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Inflammatory Myositis Donor PBMCs: DM Type I IFN Biology, PM CD8+ Cytotoxicity, Antisynthetase Syndrome, and NAM 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.

Inflammatory myopathies are a heterogeneous group of autoimmune muscle diseases united by immune-mediated muscle injury but mechanistically diverse across four major subtypes: dermatomyositis (DM), polymyositis (PM), antisynthetase syndrome (ASyS), and necrotizing autoimmune myopathy (NAM/IMNM). Each subtype has a distinct peripheral immune signature, a distinct autoantibody profile, and distinct therapeutic targets. DM carries the highest type I interferon score among all autoimmune diseases, making DM peripheral blood the benchmark disease context for JAK inhibitor IFN pharmacodynamic research. NAM involves complement-mediated myocyte necrosis relevant to C5 inhibitor development. ASyS features anti-aminoacyl-tRNA synthetase-specific B cells relevant to B cell depletion studies. PM involves CD8+ T cell-mediated direct myocyte invasion accessible through TCR repertoire and cytotoxicity assays.

Dermatomyositis: The Highest Type I IFN Signature in Autoimmunity

Dermatomyositis is characterized by perimysial inflammation driven predominantly by plasmacytoid dendritic cells (pDCs), CD4+ T cells, and type I interferon signaling. DM carries the highest ISG expression scores among autoimmune diseases — dramatically elevated MX1, IFI44L, IFIT1, IFIT3, and ISG15 are detectable in peripheral blood mononuclear cells at baseline, without stimulation. This IFN-I signature is driven by pDC activation in muscle and skin tissue, with systemic type I IFN spillover into circulation producing the elevated PBMC ISG profile.

DM-specific autoantibodies and their research implications:

  • Anti-TIF1-gamma (anti-p155/140): Most common DM-specific antibody; associated with malignancy-associated DM in adults and severe juvenile DM. TIF1-gamma reactive B cells and T cells provide an autoantigen-specific research system for cancer-associated autoimmunity at the intersection of tumor immunity and self-tolerance.
  • Anti-NXP2 (anti-MJ): Associated with muscle calcinosis in juvenile DM and malignancy in adult DM. NXP2-specific B cell characterization in DM PBMCs enables studying B cell tolerance failure to nuclear protein autoantigens.
  • Anti-MDA5: Associated with rapidly progressive ILD (RP-ILD), ulcerative cutaneous disease, and minimal myopathy. Anti-MDA5 DM has the highest IFN-I score among DM subtypes and is the highest-risk subtype for acute fatal respiratory disease — the primary therapeutic target for JAK inhibitor emergency intervention programs.
  • Anti-Mi-2: Classic DM antibody associated with proximal muscle weakness and skin features; lower IFN score than anti-MDA5; associated with better prognosis and treatment response.

JAK Inhibitor IFN Pharmacodynamics: DM as the Benchmark System

Baricitinib and tofacitinib have shown efficacy in DM clinical trials, with ISG score reduction serving as the primary pharmacodynamic endpoint. DM peripheral blood PBMCs provide the highest-signal IFN pharmacodynamic platform among autoimmune diseases:

  • Baseline ISG expression is 5- to 20-fold elevated versus healthy controls in active DM, providing a wide dynamic range for measuring JAK inhibitor-induced ISG suppression
  • STAT1 phosphorylation (IFN-alpha/beta downstream, JAK1/TYK2 pathway) is elevated in unstimulated DM monocytes and measurably inhibited by JAK1/2 inhibitors at therapeutic concentrations
  • IFN-alpha secretion by DM pDCs in culture can be suppressed by JAK inhibitors (TYK2 target) and by anti-IFNAR antibodies — DM pDC preparations provide the most active IFN-alpha-producing cell population available from autoimmune PBMC sources

Polymyositis: CD8+ T Cell-Mediated Myocyte Invasion

PM (as currently defined, recognizing that many historical PM cases are now reclassified as anti-Jo-1-positive ASyS, anti-SRP NAM, or overlap syndromes) involves endomysial CD8+ T cell infiltration with invasion of non-necrotic muscle fibers. Key CD8+ T cell features in PM peripheral blood:

