Acidified Chloroquine Treatment for the Removal of Class I HLA Antigens

Srivastava, Alok; Pearson, Helen; Bryant, Jennifer; Favaloro, Emmanuel J.; Coulits, Nelly; Jindra, Jan; Wylie, Brenton

doi:10.1159/000462404

Cited by 9 publications

(9 citation statements)

References 13 publications

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“…3). The concentration and pH of chloroquine solution (0·2 m , pH 4·0) were selected in accordance with the previous study [25] and were also confirmed using MAIPA evaluation of treated and untreated platelets which were incubated with control sera (apdia, 900003). In the present study, chloroquine treatment along with appropriate stripping causes minimal damage to platelets, and as outlined in the results section, the PR‐screening performance of SB and FC assays was satisfactory after treatment.…”

Section: Discussionmentioning

confidence: 99%

Slot blotting and flow cytometry: two efficient assays for platelet antibody screening among patients with platelet refractoriness

et al. 2020

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Background and Objectives Frequent platelet transfusion may lead to the formation of alloantibodies and immune‐mediated platelet destruction. Currently, identifying economic and effective screening methods is necessary for the management of platelet transfusion while different tests were recommended. The present study aims to challenge the performance of slot blotting (SB) and flow cytometry (FC) assays in detecting immune platelet refractoriness. Materials and Methods Sera from 118 patients who received blood components and were clinically suspected of platelet refractoriness were enrolled. Platelet‐reactive antibodies were explored in parallel by SB, FC and monoclonal antibody‐specific immobilization of platelet antigens (MAIPA) techniques. In a further study, chloroquine‐treated platelets were incubated with MAIPA‐positive serum, and then, the results of the SB and FC techniques were compared. Results Using MAIPA as a reference, antibodies were detected in 51 sera, with specificity for human leucocyte antigens (HLA), human platelet antigens (HPA) or both HLA/HPA, in 27, 18 and 6 patients, respectively. The sensitivity and specificity of SB and FC were 86·3%, 88·1%, 82·4% and 95·5%, respectively. The Spearman correlation revealed significant (P < 0·001) correlations between FC (r = 0·763) and SB (r = 0·738) with MAIPA. In respect to HPA antibody detection, SB had 83·3% sensitivity and 92·6% specificity compared to 91·7% and 96·3% for FC while both approaches are acceptable (P < 0·001, r = 0·69; P < 0·001, r = 0·773) and can be recommended. Conclusions The present study acknowledges that among the used methods, the flow cytometry's performance is the most appropriate, but slot blotting, with acceptable sensitivity, can be used as an acceptable and convenient procedure for platelet antibody screening.

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Section: Discussionmentioning

confidence: 99%

Slot blotting and flow cytometry: two efficient assays for platelet antibody screening among patients with platelet refractoriness

et al. 2020

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“…Aggregation responses were still preserved after acidified CQ treatment [196]. After treatment of platelets with citric acid at pH 3 and CQ, the expression of HLA class I was significantly reduced, while the density of the molecules GPIa/IIa, GPIIb, and GPIIb/IIIa (GP = glycoprotein) carrying thrombocyte-specific antigens was not or only weakly decreased on the surface of the platelets [197].…”

Section: Cq and Removal Of Platelet Membrane Antigensmentioning

confidence: 94%

Antiplatelet and Antileukocyte Effects of Cardiovascular,Immunomodulatory and Chemotherapeutic Drugs

Nosáľ¹

2006

CHAMC

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In vitro and ex vivo interactions of betaadrenoceptor blocking drugs, antihistamines and chloroquine with blood platelets and polymorphonuclear leukocytes resulted in different alterations of regulatory functions of these blood cells. Inhibition of platelet aggregation, arachidonate regulatory pathway, 5-hydroxytryptamine transportation, removal of platelet membrane receptors, inhibition of second messenger pathways at subcellular level and suppression of phagocytosis are indicative of nonreceptor rather than specific receptor interactions. Binding of drugs with biomembranes is reversible depending on the ionic charge of the molecule and hydrophobicity of the bilayer, partition coefficient, pH and pKa of the amphiphilic molecules and other physico-chemical properties of amphiphilic drugs. Alterations in the drug molecule structure alters the drug-phospholipid binding profile. Any change in the metabolism of membrane phospholipids directly or indirectly influences one or more of the important components of the phospholipid-signalling pathway. In addition to changes in phospholipase A, C and D activities, protein kinase C, calmodulin-phosphodiesterase, Ca2+,Mg2+-ATPase, Na+,K+-ATPase and other messengers were found to be changed in cells and tissue after cationic amphiphilic drug (CAD) administration. Although not much has been understood of the mechanism by which some CAD affect immune functions, there are good reasons to suggest that these effects might occur. CADs share sufficient similarities in their structure even though they come from diverse pharmacological classes. CADs affect ion transport, immune functions, tumour growth, serotonin metabolism and several other functions in the body. Extensive therapeutic use and associated side effects have generated a great deal of interest in understanding the nonreceptor interactions with CADs.

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“…If the patient's HLA/platelet antibody screen was positive, platelet crossmatches were performed (Immucor) against platelet units in inventory, and platelets were harvested from a crossmatch-compatible platelet unit for use in testing. If a crossmatch compatible plateletpheresis unit was not available, and the HLA screen done following treatment of the Ready-Screen plate with chloroquine diphosphate (CDP) (Gamma Biologics, Houston, Texas) was negative, the Capture-P platelet crossmatch strips were treated with CDP prior to use in testing for drug-dependent platelet antibodies (Srivastava et al, 1993). Testing for DDPAs could not be performed on samples for which no compatible platelet units were available, but this did not occur in this set of patients.…”

Section: Methodsmentioning

confidence: 99%

Detection of drug‐dependent, platelet‐reactive antibodies by solid‐phase red cell adherence assays

1997

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Summary.We developed a simple modification of the solidphase red cell adherence (SPRCA) assay system that can be used to identify drug-dependent platelet antibodies (DDPAs) reactive by either the hapten or immune complex reaction mechanisms. Between January 1994 and August 1996 we tested sera from 173 patients [123 (71%) with unexplained thrombocytopenia and 50 (29%) because of poor responses to platelet transfusions not explicable by alloimmunization or the clinical situation] for DDPAs possibly associated with the receipt of 61 different drugs. We correlated positive results with patients' clinical courses. DDPAs were identified in samples from 138 (80%) of the patients tested. Antibodies reactive only by the hapten mechanism were identified in 51 (37%) of those sera exhibiting positive reactions. The clinical courses of 108 (78%) patients were evaluable. Discontinuation of the implicated drug(s) resulted in prompt (<5 d) resolution of the thrombocytopenia or improvement in response to transfusion in all of these patients. In four cases thrombocytopenia returned upon re-exposure to the implicated drug. This adaptation of SPRCA provides a simple means of investigating the possibility of DDPAs and documents a higher frequency of these antibodies than has previously been suspected.

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Acidified Chloroquine Treatment for the Removal of Class I HLA Antigens

Cited by 9 publications

References 13 publications

Slot blotting and flow cytometry: two efficient assays for platelet antibody screening among patients with platelet refractoriness

Slot blotting and flow cytometry: two efficient assays for platelet antibody screening among patients with platelet refractoriness

Antiplatelet and Antileukocyte Effects of Cardiovascular,Immunomodulatory and Chemotherapeutic Drugs

Detection of drug‐dependent, platelet‐reactive antibodies by solid‐phase red cell adherence assays

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