Type I interferon in patients with systemic autoimmune rheumatic disease is associated with haematological abnormalities and specific autoantibody profiles

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Type I interferon in patients with systemic autoimmune rheumatic disease is associated with haematological abnormalities and specific autoantibody profiles. / Reynolds, John A.; Briggs, Tracy A; Rice, Gillian I; Darmalinggam, Sathya; Bondet, Vincent; Bruce, Ellen; Khan, Mumtaz; Haque, Sahena; Chinoy, Hector; Herrick, Ariane L; McCarthy, Eoghan M; Zeef, Leo A.H.; Hayes, Andrew; Duffy, Darragh; Parker, Ben; Bruce, Ian N.

In: Arthritis Research & Therapy, Vol. 21, 147, 14.06.2019.

Research output: Contribution to journalArticle

Harvard

Reynolds, JA, Briggs, TA, Rice, GI, Darmalinggam, S, Bondet, V, Bruce, E, Khan, M, Haque, S, Chinoy, H, Herrick, AL, McCarthy, EM, Zeef, LAH, Hayes, A, Duffy, D, Parker, B & Bruce, IN 2019, 'Type I interferon in patients with systemic autoimmune rheumatic disease is associated with haematological abnormalities and specific autoantibody profiles', Arthritis Research & Therapy, vol. 21, 147. https://doi.org/10.1186/s13075-019-1929-4

APA

Reynolds, J. A., Briggs, T. A., Rice, G. I., Darmalinggam, S., Bondet, V., Bruce, E., Khan, M., Haque, S., Chinoy, H., Herrick, A. L., McCarthy, E. M., Zeef, L. A. H., Hayes, A., Duffy, D., Parker, B., & Bruce, I. N. (2019). Type I interferon in patients with systemic autoimmune rheumatic disease is associated with haematological abnormalities and specific autoantibody profiles. Arthritis Research & Therapy, 21, [147]. https://doi.org/10.1186/s13075-019-1929-4

Vancouver

Author

Reynolds, John A. ; Briggs, Tracy A ; Rice, Gillian I ; Darmalinggam, Sathya ; Bondet, Vincent ; Bruce, Ellen ; Khan, Mumtaz ; Haque, Sahena ; Chinoy, Hector ; Herrick, Ariane L ; McCarthy, Eoghan M ; Zeef, Leo A.H. ; Hayes, Andrew ; Duffy, Darragh ; Parker, Ben ; Bruce, Ian N. / Type I interferon in patients with systemic autoimmune rheumatic disease is associated with haematological abnormalities and specific autoantibody profiles. In: Arthritis Research & Therapy. 2019 ; Vol. 21.

Bibtex

@article{9315c8fcf5214b43853732e9d1fde0c2,
title = "Type I interferon in patients with systemic autoimmune rheumatic disease is associated with haematological abnormalities and specific autoantibody profiles",
abstract = "OBJECTIVES: To investigate the relationships between interferon alpha (IFNα) and the clinical and serological phenotype of patients with systemic autoimmune rheumatic disease (SARDs) in order to determine whether a distinct subpopulation of patients can be identified.METHODS: We recruited patients with at least 1 SARD clinical feature and at least 1 SARD-related autoantibody from two NHS Trusts in Greater Manchester. A 6-gene interferon-stimulated gene (ISG) score was calculated in all patients, and in a subgroup, a 30-gene ISG score was produced using NanoString. A digital Single Molecule Array (Simoa) was used to measure plasma IFNα protein. In an exploratory analysis, whole blood RNA sequencing was conducted in 12 patients followed by RT-qPCR confirmation of expression of 6 nucleic acid receptors (NARs) in the whole cohort.RESULTS: Sixty three of 164 (38%) patients had a positive ISG score. The 3 measures of IFNα all correlated strongly with each other (p < 0.0001). There were no differences in mucocutaneous or internal organ involvement between the ISG subgroups. The ISG-positive group had increased frequency of specific autoantibodies and haematological abnormalities which remained significant after adjusting for the SARD subtype. Expression of DDX58, MB21D1 and TLR7 was correlated with the ISG score whilst TLR3, TLR9 and MB21D1 were associated with neutrophil count.CONCLUSION: In SARD patients, IFNα-positivity was associated with specific autoantibodies and haematological parameters but not with other clinical features. The variable NAR expression suggests that different pathways may drive IFNα production in individual patients. The identification of an IFNα-positive subgroup within a mixed SARD cohort supports a pathology-based approach to treatment.",
keywords = "Autoantibodies, Interferon alpha, Systemic autoimmune rheumatic disease",
author = "Reynolds, {John A.} and Briggs, {Tracy A} and Rice, {Gillian I} and Sathya Darmalinggam and Vincent Bondet and Ellen Bruce and Mumtaz Khan and Sahena Haque and Hector Chinoy and Herrick, {Ariane L} and McCarthy, {Eoghan M} and Zeef, {Leo A.H.} and Andrew Hayes and Darragh Duffy and Ben Parker and Bruce, {Ian N}",
year = "2019",
month = jun,
day = "14",
doi = "10.1186/s13075-019-1929-4",
language = "English",
volume = "21",
journal = "Arthritis Research & Therapy",
issn = "1478-6354",
publisher = "Springer",

}

RIS

TY - JOUR

T1 - Type I interferon in patients with systemic autoimmune rheumatic disease is associated with haematological abnormalities and specific autoantibody profiles

AU - Reynolds, John A.

