Complement activating ABO IgM/IgG act synergistically to cause erythrophagocytosis: implications among minor ABO incompatible platelet transfusions

2020 ◽  
Author(s):  
Priyanka Pandey ◽  
Waseem Q. Anani ◽  
Tina Pugh ◽  
Jerome L. Gottschall ◽  
Gregory A Denomme
Keyword(s):  
Complement Activation ◽  
Complement C3 ◽  
Transfusion Reaction ◽  
Single Donor ◽  
Healthy Donors ◽  
Hemolytic Transfusion Reaction ◽  
Group A ◽  
Donor Sample ◽  
Donor Plasma

Abstract Background Typically minor ABO incompatible platelet products are transfused without any incident, yet serious hemolytic transfusion reactions occur. To mitigate these events, ABO ‘low titer’ products are used for minor ABO incompatible transfusions. We sought to understand the role of IgG and complement activation by anti-A on extravascular hemolysis. Samples evaluated: i) Group O plasma from a blood donor whose apheresis platelet product resulted in an extravascular transfusion reaction, ii) Group O plasma from 12 healthy donors with matching titers that activated complement (N = 6) or not (N = 6), and iii) Group O sera from 10 patients with anti-A hemolysin activity. Monocytes from healthy donors were co-incubated with anti-A-sensitized fluorescently-labeled Group A1+ RBCs with and without fresh Group A serum, as a source of complement C3, and phagocytosis was analyzed by flow cytometry. The plasma and sera had variable direct agglutinating (IgM) and indirect (IgG) titers. Results None of 12 selected samples showed monocyte-dependent erythrophagocytosis with or without complement activation. The donor sample causing a hemolytic transfusion reaction and 2 of the 10 patient sera with hemolysin activity showed significant erythrophagocytosis (>10%) only when complement C3 was activated. The single donor plasma and two sera demonstrating significant erythrophagocytosis had high IgM (≥128) and IgG titers (>1024). The donor plasma anti-A was IgG1, while the patient sera were an IgG3 and an IgG1 plus IgG2. Conclusion High anti-A IgM/IgG titers act synergistically to cause significant monocyte erythrophagocytosis by activating complement C3, thus engaging both Fcγ- and CR1-receptors.

Immune complex binding Streptococcus pyogenes type M12/emm12 in experimental glomerulonephritis

2013 ◽  
Vol 62 (9) ◽  
pp. 1272-1280 ◽  
Author(s):  
Larissa Burova ◽  
Peter Pigarevsky ◽  
Nadezhda Duplik ◽  
Vlada Snegova ◽  
Alexander Suvorov ◽  
...  
Keyword(s):  
Rabbit Model ◽  
Complement C3 ◽  
Poststreptococcal Glomerulonephritis ◽  
Tnf Α ◽  
Rabbit Igg ◽  
Renal Changes ◽  
Group A ◽  
Study Type ◽  
Binding Component

In a rabbit model, we have previously reported evidence for a pathogenic role of streptococcal IgG Fc-binding proteins (IgGFcBP) in poststreptococcal glomerulonephritis (PSGN). These proteins, of the M protein family, were shown to trigger anti-IgG production and enhance renal deposition of IgG and/or immune complexes (ICs), with resulting activation of complement and cytokine cascades. In the present study, type M12/emm12, group A streptococci (GAS) were found often to bind artificial ICs, viz. peroxidase–anti-peroxidase rabbit IgG (PAP) or tetanus toxoid–anti-tetanus human IgG (TAT), rather than monomeric IgG. Animals injected with each of four IC binding clinical isolates (from patients with scarlet fever or PSGN) showed pronounced inflammatory and degenerative glomerular changes, morphologically similar to human PSGN, with membrane thickening and IgG and complement C3 deposition, as well as secretion of IL-6 and TNF-α by mesangial and endothelial cells. In contrast, non-binding strains (two from asymptomatic carriers and one from a PSGN case) failed to trigger any renal changes. Only the IC binding strains induced elevated titres of anti-IgG. Though the streptococcal binding component(s) has not been demonstrated, the selective binding of ICs by type M12/emm12 strains appears important for the well-known, marked nephritogenic potential of this GAS type.

