Autoimmune hemolytic anemia associated with IgA autoantibody

Suzuki, Shinya; Amano, Tetsuki; Mitsunaga, Mikio; Yagyu, Fumito; Ofuji, Tadashi

doi:10.1016/0090-1229(81)90213-0

Cited by 18 publications

(12 citation statements)

References 18 publications

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“…The depositions of IgA in the mesangium in IgA nephropathy [l] and in the vessels of the skin in Henoch-Schonlein purpura [Z] are frequently accompanied by C3. In dermatitis herpetiformis [3] and autoimmune hemolytic anemia [4] IgA and C3 deposits also have been observed in the vessels of the skin and on the patients red blood cells, respectively. These findings suggest that IgA-containing immune complexes are able to activate the complement (C) system.…”

Section: Introductionmentioning

confidence: 99%

Activation of the alternative pathway of complement by human serum IgA

et al. 1987

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In order to study the activation of complement by soluble aggregates of human polyclonal serum IgA, lysis of sheep erythrocytes (E) coated with several IgA preparations was used as a model. A complement nonactivating monoclonal mouse IgG1 against IgA was used to coat the cells. IgA, isolated from normal human serum, was aggregated by either N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP), glutaraldehyde, carbodiimide or heating. Depending on the size of the aggregates, and on the method of aggregation, E coated with aggregated IgA (E gamma 1.AIgA) could be lysed. The alternative pathway of complement appeared to mediate the lysis because the latter was observed in the presence of EGTA containing 5 mM Mg2+ (MgEGTA) and properdin (P) was deposited on the cells. Furthermore, no lysis was observed in C3-deficient serum. In the absence of AIgA the cells were not lysed, and no P deposition was observed. In another set of experiments E gamma 1.AIgA were first reacted with purified C3, B, D and P for 30 min at 30 degrees C, and subsequently in rat serum EDTA at 37 degrees C. Lysis occurred when E gamma 1.AIgA were prepared using SPDP-, glutaraldehyde- or carbodiimide-AIgA. Incubation of 100 micrograms/ml SPDP-AIgA with normal human serum for 30 min at 37 degrees C in the presence or absence of MgEGTA also induced consumption of total complement. The other soluble AIgA preparations were less effective in activating complement. These results suggest that polymeric serum IgA is capable of activating the alternative pathway of complement.

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Section: Introductionmentioning

confidence: 99%

Activation of the alternative pathway of complement by human serum IgA

et al. 1987

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“…The presence of receptors for IgA (Fca-receptors, FcaR) on the cell membrane of about all blood cell populations [4,9] suggest a variety of different functions for serum IgA. FcaR may play a role in antibody-dependent cellmediated cytotoxicity [10][11][12], in the regula tion of IgA synthesis [4], in the clearance of IgA IC from the circulation [13] and opsoni zation of antigens. Furthermore, IgA may induce inflammation through activation of Fig.…”

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confidence: 99%

Immunoglobulin A: Interaction with Complement, Phagocytic Cells and Endothelial Cells

Stad

et al. 1991

Complement Inflamm

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Deposits of IgA together with complement (C) in different organs support the hypothesis that IgA can trigger inflammatory mechanisms. Some inflammatory mechanisms may be caused by activation of C and phagocytic cells. Therefore, it is essential to understand the interaction of IgA with C and phagocytic cells. Studies will be described demonstrating that polymeric human serum IgA is able to activate the alternative pathway of C and that the activating principle is located in the intact F(ab')2 portion of the molecule. Activation of C is dependent on the molecular composition of IgA, as derived from results obtained with rat monoclonal IgA antibodies. Furthermore, it is demonstrated that polymeric IgA (pIgA) and dimeric IgA (dIgA) are potent activators of C in a homologous rat model, whereas monomeric IgA (mIgA) has a very poor C-activating potential. The interaction of IgA with phagocytic cells induces phagocytosis and release of H2O2 by granulocytes, which may contribute to tissue damage. Tittle is known about the clearance mechanism of IgA. It is shown in this report that Kupffer cells and C play an important role in the clearance of IgA immune complexes (IC). Clearance of large-sized IgA IC occurs via different receptors present on Kupffer cells. Finally, a new aspect will be described: the interaction of IgA with endothelial cells. Rat liver endothelial cells are able to eliminate IgA IC from the circulation via specific receptors when no Kupffer cells are present. These observations may contribute to our knowledge on diseases such as IgA nephropathy and Henoch-Schönlein purpura. The studies summarized and presented here illustrate the inflammatory potential of IgA.