AU - Briggs, Tracy A

AU - Rice, Gillian I

AU - Darmalinggam, Sathya

AU - Bondet, Vincent

AU - Bruce, Ellen

AU - Khan, Mumtaz

AU - Haque, Sahena

AU - Chinoy, Hector

AU - Herrick, Ariane L

AU - McCarthy, Eoghan M

AU - Zeef, Leo A.H.

AU - Hayes, Andrew

AU - Duffy, Darragh

AU - Parker, Ben

AU - Bruce, Ian N

PY - 2019/6/14

Y1 - 2019/6/14

N2 - OBJECTIVES: To investigate the relationships between interferon alpha (IFNα) and the clinical and serological phenotype of patients with systemic autoimmune rheumatic disease (SARDs) in order to determine whether a distinct subpopulation of patients can be identified.METHODS: We recruited patients with at least 1 SARD clinical feature and at least 1 SARD-related autoantibody from two NHS Trusts in Greater Manchester. A 6-gene interferon-stimulated gene (ISG) score was calculated in all patients, and in a subgroup, a 30-gene ISG score was produced using NanoString. A digital Single Molecule Array (Simoa) was used to measure plasma IFNα protein. In an exploratory analysis, whole blood RNA sequencing was conducted in 12 patients followed by RT-qPCR confirmation of expression of 6 nucleic acid receptors (NARs) in the whole cohort.RESULTS: Sixty three of 164 (38%) patients had a positive ISG score. The 3 measures of IFNα all correlated strongly with each other (p < 0.0001). There were no differences in mucocutaneous or internal organ involvement between the ISG subgroups. The ISG-positive group had increased frequency of specific autoantibodies and haematological abnormalities which remained significant after adjusting for the SARD subtype. Expression of DDX58, MB21D1 and TLR7 was correlated with the ISG score whilst TLR3, TLR9 and MB21D1 were associated with neutrophil count.CONCLUSION: In SARD patients, IFNα-positivity was associated with specific autoantibodies and haematological parameters but not with other clinical features. The variable NAR expression suggests that different pathways may drive IFNα production in individual patients. The identification of an IFNα-positive subgroup within a mixed SARD cohort supports a pathology-based approach to treatment.

AB - OBJECTIVES: To investigate the relationships between interferon alpha (IFNα) and the clinical and serological phenotype of patients with systemic autoimmune rheumatic disease (SARDs) in order to determine whether a distinct subpopulation of patients can be identified.METHODS: We recruited patients with at least 1 SARD clinical feature and at least 1 SARD-related autoantibody from two NHS Trusts in Greater Manchester. A 6-gene interferon-stimulated gene (ISG) score was calculated in all patients, and in a subgroup, a 30-gene ISG score was produced using NanoString. A digital Single Molecule Array (Simoa) was used to measure plasma IFNα protein. In an exploratory analysis, whole blood RNA sequencing was conducted in 12 patients followed by RT-qPCR confirmation of expression of 6 nucleic acid receptors (NARs) in the whole cohort.RESULTS: Sixty three of 164 (38%) patients had a positive ISG score. The 3 measures of IFNα all correlated strongly with each other (p < 0.0001). There were no differences in mucocutaneous or internal organ involvement between the ISG subgroups. The ISG-positive group had increased frequency of specific autoantibodies and haematological abnormalities which remained significant after adjusting for the SARD subtype. Expression of DDX58, MB21D1 and TLR7 was correlated with the ISG score whilst TLR3, TLR9 and MB21D1 were associated with neutrophil count.CONCLUSION: In SARD patients, IFNα-positivity was associated with specific autoantibodies and haematological parameters but not with other clinical features. The variable NAR expression suggests that different pathways may drive IFNα production in individual patients. The identification of an IFNα-positive subgroup within a mixed SARD cohort supports a pathology-based approach to treatment.

KW - Autoantibodies

KW - Interferon alpha

KW - Systemic autoimmune rheumatic disease

UR - http://www.scopus.com/inward/record.url?scp=85067275512&partnerID=8YFLogxK

U2 - 10.1186/s13075-019-1929-4

DO - 10.1186/s13075-019-1929-4

M3 - Article

C2 - 31200750

VL - 21

JO - Arthritis Research & Therapy

JF - Arthritis Research & Therapy

SN - 1478-6354

M1 - 147

ER -