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CD59 is a blood group antigen
Abstracts / Molecular Immunology 56 (2013) 240–316
Conclusion: Our data indicate that SLE patient-derived anti-C1q are able to activate the classical pathway of complement in an in vitro assay by secondary binding of C1 molecules leading to C4b deposition.
279
P CD 21 Serum C3 levels are associated with the clinical manifestations and disease activity of microscopic polyangiitis D. Liu 1,2,3 , Y. Chen 3 , X. Min 1 , N. Wang 1 , Y. Jia 2 , K. Li 1,∗
http://dx.doi.org/10.1016/j.molimm.2013.05.113 P CD 20 CD59 is a blood group antigen M. Anliker 1,∗ , I. von Zabern 1 , B. Höchsmann 1 , C. DohnaSchwake 2 , H. Kyrieleis 3 , H. Schrezenmeier 1 , C. Weinstock 1 1
Inst. f. Klin. Transfusionsmedizin und Immungenetik Ulm, DRK BSD Baden-Württ.-Hessen, University of Ulm, Ulm, Germany 2 University Hospital of Essen, Essen, Germany 3 Hospital Bethanien, Moers, Germany Question: Homologous restriction factor (HRF), Membrane inhibitor of reactive lysis (MIRL), membrane attack complex inhibitory factor (MACIF) and CD59 are a few of the many designations for a glycoprotein of approximately 20 kDa that binds to the terminal complement complex C5b-9 and thereby limits the polymerization of C9. Although CD59 is known since a long time as part of the erythrocyte membrane, it so far has not been defined as a blood group antigen. Here, we give evidence for the presence of an anti-CD59 antibody in a patient affected by a homozygous CD59 deficiency. Methods: Erythrocyte membrane CD59 and CD55 were determined by flow cytometry using FITC labelled anti-human-CD59 and PE labelled anti-human-CD55 (Becton Dickinson Pharmingen). His tagged and non-glycosylated recombinant soluble CD59 protein was obtained in lyophilized form (Creative Bio Mart). Results: Six cases of an isolated deficiency of CD59 with two molecular bases have been published so far. An additional case of an isolated homozygous CD59 defect in a child of Turkish origin caused by the deletion c.146delA has been reported. The erythrocytes of the affected child lacked CD59. The plasma contained an antibody against a high frequency erythrocyte antigen, likely acquired by transfusions. To identify the specificity of the antibody, soluble recombinant CD59 was added to the plasma of the CD59 deficient patient. As controls, monoclonal anti-CD59 and monoclonal anti-CD55 were used instead of plasma. Flow cytometric analysis demonstrated inhibition of the patient antibody and of commercial monoclonal anti-CD59 by the recombinant soluble CD59 protein while the reactivity of anti-CD55 remained unaffected. The CD59 deficiency was inherited from the parents who both were heterozygous for the same allele. Conclusions: We give evidence that a CD59 deficient patient had formed an anti-CD59 antibody, easily detectable by blocking the antibody reactivity by recombinant soluble CD59. The erythrocyte membrane glycoprotein CD59 is well characterized on a molecular level, but this is the first demonstration of a human antibody directed against it. Therefore, CD59 is a blood group antigen and represents a candidate for the definition of a new blood group system. http://dx.doi.org/10.1016/j.molimm.2013.05.114
1
The Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Core Research Laboratory, Xi’an, China 2 Peking University People’s Hospital, Department of Rheumatology and Immunology, Beijing, China 3 The Fifth Hospital of Xi’an, Department of Rheumatology, Xi’an, China
