Emerging clinical phenotypes associated with anti-cytokine autoantibodies

Vincent, Thierry; Plawecki, Maëlle; Goulabchand, Radjiv; Guilpain, Philippe; Eliaou, J.-F.

doi:10.1016/j.autrev.2015.01.015

Cited by 35 publications

(36 citation statements)

References 110 publications

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“…As CRP is an inflammatory marker induced by IL-6 [55], and since this correlation was unique to IL-6-specific c-aAb, these data suggest the presence of cytokine inhibitory levels of IL-6-specific c-aAb. This finding is in concordance with previous experimental observations [11–13, 39, 40]. Apparently the correlation was not affected by smoking status, despite smoking being known to affect CRP levels [44, 56].…”

Section: Discussionsupporting

confidence: 93%

Prevalence and correlation of cytokine-specific autoantibodies with epidemiological factors and C-reactive protein in 8,972 healthy individuals: Results from the Danish Blood Donor Study

et al. 2017

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Natural cytokine-specific autoantibodies (c-aAb) have been measured in healthy and diseased individuals, and have been considered as both endogenous immune-regulators and pathogenic factors. Overall, the etiology and potential pathology of c-aAb are still undefined. To further characterize the sero-prevalence, predictors and consequences of high c-aAb levels, we performed the largest population-based study of c-aAb to date, using participants and epidemiological data from the Danish Blood Donor Study. Using a validated bead-based multiplex assay we assessed plasma levels of IL-1α, IL-6, IL-10, IFNα and GM-CSF-specific c-aAb in 8,972 healthy blood donors. Trace levels of at least one of the investigated c-aAb could be measured in 86% of the participants. The presence of high levels of potentially inhibitory c-aAb was generally associated with increasing age and male or female sex, depending on the c-aAb in question. A negative correlation between high levels of IL-6-specific c-aAb and plasma levels of C-reactive protein was observed, indicating cytokine-neutralizing levels of c-aAb in healthy blood donors. There was no substantial correlation between high levels of the five individual c-aAb investigated in this study. These data suggest that autoimmunity against endogenous cytokines is a relatively common phenomenon in healthy individuals, and that predictive factors for high, potentially neutralizing c-aAb levels vary depending on the cytokine in question, and may differ from predictors of general c-aAb presence.

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Section: Discussionsupporting

confidence: 93%

Prevalence and correlation of cytokine-specific autoantibodies with epidemiological factors and C-reactive protein in 8,972 healthy individuals: Results from the Danish Blood Donor Study

et al. 2017

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“…1). The level of soluble factors produced is typically one of many parameters regulated by these interactions [80, 81]. …”

Section: Discussionmentioning

confidence: 99%

Expression Density of Receptors as a Potent Regulator of Cell Function and Property in Health and Pathology

Sennikov

Alshevskaya

Zhukova

et al. 2018

Int Arch Allergy Immunol

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The expression of cytokine receptors has a crucial role in many cellular processes. Recent studies reported that changes of receptor expression could control the action of mediators on target cells. The initiation of different signaling pathways and, therefore, specific effects on cells, depends on certain components forming the cytokine-receptor complex. These mechanisms control the immune response and affect both the course of diseases (oncological, autoimmune, inflammatory) and the effectiveness of therapy. This review describes the potential of immune mediator receptors to regulate the efficiency of cytokine activity during pathologic processes and ensure the variability of their biological effects. Our aim was to investigate the spectrum of potential roles of changes in mediator receptor expression for main classes of pathologies. For all major types of immune mediators (cytokines, interleukins, chemokines, growth factors, and tumor necrosis factors), it has been shown that changes in their receptor expression are associated with impaired functioning of the organism in chronic diseases.

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“…Importantly, while levels of serum BAFF correlated positively with disease activity in our patients, levels of anti‐BAFF antibody were correlated negatively with levels of its target cytokine, anti‐dsDNA antibody and clinical disease activity. This suggests that the presence of these autoantibodies does not merely reflect an autoimmune response to high levels of circulating BAFF, but is demonstrative of the known phenomenon of anti‐pathogenic cytokine autoantibodies influencing the course of autoimmune disease . Endogenous anti‐BAFF autoantibodies may blunt the effects of overproduced BAFF through forming complexes with BAFF, thereby enhancing its clearance.…”

Section: Discussionmentioning

confidence: 99%

“…Data are mean 6 standard error of the mean (s.e.m.). high levels of circulating BAFF, but is demonstrative of the known phenomenon of anti-pathogenic cytokine autoantibodies influencing the course of autoimmune disease [4]. Endogenous anti-BAFF autoantibodies may blunt the effects of overproduced BAFF through forming complexes with BAFF, thereby enhancing its clearance.…”

Section: Discussionmentioning

confidence: 99%

Associations of B cell-activating factor (BAFF) and anti-BAFF autoantibodies with disease activity in multi-ethnic Asian systemic lupus erythematosus patients in Singapore

Howe

Thong

Kong

et al. 2017

Clinical and Experimental Immunology

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To measure the levels of B cell-activating factor (BAFF) and endogenous anti-BAFF autoantibodies in a cohort of multi-ethnic Asian systemic lupus erythematosus (SLE) patients in Singapore, to determine their correlation with disease activity. Serum samples from 121 SLE patients and 24 age- and sex-matched healthy controls were assayed for BAFF and anti-BAFF immunoglobulin (Ig)G antibody levels by enzyme-linked immunosorbent assay (ELISA). The lowest reliable detection limit for anti-BAFF-IgG antibody levels was defined as 2 standard deviations (s.d.) from blank. Correlation of serum BAFF and anti-BAFF IgG levels with disease activity [scored by SLE Activity Measure revised (SLAM-R)], and disease manifestations were determined in these 121 patients. SLE patients had elevated BAFF levels compared to controls; mean 820 ± 40 pg/ml and 152 pg ± 45/ml, respectively [mean ± standard error of the mean (s.e.m.), P < 0·01], which were correlated positively with anti-dsDNA antibody levels (r = 0·253, P < 0·03), and SLAM-R scores (r = 0·627, P < 0·01). In addition, SLE patients had significantly higher levels of anti-BAFF IgG, which were correlated negatively with disease activity (r = -0·436, P < 0·01), levels of anti-dsDNA antibody (r = -0·347, P < 0·02) and BAFF (r = -0·459, P < 0·01). The majority of patients in this multi-ethnic Asian SLE cohort had elevated levels of BAFF and anti-BAFF antibodies. Anti-BAFF autoantibody levels correlated negatively with clinical disease activity, anti-dsDNA and BAFF levels, suggesting that they may be disease-modifying. Our results provide further information about the complexity of BAFF pathophysiology in different SLE disease populations and phenotypes, and suggest that studies of the influence of anti-cytokine antibodies in different SLE populations will be required when selecting patients for trials using targeted anti-cytokine therapies.

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Emerging clinical phenotypes associated with anti-cytokine autoantibodies

Cited by 35 publications

References 110 publications

Prevalence and correlation of cytokine-specific autoantibodies with epidemiological factors and C-reactive protein in 8,972 healthy individuals: Results from the Danish Blood Donor Study

Prevalence and correlation of cytokine-specific autoantibodies with epidemiological factors and C-reactive protein in 8,972 healthy individuals: Results from the Danish Blood Donor Study

Expression Density of Receptors as a Potent Regulator of Cell Function and Property in Health and Pathology

Associations of B cell-activating factor (BAFF) and anti-BAFF autoantibodies with disease activity in multi-ethnic Asian systemic lupus erythematosus patients in Singapore

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