Production of the effector cytokine interleukin-17, rather than interferon- , is more strongly associated with autoimmune hemolytic anemia

Hall, Andrew M.; Zamzami, Omar M.; Whibley, Natasha; Hampsey, Daniel P.; Haggart, A. M.; Vickers, Mark A.; Barker, Robert N.

doi:10.3324/haematol.2011.060822

Cited by 19 publications

(21 citation statements)

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“…In people with AIHA, increased frequencies of Th17 cells in peripheral blood and an increased serum concentration of IL-17 have been observed; the concentration of IL-17 was also correlated with disease activity [44,45]. Interleukin-17 is also able to cause activation of phagocytes, resulting in release of CXCL-8, IL-6 and TNFα [46].…”

Section: Discussionmentioning

confidence: 99%

Characterisation of the Immunophenotype of Dogs with Primary Immune-Mediated Haemolytic Anaemia

Swann

Woods

et al. 2016

PLoS ONE

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BackgroundImmune-mediated haemolytic anaemia (IMHA) is reported to be the most common autoimmune disease of dogs, resulting in significant morbidity and mortality in affected animals. Haemolysis is caused by the action of autoantibodies, but the immunological changes that result in their production have not been elucidated.AimsTo investigate the frequency of regulatory T cells (Tregs) and other lymphocyte subsets and to measure serum concentrations of cytokines and peripheral blood mononuclear cell expression of cytokine genes in dogs with IMHA, healthy dogs and dogs with inflammatory diseases.Animals19 dogs with primary IMHA, 22 dogs with inflammatory diseases and 32 healthy control dogs.MethodsResidual EDTA-anti-coagulated blood samples were stained with fluorophore-conjugated monoclonal antibodies and analysed by flow cytometry to identify Tregs and other lymphocyte subsets. Total RNA was also extracted from peripheral blood mononuclear cells to investigate cytokine gene expression, and concentrations of serum cytokines (interleukins 2, 6 10, CXCL-8 and tumour necrosis factor α) were measured using enhanced chemiluminescent assays. Principal component analysis was used to investigate latent variables that might explain variability in the entire dataset.ResultsThere was no difference in the frequency or absolute numbers of Tregs among groups, nor in the proportions of other lymphocyte subsets. The concentrations of pro-inflammatory cytokines were greater in dogs with IMHA compared to healthy controls, but the concentration of IL-10 and the expression of cytokine genes did not differ between groups. Principal component analysis identified four components that explained the majority of the variability in the dataset, which seemed to correspond to different aspects of the immune response.ConclusionsThe immunophenotype of dogs with IMHA differed from that of dogs with inflammatory diseases and from healthy control dogs; some of these changes could suggest abnormalities in peripheral tolerance that permit development of autoimmune disease. The frequency of Tregs did not differ between groups, suggesting that deficiency in the number of these cells is not responsible for development of IMHA.

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Section: Discussionmentioning

confidence: 99%

Characterisation of the Immunophenotype of Dogs with Primary Immune-Mediated Haemolytic Anaemia

Swann

Woods

et al. 2016

PLoS ONE

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“…The activation of these specific Th cells hence holds out the prospect of safe, effective treatments for WAIHA. The evidence presented by Hall et al [60] and Xu et al [61] indicated alternative ways to develop potential new immunotherapy methods by clarifying the roles of Th17 cells in the development of AIHA. Blocking the activity of the Th17 pathway may be a complementary or more effective treatment strategy than inhibiting Th1 responses.…”

Section: Elucidation Of Mechanism Of Waiha Contributes To Developimentioning

confidence: 99%

Immunotherapy Treatments of Warm Autoimmune Hemolytic Anemia

Liu

2013

Clinical and Developmental Immunology

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Warm autoimmune hemolytic anemia (WAIHA) is one of four clinical types of autoimmune hemolytic anemia (AIHA), with the characteristics of autoantibodies maximally active at body temperature. It produces a variable anemia—sometimes mild and sometimes severe. With respect to the absence or presence of an underlying condition, WAIHA is either idiopathic (primary) or secondary, which determines the treatment strategies in practice. Conventional treatments include immune suppression with corticosteroids and, in some cases, splenectomy. In recent years, the number of clinical studies with monoclonal antibodies and immunosuppressants in the treatment of WAIHA increased as the knowledge of autoimmunity mechanisms extended. This thread of developing new tools of treating WAIHA is well exemplified with the success in using anti-CD20 monoclonal antibody, Rituximab. Following this success, other treatment methods based on the immune mechanisms of WAIHA have emerged. We reviewed these newly developed immunotherapy treatments here in order to provide the clinicians with more options in selecting the best therapy for patients with WAIHA, hoping to stimulate researchers to find more novel immunotherapy strategies.

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“…One model to explain this paradox is that IL‐27 and IL‐17A exert complex reciprocal effects to boost inflammatory responses, but restrain resting cells to prevent inappropriate activation. This model may help to elucidate the pathogenesis of the growing number of autoimmune diseases in which Th17 responses are implicated .…”

Section: Discussionmentioning

confidence: 99%

Human interleukin-27: wide individual variation in plasma levels and complex inter-relationships with interleukin-17A

Forrester

Robertson

Bayoumi

et al. 2014

Clinical and Experimental Immunology

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SummaryAlthough it is widely believed that interleukin (IL)-27 is anti-inflammatory, its role in controlling human immune responses is not fully established. In particular, its interactions with T helper type 17 (Th)17 cytokines are unclear. Our aims were to establish the relationships between IL-27 and proinflammatory cytokines, including IL-17A, in human sera and cultures of peripheral blood mononuclear cells. Plasma IL-27 levels in 879 healthy humans from 163 families varied widely, but with relatively low heritability (19%). Despite IL-27 including a subunit encoded by Epstein-Barr virusinduced gene 3 (EBI3), there was no correlation of levels with serological evidence of infection with the virus. Although IL-27 has been reported to inhibit IL-17A production, we demonstrated a strong positive correlation in sera, but lower correlations of IL-27 with other proinflammatory cytokines. We verified that IL-27 inhibited IL-17A production by human peripheral blood T cells in vitro, but not that it stimulated IL-10 secretion. Importantly, addition of IL-17A decreased IL-27 production by stimulated T cells but had the opposite effect on resting T cells. Together, these data suggest a model whereby IL-27 and IL-17A exerts complex reciprocal effects to boost inflammatory responses, but restrain resting cells to prevent inappropriate activation.

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Production of the effector cytokine interleukin-17, rather than interferon- , is more strongly associated with autoimmune hemolytic anemia

Cited by 19 publications

References 53 publications

Characterisation of the Immunophenotype of Dogs with Primary Immune-Mediated Haemolytic Anaemia

Characterisation of the Immunophenotype of Dogs with Primary Immune-Mediated Haemolytic Anaemia

Immunotherapy Treatments of Warm Autoimmune Hemolytic Anemia

Human interleukin-27: wide individual variation in plasma levels and complex inter-relationships with interleukin-17A

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