Introduction: Microscopic polyangiitis (MPA) is the most commonanti-neutrophil cytoplasmic antibodies (ANCA) associated small-vessel vasculitis with specificity of the ANCA to myeloperoxidase (MPO) of neutrophils. MPA mainly affects kidneys and lungs. The kidneys are the most commonly affected organ; and kidney vasculitis can result in renal failure. The interplay of ANCA, neutrophil and complement activation has been implicated in the pathogenesis of MPA. The objective: To establish the relationship of complement activation and the disease activity of MPA and to identify potential biomarkers for this disease. Patients and methods: Blood samples were collected from 45 MPO-ANCA positive patients who had clinical diagnosis of MPA in People’s Hospital, Peking University, after informed consent. The samples, according to serum C3 levels, were divided into two groups: normal C3 group: ≥0.8 g/L (n = 18) and low C3 group: C3 < 0.8 g/L (n = 27). Inflammatory markers (i.e. ESR, CRP), renal functional markers (i.e. BUN, creatinine, 24-h urinary protein level), and lung diseases were evaluated in the two groups. Birmingham Vasculitis Activity Score-version 3 (BVAS[V3]) was calculated. Data was analyzed using t test, chi-square test, linear correlation analysis and binary logistic regression, respectively. Results: (1) Compared with normal C3 group, low C3 group had significantly lowered C4 (0.17 ± 0.08 g/L vs 0.25 ± 0.08 g/L) but significantly increased CRP (101 ± 57 mg/L vs 33 ± 33 mg/L), 24-h urinary protein (1.4 ± 1.3 g/d vs 0.6 ± 0.5 g/d), BUN (17.08 ± 9.02 mmol/L vs 8.62 ± 5.28 mmol/L) and BVAS(V3) (21.4 ± 3.6 vs 15.4 ± 3.8). (2) BVAS (V3) has a significant linear correlation with serum complement C3 level (R2 = 0.43, P < 0.01). (3) Morbidity of severe lung injury (i.e. interstitial lung disease, pneumorrhagia) in low C3 group was higher than that in normal C3 group (92.6% vs 33.3%, X2 = 17.69, P < 0.01). (4) C3, CRP and ESR levels were closely related to the occurrence of severe lung injury, and the logistic regression equation was: P(y) = 1/(1 + e−2.1+7.54×C3−0.054×CRP−0.027×ESR ), in which the overall correct percentage was 93.3%. Conclusion: Serum complement C3 levels were associated with the disease activity and clinical manifestations of MPA. Therefore, serum C3 level may represent as a biomarker for disease activity and an indicator for organ injury of MPA. http://dx.doi.org/10.1016/j.molimm.2013.05.115
Conclusion: Our data indicate that SLE patient-derived anti-C1q are able to activate the classical pathway of complement in an in vitro assay by secondary binding of C1 molecules leading to C4b deposition.
279
P CD 21 Serum C3 levels are associated with the clinical manifestations and disease activity of microscopic polyangiitis D. Liu 1,2,3 , Y. Chen 3 , X. Min 1 , N. Wang 1 , Y. Jia 2 , K. Li 1,∗
http://dx.doi.org/10.1016/j.molimm.2013.05.113 P CD 20 CD59 is a blood group antigen M. Anliker 1,∗ , I. von Zabern 1 , B. Höchsmann 1 , C. DohnaSchwake 2 , H. Kyrieleis 3 , H. Schrezenmeier 1 , C. Weinstock 1 1
Inst. f. Klin. Transfusionsmedizin und Immungenetik Ulm, DRK BSD Baden-Württ.-Hessen, University of Ulm, Ulm, Germany 2 University Hospital of Essen, Essen, Germany 3 Hospital Bethanien, Moers, Germany Question: Homologous restriction factor (HRF), Membrane inhibitor of reactive lysis (MIRL), membrane attack complex inhibitory factor (MACIF) and CD59 are a few of the many designations for a glycoprotein of approximately 20 kDa that binds to the terminal complement complex C5b-9 and thereby limits the polymerization of C9. Although CD59 is known since a long time as part of the erythrocyte membrane, it so far has not been defined as a blood group antigen. Here, we give evidence for the presence of an anti-CD59 antibody in a patient affected by a homozygous CD59 deficiency. Methods: Erythrocyte membrane CD59 and CD55 were determined by flow cytometry using FITC labelled anti-human-CD59 and PE labelled anti-human-CD55 (Becton Dickinson Pharmingen). His tagged and non-glycosylated recombinant soluble CD59 protein was obtained in lyophilized form (Creative Bio Mart). Results: Six cases of an isolated deficiency of CD59 with two molecular bases have been published so far. An additional case of an isolated homozygous CD59 defect in a child of Turkish origin caused by the