  • Activated CD8+ T cells with granzyme B, perforin, and NKG2D expression — the direct cytotoxic arsenal for MHC-I-overexpressing muscle fiber invasion
  • Oligoclonal CD8+ TCR expansions consistent with antigen-specific tissue-infiltrating T cell clones — TCR sequencing of PM PBMCs can identify muscle-autoreactive CD8+ clones for further functional characterization
  • CXCR3+CD8+ T cells reflecting IFN-gamma-driven CXCL9/10 production in muscle tissue and systemic Th1 immune activation

Antisynthetase Syndrome: ILD-Associated B Cell and T Cell Biology

Antisynthetase syndrome (ASyS) is defined by anti-aminoacyl-tRNA synthetase antibodies — anti-Jo-1 (histidyl-tRNA synthetase) most commonly, with anti-PL-7, anti-PL-12, anti-EJ, anti-OJ as less common specificities. The clinical triad of ILD, inflammatory myopathy, and inflammatory arthritis (plus Raynaud’s and mechanic’s hands) makes ASyS an overlap syndrome with distinct research considerations:

  • Anti-Jo-1-specific B cells: Jo-1-reactive memory B cells are detectable by recombinant Jo-1 protein probes in flow cytometric assays and Jo-1 antigen ELISPOT from ASyS PBMC preparations. The Jo-1-specific B cell pool represents the primary target for B cell depletion approaches in refractory ASyS.
  • ILD-associated Th17 and CXCR3+ T cells: The ILD component of ASyS is associated with elevated Th17 cells and CXCL10-driven T cell trafficking to lung parenchyma, measurable in peripheral blood. Researchers studying ILD mechanisms in autoimmune conditions — distinct from idiopathic pulmonary fibrosis — benefit from ASyS PBMCs as a T cell-active ILD disease system.
  • IL-6 and IL-17 contribution: Both IL-6 and IL-17A are elevated in ASyS serum and contribute to ILD progression and articular inflammation. JAK inhibitor and IL-17 pathway pharmacodynamics in ASyS PBMCs are relevant for researchers developing therapies for autoimmune ILD broadly.

Necrotizing Autoimmune Myopathy: Complement-Mediated Myocyte Destruction

NAM/IMNM with anti-SRP (signal recognition particle) or anti-HMGCR (3-hydroxy-3-methylglutaryl-coenzyme A reductase, statin-associated) antibodies involves IgG-mediated complement activation at muscle fiber surfaces — producing MAC-mediated myocyte necrosis without the lymphocytic infiltration that characterizes DM and PM. This complement mechanism has several PBMC-accessible research features:

  • Monocyte C5aR1 expression is elevated in active NAM, consistent with systemic complement activation from circulating immune complexes
  • Anti-SRP or anti-HMGCR IgG1 complement activation assays using NAM PBMC-derived immune complexes on complement-sensitive targets provide a functional complement activation readout
  • C5 inhibitor pharmacodynamics — measuring C5a-driven monocyte activation suppression and MAC generation inhibition — are testable in NAM PBMC and monocyte culture systems

Research Applications

  • DM — JAK inhibitor IFN pharmacodynamics: ISG score quantification, STAT1 phosphorylation inhibition, pDC IFN-alpha suppression — all in the highest-IFN disease-context available in autoimmune PBMCs
  • DM — Anti-MDA5 RP-ILD research: Fibrocyte enumeration, pro-fibrotic cytokine profiling, emergency JAK inhibitor response modeling in the highest-acuity DM subtype
  • PM — CD8+ T cell cytotoxicity: Granzyme B/perforin expression profiling, NKG2D characterization, TCR oligoclonal expansion analysis in PM-specific CD8+ T cells
  • ASyS — Anti-Jo-1 B cell biology: Antigen-specific B cell enumeration, Jo-1-specific T cell characterization, ILD-associated Th17/CXCR3 profiling
  • NAM — Complement mechanism: C5aR1 expression, complement activation assays, C5 inhibitor pharmacodynamics in the antibody-mediated necrotizing myopathy context
  • All subtypes — Rituximab pharmacodynamics: B cell depletion profiling, autoantibody titer reduction correlation with B cell compartment changes across MSA subtypes