Acute Hemolytic Transfusion Reaction Due to Pooled Platelets: A Rare but Serious Adverse Event

2020 ◽  
Author(s):  
Richard Gammon ◽  
Susan Cook ◽  
Anthony Trinkle ◽  
Korena Thomas ◽  
Kaaron Benson
Keyword(s):  
High Titer ◽  
Donor Number ◽  
Transfusion Reaction ◽  
Normal Range ◽  
Dark Urine ◽  
Hemolytic Transfusion Reaction ◽  
Group A ◽  
Relapsed Lymphoma ◽  
Blood And Urine Samples ◽  
Apheresis Platelets

Abstract A female patient aged 65 years with blood group A with relapsed lymphoma had thrombocytopenia; leukocyte-reduced group O prestorage pooled platelet concentrates (PPLTs) were transfused without adverse events. She was discharged home, but 1.5 hours later she returned with fever and dark urine. Hypotension and tachycardia developed; she was admitted to the intensive care unit. Post-transfusion blood and urine samples were obtained. Serial dilutions from 5 donor testing tubes and a simulated PLT pool were performed and read at immediate spin and IgG. Testing confirmed an acute hemolytic transfusion reaction (AHTR): elevated lactate dehydrogenase (996 U/L; normal range 135 U/L–225 U/L) and undetectable haptoglobin (<10 mg/dL; normal range 30 mg/dL–200 mg/dL) levels. Urinalysis showed dark amber urine but no significant quantity of red blood cells. At 37ºC the simulated pool and donor number 5 had high-titer anti-A. As a precaution, the donor was permanently deferred. Research has shown that PLT-associated AHTR has occurred with apheresis platelets but is very rare with whole blood–derived PLTs.

Role of complement in the pathogenesis of postpartum thyroiditis: relationship between complement activation and disease presentation and progression

1995 ◽  
Vol 133 (2) ◽  
pp. 210-215 ◽  
Author(s):  
Arthur B Parkes ◽  
Sakinah Othman ◽  
Reginald Hall ◽  
Rhys John ◽  
John H Lazarus
Keyword(s):  
Complement Activation ◽  
Thyroid Dysfunction ◽  
Clinical Syndrome ◽  
Complement C3 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Thyroid Peroxidase ◽  
Free Triiodothyronine ◽  
Postpartum Thyroiditis

Parkes AB, Othman S, Hall R, John R, Lazarus JH, Role of complement in the pathogenesis of postpartum thyroiditis: relationship between complement activation and disease presentation and progression. Eur J Endocrinol 1995;133:210–5. ISSN 0804–4643 The aim of this study was to assess whether the presentation and progression of autoimmune postpartum thyroiditis (PPT) was related to the degree of thyroid peroxidase autoantibody (TPO-ab)-mediated activation of the complement cascade. One hundred and forty-eight thyroid autoantibodypositive women have been followed during their postpartum year. Seventy-five women remained euthyroid during this time whilst the remaining 73 showed one or more episodes of thyroid dysfunction. Fourteen women showed hyperthyroid PPT, 23 showed a biphasic PPT and the remaining 36 showed hypothyroid PPT. Hyperthyroid PPT was always transient but 29 of the 59 women with hypothyroidism remained hypothyroid or still required thyroxine replacement therapy at the conclusion of the study. Thyroid autoantibodies were measured by enzyme-linked immunosorbent assay (ELISA), free triiodothyronine and free thyroxine by the Amerlex M methods and thyrotrophin by the Amerlite TSH (monoclonal) assay. Complement component C3b, immobilized as a result of classical complement pathway activation in the presence of TPO/TPO-ab complexes in vitro, was measured by ELISA. Bioactive TPO-ab were calculated as the product of the C3 index and TPO-ab level. Basal levels of complement C3 activation were seen in the euthyroid TPO-ab-positive women (C3 index 0.06 at delivery rising to 0.36 at 12 months postpartum; bioactive TPO-ab activity 0.4kIU/l at delivery rising to 10.4kIU/l at 12 months' postpartum (N = 75). These parameters were elevated progressively as the severity of the clinical syndrome increased. In 14 hyperthyroid PPT women the C3 index was 0.47 at 8 months' postpartum (bioactive TPO-ab activity=20kIU/l; p vs euthyroid group, NS). In 23 biphasic PPT women the C3 index had risen to 0.65 by 7 months' postpartum (p < 0.005 vs euthyroid group), with bioactive TPO-ab activity 81kIU/l (p < 0.005), and in 36 women with hypothyroid PPT the C3 index was 0.7 by 6 months' postpartum (p < 0.005), with bioactive TPO-ab activity 76kIU/l (p < 0.005). In women with persistent PPT the C3 index had risen to 0.76 by 5 months' postpartum, with bioactive TPO-ab activity 116kIU/l; both parameters were statistically higher in the persistent group than in the remaining 44 cases where the C3 index was 0.56, with bioactive TPO-ab activity 33 kIU/l (p < 0.005 vs euthyroid; p < 0.05 vs transient). This study of the role of complement in the pathogenesis of PPT shows that the severity and duration of the thyroid dysfunction correlates with the degree of complement activation by TPO-ab measured in vitro. AB Parkes, Autoimmunology Research Unit, Section of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, UK

scholarly journals Modulation of complement activation by pentraxin-3 in prostate cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Giovanni Stallone ◽  
Giuseppe Stefano Netti ◽  
Luigi Cormio ◽  
Giuseppe Castellano ◽  
Barbara Infante ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Complement Activation ◽  
Cellular Proliferation ◽  
Cancer Tissue ◽  
Complement Cascade ◽  
Pentraxin 3 ◽  
Group A ◽  
Group B ◽  
Terminal Complement

