Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Neutralizing autoantibodies against interferon alpha in systemic lupus erythematosus : Prevalence, age of onset, and clinical associations

Grenmyr, Elsa LU orcid ; Gullstrand, Birgitta LU ; Jern, Andreas LU ; Björklund, Niklas LU ; Kahn, Robin LU ; Kahn, Fredrik LU ; Linge, Petrus LU orcid ; Jönsen, Andreas LU and Bengtsson, Anders A. LU (2026) In Lupus 35(6). p.623-629
Abstract

Objective Type I interferons (IFN) drive systemic lupus erythematosus (SLE) pathogenesis. Some patients develop neutralizing IFN autoantibodies (anti-IFN ab), which theoretically could modify disease activity. We aimed to determine the prevalence of anti-IFN ab in patients with SLE, identify the age and when during the disease course of anti-IFN ab emerge, and assess their association with organ damage.MethodsThis cross-sectional study included 173 SLE patients from the Lund Lupus Cohort. Samples taken at routine outpatient visits were analyzed for anti-IFN ab using ELISA, and positive samples were tested for IFN neutralizing capacity with a gene-reporter assay. Longitudinal samples were analyzed to determine the time-point and age of... (More)

Objective Type I interferons (IFN) drive systemic lupus erythematosus (SLE) pathogenesis. Some patients develop neutralizing IFN autoantibodies (anti-IFN ab), which theoretically could modify disease activity. We aimed to determine the prevalence of anti-IFN ab in patients with SLE, identify the age and when during the disease course of anti-IFN ab emerge, and assess their association with organ damage.MethodsThis cross-sectional study included 173 SLE patients from the Lund Lupus Cohort. Samples taken at routine outpatient visits were analyzed for anti-IFN ab using ELISA, and positive samples were tested for IFN neutralizing capacity with a gene-reporter assay. Longitudinal samples were analyzed to determine the time-point and age of first positive sample. Demographic and clinical data were obtained from research registries.ResultsEighteen (10.4%) patients were positive for anti-IFN ab by ELISA. Among these, antibodies from nine patients (5.2%) displayed IFN neutralizing capacity. No statistically significant differences were detected between patients positive for neutralizing antibodies and antibody-negative patients with respect to demography, organ damage or ACR classification criteria. The group with neutralizing antibodies were slightly older (median age 59 vs 45 years, p = .14) and had a higher proportion of renal involvement (67% vs 33%, p = .088). Longitudinal analysis of samples from patients with neutralizing anti-IFN ab revealed two age-related patterns: late-onset (≥65 years, n = 4), including one patient positive at diagnosis at age 69, and early-onset (≤40 years, n = 5), with antibodies present at or soon after diagnosis in four cases. Organ damage did not differ between patients with or without neutralizing antibodies (p = .65). At the latest follow-up (2–38 years after anti-IFN ab detection), three of nine patients remained free of organ damage.ConclusionsApproximately 5% of SLE patients have neutralizing anti-IFN antibodies, which may present early in disease or develop later in life. While late-onset antibodies may reflect age-related changes in immune regulation and early-onset antibodies could potentially modulate IFN-driven mechanisms, our data do not support a protective effect against organ damage.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
disease phenotypes, interferon, neutralizing interferon autoantibodies, organ damage, Systemic lupus erythematosus
in
Lupus
volume
35
issue
6
pages
7 pages
publisher
SAGE Publications
external identifiers
  • pmid:41790986
  • scopus:105031938143
ISSN
0961-2033
DOI
10.1177/09612033261432154
language
English
LU publication?
yes
id
714dba80-1a7f-4f99-87a9-2ce62f295bc2
date added to LUP
2026-04-21 16:23:40
date last changed
2026-07-02 03:11:25
@article{714dba80-1a7f-4f99-87a9-2ce62f295bc2,
  abstract     = {{<p>Objective Type I interferons (IFN) drive systemic lupus erythematosus (SLE) pathogenesis. Some patients develop neutralizing IFN autoantibodies (anti-IFN ab), which theoretically could modify disease activity. We aimed to determine the prevalence of anti-IFN ab in patients with SLE, identify the age and when during the disease course of anti-IFN ab emerge, and assess their association with organ damage.MethodsThis cross-sectional study included 173 SLE patients from the Lund Lupus Cohort. Samples taken at routine outpatient visits were analyzed for anti-IFN ab using ELISA, and positive samples were tested for IFN neutralizing capacity with a gene-reporter assay. Longitudinal samples were analyzed to determine the time-point and age of first positive sample. Demographic and clinical data were obtained from research registries.ResultsEighteen (10.4%) patients were positive for anti-IFN ab by ELISA. Among these, antibodies from nine patients (5.2%) displayed IFN neutralizing capacity. No statistically significant differences were detected between patients positive for neutralizing antibodies and antibody-negative patients with respect to demography, organ damage or ACR classification criteria. The group with neutralizing antibodies were slightly older (median age 59 vs 45 years, p = .14) and had a higher proportion of renal involvement (67% vs 33%, p = .088). Longitudinal analysis of samples from patients with neutralizing anti-IFN ab revealed two age-related patterns: late-onset (≥65 years, n = 4), including one patient positive at diagnosis at age 69, and early-onset (≤40 years, n = 5), with antibodies present at or soon after diagnosis in four cases. Organ damage did not differ between patients with or without neutralizing antibodies (p = .65). At the latest follow-up (2–38 years after anti-IFN ab detection), three of nine patients remained free of organ damage.ConclusionsApproximately 5% of SLE patients have neutralizing anti-IFN antibodies, which may present early in disease or develop later in life. While late-onset antibodies may reflect age-related changes in immune regulation and early-onset antibodies could potentially modulate IFN-driven mechanisms, our data do not support a protective effect against organ damage.</p>}},
  author       = {{Grenmyr, Elsa and Gullstrand, Birgitta and Jern, Andreas and Björklund, Niklas and Kahn, Robin and Kahn, Fredrik and Linge, Petrus and Jönsen, Andreas and Bengtsson, Anders A.}},
  issn         = {{0961-2033}},
  keywords     = {{disease phenotypes; interferon; neutralizing interferon autoantibodies; organ damage; Systemic lupus erythematosus}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{623--629}},
  publisher    = {{SAGE Publications}},
  series       = {{Lupus}},
  title        = {{Neutralizing autoantibodies against interferon alpha in systemic lupus erythematosus : Prevalence, age of onset, and clinical associations}},
  url          = {{http://dx.doi.org/10.1177/09612033261432154}},
  doi          = {{10.1177/09612033261432154}},
  volume       = {{35}},
  year         = {{2026}},
}