IgA-mediated human autoimmune hemolytic anemia as a result of hemagglutination in the spleen, but independent of complement activation and FcαRI.
نویسندگان
چکیده
Autoimmune hemolytic anemia (AIHA) due to warm-acting IgA autoantibodies is rare. We explored the pathogenic mechanisms underlying destruction of red blood cells (RBCs) in a patient with severe AIHA mediated exclusively by polymeric immunoglobulin A (pIgA) anti-Band 3 autoantibodies. The follow-up period was 17 months. RBCs were not destroyed by complement activation as no deposition of complement was observed on the patient's RBCs. pIgA eluted from the patient's RBCs did not induce RBC destruction through phagocytosis by monocytes or antibody-dependent cell-mediated cytotoxicity by natural killer cells. Induction of eryptosis (ie, RBC apoptosis) due to direct alteration of the RBC membrane by pIgA autoantibodies was also excluded. By contrast, upon incubation with pIgA-opsonized RBCs, substantial RBC membrane transfers (ie, trogocytosis) to monocytes were observed that might contribute to RBC immune destruction. This effect was poorly inhibited by blockers of Fc receptors, excluding a major contribution of FcαRI to this process. Histologic analysis revealed a massive accumulation of agglutinated RBCs with little sign of erythrophagocytosis in the spleen. These results, together with the efficacy of splenectomy 17 months after AIHA onset, suggest that the trapping and subsequent sequestration of agglutinated RBCs in the spleen are the principal pathogenic mechanisms of pIgA-mediated AIHA.
منابع مشابه
IgA-mediated human autoimmune hemolytic anemia as a result of hemagglutination in the spleen, but independently of complement activation and FcαRI
متن کامل
IgM and IgA anti-erythrocyte autoantibodies induce anemia in a mouse model through multivalency-dependent hemagglutination but not through complement activation.
By generating IgM and IgA switch variants of the 34-3C IgG2a anti-red blood cell (RBC) autoantibody, we evaluated the pathogenic activity of these 2 isotypes in view of the Fc-associated effector functions (ie, complement activation and polyvalency-dependent agglutination). We found that polymeric forms of 34-3C IgM and IgA anti-RBC autoantibody were as pathogenic as IgG2a, which was the most p...
متن کاملInfluence of splenectomy on immunoglobulins and complement components in major thalassemia
Abstract Introduction: Thalassemia is the most common hereditary anemia in Iran. The aim of this study was to evaluate the humoral immune system and assess the effect of splenectomy on the serum level of immunoglobulins IgG, IgM, and IgA and complement components in patients with major thalassemia. Materials and Methods: This interventional semi-experimental study (before-after) was performed...
متن کاملImmune-mediated hemolytic anemia in cats referring to Veterinary Teaching Hospital of Tehran (2006-2007)
Immune-mediated hemolytic anemia (IMHA) is characterized by the destruction of erythrocytes or sometimes bone marrow erythroid precursors mediated by immunoglobulins (IgG, IgM), with or without complement (C 3). The main objectives of this study were to assess the laboratory test results of IMHA and to investigate its possible underlying causes in cats referring to the Veterinary Teaching Hosp...
متن کاملAutoimmune Hemolytic Anemia preceding the Diagnosis of Primary Central Nervous System Lymphoma
In this study, a 2.5-year-old boy suffering from a febrile seizure with normal laboratory tests and a history of immune hemolytic anemia was examined. Brain MRI demonstrated some tumors in the frontal, parietal, and occipital lobe that corroborated the pathology results of primary central nervous system lymphoma for the patient. The patient was treated with high- dose of Methotrexate. Our re...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Blood
دوره 116 20 شماره
صفحات -
تاریخ انتشار 2010