Versiti - Brian Curtis, PhD | Versiti Blood Research Institute

Research Interests

Drug-Dependent Antibodies

Some people develop antibodies against their platelets, red blood cells, or white blood cells following receipt of medications. Our Platelet & Neutrophil Immunology Reference Lab currently tests for drug-dependent platelet and white blood cell antibodies, and to date, we have identified drug-dependent antibodies in patients’ blood samples for over 60 drugs, including vancomycin, sulfa-drugs, beta-lactam antibiotics, and even over-the-counter medications like ibuprofen and Tylenol (view complete list). We currently have laboratory and clinical studies in progress, together with researchers at BRI, to better understand the formation of drug-dependent antibodies and their clinical significance.

Low Frequency Human Platelet Alloantigens (HPA)

The Platelet & Neutrophil Immunology Lab performs testing on over 400 samples each year to aid physicians in the clinical diagnosis of fetal & neonatal alloimmune thrombocytopenia (FNAIT). FNAIT is a disorder in pregnancy in which a mother makes antibodies against her baby’s platelets resulting in destruction of the baby’s platelets leading to severe bleeding into the baby’s brain (ICH) and even death. It is thus important that laboratory testing for FNAIT be thorough, including the ability to detect maternal antibodies reactive with low frequency or new HPA (view list Platelet Antigen Database). We are working with cutting-edge methods to detect and characterize newly discovered HPA.

Leukocyte Antibodies in TRALI

Transfusion-Related Acute Lung Injury (TRALI) is a severe reaction that some patients experience following transfusion of blood or plasma. TRALI is currently the number one cause of transfusion-related death reported to the Food and Drug Administration (FDA). In a significant number of TRALI cases, the plasma from donors of the implicated blood products contains leukocyte antibodies (HLA and neutrophil) that cause activation of the patient’s neutrophils, leading to TRALI. One of the antigens targeted by such antibodies is designated human neutrophil antigen (HNA)-3a, which has been implicated in numerous severe cases of TRALI, many of them fatal. We identified the protein carrier (CTL2) of HNA-3a and HNA-3b, alleles of gene SLC44A2. We are also investigating the use of tests that could be used to screen blood donors for antibodies against HNA-3 as a TRALI risk-reduction measure.