OrganaBio Inflammatory Myositis Donor Collection Specifications

  • Subtype documented: DM, PM, ASyS, NAM/IMNM; diagnosis confirmed by rheumatologist or neurologist
  • MSA profile documented: anti-Mi-2, anti-TIF1-gamma, anti-NXP2, anti-MDA5, anti-SAE (DM); anti-Jo-1, anti-PL-7/12, anti-EJ, anti-OJ (ASyS); anti-SRP, anti-HMGCR (NAM)
  • Disease activity documented: CK level at collection, CDASI (DM) or MMT8 muscle strength, ILD status (CT-confirmed where available)
  • Treatment history documented: glucocorticoids, azathioprine, MMF, rituximab, IVIG, JAK inhibitor use
  • Anti-MDA5-positive DM cohort available with RP-ILD documentation
  • Same-day processing from apheresis; 30-minute standard; >80% post-thaw viability
  • Available as isolated PBMCs, leukopaks, or fresh whole blood

Related resources: SLE Donor PBMCs: Type I IFN signature comparison | Systemic Sclerosis Donor PBMCs: ILC2s, fibrocytes, and IFN biology | 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.

Meram Alamoudi

Senior Cell Processing Specialist

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.

Valeria Beckhoff-Ferrero

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.

During her studies, Valeria worked at Thomas Jefferson University Hospital’s Radiation Oncology department, where she engineered various devices to aid in hyperthermia treatments. Additionally, Valeria co-authored multiple publications on magnetic resonance guided focused ultrasound and radiation antennas for hyperthermia treatments.

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Director, Regional Scientific Sales

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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.

Thelma has a proven track record in multiple corporate healthcare cultures having worked for Mercy Hospital where she was Senior Program Director of their Diabetes Treatment Center and Director of their Surgical Weight Loss Program. She enhanced these service lines awareness in the community, improved both lines’ clinical outcomes, and built volume growth while maintaining ongoing physician support. She served in a similar capacity for American Healthways.

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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Dominic Mancini brings 12 years of experience working the interfaces between Analytical Development, Process Development, Quality, and Manufacturing Science to OrganaBio. A lifelong learner, Dominic enjoys solving the many scientific and operational challenges presented in the field of cell and gene therapy.

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.

Previously, Christopher held positions with the Association for the Advancement of Blood and Biotherapies (AABB), Virgin Health Bank, Ventana Medical Systems, and Celgene.

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.

While working with Virgin Health Bank in the State of Qatar and the United Kingdom, Christopher advanced through a series of executive roles. He joined Virgin Health Bank as the Director of Operations, during which time he managed the successful design, and build out of a new state-of-the-art cGMP facility, the first in the Middle East. As Director and Chief Executive Officer, he directed the launch of the first Arab-centric stem cell bank, and strategically guided the organization to enhanced shareholder value and expansion across the Middle East and UK. In these roles, he also oversaw global corporate operations, research collaborations, product portfolio expansion, and regulatory framework.

Christopher managed the Detection and Chemistry Assay Development Group for Ventana Medical Systems, a global leader and innovator of tissue-based diagnostic solutions. In this role, he directed overall program goals, optimized resources, and guided technical and product direction in global regulated environments.

Prior to Ventana Medical Systems, he held the position of Director of Operations for the high-growth Cellular Therapeutics Division of Celgene. As a senior-level scientist and member of the executive team, he directed divisional operations, medical affairs and executed business and scientific strategic planning.

Danielle Smyla

Senior Director, Quality Assurance

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.

Prior to joining OrganaBio, Danielle was a key member of the Quality Management team at Canon BioMedical, where she led the cross-functional development and implementation of their Quality Management System. She also managed a team of Quality Specialists and Sr. Specialists, coaching them in the implementation, management and identification of improvements to quality processes.

Ms. Smyla’s Quality-focused career is complimented by valuable hands-on experience in GMP product manufacturing, as well as R&D laboratory experimentation and formulation work in support of product development.

Danielle has earned a Master’s in Biotechnology from the Johns Hopkins University and a Bachelor of Science in Chemistry from the George Washington University.

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.

Earlier in her career, Dr. Alter led preclinical R&D for IL-15–based immunotherapies at Altor BioScience (now ImmunityBio), contributing to programs that advanced into the clinic and co-authoring numerous peer-reviewed publications. She holds a Ph.D. in Immunology from the University of Miami Miller School of Medicine and an M.Sc. in Microbiology from Florida Atlantic University, and is a registered Patent Agent licensed to practice before the U.S. Patent and Trademark Office.

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.

Oscar Robles

Director, Quality Systems

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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