deletion c.146delA has been reported. The erythrocytes of the affected child lacked CD59. The plasma contained an antibody against a high frequency erythrocyte antigen, likely acquired by transfusions. To identify the specificity of the antibody, soluble recombinant CD59 was added to the plasma of the CD59 deficient patient. As controls, monoclonal anti-CD59 and monoclonal anti-CD55 were used instead of plasma. Flow cytometric analysis demonstrated inhibition of the patient antibody and of commercial monoclonal anti-CD59 by the recombinant soluble CD59 protein while the reactivity of anti-CD55 remained unaffected. The CD59 deficiency was inherited from the parents who both were heterozygous for the same allele. Conclusions: We give evidence that a CD59 deficient patient had formed an anti-CD59 antibody, easily detectable by blocking the antibody reactivity by recombinant soluble CD59. The erythrocyte membrane glycoprotein CD59 is well characterized on a molecular level, but this is the first demonstration of a human antibody directed against it. Therefore, CD59 is a blood group antigen and represents a candidate for the definition of a new blood group system. http://dx.doi.org/10.1016/j.molimm.2013.05.114
1
The Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Core Research Laboratory, Xi’an, China 2 Peking University People’s Hospital, Department of Rheumatology and Immunology, Beijing, China 3 The Fifth Hospital of Xi’an, Department of Rheumatology, Xi’an, China
Introduction: Microscopic polyangiitis (MPA) is the most commonanti-neutrophil cytoplasmic antibodies (ANCA) associated small-vessel vasculitis with specificity of the ANCA to myeloperoxidase (MPO) of neutrophils. MPA mainly affects kidneys and lungs. The kidneys are the most commonly affected organ; and kidney vasculitis can result in renal failure. The interplay of ANCA, neutrophil and complement activation has been implicated in the pathogenesis of MPA. The objective: To establish the relationship of complement activation and the disease activity of MPA and to identify potential biomarkers for this disease. Patients and methods: Blood samples were collected from 45 MPO-ANCA positive patients who had clinical diagnosis of MPA in People’s Hospital, Peking University, after informed consent. The samples, according to serum C3 levels, were divided into two groups: normal C3 group: ≥0.8 g/L (n = 18) and low C3 group: C3 < 0.8 g/L (n = 27). Inflammatory markers (i.e. ESR, CRP), renal functional markers (i.e. BUN, creatinine, 24-h urinary protein level), and lung diseases were evaluated in the two groups. Birmingham Vasculitis Activity Score-version 3 (BVAS[V3]) was calculated. Data was analyzed using t test, chi-square test, linear correlation analysis and binary logistic regression, respectively. Results: (1) Compared with normal C3 group, low C3 group had significantly lowered C4 (0.17 ± 0.08 g/L vs 0.25 ± 0.08 g/L) but significantly increased CRP (101 ± 57 mg/L vs 33 ± 33 mg/L), 24-h urinary protein (1.4 ± 1.3 g/d vs 0.6 ± 0.5 g/d), BUN (17.08 ± 9.02 mmol/L vs 8.62 ± 5.28 mmol/L) and BVAS(V3) (21.4 ± 3.6 vs 15.4 ± 3.8). (2) BVAS (V3) has a significant linear correlation with serum complement C3 level (R2 = 0.43, P < 0.01). (3) Morbidity of severe lung injury (i.e. interstitial lung disease, pneumorrhagia) in low C3 group was higher than that in normal C3 group (92.6% vs 33.3%, X2 = 17.69, P < 0.01). (4) C3, CRP and ESR levels were closely related to the occurrence of severe lung injury, and the logistic regression equation was: P(y) = 1/(1 + e−2.1+7.54×C3−0.054×CRP−0.027×ESR ), in which the overall correct percentage was 93.3%. Conclusion: Serum complement C3 levels were associated with the disease activity and clinical manifestations of MPA. Therefore, serum C3 level may represent as a biomarker for disease activity and an indicator for organ injury of MPA. http://dx.doi.org/10.1016/j.molimm.2013.05.115