Human Subjects Research Projects

Exploratory Characterization of Mast Cell Regulatory Gene Mutations in Mast Cell Activation syndrome (MCAS)
This study of 20 MCAS patients ages 18-50 and 20 age/sex/race-matched healthy control subjects is taking a blood sample from each subject, extracting the mast cells, and performing in these extracts whole-gene sequencing of a number of mast cell regulatory genes in order to determine the frequencies of mutations in these genes in MCAS patients vs. healthy controls. This study will help address the question of how commonly MCAS is a clonal disorder (i.e., rooted in mutations (whether acquired or inherited) in the mast cells' genetic program). If clonality is found to be common, future studies will attempt to clarify the molecular and clinical consequences of the various mutations found and to identify treatments for variants of MCAS defined by their mutational profiles. 
For more information, please contact principal investigator Lawrence B. Afrin, MD.

Genomic Profiling of Urticaria Pigmentosa
This study is taking blood samples from patients with the form of cutaneous mastocytosis called urticaria pigmentosa (UP) and performing whole genome sequencing to try to identify genetic mutations which may cause UP. This is the first study to perform a comprehensive genetic assessment of UP. For more information, please contact co-principal investigators Dr. Sheilagh Maguiness with the University of Minnesota Department of Dermatology and Dr. Lucie Turcotte with the University of Minnesota Division of Pediatric Hematology/Oncology.

Non-Human Subjects Research Projects

Mast Cells in Luminal Gastrointestinal Tract Biopsies from Patients with Graft-vs.-Host Disease
There are features of graft vs. host disease (GVHD, a disease suffered post-transplant by many stem cell transplant patients which often is difficult to control) suggesting increased numbers and/or activation of mast cells may contribute significantly to the development and course of the disease. Luminal gastrointestinal (GI) biopsies often are obtained in GVHD patients in efforts to understand what is causing the GI symptoms in such patients. Mast cells are essentially impossible to identify as such on routine pathological analysis of GI tract biopsies and often masquerade as other common types of cells such as lymphocytes. As such, it is possible that mast cell disease is present in GI GVHD but is going undetected. This exploratory study is examining luminal GI tract biopsies taken in the past from stem cell transplant patients with GVHD to characterize the presence of mast cells in such biopsies. For more information, please contact co-principal investigators Dr. Celalettin Ustun with the University of Minnesota Division of Hematology, Oncology & Transplantation and Dr. Mahmoud Khalifa with the University of Minnesota Department of Pathology.


