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Hashimoto’s Thyroiditis Donor PBMCs: Th1 Cytotoxic Mechanism, Treg Deficiency, and Thyroid Autoimmunity Research

Research Use Only (RUO). All OrganaBio disease-state donor material is intended for laboratory research, drug discovery, and non-clinical studies only. Not for therapeutic, diagnostic, or clinical manufacturing use.

Reviewed by Sarah Alter, Ph.D. — Scientific Affairs, OrganaBio. 15 years of immunology research spanning autoimmunity, cancer, and infectious disease. University of Miami Miller School of Medicine. Registered Patent Agent.

Hashimoto’s thyroiditis (autoimmune thyroiditis) is the most common autoimmune disease globally, affecting approximately 5% of the population, and the leading cause of hypothyroidism in iodine-sufficient regions. Its mechanism is cytotoxic rather than stimulatory — Th1-dominant CD4+ T cells and CD8+ cytotoxic T cells destroy thyroid follicular cells, with anti-TPO (thyroperoxidase) and anti-thyroglobulin (anti-Tg) autoantibodies serving as markers of the immune process rather than primary effectors. Despite its prevalence, Hashimoto’s has no approved immunological therapy — levothyroxine replacement is the standard of care — making it an active area for Treg restoration, low-dose IL-2, and tolerogenic approaches that require disease-state PBMC material.

Th1-Dominant T Cell Mechanism in Hashimoto’s PBMCs

The thyroid destruction in Hashimoto’s is driven primarily by Th1 CD4+ T cells (IFN-gamma, TNF-alpha production) and CD8+ cytotoxic T cells (perforin/granzyme B-mediated thyrocyte killing). Key measurable features in Hashimoto’s peripheral blood:

  • Th1 elevation: IFN-gamma+CD4+ T cells are elevated in Hashimoto’s versus healthy controls. This Th1 dominance contrasts with the Th2 skew of Graves’ disease, and is the mechanistic basis for the predominantly destructive (cytotoxic) rather than stimulatory autoimmunity of Hashimoto’s.
  • CD8+ T cell activation: Activated CD8+ T cells with granzyme B expression and thyroid-reactive specificity are present in Hashimoto’s peripheral blood. TCR repertoire analysis shows oligoclonal CD8+ expansions consistent with antigen-driven responses to thyroid autoantigens (TPO, thyroglobulin).
  • CXCR3+ T cells: Both CXCR3+CD4+ and CXCR3+CD8+ T cell frequencies are elevated, reflecting ongoing IFN-gamma-driven CXCL9/10 production in the thyroid gland and the systemic Th1 immune activation state.

Anti-TPO and Anti-Tg Autoantibodies: B Cell Context for Research

Anti-TPO antibodies are present in over 90% of Hashimoto’s patients and anti-Tg in approximately 60-80%. Unlike TSI in Graves’ disease, anti-TPO and anti-Tg antibodies are not considered primary effectors — their pathogenic contribution, if any, is complement-mediated and secondary to T cell-driven thyrocyte destruction. Nevertheless, anti-TPO and anti-Tg-producing B cells in Hashimoto’s peripheral blood provide:

  • A B cell tolerance breakdown model for studying why TPO and Tg autoantigens fail to tolerize B cells in Hashimoto’s
  • Anti-TPO titer as a pharmacodynamic endpoint for immunomodulatory interventions (low-dose IL-2, selenium, anti-CD20 studies)
  • A high-prevalence autoimmune disease B cell system for general autoimmune B cell mechanism studies with accessible donor recruitment

Treg Deficiency: The Primary Therapeutic Target

FoxP3+CD25highCD4+ Tregs are reduced in active Hashimoto’s disease and correlate inversely with anti-TPO titer and lymphocytic infiltration severity. The Treg deficiency in Hashimoto’s is the therapeutic target of primary interest for emerging immunomodulatory approaches:

  • Low-dose IL-2: Phase 2 trials are ongoing for low-dose IL-2 in Hashimoto’s (and other autoimmune thyroid diseases) based on Treg expansion pharmacodynamics. Hashimoto’s donor PBMCs provide the IL-2-deprived Treg compartment for measuring low-dose IL-2 Treg expansion responses ex vivo.
  • Selenium: Selenium supplementation reduces anti-TPO titers in Hashimoto’s patients in randomized trials, with proposed mechanisms including antioxidant effects on dendritic cell maturation and indirect Treg support. Measuring selenium effects on Treg frequency and function in Hashimoto’s PBMCs is an accessible pharmacodynamic readout.
  • Tolerogenic DCs: Tolerogenic dendritic cell programs that expand antigen-specific Tregs are in preclinical development; Hashimoto’s PBMCs provide a high-prevalence autoimmune thyroid disease system for initial ex vivo feasibility studies.