Abstract Pentraxin 3 (PTX3) is an essential component of the innate immune system and a recognized modulator of Complement cascade. The role of Complement system in the pathogenesis of prostate cancer has been largely underestimated. The aim of our study was to investigate the role of PTX3 as possible modulator of Complement activation in the development of this neoplasia. We performed a single center cohort study; from January 2017 through December 2018, serum and prostate tissue samples were obtained from 620 patients undergoing prostate biopsy. A group of patients with benign prostatic hyperplasia (BPH) underwent a second biopsy within 12–36 months demonstrating the presence of a prostate cancer (Group A, n = 40) or confirming the diagnosis of BPH (Group B, N = 40). We measured tissue PTX3 protein expression together with complement activation by confocal microscopy in the first and second biopsy in group A and B patients. We confirmed that that PTX3 tissue expression in the first biopsy was increased in group A compared to group B patients. C1q deposits were extensively present in group A patients co-localizing and significantly correlating with PTX3 deposits; on the contrary, C1q/PTX3 deposits were negative in group B. Moreover, we found a significantly increased expression of C3a and C5a receptors within resident cells in group A patient. Interestingly, C1q/PTX3 deposits were not associated with activation of the terminal Complement complex C5b-9; moreover, we found a significant increase of Complement inhibitor CD59 in cancer tissue. Our data indicate that PTX3 might play a significant pathogenic role in the development of this neoplasia through recruitment of the early components of Complement cascade with hampered activation of terminal Complement pathway associated with the upregulation of CD59. This alteration might lead to the PTX3-mediated promotion of cellular proliferation, angiogenesis and insensitivity to apoptosis possible leading to cancer cell invasion and migration.

scholarly journals Nonspecific complement activation by streptococcal structures. II. Properdin-independent initiation of the alternate pathway.

1976 ◽  
Vol 143 (6) ◽  
pp. 1352-1366 ◽  
Author(s):  
J W Tauber ◽  
M J Polley ◽  
J B Zabriskie
Keyword(s):  
Complement Activation ◽  
Group A Streptococci ◽  
Complement Pathway ◽  
Defense System ◽  
Plant Polysaccharides ◽  
Microbial Structures ◽  
Alternate Pathway ◽  
Alternate Complement Pathway ◽  
Group A

Complement consumption by isolated membranes and walls from Group A streptococci and various other gram-positive microbes has been tested. These microbial structures were found to activate the alternate complement pathway. However, unlike endotoxin, inulin, or other plant polysaccharides, activation of complement by our material was found to bypass properdin. The activating factor(s) also differs from cobra venom in its/their requirement for factor D. Preliminary experiments suggest this factor isolated from membranes to be a protein and to have a mol wt greater than 40-60,000 daltons. Our studies have led us to speculate that the phylogenetic role of the alternate complement pathway may be the primordial nonspecific defense system which has retained certain fundamental aspects up to the present time.

scholarly journals Acute Hemolytic Transfusion Reaction in Group B Recipient Associated with Group A Apheresis Platelet Donor: Case Report and Literature Review

2018 ◽  
Vol 2018 ◽  
pp. 1-4 ◽  
Author(s):  
Tracy R. Shachner ◽  
Christopher T. Clark
Keyword(s):  
Case Report ◽  
High Titer ◽  
Transfusion Reaction ◽  
Potential Adverse Event ◽  
Hemolytic Transfusion Reaction ◽  
Group A ◽  
Unknown Status ◽  
Group B ◽  
Apheresis Platelets ◽  
Transfusion Reactions

Acute hemolytic transfusion reaction is a known but rare potential adverse event related to platelet transfusion. Most reported cases of platelet-related hemolytic transfusion reaction have resulted from transfusion of platelets from group O donor to group A recipient. We identified only one prior case report in the literature of hemolytic transfusion reactions resulting from transfusion of apheresis platelets from group A donor to group B recipient. In that case report, two platelet units were obtained from a single donation and transfused into two separate patients. Both patients exhibited acute hemolytic reactions. The donor is reported to have high anti-B titers, as well as report of probiotic use. We report a case of acute hemolytic reaction in group B recipient following transfusion of apheresis platelets from group A donor with high-titer anti-B but unknown status of probiotic use. This case demonstrates that while low, there still exists potential risk for hemolysis from out-of-group A plasma transfusion.

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