Th2 cytokine role in autoimmune haemolytic anaemia (AIHA) pathogenesis

BACKGROUND: AIHA is characterised by the destruction of antibody-coated red blood cells, but the mechanism that initiates the production of autoantibodies remains unclear. We have studied the proliferative response and the spontaneous and mitogen-induced (PHA and OKT3) synthesis of IFN-g, IL-2 and IL-4 by peripheral blood mononuclear cells from patients with AIHA before any treatment to investigate the activation of Th1 and Th2 subsets. METHODS: Thirteen AIHA patients, both idiopathic and associated with other diseases, were studied by ELISA methods and H3 thymidine incorporation to determine in vitro cytokine production and T cell proliferative response, respectively. RESULTS: Under basal conditions the proliferative response induced in peripheral blood mononuclear cells was enhanced in AIHA patients suggesting a basal state of hyperactivation. This increase in proliferative response can be related to the basal enhanced levels of IL-2 (p<0.04), a key cytokine, that regulates the growth, differentiation and function of lymphocytes. High IL-2 levels in AIHA patients supernatants, with or without OKT3 stimulation, justify the high basal activation of T lymphocytes. Under basal conditions levels of IFN-g are decreased and IL-4 levels are increased. CONCLUSIONS: AIHA is characterised by the destruction of antibody-coated red blood cells, but the mechanism that initiates the production of autoantibodies remains unclear. But looking to this data it is possible to suppose that there is a prevalent contribution of Th2 lymphocytes to the pathogenesis of AIHA.     

Rituximab instead of splenectomy in 4 children with chronic or refractory autoimmune haemolytic anaemia

4 children, a boy aged 10 years and 3 girls aged 3, 3, and 16 years, suffering from chronic or refractory autoimmune haemolytic anaemia (AIHA), who were dependent on high doses of steroids and were refractory to immunosuppressants, were treated with rituximab at a dose of 375 mg/m2 once a week for 3 or 4 weeks as an alternative to splenectomy. Rituximab is a monoclonal anti-CD20 antibody that prevents the production ofautoantibodies by selective destruction of B-lymphocytes. Haemoglobin levels increased and the parameters of chronic haemolysis (reticulocyte count, lactate dehydrogenase activity, bilirubin concentration) decreased to normal values. 3 patients were taken off corticosteroids completely; 1 of these was also no longer dependent on blood transfusions. Circulating B-lymphocytes were absent for 6 to 15 months after the treatment and the rituximab was well-tolerated. During the treatment, immunoglobulins were substituted and infectious complications were not seen. Rituximab was valuable in the treatment of chronic or refractory AIHA and eliminated the need for splenectomy. 1 patient did not respond to rituximab.     

Severe anaemia caused by Human Parvovirus B19 infection in a patient with autoimmune haemolytic anaemia and a B-cell non-Hodgkin lymphoma

A 65-year-old man with a 15-year history of 'leukemicised' low-grade lymphocytic B-cell non-Hodgkin lymphoma with a low-titre of IgM kappa paraprotein was admitted with severe anaemia and reticulocytopenia. Treatment with prednisone and chlorambucil had been started two weeks earlier because of a recently diagnosed Coombs-positive haemolytic anaemia. He also received a blood transfusion at that time. During his stay in the hospital, a crista biopsy was performed that revealed no signs of bone marrow suppression but markedly enlarged pro-erythroblasts. Although a serologic test for Human Parvovirus-B19 was negative, PCR showed a sharply increased viral load with more than 1 x 10(11) copies/ml, compatible with a primary parvovirus infection. In retrospect, an earlier transfusion of blood that had not been screened for parvovirus was probably the culprit. Treatment with human immunoglobulin was effective in lowering the viral load and normalising the haemoglobin. This case illustrates that reticulocytopenia in a patient with a haematologic disorder accompanied by a shortened erythrocyte life-span is suggestive for a primary parvovirus infection, especially following a recent transfusion. To prevent transmission of Human Parvovirus B19 via blood transfusion, the Health Council of the Netherlands published a guideline indicating that patients at high risk for a complicated infection with Human Parvovirus B19 should be given 'virus-free' blood products.     

Fatal haemolytic anaemia complicating a case of common variable hypogammaglobulinaemia

A fatal case of common variable hypogammaglobulinaemia (CVH) is described. The patient presented with fulminant haemolytic anaemia. Post mortem examination revealed evidence of chronic hypogammaglobulinaemia.