Research Publications

  • Afrin LB, Self S, Menk J, Lazarchick J. Characterization of Mast Cell Activation Syndrome. Am J Med Sci, 2017 Mar, in press, DOI: 10.1016/j.amjms.2016.12.013.
  • Seneviratne S, Maitland A, Afrin LB. Mast Cell Disorders in Ehlers-Danlos Syndrome. Am J Med Genetics Pt C Sem Med Genetics 2017, in press, DOI: 10.1002/ajmg.c.31555.
  • Lortholary O, Chandesris MO, Bulai Livideanu C, Paul C, Guillet G, Jassem E, Niedoszytko M, Barete S, Verstovsek S, Grattan C, Damaj G, Canioni D, Fraitag S, Lhermitte L, Georgin Lavialle S, Frenzel L, Afrin LB, Hanssens K, Agopian J, Gaillard R, Kinet JP, Auclair C, Mansfield C, Moussy A, Dubreuil P, Hermine O. Masitinib for treatment of severely symptomatic indolent systemic mastocytosis: a randomised, placebo-controlled, phase 3 study. Lancet 2017 Jan 6, pii: S0140-6736(16)31403-9 [e-pub ahead of print] , DOI: 10.1016/S0140-6736(16)31403-9.
  • Afrin LB, Cichocki F, Hoeschen A, Beckman K, Gupta K, Nguyen J, Silverstein K, Mills L. Mast cell regulatory gene variants are common in mast cell activation syndrome. Am Soc Hematol Annu Mtg 2016, Blood 2016 128:4878  
  • Ustun C, Arock M, Kluin-Nelemans HC, Reiter A, Sperr WR, George T, Horny HP, Hartmann K, Sotlar K, Damaj G, Hermine O, Verstovsek S, Metcalfe DD, Gotlib J, Akin C, Valent P. Advanced systemic mastocytosis: from molecular and genetic progress to clinical practice. Haematologica 2016 Oct;101(10):1133-1143 [PMID: 27694501 DOI: 10.3324/haematol.2016.146563].
  • He F, Horny HP, Boone J, Raza A, Griffith M, Hurley P, Dolan M, Cayci Z, Linden MA, McKenna R, Ustun C. Anaplastic mast cell sarcoma: a unique pathologic entity in mastocytosis. Leuk Lymphoma 2016 Nov 3:1-3 [e-pub ahead of print], PMID: 27808598 DOI: 10.1080/10428194.2016.1250265.
  • Ustun C, et al. Consensus Opinion on Allogeneic Hematopoietic Cell Transplantation in Advanced Systemic Mastocytosis, Biol Blood Marrow Transpl 2016 Aug;22(8):1348-56 [PMID: 27131865, DOI: 10.1016/j.bbmt.2016.04.018]
  • Molderings GJ, Haenisch B, Brettner S, Homann J, Dumoulin FL, Panse J, Butterfield J, Afrin LB. Pharmacological treatment options of systemic mast cell activation disease. Naunyn Schmiedebergs Arch Pharmacol 2016 Jul;389(7):671-94, PMID: 27132234, DOI: 10.1007/s00210-016-1247-1.
  • Afrin LB, Butterfield J, Raithel M, Molderings GJ (2016). Often seen, rarely recognized: mast cell activation disease – a guide to diagnostic and therapeutic options. Ann Med 2016 May;48(3):190-201, PMID: 27012973, DOI: 10.3109/07853890.2016.1161231.
  • Afrin LB, Butterfield JH, Raithel M, Molderings GJ.  Often seen, rarely recognized: mast cell activation disease - a guide to diagnosis and therapeutic options.  Ann Med. 2016 May;48(3):190-201 [PMID: 27012973  DOI: 10.3109/07853890.2016.1161231].
  • Afrin LB.  A new era for an old cell: heightened appreciation of mast cell disease emerges.  Transl Res 2016 Mar 10 pii: S1931-5244(16)00072-4 [PMID: 27016701  DOI: 10.1016/j.trsl.2016.03.003].
  • Ustun C, Smith A, Cayci Z, Courville EL, Corbacioglu S, Akin C, Horny HP, Valent P, Devine S, Weisdorf DJ.  Allogeneic hematopoietic cell transplantation in systemic mastocytosis: Is there a high risk for veno-occlusive disease?  Eur J Haematol 2015 Dec 17, doi: 10.1111/ejh.12720.
  • Ustun C, Courville E.  Resolution of osteosclerosis in SM after allogeneic hematopoietic cell transplantation.  Blood 2016.
  • Afrin LB (2016). Mast cell activation disease and the modern epidemic of chronic inflammatory disease. Transl Res 2016, doi: 10.1016/j.trsl.2016.01.003.
  • Aich A, Afrin LB, Gupta K (2015). Mast cell-mediated mechanism(s) of nociception. Int J Mol Sci 2015 Dec 4;16(12):29069-92, doi: 10.3390/ijms161226151, PMID: 26690128.
  • Afrin LB (2015). Utility of Continuous Diphenhydramine Infusion in Severe Mast Cell Activation Syndrome. Blood 2015 126:5194.
  • Zenker N, Afrin LB (2015). Utilities of Various Mast Cell Mediators in Diagnosing Mast Cell Activation Syndrome. Blood 2015 126:5174.
  • Afrin LB (2015). Mast cell activation syndrome: a chameleon that confounds diagnostics and treatment for other disorders. The Dysautonomia Project: Understanding Autonomic Nervous System Disorders for Physicians and Patients; Freeman K, Goldstein DS, Thompson CR, eds., Bardolf & Company, Sarasota, FL, ISBN 978-1-938842-24-5, pp. 135-139.
  • Afrin LB, Pöhlau D, Raithel M, Haenisch B, Dumoulin FL, Homann J, Mauer UM, Harzer S, Molderings GJ (2015). Mast Cell Activation Disease: An Underappreciated Cause of Neurologic and Psychiatric Symptoms and Diseases. Brain Behav Immun 2015, doi: 10.1016/j.bbi.2015.07.002, PMID: 26162709.
