IgG Warm Autoantibody Research Articles

PB1970 AUOTOIMMUNE HEMOLITIC ANEMIA (AIHA) IN CHILDHOOD. IS PRIMARY IMMUNE DISORDERS MORE OFTEN THAN EXPECTED IN ETIOLOGY OF SECONDARY AIHA

Background:Auotoimmune hemolitic anemia (AIHA) results from redcell destruction due to circulating antibodies against redcell membrane antigens. They are classified etiologically into primary and secondary such as primary immune disorders (PID), infectious disease and connective tissue disorders (CTD).Aims:Herein, we aimed to evaluation of etiology in cases with AIHA.Methods:62 cases diagnosed on positive direct antiglobulin test (DAT)at department of pediatric hematology in Erciyes University Hospital were included in the study and their records have been retrosectively examined.Results:Mean age of all cases was 61.9 ± 51.9 months (range of 1‐92 months). The cases showed a male predilection (M:F = 1.2). The results showed that 34 of 62 cases had primary 28 secondary AIHA (12 PID, 7 infections, 4 CTD, 3 Hodgkin disease, 2 endocrinopathies) respectively. Mean Hb value in cases with AIHA was 6.9 ± 2.5 g/dl and mean Hb value in cases with secondary AIHA was 6.8‐2.6 g/dl. All of them had mean low level of haptoglobulin (7.2 mg/dl in primary AIHA, 6.2 mg/dl in secondary AIHA) and they had mean high level of total bilurubin (4.9 mg/dl in primary AIHA and 1.4 mg/dl in secondary AIHA). There was no significant difference of mean Hb value in two groups (p = 0.783) but there was significant difference of mean bilurubin value in two groups (p = 0.001). One Case with secondary AIHA had IgM cold autoantibody and 61 cases had IgG warm autoantibody. The cases with primary AIHA had more strong positive IgG autoantibody than the cases with secondary AIHA and there was significant difference of IgG autoantibody positivity in two groups (p = 0.044).Summary/Conclusion:AIHA presented with severe anemia and laboratory evidence of marked hemolysis. Especially, PID is more often than expected in etiology of secondary AIHA.

Serological Characteristics of Patients with Autoimmune Hemoly-tic Anemia and Efficacy and Safety of Incompatible Transfusion of Red Blood Cells

To explore the serological characteristics of patients with autoimmune hemolytic anemia（AIHA） and analyze its clinical efficacy and safety of incompatible red blood cell transfusion. Sixty AIHA patients admitted in our hospital from January 2014 to January 2018 were selected. The blood type serological characteristics of 60 patients were analyzed retrospectively. According to the type of autoantibody and the composition of different red blood cells, the efficacy and safety of erythrocyte infusions were evaluated respectively. The screen results of irregular antibody in 60 AIHA patients were positive, and the direct anti-human globulin test also was positive, including 8 cases of cold autoantibodies (13.33%), 49 cases of IgG warm autoantibodies (81.67%), and 3 cases of warm cold double autoantibodies (5%). The irregular anti-body identification test confirmed the existence of homoantiboby in 17 cases (28.33%). Out of 60 cases 34 received incompatible red blood cell (RBC) infusion for 108 time including ABO homotype non washing RBC (81 tirnes) and O type washing RBC (27 times). The infusion results showed that the total [JP2]effective rate was 57.41(62/108), total partial effective rate was 14.81% (16/108) and total ineffective rate was 27.78% (30/108).The infusion of ABO homotype non-washing RBC for 81 time showed that the effective rate was 58.02%[JP] (47/81) , partial effective rate was 12.35 (10/81) and ineffective rate was 29.67% (24/81); the infusion of O type washing RBC for 27 times showed that the effective rate was 55.56% (15/27), partial effective rate was 22.22% (6/27) and ineffective rate was 22.22% (6/27), there was no significant difference in effective rate between 2 kinds of infusion (P>0.05). The comparison of different antibody type infusion showed that in the infusion of IgM cold autoantiboay for 12 times, the effective rate was 41.67% (5/12), partial effective rate was 33.33% (4/12) and ineffective rate was 25% (3/12); in the infusion of IgG warm antoantibody for 93 times. The effective rate was 58.06% (54/93),partial effective rate was 12.90% (12/93) and ineffective rale was 29.04% (27/93), there was also no significant difference in effective rate between 2 kinds of infusion(P>0.05). However, in infusion of cold/warm double autoantibody for 3 times, the effective rate was 100% (3/3), moreover, the hemotytic reaction of infusion was not observed during the treatment . The infusion of ABO homotype non-washing RBC and O type washing RBC both possess the high safely and efficacy for treatment of patients with AIHA, but the use of ABO homotype non-washing RBC can effectively avoid the excessive use of O type washing RBC.