Lab

Grant Support

Selected Publications

Curtis BR, Edwards JT, Hessner MJ, Klein JP, Aster RH. Blood group A and B antigens are strongly expressed on platelets of some individuals. Blood 2000; 96:1574-1581.
Aitman TJ, Cooper LD, Norsworthy JP, Wahid FN, Gray JK, Curtis BR, McKeigue PM, Kwiatkowski D, Greenwood BM, Snow RW, Hill AV, Scott J. Malaria susceptibility and CD36 mutation. Nature 2000; 405: 1015-1016.
Curtis BR, Bussel JB, Manco-Johnson M, Aster RH, McFarland JG. Fetal and neonatal alloimmune thrombocytopenia in pregnancies involving in vitro fertilization: a report of four cases. Am J Obstet and Gynecol 2005; 192:543-547.
Von Drygalski A, Curtis BR, Bougie DW, McFarland JG, Ahl S, Limbu I, Baker KR, Aster RH. Vancomycin-induced immune thrombocytopenia. N Engl J Med 2007; 356:904-910.
Podrez EA, Byzova TV, Febbraio M, Salomon RG, Ma Y, Valiyaveettil M, Poliakov E, Sun M, Finton PJ, Curtis BR, Chen J, Zhang R, Silverstein RL, Hazen SL. Platelet CD36 links hyperlipidemia, oxidant stress and a prothrombotic phenotype. Nature Medicine 2007; 13:1086-1095.
Curtis BR, Fick A, Lochowicz, McFarland JG, A, Ball RH, Peterson, JA, Aster RH. Neonatal alloimmune thrombocytopenia (NATP) associated with maternal fetal incompatibility for blood group B. Transfusion 2008; 48:358-364.
Curtis BR, Cox NJ, Sullivan MJ, Konkashbaev A, Bowens K, Hansen K, Aster RH. The neutrophil alloantigen HNA-3a (5b) is located on choline transporter- like protein 2 (CTL2) and appears to be encoded by an R>Q154 amino acid substitution. Blood 2010; 115:2073-2076.
Reese JA, Li X, Hauben M, Aster RH, Bougie DW, Curtis BR, George JN, Vesely SK. Identifying drugs that cause acute thrombocytopenia: an analysis using 3 distinct methods. Blood 2010; 116(12):2127-2133.
Achterbergh R, Vermeer E, Curtis BR, Porcelijn L, Aster RH, Deenik W, Daemen-Gubbels K. Thrombocytopenia in a nutshell. Lancet 2012; 379:776.
Bowens K, Sullivan M, Curtis BR. Determination of neutrophil alloantigen HNA-3a and HNA-3b genotype frequencies in six racial groups by high-throughput 5’ exonuclease assay. Transfusion 2012 Nov; 52(11):2368-2374.
Curtis BR, McFarland JG. Human platelet antigens - 2013. Vox Sang 2014; 106:93-102.
Curtis BR. Recent progress in understanding the pathogenesis of fetal and neonatal alloimmune thrombocytopenia. Br J Haematol 2015; 171, 671–682.
Curtis BR, Roman A, Sullivan M, Raven C, Larison J, Weitekamp L. Two Cases of Maternal Alloimmunization Against Human Neutrophil Alloantigen-4b, One Causing Severe Alloimmune Neonatal Neutropenia. Transfusion 2016;56:101–106.
Metzner K, Bauer J, Ponzi H, Ujcich A, Curtis BR. Detection and identification of platelet antibodies using a sensitive multiplex assay system - Platelet Antibody Bead Array (PABA). Transfusion Jul 2017; 57(7):1724-1733.
Sullivan MJ, Kuhlmann R, Peterson J, Curtis BR. A new low frequency alloantigen (Domb) located on platelet glycoprotein IIIa as a cause of maternal sensitization leading to neonatal alloimmune thrombocytopenia. Transfusion Jul 2017; 57(7):1847-1848.
Curtis BR. Non-chemotherapy drug-induced neutropenia: key points to manage the challenges. Hematology Am Soc Hematol Educ Program. Dec 2017; 2017(1):187-193. doi: 10.1182/asheducation-2017.1.187.
Curtis BR, Hsu Y-MS, Podoltsev N, Lacy J, Curtis S, DeSimone R, Samuel MS, Bougie DW, Aster RH. Patients treated with oxaliplatin are at risk for thrombocytopenia caused by multiple drug-dependent antibodies. Blood Mar 2018;131(13):1486-1489. doi: 10.1182/blood-2017-10-812461
Thinn AMM, Wang Z, Zhou D, Zhao Y, Curtis BR, Zhu J. A The autonomous conformational regulation of β3 integrin and the conformation-dependent property of HPA-1a alloantibodies. PNAS Sept 2018; 115(39):E9105-E9114. doi: 10.1073/pnas.1806205115. PMID:30209215
Zhi H, Ahlen MT, Thinn AMM, Lertkiatmongkol P, Weiler H, Curtis B, Skogen B, Zhu J, Newman PJ. High-resolution mapping of the polyclonal immune response to the human platelet alloantigen HPA-1a (PlA1). Blood Advances Nov 2018; 2(21):3001-3011. doi: 10.1182/bloodadvances.2018023341.
Zhang N, Santoso S, Aster RH, Curtis BR, and Newman PJ. Bioengineered iPSC-derived megakaryocytes for the detection of platelet-specific patient alloantibodies. Blood 2019; 134(22):e1-e8. doi: 10.1182/blood.2019002225.
Hawkins J, Aster R, Curtis BR. Post-transfusion purpura: current perspectives. J Blood Med. Dec 2019; 10:405-415. doi: 10.2147/JBM.S189176
Kjær M, Geisen C, Akkök ÇA, Wikman A, Sachs U, Bussel JB, Nielsen K, Walles K, Curtis BR, Vidarsson G, Järås K, Skogen B. Strategies to develop a prophylaxis for the prevention of HPA-1a immunization and fetal and neonatal alloimmune thrombocytopenia. Transfus Apher Sci 2020 Feb;59(1):102712. doi: 10.1016/j.transci.2019.102712. Epub 2019 Dec 31.
Bannow BS, Warad DM, Jones CG, Pechauer SM, Curtis BR, Bougie DW, Sharma R, Grill DE, Redman MW, Khalighi PR, Leger RR, Pruthi RK, Chen D, Sabath DE, Aster RH, Garcia DA, Padmanabhan A. A prospective, blinded study of a PF4-dependent assay for HIT diagnosis. Blood 2021 Feb 25;137(8):1082-1089. doi: 10.1182/blood.2020008195.
Gemlyn G, Friedman KD, Curtis BR, Lind SE. Successful treatment of thrombotic thrombocytopenia with cerebral sinus venous thrombosis following Ad26.COV2.S vaccination. Am J Hematol 2021 Aug 1;96(8):E301-E303. doi: 10.1002/ajh.26237. Epub 2021 Jun 1.
Zachary A. Colvin, Jennifer Schiller, Shirng-Wern Tsaih, Ruchika Sharma, Rachael Grace, Jennifer J McIntosh, Brian R. Curtis. The Role of HLA Antibodies in Suspected Cases of Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT). Transfusion 2023;Jun;63(6):1141-1149. doi: 10.1111.
Behnaz Bayat,Jonas Lowack, Marie Audrain, Laure Croisille, BR Curtis, et al. World HNA investigation survey (WHIS). Vox Sang 2023;118:763–774. doi: 10.1111/vox.13500. PMID: 37608544
L Shen, A Wong, S Oneda, BR Curtis, J Schroeder, T Zanardi, JA Engelhardt, SP Henry, P Narayanan. Complement C3d/C4d Deposition on Platelets Correlates with 2'-O-Methoxyethyl Antisense Oligonucleotide-Induced Thrombocytopenia in Monkeys. Nucleic Acid Ther 2023; Jun;33(3):209-225. doi: 10.1089.
Nanyan Zhang, Brian R. Curtis, Peter J. Newman. O-linked sialic acid residues on platelet membrane glycoprotein (GP) IIb mask the human HPA-9b alloepitope. Blood 2023;Sep 22:doi:10.1182/blood.2023021122. PMID: 37738558.