  • Afrin LB, Cichocki F, Patel K, Molderings GJ (2015). Successful treatment of mast cell activation syndrome with sunitinib. Eur J Haematol 2015, doi: 10.1111/ejh.12606, PMID: 26072665.
  • Afrin LB, Khoruts A (2015). Mast cell activation disease and microbiotic interactions. Clin Ther 2015 May, doi: 10.1016/j.clinthera.2015.02.008, PMID: 25773459.
  • Randall N, Courville EL, Baughn L, Afrin L, Ustun C (2015). Bosutinib, A Lyn/Btk-Inhibiting Tyrosine Kinase Inhibitor, Is Ineffective In Advanced Systemic Mastocytosis. American Journal of Hematology 2015, doi: 10.1002/ajh.23942, PMID: 25641616.
  • Ustun C, Reiter A, Scott BL, Nakamura R, Damaj G, Kreil S, Shanley R, Hogan WJ, Perales MA, Shore T, Baurmann H, Stuart R, Gruhn B, Doubek M, Hsu JW, Tholouli E, Gromke T, Godley LA, Pagano L, Gilman A, Wagner EM, Shwayder T, Bornhäuser M, Papadopoulos EB, Böhm A, Vercellotti G, Van Lint MT, Schmid C, Rabitsch W, Pullarkat V, Legrand F, Yakoub-Agha I, Saber W, Barrett J, Hermine O, Hagglund H, Sperr WR, Popat U, Alyea EP, Devine S, Deeg HJ, Weisdorf D, Akin C, Valent P. Hematopoietic stem-cell transplantation for advanced systemic mastocytosis. J Clin Oncol 2014 Oct 10;32(29):3264-74 [PMID: 25154823 DOI: 10.1200/JCO.2014.55.2018]
  • Afrin LB (2014). Mast Cell Activation Syndrome as a Significant Comorbidity in Sickle Cell Disease. American Journal of Medical Sciences 2014 Dec;348(6):460-464, doi: 10.1097/MAJ.0000000000000325, PMID: 25171546.
  • Ustun C, Cayci Z, Courville E.  A patient with skin lesions, osteosclerosis and hepatosplenomegaly.  Br J Haematol 2014 Nov;167(3):291 [PMID: 25039362  DOI: 10.1111/bjh.13034]
  • Afrin LB (2014). The presentation, diagnosis, and treatment of mast cell activation syndrome. Curr Allergy Clin Immunol 2014 Sep;27(3):72-83. Article.
  • Valent P, Sotlar K, Sperr WR, Escribano L, Yavuz S, Reiter A, George TI, Kluin-Nelemans HC, Hermine O, Butterfield JH, Hägglund H, Ustun C, Hornick JL, Triggiani M, Radia D, Akin C, Hartmann K, Gotlib J, Schwartz LB, Verstovsek S, Orfao A, Metcalfe DD, Arock M, Horny HP. Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal. Ann Oncol 2014 Sep;25(9):1691-700 [PMID: 24675021 DOI: 10.1093/annonc/mdu047]
  • Afrin LB, Spruill L, Schabel S, Pierce-Young J (2014). Improved metastatic uterine papillary serous cancer outcome with treatment of mast cell activation syndrome. Oncology 28(2):129-131,134, PMID: 24701700.
  • Afrin LB, Molderings GJ (2014). A concise, practical guide to diagnostic assessment for mast cell activation disease. World J Hematol 3(1):1-17, doi:10.5315/wjh.v3.i1.1.
  • Afrin LB. Utility of hydroxyurea in mast cell activation syndrome (2013). Experimental Hematology and Oncology 2:28, pp. 1-8, PMID: 24192267.
  • Afrin L.B. (2013). Presentation, Diagnosis, and Management of Mast Cell Activation Syndrome. Mast Cells: Phenotypic Features, Biological Functions, and Role in Immunity; Murray, D., ed., Nova Science Publishers, ISBN 1626181667, 9781626181663, pp. 155-231, available on-line.
  • Afrin LB, Wan Z, Hill E (2013). Characterization of Common Blood Test Abnormalities Potentially Aiding Diagnosis of Mast Cell Activation Syndrome: A Preliminary Analysis. Blood 122(21):5420.
  • Afrin LB (2013). Non-histaminergic idiopathic angioedema may be a presentation of mast cell activation syndrome. J Investig Allergol Clin Immunol 23(3):212, PMID: 23967766.
  • Afrin LB (2012). Sclerosing Mediastinitis and Mast Cell Activation Disorder. Pathology Research and Practice 208(3):181-185, doi:10.1016/j.prp.2011.12.005, PMID: 22296862.
  • Afrin LB (2012). Mast Cell Activation Disorder Masquerading as Agranulocytosis. Military Medicine 177(1):113-117, PMID: 22338992.
  • Molderings GJ, Brettner S, Homann J, Afrin LB (2011). Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options. Journal of Hematology and Oncology 4:10, pp. 1-8, doi: 10.1186/1756-8722-4-10; PMID: 21418662.
  • Afrin LB (2011). KIT-D816V in Acute Myelogenous Leukemia May Signify Co-Presence of Mast Cell Disease. (e-Letter.) Blood, 2011 Mar 24, published on-line response to Park JH, Hedvat CV, Tallman MS. Blood consult: acute myeloid leukemia and the t(8;21)(q22;22). Blood 2011 Mar 10;117(10):2775-2777.
  • Afrin LB (2011). Polycythemia from Mast Cell Activation Syndrome: Lessons Learned. American Journal of Medical Sciences 342(1):44-49, doi: 10.1097/MAJ.0b013e31821d41dd, PMID: 21642812.
  • Afrin LB (2011). Burning Mouth Syndrome and Mast Cell Activation Disorder. Oral Med Oral Surg Oral Path Endodont 111(4):465-72, doi: 10.1016/j.tripleo.2010.11.030, PMID: 21420635.
  • Afrin LB (2010). Mast Cell Activation Disorder Masquerading as Pure Red Cell Aplasia. International Journal of Hematology 91(5):907-908, doi: 10.1007/s12185-010-0605-x, PMID: 20526893.