Suppression of elevations in serum C reactive protein levels by anti-IL-6 autoantibodies in two patients with severe bacterial infections

Nanki, Toshihiro; Onoue, Ikumi; Nagasaka, Kenji; Takayasu, Aiko; Ebisawa, Masashi; Hosoya, Tadashi; Shirai, Toshizumi; Sugihara, Takahiko; Hirata, Satoshi; Kubota, Tetsuo; Harigai, Masayoshi; Miyasaka, Nobuyuki

doi:10.1136/annrheumdis-2012-202768

Cited by 48 publications

(26 citation statements)

References 9 publications

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“…This finding may reflect chronic disease and uremia‐associated systemic inflammation in the investigated cohort, but it has also been reported in a study of 8,972 healthy Danish blood donors . Associations between post‐transplantation MACE and IL‐10‐specific c‐aAbs only are consistent with observations that individual c‐aAbs are linked to lacunar defects . We found no significant correlations between levels of IL‐10‐specific c‐Abs and markers of systemic inflammation.…”

Section: Discussionsupporting

confidence: 90%

IL‐10‐specific autoantibodies predict major adverse cardiovascular events in kidney transplanted patients ‐ a retrospective cohort study

et al. 2019

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End-stage renal failure is associated with persistent systemic inflammation. The aim of this study was to investigate if systemic inflammation at the time of kidney transplantation is linked to poor graft survival, major adverse cardiovascular events (MACE), and increased mortality, and if these processes are modulated by naturally occurring cytokine-specific autoantibodies (c-aAbs), which have been shown to regulate cytokine activity in vitro. Serum levels of cytokines, high-sensitivity C-reactive protein (hsCRP) and c-aAbs specific for interleukin (IL)-1a, tumor necrosis factor (TNF)-a, IL-6, and IL-10 were measured at the time of transplantation in a retrospective cohort study of 619 kidney transplanted patients with a median follow-up of 4.9 years (range 1.2-8.2 years). Systemic inflammation was associated with all-cause mortality in simple and multiple Cox regression analyses. IL-10-specific c-aAbs were associated with MACE after transplantation, suggesting that IL-10 may be a protective factor. Similarly, patients with a history of MACE before transplantation had lower levels of TNF-a-specific c-aAbs, hence we hypothesized that TNF may be a risk factor of MACE. These findings support that pro-inflammatory activity before transplantation is a pathological driver of MACE and all-cause mortality after transplantation. This information adds to pretransplantation risk estimation in renal transplant candidates. Transplant International 2019; 32: 933-948

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Section: Discussionsupporting

confidence: 90%

IL‐10‐specific autoantibodies predict major adverse cardiovascular events in kidney transplanted patients ‐ a retrospective cohort study

et al. 2019

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“…Its occurrence in patients with auto-Abs against IL-6 suggests that impaired STAT3-dependent IL-6 signaling may also be involved. 20,69,70 Respiratory tract infections may be favored by low IgA, IgG2, and/or IgG4 levels as well as a poor Ab response, as documented in some patients. 71,72 The occurrence of mycobacterial and viral infections is paradoxical, as biallelic LOF STAT1 mutations underlie such infections by impairing IFN-g and IFN-a/b responses, respectively, while GOF STAT1 mono-allelic mutations enhance signaling downstream of these cytokines.…”

Section: Discussionmentioning

confidence: 99%

Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype

Toubiana

Okada

Hiller

et al. 2016

Blood

455

611

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Since their discovery in patients with autosomal dominant (AD) chronic mucocutaneous candidiasis (CMC) in 2011, heterozygous STAT1 gain-of-function (GOF) mutations have increasingly been identified worldwide. The clinical spectrum associated with them needed to be delineated. We enrolled 274 patients from 167 kindreds originating from 40 countries from 5 continents. Demographic data, clinical features, immunological parameters, treatment, and outcome were recorded. The median age of the 274 patients was 22 years (range, 1-71 years); 98% of them had CMC, with a median age at onset of 1 year (range, 0-24 years). Patients often displayed bacterial (74%) infections, mostly because of Staphylococcus aureus (36%), including the respiratory tract and the skin in 47% and 28% of patients, respectively, and viral (38%) infections, mostly because of Herpesviridae (83%) and affecting the skin in 32% of patients. Invasive fungal infections (10%), mostly caused by Candida spp. (29%), and mycobacterial disease (6%) caused by Mycobacterium tuberculosis, environmental mycobacteria, or Bacille Calmette-GuÃ©rin vaccines were less common. Many patients had autoimmune manifestations (37%), including hypothyroidism (22%), type 1 diabetes (4%), blood cytopenia (4%), and systemic lupus erythematosus (2%). Invasive infections (25%), cerebral aneurysms (6%), and cancers (6%) were the strongest predictors of poor outcome. CMC persisted in 39% of the 202 patients receiving prolonged antifungal treatment. Circulating interleukin-17A-producing T-cell count was low for most (82%) but not all of the patients tested. STAT1 GOF mutations underlie AD CMC, as well as an unexpectedly wide range of other clinical features, including not only a variety of infectious and autoimmune diseases, but also cerebral aneurysms and carcinomas that confer a poor prognosis

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“…The authors concluded that anti-IL-6 AAb detection should be performed in patients presenting with severe bacterial infections associated with clinical and biological signs of inflammation but paradoxically low serum CRP concentrations [29]. Accordingly, anti-IL-6 AAbs were also observed in a 67-year-old man who developed severe thoracic empyema caused by Escherichia coli and Streptococcus intermedius but without elevation in serum CRP levels suggesting impaired IL-6 activity [30].…”

Section: Anti-il-6 Autoantibodiesmentioning

confidence: 99%

Emerging clinical phenotypes associated with anti-cytokine autoantibodies

Vincent

Plawecki

Goulabchand

et al. 2015

Autoimmunity Reviews

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Suppression of elevations in serum C reactive protein levels by anti-IL-6 autoantibodies in two patients with severe bacterial infections

Cited by 48 publications

References 9 publications

IL‐10‐specific autoantibodies predict major adverse cardiovascular events in kidney transplanted patients ‐ a retrospective cohort study

IL‐10‐specific autoantibodies predict major adverse cardiovascular events in kidney transplanted patients ‐ a retrospective cohort study

Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype

Emerging clinical phenotypes associated with anti-cytokine autoantibodies

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