About

Katelyn Connor, M.S., is a graduate of the Narrative Medicine program and serves as an adjunct professor at Columbia University. She teaches writing and literature at Manhattan College and CUNY City College of Technology. With almost a decade of experience in book publishing, her interests include composition rhetoric, illness and disability, death and dying, and spirituality in medical practice.

Research topics

• Medicine
• Immunology
• Biology
• Internal medicine
• Pathology

Selected publications

• IgG4 on the dance floor: Partners swapped by Fab-arm exchange

  Science Immunology · 2026-03-06

  articleSenior authorCorresponding

  Proteomic analysis shows that nearly all circulating human IgG4 undergoes Fab-arm exchange, creating a vast bispecific antibody repertoire.

  PublisherDOI

• Luck gone cold: A trifecta of B cell mutations associates with cryoglobulinemia

  Science Immunology · 2025-04-04

  articleSenior authorCorresponding

  Triple somatic mutations in autoreactive B cells contribute to virus-associated autoimmune disease.

  PublisherDOI

• Permissive central tolerance plus defective peripheral checkpoints licence pathogenic memory B cells in CASPR2-antibody encephalitis

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-01-14 · 2 citations

  preprintOpen access

  Abstract Autoimmunity affects 10% of the population. Within this umbrella, autoantibody-mediated diseases targeting one autoantigen provide a unique opportunity to comprehensively understand the developmental pathway of disease-causing B cells and autoantibodies. While such autoreactivities are believed to be generated during germinal centre reactions, the roles of earlier immune checkpoints in autoantigen-specific B cell tolerance are poorly understood. We address this concept in patients with CASPR2-autoantibody encephalitis and healthy controls. In both groups, comparable and high (∼0.5%) frequencies of unmutated CASPR2-reactive naïve B cells were identified. By contrast, CASPR2-reactive memory B cells were exclusive to patients, and their B cell receptors demonstrated affinity-enhancing somatic mutations with heterogenous binding kinetics. These effector molecules possessed epitope-dependent pathogenic effects in vitro neuronal cultures and in vivo. The unmutated common ancestors of these memory B cells showed a distinctive balance between strong CASPR2 reactivity and very limited binding across the remaining human proteome. Our results are the first to propose mechanisms underlying autoantigen-specific tolerance in humans. We identify permissive central tolerance, defective peripheral tolerance and heterogenous autoantibody binding properties as sequential pathogenic steps which licence CASPR2-directed pathology. By leveraging the basic immunobiology, we rationally direct tolerance-restoring approaches in CASPR2-antibody diseases. This paradigm is applicable across autoimmune conditions.

  PublisherDOI

• Oral Cladribine Capsules for Generalized Myasthenia Gravis: Design of the Actively Recruiting Phase 3 MyClad Study (P1-11.013)

  Neurology · 2025-04-07

  article

  To evaluate the efficacy and safety of a new oral formulation of cladribine versus placebo in generalized myasthenia gravis (gMG).

  PublisherDOI

• Selective degradation of pathogenic autoantibodies by lysosomal targeting chimeras for the treatment of myasthenia gravis

  medRxiv · 2025-11-19 · 1 citations

  preprintOpen access

  Abstract Myasthenia gravis, an autoimmune disease characterized by muscle weakness that can manifest in bulbar dysfunction and respiratory distress, is driven in a subset of patients by autoantibodies against muscle-specific receptor tyrosine kinase (MuSK MG). MuSK MG and other autoantibody mediated disorders are generally treated with broad immunosuppressive approaches such as corticosteroids, plasmapheresis, B cell depletion, or FcRn inhibition, which can impact patient care via systemic side effects, variable responsiveness, and increased susceptibility to infection. We developed a lysosomal targeting chimera (LYTAC) therapeutic (MuSK LYTAC) that combines a MuSK antigen “Bait” capable of selectively binding to the disease-driving antibodies with asialoglycoprotein receptor (ASGPR) ligands that target the resulting immune complexes for degradation by ASGPR-expressing hepatocytes. Our optimized MuSK Bait effectively depleted pathogenic antibodies from the serum of 10 donors with MuSK MG, supporting broad applicability across the patient population. In vitro assays using both Hep G2 cells and primary human hepatocytes demonstrated that MuSK LYTAC is pharmacologically active, promoting uptake and lysosomal degradation of autoantibodies through an ASGPR-dependent mechanism. Mouse pharmacodynamic and passive immunization disease models showed that MuSK LYTAC rapidly eliminates autoantibodies from the serum and alleviates related disease symptoms, without impacting circulating IgG levels. These results support the promise of Autoantibody Bait LYTACs (ABLates) as precision treatments for MuSK MG and other autoantibody-driven diseases that avoid generalized immunosuppression.

  PublisherOA PDFDOI

• Molecular and Functional Characterization of Self-Reactive IgA Autoantibodies in Patients with Muscle-specific Tyrosine Kinase Myasthenia Gravis (S34.007)

  Neurology · 2025-04-07

  articleSenior author

  To investigate the presence and functional role of IgA autoantibodies (Abs) in patients with muscle-specific tyrosine kinase (MuSK) myasthenia gravis (MG).