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“…According to Worlledge [27], many pa tients with only complement on the red cells show no hemolysis. A report by Suzuki et al [10], however, suggests the activation of complement by IgA autoan tibodies leading to a C3 coating of red cells, which en hances their trapping by macrophages. In a case of AIHA with pure IgA-red cell coating, Clark et al [11] demonstrated splenic sequestration and also a com plement-independent in vitro interaction of IgA-sen sitized red cells with mononuclear leukocytes.…”

Section: Discussionmentioning

confidence: 95%

“…A second patient [11] underwent splenectomy incidental to a cholecys tectomy after Vh years of therapy with steroids and azathioprine; the drug treatment could then be stopped and the direct antiglobulin test turned nega tive. In AIHA due to IgA and complement, splenec tomy was performed in 1 patient with a good result [28]; another patient had continuous steroid treatment and was still in remission after 4 months [10], Our pa tient responded well to high-dose prednisone within 5 weeks. However, the attempt to taper this drug failed and long-term steroid application remained neces sary.…”

Section: Discussionmentioning

confidence: 98%

“…The most common warm type antibodies involved are of the IgG class [3,4], IgA together with other immuno globulins is found in up to 19.3% on the surface of the erythrocytes, while IgA alone or in combination with complement is detected in less than 2% of all patients [5,6]. The identification of the autoantibodies causing the AIHA may give valuable information about the clinical course and the prognosis [7][8][9] and helps to clarify their pathogenetic role [10,11], In case of an AIHA associated with IgA alone the direct antiglobu lin test with a broad-spectrum antiserum routinely used for screening may turn out falsely negative, be cause the anti-IgA activity of such a serum is usually too weak or lacking completely [12,13].…”

Section: Introductionmentioning

confidence: 99%

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Autoimmune Hemolytic Anemia Associated with IgA – Diagnostic and Therapeutic Aspects in a Case with Long-Term Follow-Up

et al. 1987

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A 51-year-old woman presented with superficial thrombophlebitis and severe hemolytic anemia. The initial direct antiglobulin test using a broad-spectrum antiserum for screening was negative. Later testing with monospecific antisera revealed the rare finding of an autoimmune hemolytic anemia (AIHA) associated with IgA autoantibody. In IgA-AIHA the direct antiglobulin test with a broad-spectrum antiserum may be falsely negative, because a standardized anti-IgA level is not compulsory. This case illustrates the diagnostic significance of monospecific antisera in IgA-AIHA. Our patient responded well to high-dose steroids, but due to repeated exacerbations this treatment could not be tapered. Splenectomy was performed 19 months later. Since then the AIHA remained in remission, even after steroids were stopped, and although the direct antiglobulin test continued to be positive for IgA and became positive again for C3d. Available data about pathogenesis and therapy of IgA-AIHA are reviewed.

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Autoimmune hemolytic anemia associated with IgA autoantibody

Cited by 18 publications

References 18 publications

Activation of the alternative pathway of complement by human serum IgA

Activation of the alternative pathway of complement by human serum IgA

Immunoglobulin A: Interaction with Complement, Phagocytic Cells and Endothelial Cells

Autoimmune Hemolytic Anemia Associated with IgA – Diagnostic and Therapeutic Aspects in a Case with Long-Term Follow-Up

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