interleukin-8 and Anemia--Hemolytic--Autoimmune

Topics: Anemia, Hemolytic, Autoimmune; Biomarkers; Chemokine CXCL10; Cytokines; Humans; Interleukin-8

A high mortality occurs in dogs with idiopathic immune-mediated haemolytic anaemia (IMHA) during the first 2 weeks after the diagnosis. The aim of this study was to investigate the inflammatory response and coagulation abnormalities in dogs with IMHA in relation to the prognosis and to establish the contribution of whole blood tissue factor (TF) and IL-8 gene expressions. Gene expressions in dogs with IMHA were compared to healthy dogs, dogs with DIC, dogs with sepsis, and in two groups of dogs that underwent intensive care treatment but had no evidence for either DIC or sepsis. The whole blood TF and IL-8 expressions were up regulated in all non-IMHA groups. Similarly, the TF expression in IMHA dogs was high, but the intravascular IL-8 expression was not increased. The dogs with IMHA had a pronounced inflammatory response that included a high WBC, left shift and monocytosis in comparison to the other disease groups. Coagulation factor activities in IMHA dogs were decreased fitting consumptive coagulopathy and the acute phase proteins FVIII and fibrinogen were increased. The platelet parameters suggested platelet activation and high platelet turnover in IMHA dogs. The model that best explained mortality contained monocytosis, increased activated partial thromboplastin time and elevated creatinine. Whole blood TF gene expression is up regulated and may contribute to consumptive coagulopathy in dogs with IMHA. Increased TF expression by activated platelets is an alternative explanation and should be investigated.

Topics: Anemia, Hemolytic, Autoimmune; Animals; Blood Coagulation; Disseminated Intravascular Coagulation; Dog Diseases; Dogs; Female; Inflammation; Interleukin-8; Male; Prognosis; Real-Time Polymerase Chain Reaction; Sepsis; Thromboplastin

EndoS from Streptococcus pyogenes is an immunomodulating enzyme that specifically hydrolyzes glycans from human immunoglobulin G and thereby affects antibody effector functions. Autoimmune hemolytic anemia is caused by antibody-mediated red blood cell (RBC) destruction and often resists treatment with corticosteroids that also cause frequent adverse effects. We show here that anti-RhD (anti-D) and rabbit anti-human-RBC antibodies (anti-RBC) mediated destruction of RBC, ie, phagocytosis, complement activation, and hemolysis in vitro and in vivo was inhibited by EndoS. Phagocytosis by monocytes in vitro was inhibited by pretreatment of anti-D with EndoS before sensitization of RBCs and abrogated by direct addition of EndoS to blood containing sensitized RBCs. The toxic effects of monocytes stimulated with anti-D-sensitized RBCs, as measured by interleukin-8 secretion and oxygen metabolite production, was restrained by EndoS. Agglutination of RBCs and complement-mediated hemolysis in vitro in whole human blood caused by rabbit anti-RBCs was inhibited by EndoS. Development of anemia in mice caused by a murine anti-RBC immunoglobulin G2a monoclonal autoantibody and complement activation and erythrophagocytosis by Kupffer cells in the liver were reduced by EndoS. Our data indicate that EndoS is a potential therapeutic agent that might be evaluated as an alternative to current treatment regimens against antibody-mediated destruction of RBCs.

Topics: Anemia, Hemolytic, Autoimmune; Animals; Bacterial Proteins; Complement C1q; Erythrocytes; Glycoside Hydrolases; Hemolysis; Humans; Immunoglobulin G; Interleukin-8; Isoantibodies; Mice; Mice, Inbred BALB C; Monocytes; Oxygen; Phagocytosis; Rabbits; Rho(D) Immune Globulin

The clinical symptoms of patients with autoimmune haemolytic anaemia (AIHA) may range from no symptoms at all to severe haemolysis with life-threatening anaemia. The aim of the present study was to characterize the autoantibodies serologically and to evaluate their activity in vitro in monocyte monolayer assay (MMA) in consecutive direct antiglobulin test (DAT)-positive patients from a haematological department. We also aimed to evaluate the monocyte production of cytokines in vitro and relate all findings to in vivo haemolysis. Twenty-nine patients with positive DAT were included in the study and clinical characteristics were documented. The patients were divided into three groups based on laboratory parameters, severe haemolysis, moderate haemolysis and no sign of haemolysis. Severe haemolysis was related to a strongly positive DAT and positive results in MMA. When eluates were analysed in MMA, a positive result was associated with a higher concentration in the supernatants of interleukin (IL)-8 after 6 h incubation. We conclude that MMA activity and in vitro cytokine production may reflect the in vivo activity of autoantibodies. This may be of importance in understanding the mechanisms of haemolysis and in predicting the harmfulness of antibodies, especially when blood transfusions are needed.

Topics: Anemia, Hemolytic, Autoimmune; Autoantibodies; Blood Transfusion; Chemokine CCL2; Coculture Techniques; Coombs Test; Cytokines; Erythrocytes; Female; Hematologic Neoplasms; Hemolysis; Humans; Interleukin-8; Male; Monocytes; Treatment Outcome