  PublisherDOI

• AChR Autoantibody Pathogenic Properties Are Heterogeneously Distributed and Undergo Temporal Changes Among Patients With Myasthenia Gravis

  Neurology Neuroimmunology & Neuroinflammation · 2025-07-18 · 9 citations

  articleOpen accessSenior author

  BACKGROUND AND OBJECTIVES: Acetylcholine receptor (AChR) autoantibodies contribute to myasthenia gravis (MG) pathogenesis through 3 mechanisms: complement activation, receptor internalization, and acetylcholine (ACh) binding site blocking. Recently approved therapies target these autoantibodies by inhibiting the complement pathway or blocking the neonatal Fc receptor, reducing IgG autoantibody levels. However, these approaches have limitations: complement inhibitors do not address complement-independent mechanisms, and FcRn blockers only target IgG. Understanding how different pathogenic mechanisms, isotypes, and IgG subclasses are represented in the AChR autoantibody repertoire could lead to more precise application of therapeutics. To address this, we used advanced live cell-based assays to study autoantibody heterogeneity in longitudinally collected patient samples. METHODS: Serum samples (N = 210) from 50 AChR IgG+ generalized MG patients collected longitudinally over 2 years were evaluated using a set of cell-based assays to measure complement activation, receptor internalization, ACh binding site blocking, and the frequency of the IgM and IgA isotypes and IgG subclasses. RESULTS: In cross-sectional samples, IgA and IgM autoantibodies co-occurred with IgG in 10% and 12% of patients, respectively. In addition, 4% of patients had all 3 isotypes (IgA, IgM, and IgG) present simultaneously. AChR-IgG1 was found in 67.4%, followed by IgG3 (21.7%) and IgG2 (17.4%). Complement was active in 84.8%, followed by AChR internalization (63%) and blocking (30.4%). Complement and AChR internalization were simultaneously active in 45.6%, complement and blocking were active in 10.8%, and all 3 pathomechanisms were active in 17.4%. Blocking alone was active in only 2.1%; AChR internalization alone was not found. Autoantibody binding capacity was associated with the magnitude of complement activation and AChR internalization. Temporal fluctuations of autoantibody binding capacity and the associated pathogenic mechanisms were observed. Pathogenic mechanisms were not associated with disease severity in cross-sectional analyses. However, longitudinally, disease severity measures followed a similar trend to the AChR autoantibody repertoire and mediated pathogenic mechanisms in some individuals, but not others. DISCUSSION: These findings highlight subsets of patients with MG with autoantibodies that can mediate pathogenic mechanisms or include isotypes that some therapeutics may not effectively target. Consequently, we suggest incorporating comprehensive autoantibody profiling into future MG clinical trials to further investigate potential associations with treatment outcomes.

  PublisherOA PDFDOI

• B Cell Tolerance and BCR Signaling Dysregulation in NF155-Mediated Autoimmune Nodopathies

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-08-12 · 2 citations

  preprintOpen accessSenior author

  Objective: Autoimmune nodopathies (AINs) are a group of rare, acquired autoimmune neuropathies with distinct clinical features and the presence of circulating autoantibodies - often of the immunoglobulin G4 (IgG4) subclass - targeting proteins at the node of Ranvier. Defects in B cell tolerance checkpoints have been implicated in several autoimmune diseases. Prior work identified defective B cell tolerance-reflected by a high frequency of self-reactive naïve B cells-in patients with MuSK-positive myasthenia gravis (MG), mediated by IgG4 autoantibodies. Here, we investigated whether tolerance defects exist in neurofascin-155-mediated AIN (NF155-AIN), similar to MuSK+ MG. Additionally, we analyzed B and T cell transcriptomics and interactions at the single-cell level to explore the underlying pathomechanism. Methods: Using a well-established assay, we assessed B cell tolerance fidelity by generating recombinant antibodies from new emigrant (NE) and mature naïve (MN) B cell populations- directly downstream of key tolerance checkpoints-from three NF155-AIN patients, and testing these antibodies for polyreactivity and autoreactivity, thereby determining the frequency of polyreactive and autoreactive B cells. The transcriptome of peripheral blood mononuclear cells (PBMC) was studied, with a special focus on naïve B cells and CD4+ T cells at the single-cell level, along with characterization of cell-cell interactions. Results: NF155-AIN patients have an elevated frequency of polyreactive B cells in the NE (37.4% compared to 9.7% in healthy controls (HCs), p = 0.03) and MN (31.5% compared to 10.5% in HCs, p = 0.03) compartments with increased B cell clones expressing autoreactive antibodies, consistent with a breach in early tolerance checkpoints. We observed abnormal B cell receptor (BCR) signaling characterized by low CD79B, CSK, BLNK, and BTK expression, which may contribute to a breach in B cell tolerance. We also observed evidence of impaired follicular helper T cells (Tfh) and regulatory T cells (Treg), which may limit the normal development and suppression of autoreactive B cells. Moreover, comparative gene expression analysis of B cells and CD4+ T cells from three patients with chronic inflammatory demyelinating polyneuropathy (CIDP) -a related autoimmune neuropathy- confirmed that these differences are largely specific to NF155-AIN, supporting a distinct pathophysiology in this subset. Conclusion: These findings demonstrated a breach in early B cell tolerance checkpoints, defective BCR signaling, and disrupted T cell-B cell interactions in NF155-AIN, all of which may contribute to the development of pathogenic autoreactivity. These immunologic abnormalities appear distinct from those seen in CIDP, supporting NF155-AIN as a unique immunopathologic entity.