Serological characteristics and transfusion efficacy evaluation in 61 cases of autoimmune hemolytic anemia

This study was aimed to analyze the serological characteristics, efficacy and safety of incompatible RBC transfusion in patients with autoimmune hemolytic anemia (AIHA). The patients with idiopathic or secondary AIHA were analyzed retrospectively, then the serological characteristics and the incidence of adverse transfusion reactions were investigated, and the efficacy and safety of incompatible RBC transfusion were evaluated according to the different autoantibody type and infused different RBC components. The results showed that out of 61 cases of AIHA, 21 cases were idiopathic, and 40 cases were secondary. 8 cases (13.1%) had IgM cold autoantibody, 50 cases (82.0%) had IgG warm autoantibody, and 3 cases (4.9%) had IgM and IgG autoantibodies simultaneously. There were 18 cases (29.5%) combined with alloantibodies. After the exclusion of alloantibodies interference, 113 incompatible RBC transfusions were performed for 36 patients with AIHA, total efficiency rate, total partial efficiency rate and total inefficiency rate were 56.6%, 15.1% and 28.3%, respectively. Incompatible RBC transfusions were divided into non-washed RBC group and washed RBC group. The efficiency rate, partial efficiency rate and inefficiency rate in non-washed RBC group were 57.6%, 13.0% and 29.4%, respectively. The efficiency rate, partial efficiency rate and inefficiency rate in washed RBC group were 53.6%, 21.4% and 25.0%, respectively. There was no significant difference of transfusion efficacy (P > 0.05) in two groups. Incompatible RBC transfusions were also divided into IgM cold autoantibody group and IgG warm autoantibody group. The efficiency rate, partial efficiency rate and inefficiency rate in IgM cold autoantibody group were 46.2%, 30.8% and 29.4%, respectively. The efficiency rate, partial efficiency rate and inefficiency rate in IgG warm autoantibody group were 56.7%, 13.4% and 29.9%, respectively. There was no significant difference of transfusion efficacy (P > 0.05 ) in two groups. Hemolytic transfusion reaction was not observed in all incompatible RBC transfusions. It is concluded that the same ABO type of non-washed RBC transfusion and O type washed RBC transfusion are all relatively safe for the AIHA patients with severe anemia after the exclusion of alloantibodies interference. There is no significant difference of transfusion efficacy in two groups. The same ABO type of non-washed RBC transfusion is more convenient and efficient than washed RBC transfusion, and excessive use of type O RBCs can also be avoided.

A major target for warm immunoglobulin G autoantibodies: the third external loop of Band 3

Rh proteins and the Wr(b) antigen, which results from an interaction between Band 3 and glycophorin A, are the most common targets for warm immunoglobulin (Ig)G autoantibodies. Apart from autoanti-Di(b) , a scarce specificity, IgG warm autoantibodies specific for Band 3 have never been characterized by serologic methods. Blood samples from 120 patients with autoimmune hemolytic anemia (AIHA) and IgG-coated red blood cells (RBCs) were studied by serologic methods. Some autoantibodies were investigated by immunochemical methods. Autoantibodies against the third external loop of Band 3 have a distinctive pattern of reactivity in that they fail to react after RBC treatment with α-chymotrypsin and pronase, whereas papain, ficin, and trypsin have no effect. Eleven (9%) patients had pure anti-Band 3 autoantibodies. Autoanti-Band 3 antibodies were associated with other specificities in 66 (55%) patients. Immunoprecipitation and rare RBCs from a Wu+ homozygote, known to have an unusual pattern of reactivity after protease treatment, were used to confirm the Band 3 specificity. Treatment with sodium hypochlorite, believed to oxidize the Met residue at Position 559 in the third loop, showed that these autoantibodies were heterogeneous. Most antibodies reacted optimally at 37 °C, but two patients had incomplete cold IgG autoantibodies. Unlike autoantibodies to Rh proteins, warm autoanti-Band 3 activate complement and are almost totally bound to autologous RBCs. We describe the first cases of warm IgG autoantibodies specific for the third loop of Band 3. This external loop also appears as a major target in patients with warm antibody AIHA.

The Treatment of Patients with Autoimmune Thrombocytopenia with Intravenous IgG‐Anti‐D

