Autoantibodies against IFNα in patients with systemic lupus erythematosus and susceptibility for infection: a retrospective case-control study

Abstract

IFNα and anti-IFNα autoantibodies have been implicated in susceptibility both for systemic lupus erythematosus (SLE) and viral infection. We aimed to analyze the SLE disease phenotype and risk for infection associated with anti-IFN-α IgG autoantibodies in SLE patients In this multidisciplinary retrospective single referral center study, all consecutive patients with SLE admitted between January 1st and November 30th 2020 were considered. All subjects fulfilled the ACR/EULAR 2019 criteria for SLE. Anti-IFNα IgG autoantibodies were quantified at admission by ELISA. Demographic, medical history, laboratory, treatment, and outcome data were extracted from electronic medical records using a standardized data collection form. 180 patients [female 87.2%, median age of 44.4 (34–54.2) years] were included. The median disease duration was 10 years [4–20] with a median SLEDAI score of 2 [0–4] at study time. Fifty-four (30%) patients had a past-history of lupus nephritis. One hundred and forty-four (80%) had received long-term glucocorticoids and 99 (55%) immunosuppressive drugs. Overall, 127 infections—mostly bacterial and viral—were reported in 95 (52.8%) patients. Twenty SLE patients (11.1%) had positive anti-IFNα IgG autoantibodies with a titer ranging from 10 to 103 UA/mL. Age, sex, SLE phenotype and treatment did not significantly differ between SLE patients with or without anti-IFNα. Infection rate was similar in both groups except for tuberculosis which was more frequent in patients with anti-IFNα (20% vs. 3.1%, p = 0.01). The prevalence of autoantibodies against IFNα is high in SLE and associated with a higher frequency of tuberculosis.

Tuberculosis remains a leading contributor to morbidity due to serious infections in Indian patients of SLE

“…Recently, antibodies to interferon alpha have been associated with and excess risk of developing tuberculosis over other infections in SLE [ 36 ]. This could be a useful screening tool to identify those suited for latent TB prophylaxis.…”

Biological mechanisms underpinning the development of long COVID

“… 127 Pre-existing autoimmunity is associated with severe COVID-19 disease, especially in individuals with Sjögren syndrome, systemic lupus erythematosus, scleroderma, rheumatoid arthritis, myasthenia gravis, Guillain-Barre syndrome, multiple sclerosis, autoimmune hepatitis, idiopathic pulmonary fibrosis, cardiac sarcoidosis, subacute bacterial endocarditis, Dressler syndrome, and autoimmune myocarditis. 128 , 129 , 130 , 131 Autoantibodies produce diverse clinical phenotypes by disrupting and interfering with the body’s biological systems via autoreactive attack against proteins, DNA, and other cellular components. 132 However, more recently, multidimensional immune profiling of 99 patients with LC by rapid extracellular antigen profiling, a high-throughput method capable of measuring antibody reactivity to >6000 extracellular and secreted human proteins, failed to identify any stereotypical autoantibodies to distinguish patients with LC from healthy controls.…”

“… 128 Pre-existing anti-IFN-I autoantibodies are strongly associated with an increased risk of developing severe COVID-19. 128 , 129 , 130 , 131 , 134 Compared to the general population, an increased anti-IFNα autoantibody prevalence is seen in patients with systemic lupus erythematosus co-infected with COVID-19. 130 , 131 Type I IFN is a central alarm, a warning instruction for the human host to initiate immune responses to fight, neutralize, and eliminate encountered viral infections.…”

“… 128 , 129 , 130 , 131 , 134 Compared to the general population, an increased anti-IFNα autoantibody prevalence is seen in patients with systemic lupus erythematosus co-infected with COVID-19. 130 , 131 Type I IFN is a central alarm, a warning instruction for the human host to initiate immune responses to fight, neutralize, and eliminate encountered viral infections. Deficiency of type I IFNs is a hallmark of many severe COVID-19 infections.…”

High incidence of immune‐mediated inflammatory diseases in sepsis survivors: A nationwide exposed‐nonexposed epidemiological study

“…First, overproduction of proinflammatory cytokines is central to the pathogenesis of both IMIDs and severe infections [3][4][5][6][7][8][9]. Second, neutralizing anti-cytokine autoantibodies, reported in the setting of both IMIDs (such as systemic lupus erythematosus [SLE]) and severe infections (such as severe COVID- 19), play a Janus effect on IMIDs activity and infection risk [10][11][12]. Third, patients with sepsis exhibit a high prevalence of autoantibodies against self-antigens that, which, because of their role in autoimmune diseases, may pave the way for the development of IMIDs in sepsis survivors [13][14][15].…”