  PublisherOA PDFDOI

• Composition and function of AChR chimeric autoantibody receptor T cells for antigen-specific B cell depletion in myasthenia gravis

  Science Advances · 2025-02-28 · 7 citations

  articleOpen access

  In acetylcholine receptor (AChR)-seropositive myasthenia gravis (MG), anti-AChR autoantibodies impair neuromuscular transmission and cause severe muscle weakness. MG therapies broadly suppress immune function, risking infections. We designed a chimeric autoantibody receptor (CAAR) expressing the 210-amino acid extracellular domain of the AChR α subunit (A210) linked to CD137-CD3ζ cytoplasmic domains to direct T cell cytotoxicity against anti-AChRα B cells. A210-CAART incorporating a CD8α transmembrane domain (TMD8α) showed functional but unstable surface expression, partially restored by inhibiting lysosomal degradation. A210-CAART with a CD28 TMD showed sustained surface expression, independent of TMD dimerization motifs. In a mouse xenograft model, A210.TMD8α-CAART demonstrated early control of anti-AChR B cell outgrowth but subsequent rebound and loss of surface CAAR expression, whereas A210.TMD28-CAART induced sustained surface CAAR expression and target cell elimination. This study demonstrates the importance of the CD28 TMD for CAAR stability and in vivo function, laying the groundwork for future development of precision cellular immunotherapy for AChR-MG.

  PublisherDOI

• Screening for Congenital Myasthenic Syndromes in Adults With Seronegative Myasthenia Gravis Using Next-Generation Sequencing

  Neurology · 2025-09-26 · 2 citations

  article

  BACKGROUND AND OBJECTIVES: Myasthenia gravis (MG) is a disorder of the neuromuscular junction, typically associated with autoantibodies (Abs) that impair neuromuscular transmission. However, approximately 10% of cases are seronegative. Emerging evidence suggests that seronegative MG (SNMG) may be mimicked by hereditary conditions, particularly congenital myasthenic syndromes (CMSs), which require different treatments. In this study, we aimed to determine the proportion of CMS among patients diagnosed with SNMG. METHODS: We used whole-exome sequencing (WES) in adult patients (aged ≥18 years) diagnosed with SNMG who were enrolled at 3 Austrian tertiary neuromuscular centers between August 2022 and January 2024. Genetic testing was conducted in individuals who remained seronegative after comprehensive serologic testing to exclude Abs against (clustered) acetylcholine receptors, muscle-specific kinase, lipoprotein receptor-related protein 4, and voltage-gated calcium channels. Moreover, we aimed to analyze clinical and demographic factors associated with the likelihood of receiving a molecular diagnosis. RESULTS: = 0.29), no clinical or demographic factors remained significantly associated with a molecular diagnosis after correction for multiple testing. Only 1 patient with a confirmed CMS diagnosis reported a positive family history. Six individuals with CMS (86%) had either received immunomodulatory treatments (n = 4) or undergone thymectomy (n = 4). Of the 4 patients with CMS receiving immunotherapies, 3 were reported to have experienced at least a partial response. DISCUSSION: Our findings provide evidence that a considerable proportion of patients diagnosed with SNMG have an underlying hereditary etiology. Notably, a (subjective) response to immunotherapies does not exclude a molecular CMS diagnosis. In conclusion, offering genetic testing to seronegative patients with myasthenic syndromes may have profound therapeutic implications.

  PublisherDOI

Frequent coauthors

• David A. Hafler

  Broad Institute

  201 shared

• Steven H. Kleinstein

  157 shared

• Gur Yaari

  144 shared

• Simon N. Willis

  University of Melbourne

  94 shared

• Richard J. Nowak

  85 shared

• Laura Lovato

  Ospedale Maggiore di Chieri

  85 shared

• Joel N. H. Stern

  Arthur Smith Institute for Urology

  78 shared

• Luís Querol

  69 shared

Labs

• Katelyn Connor, M.S. | Columbia University School of Professional StudiesPI

Education

• Post-doctoral, Immunology

  Harvard Medical School

  2003

• PhD, Biochemistry

  Tufts University School of Medicine

  2000

• BS , Chemistry

  University of Massachusetts Amherst

  1988