Type I Interferon Signature

A subset of Hashimoto’s patients (particularly those with more severe disease or with other autoimmune comorbidities) show a measurable type I IFN signature — lower than Graves’ disease in most cohorts, but detectable by ISG expression profiling. The IFN-I component in Hashimoto’s is associated with pDC activation and contributes to the Th1 skew and CD8+ T cell activation that drives thyrocyte destruction.

Research Applications

  • Treg restoration: Low-dose IL-2 pharmacodynamics, Treg expansion quantification, FoxP3 stability studies in Hashimoto’s inflammatory context
  • Th1/CD8 cytotoxicity characterization: CXCR3+ T cell profiling, granzyme B/perforin expression in thyroid-reactive CD8+ T cells, IFN-gamma pathway pharmacodynamics
  • Anti-TPO B cell studies: TPO-specific B cell enumeration, class-switching and plasma cell differentiation studies in Hashimoto’s B cells
  • Selenium and antioxidant immunopharmacology: Anti-TPO titer reduction mechanisms, DC maturation effects, Treg support in selenium-supplemented PV culture systems
  • Comparative thyroid autoimmunity: Head-to-head Th1 (Hashimoto’s) versus Th2 (Graves’) immune signature characterization in well-matched donor cohorts

OrganaBio Hashimoto’s Donor Collection Specifications

  • Diagnosis confirmed by endocrinologist; anti-TPO and anti-Tg titer documented
  • Thyroid function at collection documented (TSH, free T4); hypothyroid versus euthyroid on levothyroxine cohorts available
  • Selenium supplementation status documented where applicable
  • Concomitant autoimmune conditions documented (Hashimoto’s frequently co-occurs with other autoimmune diseases)
  • Same-day processing from apheresis; 30-minute standard for fresh material
  • Cryopreserved lots: >80% post-thaw viability; T cell populations preserved for Th1/CD8 cytotoxicity studies
  • Available as isolated PBMCs, leukopaks, or fresh whole blood

Related resources: Graves’ Disease Donor PBMCs: TSI biology and Tfh-B cell axis | Disease-state vs. healthy donor PBMC selection framework

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Andrew Larson

Managing Director, CPC Services

Andrew joins OrganaBio as a project manager with varied experience in project management, client relations, and process improvement.

Prior to OrganaBio, Andrew was a client relations manager for the cGMP nucleic acids business unit at Aldevron, coordinating and managing contracts at each stage of the contract lifecycle in support of cell and gene therapy program development. Andrew supported small- and large-scale biotechnology and pharmaceutical clients anywhere from pre-IND work through commercial supply chain establishment. Before Aldevron, Andrew was a project manager for the commercialization and business development department for Sanford Health, a worldwide hospital institution. At Sanford Health, Andrew helped manage medical device patent and prototype development efforts for employee innovations primarily in the cardiovascular, neurovascular, and software spaces. Andrew was also an engineer for Atirix Medical Systems and supported the buildout of automated analysis worksheets to streamline radiology department quality control procedures.

Andrew received his Bachelor of Science in Physics from Minnesota State University Moorhead and his Master of Science in Biomedical Engineering from the University of Minnesota. At the University of Minnesota, Andrew was part of the Center for Magnetic Resonance Research, assisting efforts to automate MRI dataset registration and workflow improvement.

Michael Dee

Associate Director, QC and Analytical Development

Michael Dee has spent the last 17 years researching the immune system. Initially studying the recombinant cytokine IL-2 and its role in T cell subset differentiation and function at the University of Miami. He also helped elucidate the lower level of TCR diversity of T regs required to prevent autoimmunity in mice. Michael also supported construction, cloning, production, purification, and testing both in vitro and in vivo a novel IL-2/IL2Rα complex currently under clinical development with BMS. Michael also was a member of the department of immunology’s program project delineating the effect of a novel Eg7GP96 heat shock protein vaccine on tumor immunity.