Electronic Media

Chaffin J (Host), Curtis BR (Guest). (2017, Feb 13) NAIT (No. 027) [Audio podcast episode] in Blood Bank Guy
Curtis BR (Speaker). (2017, May 10) Platelet Immunology (Master Program No. 17EL-133) [Professional Development eCast] in AABB Immunohematology Boot Camp
Curtis BR (Speaker). (2019, March 6) A Newborn Infant has a Low Platelet Count - Important diagnostic features of Neonatal Alloimmune Thrombocytopenia (NAIT) [BloodFLOW (Further Learning On Web) Webinar] in beLearning by Versiti
Curtis BR, Bakchoul T (Hosts). (2019, February 25) Module 4: Drug-Induced Thrombocytopenia (No. 234427) [ISTH Academy] in Acquired Thrombocytopenia Course
Sharma R, Curtis BR (Speakers). (2020, July 23) Recent Advances in Diagnosis and Treatment of HIT. [BloodFLOW] in beLearning by Versiti

Brian

Curtis, PhD, D(ABMLI), MT(ASCP) SBB

Senior Director, Diagnostic Hematology, Senior Investigator

Transfusion Medicine, Vacular Biology & Cellular Therapy

Senior Director, Diagnostic Hematology, Senior Investigator

Education and Training

Board Certifications