Salama et al. [1] noticed that in patients with autoimmune thrombocytopenia (AITP) treated with high-dose i.v. Ig, the red cells became weakly sensitized with IgG antibodies, present in the i.v. Ig preparation. They concluded that the effect of i.v. Ig on the platelet count is due to a competition between sensitized red cells and platelets sensitized with auto-antibodies, for Fc-receptors (FcR) on splenic macrophages. This observation was the basis of their treatment of patients with AITP with i.v. anti-D IgG. Since the first publication of Salama et al. [2] on the subject, many patients have been treated in several centres. There is controversy concerning the question whether the effect of i.v. anti-D IgG is indeed due to a competition between sensitized red cells and sensitized platelets for FcR and therefore to the RhD antibodies themselves, or to other factors, also present in the anti-D preparation. This question is interesting from a theoretical but also from a practical point of view. There is a general shortage of anti-D Ig for immunoprophylaxis in D-negative women. If not the anti-D but other factors are responsible for the effect in AITP, anti-D Ig should not be used to treat patients with this disease. These considerations led us to devote an International Forum to this subject. The questions listed below were sent to 18 experts of whom 7 have contributed to the Forum. Questions (1) Do you, or your colleagues, treat patients with AITP with i.v. anti-D Ig or have you done so in the past? (2) If so, what have the results of this treatment been? (3) If treatment with anti-D causes an increase in the platelet count (a) do you think that this effect is due to a competition between anti-D IgG sensitized red cells and auto-antibody-sensitized platelets for FcR on macrophages? If so, how do you explain the simultaneous, often severe, destruction of red cells by IgG warm auto-antibodies and of platelets by auto-antibodies in Evans’ syndrome? (b) do you think that any effect on the platelet count is not due to anti-D but, e.g, to other antibodies present in the anti-D preparation? (c) do you have experience with anti-D treatment of Rh-D-negative patients with AITP? (d) do you have experience with anti-D treatment of patients with IgA platelet autoantibodies?

Autoimmune Hemolytic Anemia With Both Cold and Warm Autoantibodies

Of 144 patients with a positive direct antiglobulin test and having autoimmune hemolytic anemia (AIHA), 12 (8.3%) satisfied diagnostic criteria for both warm antibody AIHA and cold agglutinin syndrome. All 12 patients had IgG and C3d sensitizing their erythrocytes, and samples of their serum contained IgM cold autohemagglutinins optimally reactive at 4 degrees C, but with a high thermal amplitude to 37 degrees C, and IgG warm autoantibodies. All red blood cell eluates contained IgG warm autoantibodies. The 12 patients had severe hemolytic anemia that responded dramatically to corticosteroid therapy, with the mean hemoglobin level increasing from 6.3 to 12.9 g/dL. Five patients (42%) had systemic lupus erythematosus, one patient (8%) had a non-Hodgkin's lymphoma, and six patients (50%) had idiopathic AIHA; four patients (33%) had concomitant thrombocytopenia (Evans' syndrome). Nine patients (75%) were female. Four patients had unexpected alloantibodies potentially capable of in vivo hemolysis of transfused blood. Because of the severe hemolysis, the serologic findings, and the dramatic initial clinical response to corticosteroid therapy, these patients represent a distinct catagory of AIHA and should be given corticosteroid therapy quickly.

Two distinct categories of warm autoantibody reactivity with age- fractionated red cells

Using age-fractionated erythrocytes, warm autoantibodies can be classified into two distinct categories, depending on their reactivity with reticulocyte-enriched (younger) or reticulocyte-poor (older) red cell fractions. The strength of the direct antiglobulin test (DAT) on the age-fractionated red cells of 24 patients indicated that 19 (79%) had an IgG warm autoantibody that reacted preferentially with older red blood cells. In 7 of these 19 patients (37%), the DAT was negative using reticulocyte-enriched red cell fractions. We have termed this preferential reactivity of warm autoantibodies with older red cells as type I. Five of the 24 patients studied (21%) had an IgG warm autoantibody that demonstrated no preference for young or older red cells. We have termed this pattern of warm autoantibody reactivity as type II. All 5 patients having type II warm autoantibodies had severe anemia. In contrast, 6 of 19 patients having type I warm autoantibody did not have clinical evidence of anemia when tested, and 11 of the 19 had only slight to moderate anemia. Additionally, our results using type I warm autoantibody raise questions regarding the blood group specificity of warm autoantibodies. The antigen recognized by type I warm autoantibody may be a cryptantigen. Rh specificity or relative Rh specificity, often associated with warm autoantibodies, may simply be a coincidental finding.

Two Distinct Categories of Warm Autoantibody Reactivity With Age-Fractionated Red Cells

Abstract Using age-fractionated erythrocytes, warm autoantibodies can be classified into two distinct categories, depending on their reactivity with reticulocyte-enriched (younger) or reticulocyte-poor (older) red cell fractions. The strength of the direct antiglobulin test (DAT) on the age-fractionated red cells of 24 patients indicated that 19 (79%) had an IgG warm autoantibody that reacted preferentially with older red blood cells. In 7 of these 19 patients (37%), the DAT was negative using reticulocyte-enriched red cell fractions. We have termed this preferential reactivity of warm autoantibodies with older red cells as type I. Five of the 24 patients studied (21%) had an IgG warm autoantibody that demonstrated no preference for young or older red cells. We have termed this pattern of warm autoantibody reactivity as type II. All 5 patients having type II warm autoantibodies had severe anemia. In contrast, 6 of 19 patients having type I warm autoantibody did not have clinical evidence of anemia when tested, and 11 of the 19 had only slight to moderate anemia. Additionally, our results using type I warm autoantibody raise questions regarding the blood group specificity of warm autoantibodies. The antigen recognized by type I warm autoantibody may be a cryptantigen. Rh specificity or relative Rh specificity, often associated with warm autoantibodies, may simply be a coincidental finding.