While at Immunity Bio (formerly Altor Biosciences), he helped to characterize over 20 novel drugs for immune modulation and treatment of cancer.  After Immunity Bio, Michael was a founding team member of HCW Biologics, where he continued his role in design and initial production and characterization of several novel biologics. He has experience with proof of principle experiments with the generation CAR-NK and CAR T cells. His research at HCW was highlighted by his discovery of a process using novel biologics to activate and expand CIML NK cells. The process and rights were sold to Wugen and is currently in Phase I clinical trials. He also is listed as an Inventor on patent number: US20210268022A1 on method of activating regulatory T cells.

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Meram received her master’s degree in biomedical sciences from Barry University and bachelor’s in Biology from Palm Beach Atlantic University.

Before her position at OrganaBio, Meram conducted research at Larkin University where she worked on assessing the impact of Hurricane Maria on respiratory diseases in Puerto Rico, which provided her with insight into research investigation and analysis along with generation of grant documentation.

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Senior Bioprocess Scientist

Valeria Beckhoff Ferrero has over 8 years of experience in the fields of stem cell research and tissue engineering. Valeria received her Bachelor of Science in Biomedical Engineering, specializing in Biomaterials and Tissue Engineering, from Drexel University in Philadelphia. Valeria has expertise in problem solving and finding manufacturing solutions for isolating various types stem cells and other cell derived products from different tissues.

Before joining OrganaBio, Valeria was a lead manufacturing engineer at the Amnion Foundation. She aided in instituting a GMP infrastructure, including documentation, to manufacture clinical grade placental derived stem cells. In her role, she worked in perfecting isolation, culture, selection and cell maintenance processes for perinatal derived stem cells.

Valeria’s experience includes working as an Automation Engineer at the New York Stem Cell Foundation, where she aided in the creation and coding procedures for liquid handlers to manufacture induced pluripotent stem cells. At NYSF, Valeria researched new methods of sorting, reprogramming and differentiating iPSCs.

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Marisa Reinoso

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Marisa has experience leading marketing and sales life sciences programs for over a decade. Originally a lab researcher, she made the jump to marketing & sales in life sciences and never looked back.

At OrganaBio, she connects cell therapy developers on the West coast and in Asia with the healthy donor starting materials they need to develop their therapies. Prior to OrganaBio, she was the cell therapy marketing lead at Invetech, heading the launch of the company’s first cell therapy product. Marisa has led marketing programs at clinical supply companies Sherpa Clinical Packaging and PCI Pharma Services. In her spare time, Marisa enjoys traveling, eating, and pretending she’s a tennis player. She has a Bachelor of Arts in Biology from Reed College and an MBA from Portland State University.

Thelma Cela

Senior Director, Tissue Procurement

Thelma Cela is a top performing professional with over 25 years’ experience in management, leadership, business development and marketing fields with business acumen and skills in driving revenue and profit growth in multiple corporate cultures. Prior to joining OrganaBio, Thelma served as Senior Director for Health and Human Services for the Seminole Tribe of Florida. Her role had oversight for health clinics, health plan administration, the behavioral health department, and elder services. In this governmental administrative capacity, Thelma had primarily responsibility for the HHS’ divisions’ budget, capital projects, utilization management, efficiency, and efficacy.

Thelma’s prior work experiences include Vice President of Clinical Operations for OrthoNOW. In this role, she provided guidance on all clinical matters, set direction on clinical policies and procedures and monitoring healthcare policy changes. As the national Vice President of Clinical Operations, Thelma also designed, developed, and implemented guidelines and protocols and ensured compliance regarding overall patient experience.

Before joining OrthoNOW, Thelma had been recruited by Leon Medical Centers, a private healthcare company operating comprehensive medical centers to launch a new business line addressing the health and wellness of an aging population. As Director, Thelma researched, created, and launched the company’s Health Living Centers which provided first of its kind facilities in the South Florida market to offer services to the community of health aging.

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Thelma earned her MBA from Miami Regional University where she graduated Cum Laude and her undergraduate degree in Psychology is from the University of Miami.

She serves on the advisory panel for Florida International University’s Women in Business Leadership Program helping future women become future business leaders through thought leadership, barrier destruction, and the power of influence.

