences in TNFRSF1A shedding are not purely a function of the TNFRSF1A structure, but are also influenced by other features of genetic makeup and/or cellular differentiation. It is unlikely that a defect in TNFRSF1A shedding per se can fully explain the clinical features that are common to TRAPS patients with different TNFRSF1A mutations. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/15334481/Shedding_of_mutant_tumor_necrosis_factor_receptor_superfamily_1A_associated_with_tumor_necrosis_factor_receptor_associated_periodic_syndrome:_differences_between_cell_types_ L2 - https://doi.org/10.1002/art.20380 DB - PRIME DP - Unbound Medicine ER -