transforming-growth-factor-beta and Anemia--Hemolytic--Autoimmune

Autoimmune hemolytic anemia (AIHA) is due to autoantibodies with or without complement activation and involves cellular and cytokine dysregulation. Here, we investigated cytokine single-nucleotide polymorphisms (SNPs) of TNF-α, TGF-β1, IL-10, IL-6, and IFN-γ, along with their serum levels. The former were related to hematological parameters, therapy, and clinical outcome. The study included 123 consecutive patients with primary AIHA [77 warm AIHA and 46 cold agglutinin disease (CAD)], followed up for a median of 49 months. Results show that the allelic frequency of TNF-α -308 G/A polymorphisms was significantly lower in patients versus controls. Moreover, the genotypic frequency of TNF-α -308G/A and TGF-β gene codon 25 G/C genotypes was significantly lower in patients versus controls. Considering cytokine SNP genotypes associated with different gene expression levels, TNF-α high gene expression was significantly more frequent in patients, TGF-β and IL-10 high gene expression was higher in patients with more severe anemia, and TGF-β high gene expression was higher in patients with active disease. Considering treatment, TNF-α and TGF-β high gene expression was more frequent in multitreated patients and particularly in CAD. It may be speculated that this genetic predisposition to a stronger inflammatory response may result in a greater immune dysregulation and in a relapsed/refractory disease. Regarding cytokine serum levels, TNF-α and TGF-β were significantly lower, and IL-10 and IL-6 were significantly higher in patients versus controls, underlying the complex interplay between genetic background and disease features.

Topics: Anemia, Hemolytic, Autoimmune; Chronic Disease; Cytokines; Humans; Interferon-gamma; Interleukin-10; Interleukin-6; Polymorphism, Single Nucleotide; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

We here report a 47-year-old female with autoimmune myelofibrosis (AIMF) associated with liver damage caused by autoimmune hepatitis and Evans syndrome. Bone marrow biopsy revealed hypocellular marrow with grade 2 reticulin fibrosis and increased levels of B lymphocytes (CD20

Topics: Anemia, Hemolytic, Autoimmune; Bone Marrow; Drug Resistance; Female; Hepatitis, Autoimmune; Humans; Middle Aged; Prednisolone; Primary Myelofibrosis; Rituximab; Thrombocytopenia; Transforming Growth Factor beta

A case of Evans' syndrome with IgM deficiency and lymphopenia was studied before and after splenectomy. The lymphopenia was as a result of profound reduction of CD4 and CD8 cells. Study of cytokine secretion before splenectomy revealed a spontaneous Th1- and Th2-type cytokine production, and complete suppression of transforming growth factor (TGF)-beta. After splenectomy, the patient achieved clinical remission, the natural killer (NK) cell number increased and the pattern of cytokine production showed normalization of interleukin (IL)-2, IL-4, IL-10, TGF-beta and abolition of interferon (IFN)-gamma production. We conclude that splenectomy had a beneficial effect owing to an increase in NK cells and an associated increase in TGF-beta production.

Topics: Anemia, Hemolytic, Autoimmune; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Child; Cytokines; Humans; Immunoglobulin M; Interferon-gamma; Interleukin-10; Interleukin-2; Interleukin-4; Killer Cells, Natural; Lymphocyte Count; Lymphopenia; Male; Purpura, Thrombocytopenic, Idiopathic; Splenectomy; Syndrome; Th1 Cells; Th2 Cells; Transforming Growth Factor beta

The immunopathogenic mechanisms underlying idiopathic autoimmune haemolytic anaemia (AIHA) are still unknown, although regulatory cytokines are thought to play an important role. We investigated cytokine production by mitogen-stimulated whole blood cultures from 21 patients with AIHA and from 22 age- and sex-matched controls. In parallel experiments, we studied the effect of mitogen and cytokine stimulation on anti-red blood cell (RBC) IgG antibody production, assessed as both binding on autologous RBCs and secretion in culture supernatants. To quantify anti-RBC antibody, we set up a sensitive and quantitative solid phase competitive immunoassay. The results showed that in AIHA patients production of interleukin (IL)-4, IL-6 and IL-13 was significantly increased, whereas that of interferon (IFN)-gamma was reduced. Multivariate analysis showed that IFN-gamma was the only independent factor significantly associated with the reduced T-helper-1-like cytokine profile. Patients with active haemolysis showed further reduction of IFN-gamma and IL-2 production and increased secretion of transforming growth factor (TGF)-beta. In AIHA patients, mitogen stimulation, as well as IL-6, significantly increased autologous anti-RBC-binding relative to unstimulated cultures. Mitogen stimulation and addition of IL-4, IL-6, IL-10, IL-13 and TGF-beta significantly increased both autologous anti-RBC binding and antibody secretion in AIHA patients compared with controls. The results suggest that a reduced T-helper-1- and a predominant T-helper-2-like profile and elevated TGF-beta levels might play a role in the immunopathogenesis of AIHA. Furthermore, our competitive anti-RBC antibody was able to detect anti-RBC antibody production in some direct antiglobulin test (DAT)-negative AIHA patients.

Topics: Adult; Aged; Anemia, Hemolytic, Autoimmune; Antibody Formation; Autoantibodies; Binding, Competitive; Case-Control Studies; Cells, Cultured; Cytokines; Erythrocytes; Female; Humans; Immunoenzyme Techniques; Immunoglobulin G; Interferon-gamma; Interleukin-10; Interleukin-13; Interleukin-2; Interleukin-4; Interleukin-6; Male; Middle Aged; Mitogens; Multivariate Analysis; Recombinant Proteins; Stimulation, Chemical; Transforming Growth Factor beta