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Prior to OrganaBio, Dominic spent 8 years at Bluebird Bio as the company grew from 45 to 1200+ employees and from 1 clinical asset to a robust commercial pipeline. At Bluebird, Dominic initially supported the development and technology transfer of lentiviral vector manufacturing processes. As demand grew for lentiviral process and product characterization, Dominic led the development, qualification, transfer, and validation two commercial release methods. Dominic transitioned back to the Process Development organization to lead the vector manufacturing core team, increasing operational efficiency through a 5S implementation, process schedule intensification, and reverse technology transfer initiative. More recently, Dominic supported the build-out of bluebird’s Manufacturing Science & Technology team followed by the Data Systems & Analytics team, handling late-stage commercial asset support.

Dominic received his Bachelor of Chemical Engineering with Distinction from the University of Delaware. Dominic’s undergraduate research culminated in his thesis on heterologous expression of G-protein coupled receptors in Saccharomyces cerevisiae. After graduation, Dominic was the premier hire of the Zhou Laboratory at Brigham and Women’s hospital in Boston, MA. In three years, Dominic established an animal model of COPD and co-authored several papers with his collaborators in the Pulmonary division.

Christopher B. Goodman

Vice President, Quality & Regulatory Affairs

Christopher B. Goodman is a biopharmaceutical consultant and executive making a global impact in the cellular therapy technology arena. The scope of Christopher’s expertise encompasses Cellular Therapeutic Operations, Quality and Regulatory Affairs, Global Corporate Operations, Scientific Strategic Planning, Scientific R&D Collaborations, and Marketing & Commercialization.

Christopher recently joined OrganaBio as their Vice President of Regulatory Affairs. In this role, Christopher will be helping the company, its clients and partners navigate the complexities of the domestic and international regulatory requirements governing advanced cellular therapy products and manufacturing.

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While with AABB, he held the positions of Senior Director of New Products and Lead Quality Assessor, auditing both domestic and international organizations to known standards in an effort to promote and ensure patient quality care and manufactured product consistency and standardization within Cellular Therapy, Blood Banking, Transfusion Services, Perioperative and Donor Center industries and operations. He contributed greatly to the work of AABB’s accreditation program providing his deep breadth of knowledge and technical acumen on many committees during his tenure. His pioneering work in the realm of virtual assessments during the COVID pandemic allowed AABB to flex into the planning and execution of this novel approach to the maintenance of accreditation activities during a global travel crisis. His agile thinking and approach to planning provided as minimal disruption as possible to AABB’s customer facilities.

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Danielle Smyla, M.S., brings 14 years of Quality Assurance and GMP experience in the Biotechnology and Medical Device industries. Ms. Smyla is an established Quality Leader with expertise in the implementation, management and continuous improvement of Quality Management Systems for GMP operations.

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Sarah Alter, Ph.D.

Lab Director

Sarah Alter, Ph.D., is Laboratory Director at OrganaBio, LLC, where she provides technical leadership across laboratory operations, process development, product manufacturing, and clinical sample processing services supporting cell and gene therapy developers worldwide. She brings more than 20 years of immunology and translational research experience spanning autoimmunity, oncology, and infectious disease.

Since joining OrganaBio in 2018, Dr. Alter has progressed through roles of increasing responsibility, first as Director of Immunology, leading development and manufacturing of human-derived immune cell products for immuno-oncology partners and clients; then as Senior Director of Scientific Affairs, where she served as immunology subject matter expert and shaped scientific strategy across new product launches, market analyses, and client engagements. She also served as founding Managing Director of HemaCenter, LLC, OrganaBio’s FDA-registered leukapheresis collection subsidiary, where she stood up operations, recruited the medical team, and authored governing protocols and SOPs.

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Carlos Carballosa, Ph.D

Vice President, Sales

Dr. Carlos Carballosa holds a doctorate in Biomedical Engineering from the University of Miami and currently leads global sales for OrganaBio as the VP of Sales. Since joining the company in 2018, Carlos has had a hand in managing all of OrganaBio’s products and services including perinatal tissue, apheresis material, and cell processing and cryopreservation support services for clinical trials.

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Oscar Robles has over thirty years of experience in pharmaceutical and medical device industries. His main areas of expertise are in Quality Systems, Quality Assurance, Manufacturing Systems Validation, Computerized Systems Validation, implementation of GxP Computerized Systems and ERP Systems such as TrackWise, Electronic Document Management, JDEwards, SAP, and Oracle. Prior to joining OrganaBio, Oscar was a member of the Quality Management team at Apotex – Aveva Drug Delivery Systems for ten years. Oscar has earned a Master’s in Business Administration from Nova Southeastern University and a Bachelor of Science in Electrical Engineering from Florida International University.

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