Clinical features of Sjögren's syndrome patients with autoantibodies against interferons

Abstract

Background Sjögren’s syndrome (SS) is an autoimmune disease characterized by immune attack on the salivary and lacrimal glands. Given the known cytokine activation and type I interferon gene expression signature found in SS, we hypothesized that anticytokine autoantibodies might be detectable by Luciferase immunoprecipitation systems in some SS patients and correlate with clinical symptoms. Results Luciferase immunoprecipitation systems was used to screen for serum anti-cytokine autoantibodies in 57 primary SS patients and 25 healthy volunteers. Autoantibodies were detected against GMCSF, interferon-γ, -α and, -ω in one, two, two and six patients with SS, respectively. None of the healthy volunteers showed anticytokine autoantibodies and none of the SS or control subjects showed autoantibodies against interferon-λ. One 51-year old female SS subject with the highest anti-interferon-α and -ω autoantibody levels had stable autoantibody levels over the course of a year. In vitro functional testing of serum autoantibodies from this subject demonstrated partially neutralizing activity for interferon-α signaling. Clinical information on this individual revealed a low focus score and high levels of unstimulated salivary flow, suggesting the possibility that interferon-α autoantibody neutralizing activity may have contributed to the milder sicca symptoms. Conclusion Overall, these findings demonstrate that a subset of SS patients (16%) harbor autoantibodies against GMCSF, interferon-γ, interferon-ω, and interferon-α. These data support the observation that high levels of interferon-α autoantibodies may attenuate disease symptoms in SS.

Cytokine Autoantibodies Are Associated with Infection Risk and Self-Perceived Health: Results from the Danish Blood Donor Study

“…A range of c-aAb have also been labeled as phenotypic classifiers for various primary immunodeficiencies (including GM-CSF c-aAb for PAP) by the international union of immunological societies [11]. Conversely, c-aAb against pro-inflammatory interleukins (IL) have been associated with improved prognosis or reduced symptoms in some autoimmune diseases, such as rheumatoid arthritis and Sjögrens syndrome indicating that ultimately the biologic effect of c-aAb depends on the specific pathological context combined with the c-aAb specificity [12,13].…”

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“…Systemic IFN activity has been primarily linked to serological markers of B cell hyperactivity, complement consumption, and hematological aberrations [ 55 , 62 , 63 , 67 , 68 ]. Autoantibodies against IFNα and IFNω were recently detected in pSS patients [ 69 ]. Interestingly, a case with high titer of partially neutralizing anti-IFNα/ω antibodies experienced milder sicca symptoms and minimal focal infiltrates in salivary glands supporting the pathogenic role of IFN in pSS.…”